Clinical Review

From the Center for Child and Adolescent Health Research and Policy, Division of General Academic Pediatrics, Massachusetts General Hospital for Children, and the Tobacco Research and Treatment Center, Massachusetts General Hospital, Boston, MA.

Abstract

• Objective: To explain the concept of thirdhand smoke and how it can be used to protect the health of children and improve delivery of tobacco control interventions for parents in the child health care setting.
• Methods: Review of the literature and descriptive report.
• Results: The thirdhand smoke concept has been used in the CEASE intervention to improve the delivery of tobacco control counseling and services to parents. Materials and techniques have been developed for the child health care setting that use the concept of thirdhand smoke. Scientific findings demonstrate that thirdhand smoke exposure is harmful and establishes the need for clinicians to communicate the cessation imperative: the only way to protect non-smoking household members from thirdhand smoke is for all household smokers to quit smoking completely. As the scientific knowledge of thirdhand smoke increases, advocates will likely rely on it to encourage completely smoke-free places.
• Conclusion: Recent scientific studies on thirdhand smoke are impelling further research on the topic, spurring the creation of tobacco control policies to protect people from thridhand smoke and stimulating improvements to the delivery of tobacco control counseling and services to parents in child health care settings.

Key words: thirdhand smoke; smoking; tobacco; indoor air quality; smoking cessation; pediatrics.

While “thirdhand smoke” may be a relatively new term, it is rooted in an old concept—the particulate matter and residue from tobacco smoke left behind after tobacco is burned. In 1953, Dr. Ernest Wynder and his colleagues from the Washington University School of Medicine in St. Louis showed that condensate made from the residue of cigarette smoke causes cancer [1]. This residue left behind by burning cigarettes is now known as thirdhand smoke [2]. Dr. Wynder used acetone to rinse the leftover tobacco smoke residue from a smoking chamber where he had burned cigarettes. He then painted the solution of acetone and thirdhand smoke residue onto the backs of mice. The results of Dr. Wynder’s study demonstrated that exposed mice developed cancerous skin lesions, whereas mice exposed to the acetone alone did not display skin lesions. Dr. Wynder sounded an alarm bell in his manuscript when he wrote, “Such studies, in view of the corollary clinical data relating smoking to various types of cancer, appear urgent. They may result not only in furthering our knowledge of carcinogenesis, but in promoting some practical aspects of cancer prevention [1].”

Decades of research has been conducted since Dr. Wynder’s discovery to definitively conclude that smoking tobacco and exposure to secondhand tobacco smoke is harmful to human health. It is estimated that 480,000 annual premature deaths in the United States alone are attributable to smoking and exposure to secondhand smoke [3]. The World Health Organization estimates that worldwide tobacco use is responsible for more than 7 million deaths per year, with 890,000 of those deaths caused by secondhand smoke exposure of nonsmokers [4]. Epidemiological evidence of the harm posed by tobacco has spurred the U.S Surgeon General to conclude that there is no risk-free level of exposure to tobacco smoke [5]. Despite the overwhelming evidence implicating tobacco as the cause of an unprecedented amount of disease resulting from the use of a consumer product, only recently has a dedicated research agenda been pursued to study what Dr. Wynder urgently called for back in 1953: further exploration of the health effects of thirdhand tobacco smoke.

The term "thirdhand smoke" was first coined in 2006 by researchers with the Clinical Effort Against Secondhand Smoke Exposure (CEASE) program at Massachusetts General Hospital in Boston [6], and recent research has begun to shed considerable light on the topic. In 2011, a research consortium of scientists funded by the Tobacco-Related Disease Research Program [7] in California was set up to conduct pioneering research on the characterization, exposure and health effects of thirdhand tobacco smoke [8]. Research findings from this consortium and other scientists from around the world are quickly expanding and disseminating knowledge on this important topic.

While the research on thirdhand smoke is ongoing, this paper summarizes the current literature most relevant to the pediatric population and outlines clinical and policy recommendations to protect children and families from the harms of exposure to thirdhand smoke.

What Is Thirdhand Smoke and How Is It Different from Secondhand Smoke?

Thirdhand smoke is a result of combusted tobacco, most often from smoking cigarettes, pipes, cigars, or cigarillos. Thirdhand smoke remains on surfaces and in dust for a longtime after smoking happens, reacts with oxidants and other compounds to form secondary pollutants, and is re-emitted as a gas and/or resuspended when particles are disturbed and go back into the air where they can be inhaled [9]. One dramatic example of how thirdhand smoke can remain on surfaces long after secondhand smoke dissipates was discovered on the ornate constellation ceiling in the main concourse of the Grand Central Terminal in New York City. According to Sam Roberts, a correspondent for the New York Times and the author of a book about the historic train station, the dark residue that accumulated on the concourse ceiling over decades and was originally believed to be the result of soot from train engines was primarily residue from tobacco smoke [10–12]. It wasn’t until a restoration in the 1990s when workers scrubbed the tar and nicotine residue from the ceiling could the elaborate design of the zodiac signs and constellations be seen again [13]. A similar process takes place inside homes, where smoke residue accumulates on surfaces such as walls and ceilings after smoking happens. Owners of homes that have been previously smoked in are faced with unanswered questions about how to clean up the toxic substances left behind.

When tobacco is smoked, the particulates contained in secondhand smoke settle on surfaces; this contamination is absorbed deep into materials such as hair, clothes, carpeting, furniture, and wallboard [9,14]. After depositing onto surfaces, the chemicals undergo an aging process, which changes the chemical structure of the smoke pollutants. The nicotine in thirdhand smoke residue reacts with common indoor air pollutants, such as nitrous acid and ozone, to form hazardous substances. When the nicotine present in thirdhand smoke reacts with nitrous acid, it forms carcinogenic tobacco-specific nitrosamines such as NNK and NNN [15–17]. Nicotine also reacts with ozone to form additional harmful ultrafine particles that can embed deep within the lungs when inhaled [18]. As thirdhand smoke ages, it becomes more toxic [15]. The aged particles then undergo a process called “off-gassing,” in which gas is continuously re-emitted from these surfaces back into the air [19]. This process of off-gassing occurs long after cigarettes have been smoked indoors [19,20]. Thirdhand smoke particles can also be inhaled when they get resuspended into the air after contaminated surfaces are disturbed [21].

Common practices employed by smokers, like smoking in different rooms, using fans to diffuse the smoke, or opening windows, do not prevent the formation and inhalation of thirdhand smoke by people living or visiting these indoor spaces [22]. Environments with potential thirdhand smoke exposure include homes of smokers [23], apartments and homes previously occupied by smokers [24], multiunit housing where smoking is permitted [25], automobiles that have been smoked in [26], hotel rooms where smoking is permitted [27], and other indoor places where smoking has occurred.

Research Supports Having Completely Smoke-Free Environments

Recent research has shown that exposure to thirdhand smoke is harmful. These findings, many of which are described below, offer strong support in favor of advocating for environments free of thirdhand smoke contamination for families and children.

Genetic Damage from Thirdhand Smoke Exposure

In 2013, researchers from the Lawrence Berkeley National Laboratory were the first to demonstrate that thirdhand smoke causes significant genetic damage to human cells [28]. Using in vitro assays, the researchers showed that thirdhand smoke is a cause of harm to human DNA in the form of strand breaks and oxidative damage, which leads to mutations that can cause cancer. The researches also specifically tested the effect of NNA, a tobacco-specific nitrosamine that is commonly found in thirdhand smoke but not in secondhand smoke, on human cell cultures and found that it caused significant damage to DNA [28].

Children Show Elevated Biomarkers of Thirdhand Smoke Exposure in Their Urine and Hair Samples

In 2004, Matt and colleagues described how they collected household dust samples from living rooms and infants’ bedrooms [23]. Their research demonstrated that nicotine accumulated on the living room and infants’ bedroom surfaces of the homes belonging to smokers. Significantly higher amounts of urine cotinine, a biomarker for exposure to nicotine, were detected among infants who lived in homes where smoking happens inside compared to homes where smokers go outside to smoke [23]. As well, a study published in 2017 that measured the presence of hand nicotine on children of smokers who presented to the emergency room for an illness possibly related to tobacco smoke exposure detected hand nicotine on the hands of each child who participated in this pilot study. The researchers found a positive correlation between the amount of nicotine found on children’s hands and the amount of cotinine, a biomarker for nicotine exposure, detected in the children’s saliva [29].

Children Are Exposed to Higher Ratios of Thirdhand Smoke than Adults

In 2009, researchers discovered that the thirdhand smoke ratio of tobacco-specific nitrosamines to nicotine increases during the aging process [9]. Biomarkers measured in the urine can now be used to estimate the degree to which people have been exposed to secondhand or thirdhand smoke based on the ratio of the thirdhand smoke biomarker NNK and nicotine. Toddlers who live with adults who smoke have higher NNK/nicotine ratios, suggesting that they are exposed to a higher ratio of thirdhand smoke compared to secondhand smoke than adults [30]. Young children are likely exposed to higher ratios of thirdhand smoke as they spend more time on the floor, where thirdhand smoke accumulates. They frequently put their hands and other objects into their mouths. Young children breathe faster than adults, increasing their inhalation exposure and also have thinner skin, making dermal absorption more efficient [9].

Modeling Excess Cancer Risk

A 2014 United Kingdom study used official sources of toxicological data about chemicals detected in thirdhand smoke–contaminated homes to assess excess cancer risk posed from thirdhand smoke [17]. Using dust samples collected from homes where a smoker lived, they estimate that the median lifetime excess cancer risk from the exposure to all the nitrosamines present in thirdhand smoke is 9.6 additional cancer cases per 100,000 children exposed and could be as high as 1 excess cancer case per 1000 children exposed. The researchers concluded that young children aged 1 to 6 are at an especially increased risk for cancer because of their frequent contact with surfaces contaminated with thirdhand smoke and their ingestion of the particulate matter that settles on surfaces after smoking takes place [17].

Infants in Health Care Facilities Are Exposed to Thirdhand Smoke

Researchers have observed biomarkers confirming thirdhand smoke exposure in the urine of infants in the NICU. Found in incubators and cribs, particulates are likely being deposited in the NICU from visitors who have thirdhand smoke on their clothing, skin, and hair [31].

Animal Studies Link Thirdhand Smoke Exposure to Common Human Disease

Mice exposed to thirdhand smoke under conditions meant to simulate levels similar to human exposure are pre-diabetic, are at higher risk of developing metabolic syndrome, have inflammatory markers in the lungs that increase the risk for asthma, show slow wound healing, develop nonalcoholic fatty liver disease, and become behaviorally hyperactive [32]. Another recent study published in 2017 showed that mice exposed to thirdhand smoke after birth weighed less than mice not exposed to thirdhand smoke. Additionally, mice exposed to thirdhand smoke early in life showed changes in white blood cell counts that persisted into adulthood [9,33].

Summary

In summary, recent research makes a compelling case for invoking the precautionary principle to ensure that children avoid exposures to thirdhand smoke in their homes, cars, and healthcare settings. Studies reveal that:

• children live in homes where thirdhand smoke is present and this exposure is detectable in their bodies [23]
• concentrations of thirdhand smoke exposure observed in children are disproportionately higher than adults [30]
• chemicals present in thirdhand smoke cause damage to DNA [28]
• thirdhand smoke contains carcinogens that put exposed children at increased risk of cancer [17]
• thirdhand smoke is being detected within medical settings [34] and in the bodies of medically-vulnerable children [29], and
• animal studies have linked exposure to thirdhand smoke to a number of adverse health conditions commonly seen in today’s pediatric population such as metabolic syndrome, prediabetes, asthma, hyperactivity [32] and low birth weight [33].

Using the Thirdhand Smoke Concept in Clinical Practice

The clinical setting is an ideal place to address thirdhand smoke with families as a component of a comprehensive tobacco control strategy.

The Cessation Imperative—A Novel Motivational Message Prompted by Thirdhand Smoke

While there are potentially many ways to address thirdhand smoke exposure with families, the CEASE program has been used in the primary care setting to train child health care clinicians and office staff to address second- and thirdhand smoke. The training also educates clinicians on providing cessation counseling and resources to families with the goal of helping all family members become tobacco free, as well as to helping families keep completely smoke-free homes and cars [35,36]. The concept of thirdhand smoke creates what we have coined the cessation imperative [36]. The cessation imperative is based on the notion that the only way to protect non-smoking family and household members from thirdhand smoke is for all household smokers to quit smoking completely. Smoking, even when not in the presence of children, can expose others to toxic contaminates that settle on the surfaces of the home, the car as well as to the skin, hair, and clothing of family members who smoke. A discussion with parents about eliminating only secondhand smoke exposure for children does not adequately address how continued smoking, even when children are not present, can be harmful. The thirdhand smoke concept can be presented early, making it an efficient way to advocate for completely smoke-free families.

Thirdhand Smoke Counseling Helps Clinicians Achieve Key Tobacco Control Goals

The American Academy of Pediatrics (AAP) and the American Academy of Family Physicians (AAFP) recommend that health care providers deliver advice to parents regarding establishing smoke-free homes and cars and provide information about how their smoking adversely affects their children’s health [37,38]. It is AAP and AAFP policy that health care providers provide tobacco dependence treatment and referral to cessation services to help adult family members quit smoking [38,39]. Successfully integrating counseling around the topic of thirdhand smoke into existing smoking cessation service delivery is possible. The CEASE research and implementation team developed and disseminated educational content to clinicians about thirdhand smoke through AAP courses delivered online [40] as well as made presentations to clinicians at AAP-sponsored training sessions. Thirdhand smoke messaging has been included in the CEASE practice trainings so that participating clinicians in pediatric offices are equipped to engage parents on this topic. Further information about these educational resources and opportunities can be obtained from the AAP Julius B. Richmond Center of Excellence website [41] and from the Massachusetts General Hospital CEASE program’s website [42].

Counseling parents about thirdhand smoke can help assist parents with their smoking in the critical context of their child’s care. Most parents see their child’s health care clinician more often than their own [43]. Increasing the number of pediatric clinical encounters where parental smoking is addressed while also increasing the effectiveness of these clinical encounters by increasing parents’ motivation to protect their children from tobacco smoke exposure are important goals. The topic of thirdhand smoke is a novel concept that clinicians can use to engage with parents around their smoking in a new way. Recent research conducted by the CEASE team suggests that counseling parents in the pediatric setting about thirdhand smoke can be useful in helping achieve tobacco control goals with families. Parent’s belief about thirdhand smoke is associated with the likelihood the parent will take concrete steps to protect their child. Parents who believe thirdhand smoke is harmful are more likely to protect their children from exposure by adopting strictly enforced smoke-free home and car rules [44]. Parents who changed their thirdhand smoke beliefs over the course of a year to believing that thirdhand smoke is harmful were more likely to try to quit smoking [44].

Child health care clinicians are effective at influencing parents’ beliefs about the potential harm thirdhand smoke poses to their children. Parents who received advice from pediatricians to quit smoking or to adopt smoke-free home or policies were more likely to believe that thirdhand smoke was harmful to the health of children [45]. Fathers (as compared with mothers) and parents who smoked more cigarettes each day were less likely to accept that thirdhand smoke is harmful to children [45]. Conversely, delivering effective educational messages and counseling around the topic of thirdhand smoke to parents may help promote smoke-free rules and acceptance of cessation assistance.

Protect Patients from Thirdhand Smoke Risks

All health care settings should be completely smoke-free. Smoking bans help protect all families and children from second and thirdhand smoke exposure. It is especially important for medically vulnerable children to visit facilities free from all forms of tobacco smoke contamination. CEASE trainings encourage practices to implement a zone of wellness on the grounds of the healthcare facility by completely banning smoking. The CEASE implementation team also trains practice leaders to reach out to all staff that use tobacco and offer resources and support for quitting. Having a non-smoking staff sets a great example for families who visit the healthcare facility, and reduces the likelihood of bringing thirdhand smoke contaminates into the facility. Creating a policy that addresses thirdhand smoke exposure is a concrete step that health care organizations can take to protect patients.

Thirdhand Smoke Resources Developed and/or Used by the CEASE Program

The CEASE program has developed and/or identified a number of clinical resources to educate parents and clinicians about thirdhand smoke. These free resources can enhance awareness of thirdhand smoke and help promote the use of the thirdhand smoke concept in clinical practice.

• Posters with messages designed to educate parents about thirdhand smoke to encourage receipt of cessation resources were created for use in waiting areas and exam rooms of child health care practices. A poster for clinical practice (Figure 1) can be downloaded and printed from the CEASE program website [42].
• Health education handouts that directly address thirdhand smoke exposure are available. The handouts can be taken home to family members who are not present at the visit and contain the telephone number for the tobacco quitline service, which connects smokers in the United States with free telephone support for smoking cessation. Handouts for clinical practice can be downloaded and printed from the CEASE program website. Figure 2 shows a handout that encourages parents to keep a smoke-free car by pointing out that tobacco smoke stays in the car long after the cigarette is out.
  
• Videos about thirdhand smoke can be viewed by parents while in child health care offices or shared on practice websites or social media platforms. The CEASE program encourages practices to distribute videos about thirdhand smoke to introduce parents to the concept of thirdhand smoke and to encourage parents to engage in a discussion with their child’s clinicians about ways to limit thirdhand smoke exposure. Suitable videos for parental viewing include the 2 listed below, which highlight information from the Thirdhand Smoke Research Consortium.
    -University of California Riverside https://youtu.be/i1rhqRy-2e8
   -San Diego State University https://youtu.be/rqzi-9sXLdU
• Letters for landlords and management companies were created to stress the importance of providing a smoke-free living environment for children. The letters are meant to be signed by the child’s health care provider. The letters state that eliminating smoking in their buildings would result in landlords that “Pay less for cleaning and turnover fees.” Landlord letter templates can be downloaded and printed from the CEASE program website [42].
• Educational content for child health care clinicians about thirdhand smoke and how to counsel parents is included in the American Academy of Pediatrics Education in Quality Improvement for Pediatric Practice (EQIPP) online course entitled “Eliminating Tobacco” Use and Exposure to Secondhand Smoke. A section devoted to educating clinicians on the topic of thirdhand smoke is presented in this course. The course can be accessed through the AAP website and it qualifies for American Board of Pediatrics maintenance of certification part IV credit [40].

The CEASE team has worked with mass media outlets to communicate the messages about thirdhand smoke to build public awareness. The Today Show helped to popularize the concept of thirdhand smoke in 2009 after a paper published in the journal Pediatrics linked thirdhand smoke beliefs to home smoking bans [2].

Systems Approaches to Reduce Thirdhand Smoke Exposure

Public Policy Approaches

A clear policy agenda can help people protect their families from exposure to thirdhand smoke [46]. Policy approaches that have worked for lead, asbestos, and radon are examples of common household contaminants that are regulated using different mechanisms in an effort to protect the public health [46]. Strengths and weaknesses in each of these different approaches should be carefully considered when developing a comprehensive policy agenda to address thirdhand smoke. Recently, research on the health effects of thirdhand smoke spurred the passage of California legislative bill AB 1819 that “prohibits smoking tobacco at all times in the homes of licensed family child care homes and in areas where children are present [47].” As well, a recent US Department of Housing and Urban Development rule was finalized that requires all public housing agencies to implement a smoke-free policy by 30 July 2018 [48]. Smoke-free housing protects occupants from both secondhand and thirdhand smoke exposure. Pediatricians and other child health care professionals are well positioned to advocate for legislative actions that protect children from harmful exposures to thirdhand smoke.

Practice Change in Child Health Care Settings

Designing health care systems to screen for tobacco smoke exposure and to provide evidence-based cessation resources for all smokers is one of the best ways to reduce exposures to thirdhand smoke. Preventing thirdhand smoke exposure can work as novel messaging to promote tobacco cessation programs. Developing electronic medical record systems that allow for documentation of the smoking status of household members and whether or not homes and cars are completely smokefree can be particularly helpful tools for child health care providers when addressing thirdhand smoke with families. Good documentation about smoke-free homes and cars can enhance follow-up discussions with families as they work towards reducing thirdhand smoke exposures.

Summary

The thirdhand smoke concept has been used to improve delivery of tobacco control counseling and services for parents in the child health care context. Free materials are available that utilize thirdhand smoke messaging. As the science of thirdhand smoke matures, it will increasingly be used to help promote completely smoke-free places. The existing research on thirdhand smoke establishes the need for clinicians to communicate the cessation imperative. By using it, clinicians can help all smokers and non-smokers understand that there is no way to smoke tobacco without exposing friends and family.

Corresponding author: Jeremy E. Drehmer, MPH, 125 Nashua St., Suite 860, Boston, MA 02114, jdrehmer@ mgh.harvard.edu.

Financial disclosures: None

From the Center for Child and Adolescent Health Research and Policy, Division of General Academic Pediatrics, Massachusetts General Hospital for Children, and the Tobacco Research and Treatment Center, Massachusetts General Hospital, Boston, MA.

Abstract

• Objective: To explain the concept of thirdhand smoke and how it can be used to protect the health of children and improve delivery of tobacco control interventions for parents in the child health care setting.
• Methods: Review of the literature and descriptive report.
• Results: The thirdhand smoke concept has been used in the CEASE intervention to improve the delivery of tobacco control counseling and services to parents. Materials and techniques have been developed for the child health care setting that use the concept of thirdhand smoke. Scientific findings demonstrate that thirdhand smoke exposure is harmful and establishes the need for clinicians to communicate the cessation imperative: the only way to protect non-smoking household members from thirdhand smoke is for all household smokers to quit smoking completely. As the scientific knowledge of thirdhand smoke increases, advocates will likely rely on it to encourage completely smoke-free places.
• Conclusion: Recent scientific studies on thirdhand smoke are impelling further research on the topic, spurring the creation of tobacco control policies to protect people from thridhand smoke and stimulating improvements to the delivery of tobacco control counseling and services to parents in child health care settings.

Key words: thirdhand smoke; smoking; tobacco; indoor air quality; smoking cessation; pediatrics.

While “thirdhand smoke” may be a relatively new term, it is rooted in an old concept—the particulate matter and residue from tobacco smoke left behind after tobacco is burned. In 1953, Dr. Ernest Wynder and his colleagues from the Washington University School of Medicine in St. Louis showed that condensate made from the residue of cigarette smoke causes cancer [1]. This residue left behind by burning cigarettes is now known as thirdhand smoke [2]. Dr. Wynder used acetone to rinse the leftover tobacco smoke residue from a smoking chamber where he had burned cigarettes. He then painted the solution of acetone and thirdhand smoke residue onto the backs of mice. The results of Dr. Wynder’s study demonstrated that exposed mice developed cancerous skin lesions, whereas mice exposed to the acetone alone did not display skin lesions. Dr. Wynder sounded an alarm bell in his manuscript when he wrote, “Such studies, in view of the corollary clinical data relating smoking to various types of cancer, appear urgent. They may result not only in furthering our knowledge of carcinogenesis, but in promoting some practical aspects of cancer prevention [1].”

Decades of research has been conducted since Dr. Wynder’s discovery to definitively conclude that smoking tobacco and exposure to secondhand tobacco smoke is harmful to human health. It is estimated that 480,000 annual premature deaths in the United States alone are attributable to smoking and exposure to secondhand smoke [3]. The World Health Organization estimates that worldwide tobacco use is responsible for more than 7 million deaths per year, with 890,000 of those deaths caused by secondhand smoke exposure of nonsmokers [4]. Epidemiological evidence of the harm posed by tobacco has spurred the U.S Surgeon General to conclude that there is no risk-free level of exposure to tobacco smoke [5]. Despite the overwhelming evidence implicating tobacco as the cause of an unprecedented amount of disease resulting from the use of a consumer product, only recently has a dedicated research agenda been pursued to study what Dr. Wynder urgently called for back in 1953: further exploration of the health effects of thirdhand tobacco smoke.

The term "thirdhand smoke" was first coined in 2006 by researchers with the Clinical Effort Against Secondhand Smoke Exposure (CEASE) program at Massachusetts General Hospital in Boston [6], and recent research has begun to shed considerable light on the topic. In 2011, a research consortium of scientists funded by the Tobacco-Related Disease Research Program [7] in California was set up to conduct pioneering research on the characterization, exposure and health effects of thirdhand tobacco smoke [8]. Research findings from this consortium and other scientists from around the world are quickly expanding and disseminating knowledge on this important topic.

While the research on thirdhand smoke is ongoing, this paper summarizes the current literature most relevant to the pediatric population and outlines clinical and policy recommendations to protect children and families from the harms of exposure to thirdhand smoke.

What Is Thirdhand Smoke and How Is It Different from Secondhand Smoke?

Thirdhand smoke is a result of combusted tobacco, most often from smoking cigarettes, pipes, cigars, or cigarillos. Thirdhand smoke remains on surfaces and in dust for a longtime after smoking happens, reacts with oxidants and other compounds to form secondary pollutants, and is re-emitted as a gas and/or resuspended when particles are disturbed and go back into the air where they can be inhaled [9]. One dramatic example of how thirdhand smoke can remain on surfaces long after secondhand smoke dissipates was discovered on the ornate constellation ceiling in the main concourse of the Grand Central Terminal in New York City. According to Sam Roberts, a correspondent for the New York Times and the author of a book about the historic train station, the dark residue that accumulated on the concourse ceiling over decades and was originally believed to be the result of soot from train engines was primarily residue from tobacco smoke [10–12]. It wasn’t until a restoration in the 1990s when workers scrubbed the tar and nicotine residue from the ceiling could the elaborate design of the zodiac signs and constellations be seen again [13]. A similar process takes place inside homes, where smoke residue accumulates on surfaces such as walls and ceilings after smoking happens. Owners of homes that have been previously smoked in are faced with unanswered questions about how to clean up the toxic substances left behind.

When tobacco is smoked, the particulates contained in secondhand smoke settle on surfaces; this contamination is absorbed deep into materials such as hair, clothes, carpeting, furniture, and wallboard [9,14]. After depositing onto surfaces, the chemicals undergo an aging process, which changes the chemical structure of the smoke pollutants. The nicotine in thirdhand smoke residue reacts with common indoor air pollutants, such as nitrous acid and ozone, to form hazardous substances. When the nicotine present in thirdhand smoke reacts with nitrous acid, it forms carcinogenic tobacco-specific nitrosamines such as NNK and NNN [15–17]. Nicotine also reacts with ozone to form additional harmful ultrafine particles that can embed deep within the lungs when inhaled [18]. As thirdhand smoke ages, it becomes more toxic [15]. The aged particles then undergo a process called “off-gassing,” in which gas is continuously re-emitted from these surfaces back into the air [19]. This process of off-gassing occurs long after cigarettes have been smoked indoors [19,20]. Thirdhand smoke particles can also be inhaled when they get resuspended into the air after contaminated surfaces are disturbed [21].

Common practices employed by smokers, like smoking in different rooms, using fans to diffuse the smoke, or opening windows, do not prevent the formation and inhalation of thirdhand smoke by people living or visiting these indoor spaces [22]. Environments with potential thirdhand smoke exposure include homes of smokers [23], apartments and homes previously occupied by smokers [24], multiunit housing where smoking is permitted [25], automobiles that have been smoked in [26], hotel rooms where smoking is permitted [27], and other indoor places where smoking has occurred.

Research Supports Having Completely Smoke-Free Environments

Recent research has shown that exposure to thirdhand smoke is harmful. These findings, many of which are described below, offer strong support in favor of advocating for environments free of thirdhand smoke contamination for families and children.

Genetic Damage from Thirdhand Smoke Exposure

In 2013, researchers from the Lawrence Berkeley National Laboratory were the first to demonstrate that thirdhand smoke causes significant genetic damage to human cells [28]. Using in vitro assays, the researchers showed that thirdhand smoke is a cause of harm to human DNA in the form of strand breaks and oxidative damage, which leads to mutations that can cause cancer. The researches also specifically tested the effect of NNA, a tobacco-specific nitrosamine that is commonly found in thirdhand smoke but not in secondhand smoke, on human cell cultures and found that it caused significant damage to DNA [28].

Children Show Elevated Biomarkers of Thirdhand Smoke Exposure in Their Urine and Hair Samples

In 2004, Matt and colleagues described how they collected household dust samples from living rooms and infants’ bedrooms [23]. Their research demonstrated that nicotine accumulated on the living room and infants’ bedroom surfaces of the homes belonging to smokers. Significantly higher amounts of urine cotinine, a biomarker for exposure to nicotine, were detected among infants who lived in homes where smoking happens inside compared to homes where smokers go outside to smoke [23]. As well, a study published in 2017 that measured the presence of hand nicotine on children of smokers who presented to the emergency room for an illness possibly related to tobacco smoke exposure detected hand nicotine on the hands of each child who participated in this pilot study. The researchers found a positive correlation between the amount of nicotine found on children’s hands and the amount of cotinine, a biomarker for nicotine exposure, detected in the children’s saliva [29].

Children Are Exposed to Higher Ratios of Thirdhand Smoke than Adults

In 2009, researchers discovered that the thirdhand smoke ratio of tobacco-specific nitrosamines to nicotine increases during the aging process [9]. Biomarkers measured in the urine can now be used to estimate the degree to which people have been exposed to secondhand or thirdhand smoke based on the ratio of the thirdhand smoke biomarker NNK and nicotine. Toddlers who live with adults who smoke have higher NNK/nicotine ratios, suggesting that they are exposed to a higher ratio of thirdhand smoke compared to secondhand smoke than adults [30]. Young children are likely exposed to higher ratios of thirdhand smoke as they spend more time on the floor, where thirdhand smoke accumulates. They frequently put their hands and other objects into their mouths. Young children breathe faster than adults, increasing their inhalation exposure and also have thinner skin, making dermal absorption more efficient [9].

Modeling Excess Cancer Risk

A 2014 United Kingdom study used official sources of toxicological data about chemicals detected in thirdhand smoke–contaminated homes to assess excess cancer risk posed from thirdhand smoke [17]. Using dust samples collected from homes where a smoker lived, they estimate that the median lifetime excess cancer risk from the exposure to all the nitrosamines present in thirdhand smoke is 9.6 additional cancer cases per 100,000 children exposed and could be as high as 1 excess cancer case per 1000 children exposed. The researchers concluded that young children aged 1 to 6 are at an especially increased risk for cancer because of their frequent contact with surfaces contaminated with thirdhand smoke and their ingestion of the particulate matter that settles on surfaces after smoking takes place [17].

Infants in Health Care Facilities Are Exposed to Thirdhand Smoke

Researchers have observed biomarkers confirming thirdhand smoke exposure in the urine of infants in the NICU. Found in incubators and cribs, particulates are likely being deposited in the NICU from visitors who have thirdhand smoke on their clothing, skin, and hair [31].

Animal Studies Link Thirdhand Smoke Exposure to Common Human Disease

Mice exposed to thirdhand smoke under conditions meant to simulate levels similar to human exposure are pre-diabetic, are at higher risk of developing metabolic syndrome, have inflammatory markers in the lungs that increase the risk for asthma, show slow wound healing, develop nonalcoholic fatty liver disease, and become behaviorally hyperactive [32]. Another recent study published in 2017 showed that mice exposed to thirdhand smoke after birth weighed less than mice not exposed to thirdhand smoke. Additionally, mice exposed to thirdhand smoke early in life showed changes in white blood cell counts that persisted into adulthood [9,33].

Summary

In summary, recent research makes a compelling case for invoking the precautionary principle to ensure that children avoid exposures to thirdhand smoke in their homes, cars, and healthcare settings. Studies reveal that:

• children live in homes where thirdhand smoke is present and this exposure is detectable in their bodies [23]
• concentrations of thirdhand smoke exposure observed in children are disproportionately higher than adults [30]
• chemicals present in thirdhand smoke cause damage to DNA [28]
• thirdhand smoke contains carcinogens that put exposed children at increased risk of cancer [17]
• thirdhand smoke is being detected within medical settings [34] and in the bodies of medically-vulnerable children [29], and
• animal studies have linked exposure to thirdhand smoke to a number of adverse health conditions commonly seen in today’s pediatric population such as metabolic syndrome, prediabetes, asthma, hyperactivity [32] and low birth weight [33].

Using the Thirdhand Smoke Concept in Clinical Practice

The clinical setting is an ideal place to address thirdhand smoke with families as a component of a comprehensive tobacco control strategy.

The Cessation Imperative—A Novel Motivational Message Prompted by Thirdhand Smoke

While there are potentially many ways to address thirdhand smoke exposure with families, the CEASE program has been used in the primary care setting to train child health care clinicians and office staff to address second- and thirdhand smoke. The training also educates clinicians on providing cessation counseling and resources to families with the goal of helping all family members become tobacco free, as well as to helping families keep completely smoke-free homes and cars [35,36]. The concept of thirdhand smoke creates what we have coined the cessation imperative [36]. The cessation imperative is based on the notion that the only way to protect non-smoking family and household members from thirdhand smoke is for all household smokers to quit smoking completely. Smoking, even when not in the presence of children, can expose others to toxic contaminates that settle on the surfaces of the home, the car as well as to the skin, hair, and clothing of family members who smoke. A discussion with parents about eliminating only secondhand smoke exposure for children does not adequately address how continued smoking, even when children are not present, can be harmful. The thirdhand smoke concept can be presented early, making it an efficient way to advocate for completely smoke-free families.

Thirdhand Smoke Counseling Helps Clinicians Achieve Key Tobacco Control Goals

The American Academy of Pediatrics (AAP) and the American Academy of Family Physicians (AAFP) recommend that health care providers deliver advice to parents regarding establishing smoke-free homes and cars and provide information about how their smoking adversely affects their children’s health [37,38]. It is AAP and AAFP policy that health care providers provide tobacco dependence treatment and referral to cessation services to help adult family members quit smoking [38,39]. Successfully integrating counseling around the topic of thirdhand smoke into existing smoking cessation service delivery is possible. The CEASE research and implementation team developed and disseminated educational content to clinicians about thirdhand smoke through AAP courses delivered online [40] as well as made presentations to clinicians at AAP-sponsored training sessions. Thirdhand smoke messaging has been included in the CEASE practice trainings so that participating clinicians in pediatric offices are equipped to engage parents on this topic. Further information about these educational resources and opportunities can be obtained from the AAP Julius B. Richmond Center of Excellence website [41] and from the Massachusetts General Hospital CEASE program’s website [42].

Counseling parents about thirdhand smoke can help assist parents with their smoking in the critical context of their child’s care. Most parents see their child’s health care clinician more often than their own [43]. Increasing the number of pediatric clinical encounters where parental smoking is addressed while also increasing the effectiveness of these clinical encounters by increasing parents’ motivation to protect their children from tobacco smoke exposure are important goals. The topic of thirdhand smoke is a novel concept that clinicians can use to engage with parents around their smoking in a new way. Recent research conducted by the CEASE team suggests that counseling parents in the pediatric setting about thirdhand smoke can be useful in helping achieve tobacco control goals with families. Parent’s belief about thirdhand smoke is associated with the likelihood the parent will take concrete steps to protect their child. Parents who believe thirdhand smoke is harmful are more likely to protect their children from exposure by adopting strictly enforced smoke-free home and car rules [44]. Parents who changed their thirdhand smoke beliefs over the course of a year to believing that thirdhand smoke is harmful were more likely to try to quit smoking [44].

Child health care clinicians are effective at influencing parents’ beliefs about the potential harm thirdhand smoke poses to their children. Parents who received advice from pediatricians to quit smoking or to adopt smoke-free home or policies were more likely to believe that thirdhand smoke was harmful to the health of children [45]. Fathers (as compared with mothers) and parents who smoked more cigarettes each day were less likely to accept that thirdhand smoke is harmful to children [45]. Conversely, delivering effective educational messages and counseling around the topic of thirdhand smoke to parents may help promote smoke-free rules and acceptance of cessation assistance.

Protect Patients from Thirdhand Smoke Risks

All health care settings should be completely smoke-free. Smoking bans help protect all families and children from second and thirdhand smoke exposure. It is especially important for medically vulnerable children to visit facilities free from all forms of tobacco smoke contamination. CEASE trainings encourage practices to implement a zone of wellness on the grounds of the healthcare facility by completely banning smoking. The CEASE implementation team also trains practice leaders to reach out to all staff that use tobacco and offer resources and support for quitting. Having a non-smoking staff sets a great example for families who visit the healthcare facility, and reduces the likelihood of bringing thirdhand smoke contaminates into the facility. Creating a policy that addresses thirdhand smoke exposure is a concrete step that health care organizations can take to protect patients.

Thirdhand Smoke Resources Developed and/or Used by the CEASE Program

The CEASE program has developed and/or identified a number of clinical resources to educate parents and clinicians about thirdhand smoke. These free resources can enhance awareness of thirdhand smoke and help promote the use of the thirdhand smoke concept in clinical practice.

• Posters with messages designed to educate parents about thirdhand smoke to encourage receipt of cessation resources were created for use in waiting areas and exam rooms of child health care practices. A poster for clinical practice (Figure 1) can be downloaded and printed from the CEASE program website [42].
• Health education handouts that directly address thirdhand smoke exposure are available. The handouts can be taken home to family members who are not present at the visit and contain the telephone number for the tobacco quitline service, which connects smokers in the United States with free telephone support for smoking cessation. Handouts for clinical practice can be downloaded and printed from the CEASE program website. Figure 2 shows a handout that encourages parents to keep a smoke-free car by pointing out that tobacco smoke stays in the car long after the cigarette is out.
  
• Videos about thirdhand smoke can be viewed by parents while in child health care offices or shared on practice websites or social media platforms. The CEASE program encourages practices to distribute videos about thirdhand smoke to introduce parents to the concept of thirdhand smoke and to encourage parents to engage in a discussion with their child’s clinicians about ways to limit thirdhand smoke exposure. Suitable videos for parental viewing include the 2 listed below, which highlight information from the Thirdhand Smoke Research Consortium.
    -University of California Riverside https://youtu.be/i1rhqRy-2e8
   -San Diego State University https://youtu.be/rqzi-9sXLdU
• Letters for landlords and management companies were created to stress the importance of providing a smoke-free living environment for children. The letters are meant to be signed by the child’s health care provider. The letters state that eliminating smoking in their buildings would result in landlords that “Pay less for cleaning and turnover fees.” Landlord letter templates can be downloaded and printed from the CEASE program website [42].
• Educational content for child health care clinicians about thirdhand smoke and how to counsel parents is included in the American Academy of Pediatrics Education in Quality Improvement for Pediatric Practice (EQIPP) online course entitled “Eliminating Tobacco” Use and Exposure to Secondhand Smoke. A section devoted to educating clinicians on the topic of thirdhand smoke is presented in this course. The course can be accessed through the AAP website and it qualifies for American Board of Pediatrics maintenance of certification part IV credit [40].

The CEASE team has worked with mass media outlets to communicate the messages about thirdhand smoke to build public awareness. The Today Show helped to popularize the concept of thirdhand smoke in 2009 after a paper published in the journal Pediatrics linked thirdhand smoke beliefs to home smoking bans [2].

Systems Approaches to Reduce Thirdhand Smoke Exposure

Public Policy Approaches

A clear policy agenda can help people protect their families from exposure to thirdhand smoke [46]. Policy approaches that have worked for lead, asbestos, and radon are examples of common household contaminants that are regulated using different mechanisms in an effort to protect the public health [46]. Strengths and weaknesses in each of these different approaches should be carefully considered when developing a comprehensive policy agenda to address thirdhand smoke. Recently, research on the health effects of thirdhand smoke spurred the passage of California legislative bill AB 1819 that “prohibits smoking tobacco at all times in the homes of licensed family child care homes and in areas where children are present [47].” As well, a recent US Department of Housing and Urban Development rule was finalized that requires all public housing agencies to implement a smoke-free policy by 30 July 2018 [48]. Smoke-free housing protects occupants from both secondhand and thirdhand smoke exposure. Pediatricians and other child health care professionals are well positioned to advocate for legislative actions that protect children from harmful exposures to thirdhand smoke.

Practice Change in Child Health Care Settings

Designing health care systems to screen for tobacco smoke exposure and to provide evidence-based cessation resources for all smokers is one of the best ways to reduce exposures to thirdhand smoke. Preventing thirdhand smoke exposure can work as novel messaging to promote tobacco cessation programs. Developing electronic medical record systems that allow for documentation of the smoking status of household members and whether or not homes and cars are completely smokefree can be particularly helpful tools for child health care providers when addressing thirdhand smoke with families. Good documentation about smoke-free homes and cars can enhance follow-up discussions with families as they work towards reducing thirdhand smoke exposures.

Summary

The thirdhand smoke concept has been used to improve delivery of tobacco control counseling and services for parents in the child health care context. Free materials are available that utilize thirdhand smoke messaging. As the science of thirdhand smoke matures, it will increasingly be used to help promote completely smoke-free places. The existing research on thirdhand smoke establishes the need for clinicians to communicate the cessation imperative. By using it, clinicians can help all smokers and non-smokers understand that there is no way to smoke tobacco without exposing friends and family.

Corresponding author: Jeremy E. Drehmer, MPH, 125 Nashua St., Suite 860, Boston, MA 02114, jdrehmer@ mgh.harvard.edu.

Financial disclosures: None

From the Center for Child and Adolescent Health Research and Policy, Division of General Academic Pediatrics, Massachusetts General Hospital for Children, and the Tobacco Research and Treatment Center, Massachusetts General Hospital, Boston, MA.

Abstract

• Objective: To explain the concept of thirdhand smoke and how it can be used to protect the health of children and improve delivery of tobacco control interventions for parents in the child health care setting.
• Methods: Review of the literature and descriptive report.
• Results: The thirdhand smoke concept has been used in the CEASE intervention to improve the delivery of tobacco control counseling and services to parents. Materials and techniques have been developed for the child health care setting that use the concept of thirdhand smoke. Scientific findings demonstrate that thirdhand smoke exposure is harmful and establishes the need for clinicians to communicate the cessation imperative: the only way to protect non-smoking household members from thirdhand smoke is for all household smokers to quit smoking completely. As the scientific knowledge of thirdhand smoke increases, advocates will likely rely on it to encourage completely smoke-free places.
• Conclusion: Recent scientific studies on thirdhand smoke are impelling further research on the topic, spurring the creation of tobacco control policies to protect people from thridhand smoke and stimulating improvements to the delivery of tobacco control counseling and services to parents in child health care settings.

Key words: thirdhand smoke; smoking; tobacco; indoor air quality; smoking cessation; pediatrics.

While “thirdhand smoke” may be a relatively new term, it is rooted in an old concept—the particulate matter and residue from tobacco smoke left behind after tobacco is burned. In 1953, Dr. Ernest Wynder and his colleagues from the Washington University School of Medicine in St. Louis showed that condensate made from the residue of cigarette smoke causes cancer [1]. This residue left behind by burning cigarettes is now known as thirdhand smoke [2]. Dr. Wynder used acetone to rinse the leftover tobacco smoke residue from a smoking chamber where he had burned cigarettes. He then painted the solution of acetone and thirdhand smoke residue onto the backs of mice. The results of Dr. Wynder’s study demonstrated that exposed mice developed cancerous skin lesions, whereas mice exposed to the acetone alone did not display skin lesions. Dr. Wynder sounded an alarm bell in his manuscript when he wrote, “Such studies, in view of the corollary clinical data relating smoking to various types of cancer, appear urgent. They may result not only in furthering our knowledge of carcinogenesis, but in promoting some practical aspects of cancer prevention [1].”

Decades of research has been conducted since Dr. Wynder’s discovery to definitively conclude that smoking tobacco and exposure to secondhand tobacco smoke is harmful to human health. It is estimated that 480,000 annual premature deaths in the United States alone are attributable to smoking and exposure to secondhand smoke [3]. The World Health Organization estimates that worldwide tobacco use is responsible for more than 7 million deaths per year, with 890,000 of those deaths caused by secondhand smoke exposure of nonsmokers [4]. Epidemiological evidence of the harm posed by tobacco has spurred the U.S Surgeon General to conclude that there is no risk-free level of exposure to tobacco smoke [5]. Despite the overwhelming evidence implicating tobacco as the cause of an unprecedented amount of disease resulting from the use of a consumer product, only recently has a dedicated research agenda been pursued to study what Dr. Wynder urgently called for back in 1953: further exploration of the health effects of thirdhand tobacco smoke.

The term "thirdhand smoke" was first coined in 2006 by researchers with the Clinical Effort Against Secondhand Smoke Exposure (CEASE) program at Massachusetts General Hospital in Boston [6], and recent research has begun to shed considerable light on the topic. In 2011, a research consortium of scientists funded by the Tobacco-Related Disease Research Program [7] in California was set up to conduct pioneering research on the characterization, exposure and health effects of thirdhand tobacco smoke [8]. Research findings from this consortium and other scientists from around the world are quickly expanding and disseminating knowledge on this important topic.

While the research on thirdhand smoke is ongoing, this paper summarizes the current literature most relevant to the pediatric population and outlines clinical and policy recommendations to protect children and families from the harms of exposure to thirdhand smoke.

What Is Thirdhand Smoke and How Is It Different from Secondhand Smoke?

Thirdhand smoke is a result of combusted tobacco, most often from smoking cigarettes, pipes, cigars, or cigarillos. Thirdhand smoke remains on surfaces and in dust for a longtime after smoking happens, reacts with oxidants and other compounds to form secondary pollutants, and is re-emitted as a gas and/or resuspended when particles are disturbed and go back into the air where they can be inhaled [9]. One dramatic example of how thirdhand smoke can remain on surfaces long after secondhand smoke dissipates was discovered on the ornate constellation ceiling in the main concourse of the Grand Central Terminal in New York City. According to Sam Roberts, a correspondent for the New York Times and the author of a book about the historic train station, the dark residue that accumulated on the concourse ceiling over decades and was originally believed to be the result of soot from train engines was primarily residue from tobacco smoke [10–12]. It wasn’t until a restoration in the 1990s when workers scrubbed the tar and nicotine residue from the ceiling could the elaborate design of the zodiac signs and constellations be seen again [13]. A similar process takes place inside homes, where smoke residue accumulates on surfaces such as walls and ceilings after smoking happens. Owners of homes that have been previously smoked in are faced with unanswered questions about how to clean up the toxic substances left behind.

When tobacco is smoked, the particulates contained in secondhand smoke settle on surfaces; this contamination is absorbed deep into materials such as hair, clothes, carpeting, furniture, and wallboard [9,14]. After depositing onto surfaces, the chemicals undergo an aging process, which changes the chemical structure of the smoke pollutants. The nicotine in thirdhand smoke residue reacts with common indoor air pollutants, such as nitrous acid and ozone, to form hazardous substances. When the nicotine present in thirdhand smoke reacts with nitrous acid, it forms carcinogenic tobacco-specific nitrosamines such as NNK and NNN [15–17]. Nicotine also reacts with ozone to form additional harmful ultrafine particles that can embed deep within the lungs when inhaled [18]. As thirdhand smoke ages, it becomes more toxic [15]. The aged particles then undergo a process called “off-gassing,” in which gas is continuously re-emitted from these surfaces back into the air [19]. This process of off-gassing occurs long after cigarettes have been smoked indoors [19,20]. Thirdhand smoke particles can also be inhaled when they get resuspended into the air after contaminated surfaces are disturbed [21].

Common practices employed by smokers, like smoking in different rooms, using fans to diffuse the smoke, or opening windows, do not prevent the formation and inhalation of thirdhand smoke by people living or visiting these indoor spaces [22]. Environments with potential thirdhand smoke exposure include homes of smokers [23], apartments and homes previously occupied by smokers [24], multiunit housing where smoking is permitted [25], automobiles that have been smoked in [26], hotel rooms where smoking is permitted [27], and other indoor places where smoking has occurred.

Research Supports Having Completely Smoke-Free Environments

Recent research has shown that exposure to thirdhand smoke is harmful. These findings, many of which are described below, offer strong support in favor of advocating for environments free of thirdhand smoke contamination for families and children.

Genetic Damage from Thirdhand Smoke Exposure

In 2013, researchers from the Lawrence Berkeley National Laboratory were the first to demonstrate that thirdhand smoke causes significant genetic damage to human cells [28]. Using in vitro assays, the researchers showed that thirdhand smoke is a cause of harm to human DNA in the form of strand breaks and oxidative damage, which leads to mutations that can cause cancer. The researches also specifically tested the effect of NNA, a tobacco-specific nitrosamine that is commonly found in thirdhand smoke but not in secondhand smoke, on human cell cultures and found that it caused significant damage to DNA [28].

Children Show Elevated Biomarkers of Thirdhand Smoke Exposure in Their Urine and Hair Samples

In 2004, Matt and colleagues described how they collected household dust samples from living rooms and infants’ bedrooms [23]. Their research demonstrated that nicotine accumulated on the living room and infants’ bedroom surfaces of the homes belonging to smokers. Significantly higher amounts of urine cotinine, a biomarker for exposure to nicotine, were detected among infants who lived in homes where smoking happens inside compared to homes where smokers go outside to smoke [23]. As well, a study published in 2017 that measured the presence of hand nicotine on children of smokers who presented to the emergency room for an illness possibly related to tobacco smoke exposure detected hand nicotine on the hands of each child who participated in this pilot study. The researchers found a positive correlation between the amount of nicotine found on children’s hands and the amount of cotinine, a biomarker for nicotine exposure, detected in the children’s saliva [29].

Children Are Exposed to Higher Ratios of Thirdhand Smoke than Adults

In 2009, researchers discovered that the thirdhand smoke ratio of tobacco-specific nitrosamines to nicotine increases during the aging process [9]. Biomarkers measured in the urine can now be used to estimate the degree to which people have been exposed to secondhand or thirdhand smoke based on the ratio of the thirdhand smoke biomarker NNK and nicotine. Toddlers who live with adults who smoke have higher NNK/nicotine ratios, suggesting that they are exposed to a higher ratio of thirdhand smoke compared to secondhand smoke than adults [30]. Young children are likely exposed to higher ratios of thirdhand smoke as they spend more time on the floor, where thirdhand smoke accumulates. They frequently put their hands and other objects into their mouths. Young children breathe faster than adults, increasing their inhalation exposure and also have thinner skin, making dermal absorption more efficient [9].

Modeling Excess Cancer Risk

A 2014 United Kingdom study used official sources of toxicological data about chemicals detected in thirdhand smoke–contaminated homes to assess excess cancer risk posed from thirdhand smoke [17]. Using dust samples collected from homes where a smoker lived, they estimate that the median lifetime excess cancer risk from the exposure to all the nitrosamines present in thirdhand smoke is 9.6 additional cancer cases per 100,000 children exposed and could be as high as 1 excess cancer case per 1000 children exposed. The researchers concluded that young children aged 1 to 6 are at an especially increased risk for cancer because of their frequent contact with surfaces contaminated with thirdhand smoke and their ingestion of the particulate matter that settles on surfaces after smoking takes place [17].

Infants in Health Care Facilities Are Exposed to Thirdhand Smoke

Researchers have observed biomarkers confirming thirdhand smoke exposure in the urine of infants in the NICU. Found in incubators and cribs, particulates are likely being deposited in the NICU from visitors who have thirdhand smoke on their clothing, skin, and hair [31].

Animal Studies Link Thirdhand Smoke Exposure to Common Human Disease

Mice exposed to thirdhand smoke under conditions meant to simulate levels similar to human exposure are pre-diabetic, are at higher risk of developing metabolic syndrome, have inflammatory markers in the lungs that increase the risk for asthma, show slow wound healing, develop nonalcoholic fatty liver disease, and become behaviorally hyperactive [32]. Another recent study published in 2017 showed that mice exposed to thirdhand smoke after birth weighed less than mice not exposed to thirdhand smoke. Additionally, mice exposed to thirdhand smoke early in life showed changes in white blood cell counts that persisted into adulthood [9,33].

Summary

In summary, recent research makes a compelling case for invoking the precautionary principle to ensure that children avoid exposures to thirdhand smoke in their homes, cars, and healthcare settings. Studies reveal that:

• children live in homes where thirdhand smoke is present and this exposure is detectable in their bodies [23]
• concentrations of thirdhand smoke exposure observed in children are disproportionately higher than adults [30]
• chemicals present in thirdhand smoke cause damage to DNA [28]
• thirdhand smoke contains carcinogens that put exposed children at increased risk of cancer [17]
• thirdhand smoke is being detected within medical settings [34] and in the bodies of medically-vulnerable children [29], and
• animal studies have linked exposure to thirdhand smoke to a number of adverse health conditions commonly seen in today’s pediatric population such as metabolic syndrome, prediabetes, asthma, hyperactivity [32] and low birth weight [33].

Using the Thirdhand Smoke Concept in Clinical Practice

The clinical setting is an ideal place to address thirdhand smoke with families as a component of a comprehensive tobacco control strategy.

The Cessation Imperative—A Novel Motivational Message Prompted by Thirdhand Smoke

While there are potentially many ways to address thirdhand smoke exposure with families, the CEASE program has been used in the primary care setting to train child health care clinicians and office staff to address second- and thirdhand smoke. The training also educates clinicians on providing cessation counseling and resources to families with the goal of helping all family members become tobacco free, as well as to helping families keep completely smoke-free homes and cars [35,36]. The concept of thirdhand smoke creates what we have coined the cessation imperative [36]. The cessation imperative is based on the notion that the only way to protect non-smoking family and household members from thirdhand smoke is for all household smokers to quit smoking completely. Smoking, even when not in the presence of children, can expose others to toxic contaminates that settle on the surfaces of the home, the car as well as to the skin, hair, and clothing of family members who smoke. A discussion with parents about eliminating only secondhand smoke exposure for children does not adequately address how continued smoking, even when children are not present, can be harmful. The thirdhand smoke concept can be presented early, making it an efficient way to advocate for completely smoke-free families.

Thirdhand Smoke Counseling Helps Clinicians Achieve Key Tobacco Control Goals

The American Academy of Pediatrics (AAP) and the American Academy of Family Physicians (AAFP) recommend that health care providers deliver advice to parents regarding establishing smoke-free homes and cars and provide information about how their smoking adversely affects their children’s health [37,38]. It is AAP and AAFP policy that health care providers provide tobacco dependence treatment and referral to cessation services to help adult family members quit smoking [38,39]. Successfully integrating counseling around the topic of thirdhand smoke into existing smoking cessation service delivery is possible. The CEASE research and implementation team developed and disseminated educational content to clinicians about thirdhand smoke through AAP courses delivered online [40] as well as made presentations to clinicians at AAP-sponsored training sessions. Thirdhand smoke messaging has been included in the CEASE practice trainings so that participating clinicians in pediatric offices are equipped to engage parents on this topic. Further information about these educational resources and opportunities can be obtained from the AAP Julius B. Richmond Center of Excellence website [41] and from the Massachusetts General Hospital CEASE program’s website [42].

Counseling parents about thirdhand smoke can help assist parents with their smoking in the critical context of their child’s care. Most parents see their child’s health care clinician more often than their own [43]. Increasing the number of pediatric clinical encounters where parental smoking is addressed while also increasing the effectiveness of these clinical encounters by increasing parents’ motivation to protect their children from tobacco smoke exposure are important goals. The topic of thirdhand smoke is a novel concept that clinicians can use to engage with parents around their smoking in a new way. Recent research conducted by the CEASE team suggests that counseling parents in the pediatric setting about thirdhand smoke can be useful in helping achieve tobacco control goals with families. Parent’s belief about thirdhand smoke is associated with the likelihood the parent will take concrete steps to protect their child. Parents who believe thirdhand smoke is harmful are more likely to protect their children from exposure by adopting strictly enforced smoke-free home and car rules [44]. Parents who changed their thirdhand smoke beliefs over the course of a year to believing that thirdhand smoke is harmful were more likely to try to quit smoking [44].

Child health care clinicians are effective at influencing parents’ beliefs about the potential harm thirdhand smoke poses to their children. Parents who received advice from pediatricians to quit smoking or to adopt smoke-free home or policies were more likely to believe that thirdhand smoke was harmful to the health of children [45]. Fathers (as compared with mothers) and parents who smoked more cigarettes each day were less likely to accept that thirdhand smoke is harmful to children [45]. Conversely, delivering effective educational messages and counseling around the topic of thirdhand smoke to parents may help promote smoke-free rules and acceptance of cessation assistance.

Protect Patients from Thirdhand Smoke Risks

All health care settings should be completely smoke-free. Smoking bans help protect all families and children from second and thirdhand smoke exposure. It is especially important for medically vulnerable children to visit facilities free from all forms of tobacco smoke contamination. CEASE trainings encourage practices to implement a zone of wellness on the grounds of the healthcare facility by completely banning smoking. The CEASE implementation team also trains practice leaders to reach out to all staff that use tobacco and offer resources and support for quitting. Having a non-smoking staff sets a great example for families who visit the healthcare facility, and reduces the likelihood of bringing thirdhand smoke contaminates into the facility. Creating a policy that addresses thirdhand smoke exposure is a concrete step that health care organizations can take to protect patients.

Thirdhand Smoke Resources Developed and/or Used by the CEASE Program

The CEASE program has developed and/or identified a number of clinical resources to educate parents and clinicians about thirdhand smoke. These free resources can enhance awareness of thirdhand smoke and help promote the use of the thirdhand smoke concept in clinical practice.

• Posters with messages designed to educate parents about thirdhand smoke to encourage receipt of cessation resources were created for use in waiting areas and exam rooms of child health care practices. A poster for clinical practice (Figure 1) can be downloaded and printed from the CEASE program website [42].
• Health education handouts that directly address thirdhand smoke exposure are available. The handouts can be taken home to family members who are not present at the visit and contain the telephone number for the tobacco quitline service, which connects smokers in the United States with free telephone support for smoking cessation. Handouts for clinical practice can be downloaded and printed from the CEASE program website. Figure 2 shows a handout that encourages parents to keep a smoke-free car by pointing out that tobacco smoke stays in the car long after the cigarette is out.
  
• Videos about thirdhand smoke can be viewed by parents while in child health care offices or shared on practice websites or social media platforms. The CEASE program encourages practices to distribute videos about thirdhand smoke to introduce parents to the concept of thirdhand smoke and to encourage parents to engage in a discussion with their child’s clinicians about ways to limit thirdhand smoke exposure. Suitable videos for parental viewing include the 2 listed below, which highlight information from the Thirdhand Smoke Research Consortium.
    -University of California Riverside https://youtu.be/i1rhqRy-2e8
   -San Diego State University https://youtu.be/rqzi-9sXLdU
• Letters for landlords and management companies were created to stress the importance of providing a smoke-free living environment for children. The letters are meant to be signed by the child’s health care provider. The letters state that eliminating smoking in their buildings would result in landlords that “Pay less for cleaning and turnover fees.” Landlord letter templates can be downloaded and printed from the CEASE program website [42].
• Educational content for child health care clinicians about thirdhand smoke and how to counsel parents is included in the American Academy of Pediatrics Education in Quality Improvement for Pediatric Practice (EQIPP) online course entitled “Eliminating Tobacco” Use and Exposure to Secondhand Smoke. A section devoted to educating clinicians on the topic of thirdhand smoke is presented in this course. The course can be accessed through the AAP website and it qualifies for American Board of Pediatrics maintenance of certification part IV credit [40].

The CEASE team has worked with mass media outlets to communicate the messages about thirdhand smoke to build public awareness. The Today Show helped to popularize the concept of thirdhand smoke in 2009 after a paper published in the journal Pediatrics linked thirdhand smoke beliefs to home smoking bans [2].

Systems Approaches to Reduce Thirdhand Smoke Exposure

Public Policy Approaches

A clear policy agenda can help people protect their families from exposure to thirdhand smoke [46]. Policy approaches that have worked for lead, asbestos, and radon are examples of common household contaminants that are regulated using different mechanisms in an effort to protect the public health [46]. Strengths and weaknesses in each of these different approaches should be carefully considered when developing a comprehensive policy agenda to address thirdhand smoke. Recently, research on the health effects of thirdhand smoke spurred the passage of California legislative bill AB 1819 that “prohibits smoking tobacco at all times in the homes of licensed family child care homes and in areas where children are present [47].” As well, a recent US Department of Housing and Urban Development rule was finalized that requires all public housing agencies to implement a smoke-free policy by 30 July 2018 [48]. Smoke-free housing protects occupants from both secondhand and thirdhand smoke exposure. Pediatricians and other child health care professionals are well positioned to advocate for legislative actions that protect children from harmful exposures to thirdhand smoke.

Practice Change in Child Health Care Settings

Designing health care systems to screen for tobacco smoke exposure and to provide evidence-based cessation resources for all smokers is one of the best ways to reduce exposures to thirdhand smoke. Preventing thirdhand smoke exposure can work as novel messaging to promote tobacco cessation programs. Developing electronic medical record systems that allow for documentation of the smoking status of household members and whether or not homes and cars are completely smokefree can be particularly helpful tools for child health care providers when addressing thirdhand smoke with families. Good documentation about smoke-free homes and cars can enhance follow-up discussions with families as they work towards reducing thirdhand smoke exposures.

Summary

The thirdhand smoke concept has been used to improve delivery of tobacco control counseling and services for parents in the child health care context. Free materials are available that utilize thirdhand smoke messaging. As the science of thirdhand smoke matures, it will increasingly be used to help promote completely smoke-free places. The existing research on thirdhand smoke establishes the need for clinicians to communicate the cessation imperative. By using it, clinicians can help all smokers and non-smokers understand that there is no way to smoke tobacco without exposing friends and family.

Corresponding author: Jeremy E. Drehmer, MPH, 125 Nashua St., Suite 860, Boston, MA 02114, jdrehmer@ mgh.harvard.edu.

Financial disclosures: None

From RTI International, Waltham, MA, and Brown University School of Public Health, Providence, RI.

Abstract

• Objective: To review the nursing home culture change literature and identify common barriers to and facilitators of nursing home culture change adoption. Nursing home culture change aims to make nursing homes less institutional by providing more resident-centered care, making environments more homelike, and empowering direct care staff.
• Methods: We reviewed the research literature on nursing home culture change, especially as related to implementation and outcomes.
• Results: Adoption of nursing home culture change practices has been steadily increasing in the past decade, but some practices are more likely to be adopted than others. A commonly reported barrier to culture change adoption is staff resistance to change. Studies suggest that this resistance can be overcome by changes to management practices, including good communication, providing training and education, and leadership support.
• Conclusion: The numerous benefits of nursing home culture change are apparent in the literature. Barriers to its adoption may be overcome by making improvements to nursing home management practices.

Key words: nursing homes; culture change; resident-centered care.

Nursing home culture change is a philosophy and combination of diverse practices aimed at making nursing homes less institutional and more resident-centered [1]. Nursing homes have been depicted as dehumanizing “total institutions” [2–4] in which the quality of residents’ lives and the quality of care are generally poor, daily life is medically regimented, only residents’ basic physical needs receive attention [5–8], and direct care workers are subject to poor working conditions for the lowest possible pay [9,10]. Since the 1980s, transforming the culture of nursing homes to be more humanizing, resident-centered, empowering, and homelike has been a primary mission of many stakeholder groups, including nursing home residents and care workers and their advocates [11].

Comprehensive culture change requires transformation of the nursing home environment from that of an institution to that of a home, implementation of more resident-centered care practices, empowerment of direct care staff, and flattening of the traditional organizational hierarchy so that residents and direct-care workers are actively involved in planning and implementing changes that empower them [12,13]. Culture change requires both technical changes, which are relatively straightforward efforts to address issues within a system while fundamentally keeping the system intact, and adaptive changes, which are more complex and entail reforming fundamental values that underlie the system and demand changes to the system itself [14,15].

Over time, nursing home culture change has gained widespread mainstream support. In 2009, the federal government issued new interpretive guidelines for use by nursing home inspectors that call for nursing homes to have more homelike environments and to support more resident-centered care [16]. The Centers for Medicare & Medicaid Services also required state quality improvement organizations to work with nursing homes on culture change efforts [1]. Some states effectively incentivize culture change by tying nursing home reimbursement rates and pay-for-performance policies to the implementation of culture change practices [17]. In addition to federal and state regulations, some nursing home corporations encourage or require facility administrators to implement culture change practices [18]. Overall, nursing homes are pushed to implement culture change practices on many fronts. The promise of beneficial outcomes of culture change also motivates implementation of some culture change practices [19].

In this article, we discuss the key elements of culture change, review the research examining the association between culture change and outcomes, identify key barriers to culture change, and offer suggestions from the literature for overcoming resistance to culture change.

Elements of Culture Change

Changing the Physical Environment

Changing the physical environment of nursing homes to be less institutional and more homelike is a core component of culture change [1]. These include both exterior and interior changes. Exterior changes can include adding walkways, patios, and gardens; interior changes include replacing nurses’ stations with desks, creating resident common areas, introducing the use of linens in dining areas, personalizing mailboxes outside of resident rooms, and adding small kitchens on units [20]. Other ideas for making environments more homelike include providing residents with the choice of colors for painting rooms and the choice of corridor/unit names and replacing public announcement systems with staff pagers [20].

Although changes to the physical environment may be considered cost-prohibitive, many of these changes entail minor and inexpensive enhancements that can help make environments more intimate and reminiscent of home than are traditional nursing homes [21,22]. Additionally, some environmental changes, such as adding raised gardens and walkways, can be designed not only to make the environment more homelike but also to help residents to engage in meaningful activities and connect to former roles, such as those of a homemaker, gardener, or farmer [21–23].

Providing Resident-Centered Care

Making care resident-centered entails enhancing resident choice and decision making and focusing the delivery of services on residents’ needs and preferences. According to Banaszak-Holl and colleagues [24], resident-centered approaches often emphasize the importance of shifting institutional norms and values and drawing employees’ attention to the needs of residents. This cultural shift in values and norms may be signaled by the implementation of practices that strengthen residents’ autonomy regarding everyday decisions. For example, as part of a resident-centered approach, residents would be offered choices and encouraged to make their own decisions about things personally affecting them, such as what to wear or when to go to bed, eating schedules, and menus [1,17,25].

Empowering Care Aides

Nursing home staff empowerment, particularly the empowerment of nursing assistants and other “hands-on” care aides—who are the predominant workforce in nursing homes and provide the vast bulk of care [26]—is a core component of culture change [1]. Such staff empowerment generally entails enhanced participation in decision making and increased autonomy. Staff empowerment practices that were examined in a national survey of nursing home directors [17] included:

• Staff work together to cover shifts when someone cannot come to work
• Staff cross-trained to perform tasks outside of their assigned job duties
• Staff involved in planning social events
• Nursing assistants take part in quality improvement teams
• Nursing assistants know when a resident’s care plan has changed
• Nursing assistants who receive extra training or education receive bonuses or raises
• Nursing assistants can choose which the residents for whom they provide care

We found that the staff empowerment practices most commonly implemented by nursing homes included nursing assistants knowing when a resident’s care plan has changed and staff working together to cover shifts when someone can’t come to work, but it was uncommon for nursing homes to permit nursing assistants to choose which residents they care for [17].

Outcomes of Culture Change

Research over the past 2 decades has examined the outcomes of culture change and the challenges involved in its implementation. Culture change is intended to improve the quality of life for nursing home residents, but the impact of culture change interventions is not clear. Shier and colleagues [27] conducted a comprehensive review of the peer-reviewed and gray literature on culture change published between 2005 and 2012 and found that studies varied widely in scope and evidence was inconsistent. They concluded that there is not yet sufficient evidence to provide specific guidance to nursing homes interested in implementing culture change [27]. The reviewed studies (27 peer-reviewed and 9 gray literature) also were noted to include small sample sizes and restricted geographic coverage, which both limit generalizability.

Although the literature had substantial limitations, Shier and colleagues [27] found numerous beneficial outcomes of culture change. Statistically significant improvements in numerous resident outcome measures were found to be associated with the implementation of culture change practices, including measures of resident quality of life/well-being, engagement and activities, functional status, satisfaction, mood (depression), anxiety/behavior/agitation, and pain/comfort. Two quality of care and services outcome measures also showed significant improvement associated with culture change practices, including increased completion of advance care plans and improved quality of workers’ approach to residents. Various staff outcome measures also showed significant improvement associated with culture change, including improvements in staff turnover/retention, satisfaction/well-being/burnout, absenteeism, knowledge, and attitude. Additionally, studies have shown culture change to be associated with improvements in select organizational outcome measures including operations costs, occupancy rates, revenue/profits, and family satisfaction. Four of the 36 studies reported negative outcomes of culture change. These negative outcomes included increased resident fear/anxiety [28], increased resident incontinence, decreased resident engagement in activities, decreased family engagement [29,30], decreased resident well-being [31], and increased physical incidents [32]. Notably, negative outcomes often co-occurred with positive outcomes [27,28].

To address the limitations of previous culture change research, such as small sample sizes and limited geographic coverage, and to explain some of the previous equivocal findings from quality studies when the extent of culture change practice implementation was not considered or measured, we collaborated on a national study to understand whether nursing home introduction of culture change practices is associated with improved quality [33]. We identified 824 U.S. nursing homes that had implemented some culture change practices, and we classified them by level of culture change practice implementation (high versus low). In nursing homes with high levels of culture change practice implementation, the introduction of nursing home culture change was associated with significant improvements in some care processes (eg, decreased prevalence of restraints, tube feeding, and pressure ulcers; increased proportion of residents on bladder training programs) and improvements in some resident outcomes, including slightly fewer hospitalizations. Among nursing homes with lower levels of culture change practice implementation, the introduction of culture change was associated with fewer health-related and quality-of-life survey deficiencies, but also with a significant increase in the number of resident hospitalizations [33]. Conclusive evidence regarding the impact of nursing homes implementing specific culture change practices or a comprehensive array of culture change practices on resident outcomes and quality of life remains needed, but numerous benefits of culture change are apparent in the literature.

Diffusion of Culture Change Practices

As culture change is widely supported and shows promise for beneficial outcomes, culture change practices are increasingly being implemented in nursing homes nationally. In 2007, a Commonwealth Fund survey found 56% of directors of nursing in U.S. nursing homes reported any culture change implementation or leadership commitment to implementation, but only 5% reported that culture change had completely changed the way the nursing home cared for residents in all areas of the nursing home [34]. In contrast, by 2010, 85% of directors of nursing reported at least partial culture change implementation and 13% reported that culture change had completely changed the way the nursing home cared for residents in all areas [14]. In a more recent survey of nursing home administrators, 16% reported that culture change had completely changed the way the nursing home cared for residents in all areas [35].

Barriers to Culture Change Implementation

Although the growth of culture change in the nursing home industry in the past decade has been impressive, implementation of comprehensive culture change has lagged behind. This is because one notable feature of nursing home culture change is that it is a philosophy that consists of many related practices. As noted above, implementing culture change can involve changes to physical environments, resident-centered care practices, and staff empowerment. This means that facilities can choose to implement as many or as few changes as they would like, and research has shown that there has been a lot of variation in which culture change practices are implemented. For example, in previous research we found that facilities interested in attracting highly reimbursed Medicare rehabilitation patients were more likely to implement hotel-style changes to their physical environments than they were to implement resident-centered care practices or forms of staff empowerment [19]. Sterns and colleagues [36] found that facilities were more likely to implement less complex practices (eg, allowing residents to choose when they go to bed) than more complex practices (eg, involving staff and residents in organizational decision making). The authors suggest that differences in commitment of facility leaders to comprehensive culture change may have contributed to these differences.

Attributes of facility leaders and other aspects of organizational context have been shown to contribute to more and less successful culture change implementation. For example, Scalzi and colleagues [37] found that some important barriers to culture change implementation were not involving all staff in culture change activities and a lack of corporate level support for these efforts. Schuldheis [38] examined differences in organizational context and its role in culture change among 9 Oregon facilities; 3 facilities successfully implemented culture change practices and 6 facilities did not. Results showed that a facility’s existing organizational culture, attention to sustainability, management practices, and staff involvement were important to the success of the initiative. Similarly, Rosemond and colleagues [39] conducted a study involving 8 North Carolina nursing homes. They determined that unsuccessful culture change initiatives could be attributed to the organizations’ readiness for change, a lack of high quality management communications, and unfavorable perceptions of culture change by direct-care workers. A study conducted in 4 nursing homes by Munroe et al [40] found that formal culture change training provided by professional trainers produced better outcomes than informal “train the trainer” sessions provided by other facility managers. Bowers and colleagues [41] also found that unsuccessful implementation of the Green House model of culture change was likely related to a lack of training resources for staff. Similarly, after an in-depth ethnographic study of culture change implementation, Lopez [42] found that it was unrealistic to expect direct-care workers to perform their jobs in radically new ways without being provided with ongoing support from management.

Resistance to Change: A Key Barrier

Our own research sought to understand the barriers and challenges nursing home administrators faced when implementing culture change in their facilities and the strategies they used to overcome them. In interviews conducted with 64 administrators who had participated in a previous nationally representative survey about culture change implementation, administrators reported a wide variety of barriers, including old and outdated physical plants, the costs of some changes, and issues with unions [18]. A key barrier that administrators reported facing was resistance to change on the part of nursing facility staff, residents, and residents’ family members [43]. Administrators reported that residents were resistant to change primarily because they had been institutionalized in their thinking. In other words, nursing homes had essentially trained residents to expect things to be done at certain times and in certain ways. Resistance among staff reportedly included resistance to the overall concept of culture change and to specific culture change practices. Often, staff perceived that changes related to culture change implementation involved additional work or effort on their part without additional resources, but this was not the only reason for resistance. Most often staff, especially longer-term staff, simply were resistant to making any changes to their usual routines or duties.

This type of resistance to change among staff is not unique to culture change implementation and has long been a commonly cited barrier in the organizational change literature. For example, in a 1954 Harvard Business Review article, Lawrence [44] stated that resistance to change was “the most baffling and recalcitrant of the problems which business executives face.” Since that time, resistance to change has been extensively studied as have methods for overcoming such resistance.

Recommendations for Overcoming Resistance to Culture Change

In seminal work on employee resistance to change conducted shortly after World War II, Coch and French [45] challenged the concept that resistance to change was the result of flaws or inadequacies on the part of staff, which would make addressing resistance difficult. Instead, they proposed, and proved through experimental methods, that resistance arose primarily from the context within which the changes were taking place. In other words, they found that managers could ameliorate resistance to change through changes to management and leadership practices. In their experiment, resistance to change in a manufacturing plant was overcome when management effectively communicated to staff the reasons for the change and engaged staff in planning for the desired changes. Studies on the barriers and facilitators of culture change implementation in nursing facilities have similarly found that facility leaders can take steps to address, or even avoid, staff resistance to change.

In our own research, we have found that resistance to change is a common barrier faced by facility leaders. We also found that resistance to change was unique among barriers in that, although strategies used to address other types of barriers varied widely, administrators consistently reported using the same strategies to address and overcome resistance to change. These strategies all involved management and leadership activities, including education and training and improved communication. In addition, administrators discussed in detail the ways they tailored education and communication to their facility’s unique needs. They also indicated that these efforts should be ongoing, communication should be two-way, and that all staff should be included [43].

Good Communication

One important tool for avoiding or overcoming resistance to culture change that facility administrators reported was good communication. They reported that open and bidirectional communication fostered feedback about ongoing culture change efforts and encouraged engagement and buy-in from staff. They also suggested that it is important that this type of communication be ongoing. Good communication about culture change, in particular, included providing a strong rationale for the changes and involved getting input from staff before and during implementation [43].

These findings are similar to other studies of culture change which have found that culture change implementation should involve staff at all levels [37] and that facility leaders should follow through on the plans that have been communicated [39]. Interestingly, the importance of good and open communication has also been identified as important to other forms of nursing facility quality improvement [46].

Training and Education

The facility administrators we interviewed also reported providing education and training for staff about culture change in a variety of ways, including as part of regular in-service training and as a component of new employee orientation. The training materials used were often obtained from the leading culture change organizations. However, importantly, administrators reported tailoring these trainings to the specific needs of their employees or unique context of their facility. For example, administrators reported breaking up long training sessions into shorter segments provided over a longer period of time or organizing trainings to be provided to small groups on the units rather than in more didactic conference-style settings [43]. Administrators explained that providing training in this way was more palatable to staff and helped incorporate learning into everyday care.

Other studies of nursing home culture change have also found training and education to be important to implementation. For example, in a study of a labor-management partnership for culture change implementation, Leutz and colleagues [47] found training of staff from all disciplines by culture change experts to be an important element of successful implementation. Training topics included those that were very general, such as gerontology, and very specific, including person-centered care. Staff were paid for their time participating in training, which took place at their facilities to make participation easier. The trainings were also staggered over the course of several months, so that staff had time to use what they had learned between sessions and could discuss their experiences at the later sessions.

Munroe and colleagues [40] conducted a study of culture change training using pre-post test survey methods and found that formal training had more of an effect on staff than informal training. In the study, staff at 2 facilities received formal education from a consulting group while staff at 2 other facilities then received informal training from the staff of one of the formally trained facilities. An important conclusion of the authors was that the formal training did a better job than the informal training of helping facility leaders and managers view their relationships with staff differently. This suggests that facility leaders and managers may have to alter their management styles to create the supportive context within which culture change efforts can succeed [48].

Leadership Support

Good communication and training/education can be thought of as 2 examples of leadership support, and support from facility leaders and managers has been found, in multiple studies, to be critical to successful culture change efforts. For example, in a recent study of nursing facility culture change in the Netherlands, Snoeren and colleagues [49] found that facility managers can facilitate culture change implementation by supporting a variety of staff needs and promoting the facilities’ new desired values. Another study found that facilities with leaders who are supportive and foster staff flexibility, such as allowing staff to be creative in their problem-solving and have decentralized decision-making, were more likely to report having implemented culture change [24].

In a study focused specifically on facility leadership style and its relation to culture change implementation, Corazzini and colleagues [50] found an adaptive leadership style to be important to culture change implementation. Adaptive leadership styles are ones that acknowledge the importance of staff relationships and recognize that complex changes, like those often implemented in culture change efforts, require complex solutions that will likely evolve over time. These authors conclude that culture change implementation necessitates development of new normative values and behaviors and can, therefore, not be accomplished by simply generating new rules and procedures [50].

Of course, not all nursing facility leaders have the management skills needed to perform in these adaptive and flexible ways. Therefore, management training for facility leaders may be an important first step in a facility’s culture change efforts [51]. This type of training may help improve communication skills and allow facility leaders to perform in more adaptive and flexible ways to better meet the needs of their particular facility and staff. Research also suggests that culture change training for facility leaders may help them to form new and better relationships with staff [40], an important element of culture change.

Conclusion

Nursing home culture change aims to improve care quality and resident satisfaction through changes to physical environments, resident care practices, and staff empowerment. These include both relatively simple technical changes and more complex changes. Nursing home managers and leaders have reported a variety of barriers to implementing nursing home culture change. A common barrier cited is staff resistance to change. Many decades of research in the organizational change literature and more recent research on culture change implementation suggest steps that facility managers and leaders can take to avoid or overcome this resistance. These steps include providing management support, especially in the form of good communication and training and education.

Corresponding author: Denise A. Tyler, PhD, RTI International, 307 Waverly Oaks Rd., Waltham, MA 02452, [email protected].

Financial disclosures: None.

From RTI International, Waltham, MA, and Brown University School of Public Health, Providence, RI.

Abstract

• Objective: To review the nursing home culture change literature and identify common barriers to and facilitators of nursing home culture change adoption. Nursing home culture change aims to make nursing homes less institutional by providing more resident-centered care, making environments more homelike, and empowering direct care staff.
• Methods: We reviewed the research literature on nursing home culture change, especially as related to implementation and outcomes.
• Results: Adoption of nursing home culture change practices has been steadily increasing in the past decade, but some practices are more likely to be adopted than others. A commonly reported barrier to culture change adoption is staff resistance to change. Studies suggest that this resistance can be overcome by changes to management practices, including good communication, providing training and education, and leadership support.
• Conclusion: The numerous benefits of nursing home culture change are apparent in the literature. Barriers to its adoption may be overcome by making improvements to nursing home management practices.

Key words: nursing homes; culture change; resident-centered care.

Nursing home culture change is a philosophy and combination of diverse practices aimed at making nursing homes less institutional and more resident-centered [1]. Nursing homes have been depicted as dehumanizing “total institutions” [2–4] in which the quality of residents’ lives and the quality of care are generally poor, daily life is medically regimented, only residents’ basic physical needs receive attention [5–8], and direct care workers are subject to poor working conditions for the lowest possible pay [9,10]. Since the 1980s, transforming the culture of nursing homes to be more humanizing, resident-centered, empowering, and homelike has been a primary mission of many stakeholder groups, including nursing home residents and care workers and their advocates [11].

Comprehensive culture change requires transformation of the nursing home environment from that of an institution to that of a home, implementation of more resident-centered care practices, empowerment of direct care staff, and flattening of the traditional organizational hierarchy so that residents and direct-care workers are actively involved in planning and implementing changes that empower them [12,13]. Culture change requires both technical changes, which are relatively straightforward efforts to address issues within a system while fundamentally keeping the system intact, and adaptive changes, which are more complex and entail reforming fundamental values that underlie the system and demand changes to the system itself [14,15].

Over time, nursing home culture change has gained widespread mainstream support. In 2009, the federal government issued new interpretive guidelines for use by nursing home inspectors that call for nursing homes to have more homelike environments and to support more resident-centered care [16]. The Centers for Medicare & Medicaid Services also required state quality improvement organizations to work with nursing homes on culture change efforts [1]. Some states effectively incentivize culture change by tying nursing home reimbursement rates and pay-for-performance policies to the implementation of culture change practices [17]. In addition to federal and state regulations, some nursing home corporations encourage or require facility administrators to implement culture change practices [18]. Overall, nursing homes are pushed to implement culture change practices on many fronts. The promise of beneficial outcomes of culture change also motivates implementation of some culture change practices [19].

In this article, we discuss the key elements of culture change, review the research examining the association between culture change and outcomes, identify key barriers to culture change, and offer suggestions from the literature for overcoming resistance to culture change.

Elements of Culture Change

Changing the Physical Environment

Changing the physical environment of nursing homes to be less institutional and more homelike is a core component of culture change [1]. These include both exterior and interior changes. Exterior changes can include adding walkways, patios, and gardens; interior changes include replacing nurses’ stations with desks, creating resident common areas, introducing the use of linens in dining areas, personalizing mailboxes outside of resident rooms, and adding small kitchens on units [20]. Other ideas for making environments more homelike include providing residents with the choice of colors for painting rooms and the choice of corridor/unit names and replacing public announcement systems with staff pagers [20].

Although changes to the physical environment may be considered cost-prohibitive, many of these changes entail minor and inexpensive enhancements that can help make environments more intimate and reminiscent of home than are traditional nursing homes [21,22]. Additionally, some environmental changes, such as adding raised gardens and walkways, can be designed not only to make the environment more homelike but also to help residents to engage in meaningful activities and connect to former roles, such as those of a homemaker, gardener, or farmer [21–23].

Providing Resident-Centered Care

Making care resident-centered entails enhancing resident choice and decision making and focusing the delivery of services on residents’ needs and preferences. According to Banaszak-Holl and colleagues [24], resident-centered approaches often emphasize the importance of shifting institutional norms and values and drawing employees’ attention to the needs of residents. This cultural shift in values and norms may be signaled by the implementation of practices that strengthen residents’ autonomy regarding everyday decisions. For example, as part of a resident-centered approach, residents would be offered choices and encouraged to make their own decisions about things personally affecting them, such as what to wear or when to go to bed, eating schedules, and menus [1,17,25].

Empowering Care Aides

Nursing home staff empowerment, particularly the empowerment of nursing assistants and other “hands-on” care aides—who are the predominant workforce in nursing homes and provide the vast bulk of care [26]—is a core component of culture change [1]. Such staff empowerment generally entails enhanced participation in decision making and increased autonomy. Staff empowerment practices that were examined in a national survey of nursing home directors [17] included:

• Staff work together to cover shifts when someone cannot come to work
• Staff cross-trained to perform tasks outside of their assigned job duties
• Staff involved in planning social events
• Nursing assistants take part in quality improvement teams
• Nursing assistants know when a resident’s care plan has changed
• Nursing assistants who receive extra training or education receive bonuses or raises
• Nursing assistants can choose which the residents for whom they provide care

We found that the staff empowerment practices most commonly implemented by nursing homes included nursing assistants knowing when a resident’s care plan has changed and staff working together to cover shifts when someone can’t come to work, but it was uncommon for nursing homes to permit nursing assistants to choose which residents they care for [17].

Outcomes of Culture Change

Research over the past 2 decades has examined the outcomes of culture change and the challenges involved in its implementation. Culture change is intended to improve the quality of life for nursing home residents, but the impact of culture change interventions is not clear. Shier and colleagues [27] conducted a comprehensive review of the peer-reviewed and gray literature on culture change published between 2005 and 2012 and found that studies varied widely in scope and evidence was inconsistent. They concluded that there is not yet sufficient evidence to provide specific guidance to nursing homes interested in implementing culture change [27]. The reviewed studies (27 peer-reviewed and 9 gray literature) also were noted to include small sample sizes and restricted geographic coverage, which both limit generalizability.

Although the literature had substantial limitations, Shier and colleagues [27] found numerous beneficial outcomes of culture change. Statistically significant improvements in numerous resident outcome measures were found to be associated with the implementation of culture change practices, including measures of resident quality of life/well-being, engagement and activities, functional status, satisfaction, mood (depression), anxiety/behavior/agitation, and pain/comfort. Two quality of care and services outcome measures also showed significant improvement associated with culture change practices, including increased completion of advance care plans and improved quality of workers’ approach to residents. Various staff outcome measures also showed significant improvement associated with culture change, including improvements in staff turnover/retention, satisfaction/well-being/burnout, absenteeism, knowledge, and attitude. Additionally, studies have shown culture change to be associated with improvements in select organizational outcome measures including operations costs, occupancy rates, revenue/profits, and family satisfaction. Four of the 36 studies reported negative outcomes of culture change. These negative outcomes included increased resident fear/anxiety [28], increased resident incontinence, decreased resident engagement in activities, decreased family engagement [29,30], decreased resident well-being [31], and increased physical incidents [32]. Notably, negative outcomes often co-occurred with positive outcomes [27,28].

To address the limitations of previous culture change research, such as small sample sizes and limited geographic coverage, and to explain some of the previous equivocal findings from quality studies when the extent of culture change practice implementation was not considered or measured, we collaborated on a national study to understand whether nursing home introduction of culture change practices is associated with improved quality [33]. We identified 824 U.S. nursing homes that had implemented some culture change practices, and we classified them by level of culture change practice implementation (high versus low). In nursing homes with high levels of culture change practice implementation, the introduction of nursing home culture change was associated with significant improvements in some care processes (eg, decreased prevalence of restraints, tube feeding, and pressure ulcers; increased proportion of residents on bladder training programs) and improvements in some resident outcomes, including slightly fewer hospitalizations. Among nursing homes with lower levels of culture change practice implementation, the introduction of culture change was associated with fewer health-related and quality-of-life survey deficiencies, but also with a significant increase in the number of resident hospitalizations [33]. Conclusive evidence regarding the impact of nursing homes implementing specific culture change practices or a comprehensive array of culture change practices on resident outcomes and quality of life remains needed, but numerous benefits of culture change are apparent in the literature.

Diffusion of Culture Change Practices

As culture change is widely supported and shows promise for beneficial outcomes, culture change practices are increasingly being implemented in nursing homes nationally. In 2007, a Commonwealth Fund survey found 56% of directors of nursing in U.S. nursing homes reported any culture change implementation or leadership commitment to implementation, but only 5% reported that culture change had completely changed the way the nursing home cared for residents in all areas of the nursing home [34]. In contrast, by 2010, 85% of directors of nursing reported at least partial culture change implementation and 13% reported that culture change had completely changed the way the nursing home cared for residents in all areas [14]. In a more recent survey of nursing home administrators, 16% reported that culture change had completely changed the way the nursing home cared for residents in all areas [35].

Barriers to Culture Change Implementation

Although the growth of culture change in the nursing home industry in the past decade has been impressive, implementation of comprehensive culture change has lagged behind. This is because one notable feature of nursing home culture change is that it is a philosophy that consists of many related practices. As noted above, implementing culture change can involve changes to physical environments, resident-centered care practices, and staff empowerment. This means that facilities can choose to implement as many or as few changes as they would like, and research has shown that there has been a lot of variation in which culture change practices are implemented. For example, in previous research we found that facilities interested in attracting highly reimbursed Medicare rehabilitation patients were more likely to implement hotel-style changes to their physical environments than they were to implement resident-centered care practices or forms of staff empowerment [19]. Sterns and colleagues [36] found that facilities were more likely to implement less complex practices (eg, allowing residents to choose when they go to bed) than more complex practices (eg, involving staff and residents in organizational decision making). The authors suggest that differences in commitment of facility leaders to comprehensive culture change may have contributed to these differences.

Attributes of facility leaders and other aspects of organizational context have been shown to contribute to more and less successful culture change implementation. For example, Scalzi and colleagues [37] found that some important barriers to culture change implementation were not involving all staff in culture change activities and a lack of corporate level support for these efforts. Schuldheis [38] examined differences in organizational context and its role in culture change among 9 Oregon facilities; 3 facilities successfully implemented culture change practices and 6 facilities did not. Results showed that a facility’s existing organizational culture, attention to sustainability, management practices, and staff involvement were important to the success of the initiative. Similarly, Rosemond and colleagues [39] conducted a study involving 8 North Carolina nursing homes. They determined that unsuccessful culture change initiatives could be attributed to the organizations’ readiness for change, a lack of high quality management communications, and unfavorable perceptions of culture change by direct-care workers. A study conducted in 4 nursing homes by Munroe et al [40] found that formal culture change training provided by professional trainers produced better outcomes than informal “train the trainer” sessions provided by other facility managers. Bowers and colleagues [41] also found that unsuccessful implementation of the Green House model of culture change was likely related to a lack of training resources for staff. Similarly, after an in-depth ethnographic study of culture change implementation, Lopez [42] found that it was unrealistic to expect direct-care workers to perform their jobs in radically new ways without being provided with ongoing support from management.

Resistance to Change: A Key Barrier

Our own research sought to understand the barriers and challenges nursing home administrators faced when implementing culture change in their facilities and the strategies they used to overcome them. In interviews conducted with 64 administrators who had participated in a previous nationally representative survey about culture change implementation, administrators reported a wide variety of barriers, including old and outdated physical plants, the costs of some changes, and issues with unions [18]. A key barrier that administrators reported facing was resistance to change on the part of nursing facility staff, residents, and residents’ family members [43]. Administrators reported that residents were resistant to change primarily because they had been institutionalized in their thinking. In other words, nursing homes had essentially trained residents to expect things to be done at certain times and in certain ways. Resistance among staff reportedly included resistance to the overall concept of culture change and to specific culture change practices. Often, staff perceived that changes related to culture change implementation involved additional work or effort on their part without additional resources, but this was not the only reason for resistance. Most often staff, especially longer-term staff, simply were resistant to making any changes to their usual routines or duties.

This type of resistance to change among staff is not unique to culture change implementation and has long been a commonly cited barrier in the organizational change literature. For example, in a 1954 Harvard Business Review article, Lawrence [44] stated that resistance to change was “the most baffling and recalcitrant of the problems which business executives face.” Since that time, resistance to change has been extensively studied as have methods for overcoming such resistance.

Recommendations for Overcoming Resistance to Culture Change

In seminal work on employee resistance to change conducted shortly after World War II, Coch and French [45] challenged the concept that resistance to change was the result of flaws or inadequacies on the part of staff, which would make addressing resistance difficult. Instead, they proposed, and proved through experimental methods, that resistance arose primarily from the context within which the changes were taking place. In other words, they found that managers could ameliorate resistance to change through changes to management and leadership practices. In their experiment, resistance to change in a manufacturing plant was overcome when management effectively communicated to staff the reasons for the change and engaged staff in planning for the desired changes. Studies on the barriers and facilitators of culture change implementation in nursing facilities have similarly found that facility leaders can take steps to address, or even avoid, staff resistance to change.

In our own research, we have found that resistance to change is a common barrier faced by facility leaders. We also found that resistance to change was unique among barriers in that, although strategies used to address other types of barriers varied widely, administrators consistently reported using the same strategies to address and overcome resistance to change. These strategies all involved management and leadership activities, including education and training and improved communication. In addition, administrators discussed in detail the ways they tailored education and communication to their facility’s unique needs. They also indicated that these efforts should be ongoing, communication should be two-way, and that all staff should be included [43].

Good Communication

One important tool for avoiding or overcoming resistance to culture change that facility administrators reported was good communication. They reported that open and bidirectional communication fostered feedback about ongoing culture change efforts and encouraged engagement and buy-in from staff. They also suggested that it is important that this type of communication be ongoing. Good communication about culture change, in particular, included providing a strong rationale for the changes and involved getting input from staff before and during implementation [43].

These findings are similar to other studies of culture change which have found that culture change implementation should involve staff at all levels [37] and that facility leaders should follow through on the plans that have been communicated [39]. Interestingly, the importance of good and open communication has also been identified as important to other forms of nursing facility quality improvement [46].

Training and Education

The facility administrators we interviewed also reported providing education and training for staff about culture change in a variety of ways, including as part of regular in-service training and as a component of new employee orientation. The training materials used were often obtained from the leading culture change organizations. However, importantly, administrators reported tailoring these trainings to the specific needs of their employees or unique context of their facility. For example, administrators reported breaking up long training sessions into shorter segments provided over a longer period of time or organizing trainings to be provided to small groups on the units rather than in more didactic conference-style settings [43]. Administrators explained that providing training in this way was more palatable to staff and helped incorporate learning into everyday care.

Other studies of nursing home culture change have also found training and education to be important to implementation. For example, in a study of a labor-management partnership for culture change implementation, Leutz and colleagues [47] found training of staff from all disciplines by culture change experts to be an important element of successful implementation. Training topics included those that were very general, such as gerontology, and very specific, including person-centered care. Staff were paid for their time participating in training, which took place at their facilities to make participation easier. The trainings were also staggered over the course of several months, so that staff had time to use what they had learned between sessions and could discuss their experiences at the later sessions.

Munroe and colleagues [40] conducted a study of culture change training using pre-post test survey methods and found that formal training had more of an effect on staff than informal training. In the study, staff at 2 facilities received formal education from a consulting group while staff at 2 other facilities then received informal training from the staff of one of the formally trained facilities. An important conclusion of the authors was that the formal training did a better job than the informal training of helping facility leaders and managers view their relationships with staff differently. This suggests that facility leaders and managers may have to alter their management styles to create the supportive context within which culture change efforts can succeed [48].

Leadership Support

Good communication and training/education can be thought of as 2 examples of leadership support, and support from facility leaders and managers has been found, in multiple studies, to be critical to successful culture change efforts. For example, in a recent study of nursing facility culture change in the Netherlands, Snoeren and colleagues [49] found that facility managers can facilitate culture change implementation by supporting a variety of staff needs and promoting the facilities’ new desired values. Another study found that facilities with leaders who are supportive and foster staff flexibility, such as allowing staff to be creative in their problem-solving and have decentralized decision-making, were more likely to report having implemented culture change [24].

In a study focused specifically on facility leadership style and its relation to culture change implementation, Corazzini and colleagues [50] found an adaptive leadership style to be important to culture change implementation. Adaptive leadership styles are ones that acknowledge the importance of staff relationships and recognize that complex changes, like those often implemented in culture change efforts, require complex solutions that will likely evolve over time. These authors conclude that culture change implementation necessitates development of new normative values and behaviors and can, therefore, not be accomplished by simply generating new rules and procedures [50].

Of course, not all nursing facility leaders have the management skills needed to perform in these adaptive and flexible ways. Therefore, management training for facility leaders may be an important first step in a facility’s culture change efforts [51]. This type of training may help improve communication skills and allow facility leaders to perform in more adaptive and flexible ways to better meet the needs of their particular facility and staff. Research also suggests that culture change training for facility leaders may help them to form new and better relationships with staff [40], an important element of culture change.

Conclusion

Nursing home culture change aims to improve care quality and resident satisfaction through changes to physical environments, resident care practices, and staff empowerment. These include both relatively simple technical changes and more complex changes. Nursing home managers and leaders have reported a variety of barriers to implementing nursing home culture change. A common barrier cited is staff resistance to change. Many decades of research in the organizational change literature and more recent research on culture change implementation suggest steps that facility managers and leaders can take to avoid or overcome this resistance. These steps include providing management support, especially in the form of good communication and training and education.

Corresponding author: Denise A. Tyler, PhD, RTI International, 307 Waverly Oaks Rd., Waltham, MA 02452, [email protected].

Financial disclosures: None.

From RTI International, Waltham, MA, and Brown University School of Public Health, Providence, RI.

Abstract

• Objective: To review the nursing home culture change literature and identify common barriers to and facilitators of nursing home culture change adoption. Nursing home culture change aims to make nursing homes less institutional by providing more resident-centered care, making environments more homelike, and empowering direct care staff.
• Methods: We reviewed the research literature on nursing home culture change, especially as related to implementation and outcomes.
• Results: Adoption of nursing home culture change practices has been steadily increasing in the past decade, but some practices are more likely to be adopted than others. A commonly reported barrier to culture change adoption is staff resistance to change. Studies suggest that this resistance can be overcome by changes to management practices, including good communication, providing training and education, and leadership support.
• Conclusion: The numerous benefits of nursing home culture change are apparent in the literature. Barriers to its adoption may be overcome by making improvements to nursing home management practices.

Key words: nursing homes; culture change; resident-centered care.

Nursing home culture change is a philosophy and combination of diverse practices aimed at making nursing homes less institutional and more resident-centered [1]. Nursing homes have been depicted as dehumanizing “total institutions” [2–4] in which the quality of residents’ lives and the quality of care are generally poor, daily life is medically regimented, only residents’ basic physical needs receive attention [5–8], and direct care workers are subject to poor working conditions for the lowest possible pay [9,10]. Since the 1980s, transforming the culture of nursing homes to be more humanizing, resident-centered, empowering, and homelike has been a primary mission of many stakeholder groups, including nursing home residents and care workers and their advocates [11].

Comprehensive culture change requires transformation of the nursing home environment from that of an institution to that of a home, implementation of more resident-centered care practices, empowerment of direct care staff, and flattening of the traditional organizational hierarchy so that residents and direct-care workers are actively involved in planning and implementing changes that empower them [12,13]. Culture change requires both technical changes, which are relatively straightforward efforts to address issues within a system while fundamentally keeping the system intact, and adaptive changes, which are more complex and entail reforming fundamental values that underlie the system and demand changes to the system itself [14,15].

Over time, nursing home culture change has gained widespread mainstream support. In 2009, the federal government issued new interpretive guidelines for use by nursing home inspectors that call for nursing homes to have more homelike environments and to support more resident-centered care [16]. The Centers for Medicare & Medicaid Services also required state quality improvement organizations to work with nursing homes on culture change efforts [1]. Some states effectively incentivize culture change by tying nursing home reimbursement rates and pay-for-performance policies to the implementation of culture change practices [17]. In addition to federal and state regulations, some nursing home corporations encourage or require facility administrators to implement culture change practices [18]. Overall, nursing homes are pushed to implement culture change practices on many fronts. The promise of beneficial outcomes of culture change also motivates implementation of some culture change practices [19].

In this article, we discuss the key elements of culture change, review the research examining the association between culture change and outcomes, identify key barriers to culture change, and offer suggestions from the literature for overcoming resistance to culture change.

Elements of Culture Change

Changing the Physical Environment

Changing the physical environment of nursing homes to be less institutional and more homelike is a core component of culture change [1]. These include both exterior and interior changes. Exterior changes can include adding walkways, patios, and gardens; interior changes include replacing nurses’ stations with desks, creating resident common areas, introducing the use of linens in dining areas, personalizing mailboxes outside of resident rooms, and adding small kitchens on units [20]. Other ideas for making environments more homelike include providing residents with the choice of colors for painting rooms and the choice of corridor/unit names and replacing public announcement systems with staff pagers [20].

Although changes to the physical environment may be considered cost-prohibitive, many of these changes entail minor and inexpensive enhancements that can help make environments more intimate and reminiscent of home than are traditional nursing homes [21,22]. Additionally, some environmental changes, such as adding raised gardens and walkways, can be designed not only to make the environment more homelike but also to help residents to engage in meaningful activities and connect to former roles, such as those of a homemaker, gardener, or farmer [21–23].

Providing Resident-Centered Care

Making care resident-centered entails enhancing resident choice and decision making and focusing the delivery of services on residents’ needs and preferences. According to Banaszak-Holl and colleagues [24], resident-centered approaches often emphasize the importance of shifting institutional norms and values and drawing employees’ attention to the needs of residents. This cultural shift in values and norms may be signaled by the implementation of practices that strengthen residents’ autonomy regarding everyday decisions. For example, as part of a resident-centered approach, residents would be offered choices and encouraged to make their own decisions about things personally affecting them, such as what to wear or when to go to bed, eating schedules, and menus [1,17,25].

Empowering Care Aides

Nursing home staff empowerment, particularly the empowerment of nursing assistants and other “hands-on” care aides—who are the predominant workforce in nursing homes and provide the vast bulk of care [26]—is a core component of culture change [1]. Such staff empowerment generally entails enhanced participation in decision making and increased autonomy. Staff empowerment practices that were examined in a national survey of nursing home directors [17] included:

• Staff work together to cover shifts when someone cannot come to work
• Staff cross-trained to perform tasks outside of their assigned job duties
• Staff involved in planning social events
• Nursing assistants take part in quality improvement teams
• Nursing assistants know when a resident’s care plan has changed
• Nursing assistants who receive extra training or education receive bonuses or raises
• Nursing assistants can choose which the residents for whom they provide care

We found that the staff empowerment practices most commonly implemented by nursing homes included nursing assistants knowing when a resident’s care plan has changed and staff working together to cover shifts when someone can’t come to work, but it was uncommon for nursing homes to permit nursing assistants to choose which residents they care for [17].

Outcomes of Culture Change

Research over the past 2 decades has examined the outcomes of culture change and the challenges involved in its implementation. Culture change is intended to improve the quality of life for nursing home residents, but the impact of culture change interventions is not clear. Shier and colleagues [27] conducted a comprehensive review of the peer-reviewed and gray literature on culture change published between 2005 and 2012 and found that studies varied widely in scope and evidence was inconsistent. They concluded that there is not yet sufficient evidence to provide specific guidance to nursing homes interested in implementing culture change [27]. The reviewed studies (27 peer-reviewed and 9 gray literature) also were noted to include small sample sizes and restricted geographic coverage, which both limit generalizability.

Although the literature had substantial limitations, Shier and colleagues [27] found numerous beneficial outcomes of culture change. Statistically significant improvements in numerous resident outcome measures were found to be associated with the implementation of culture change practices, including measures of resident quality of life/well-being, engagement and activities, functional status, satisfaction, mood (depression), anxiety/behavior/agitation, and pain/comfort. Two quality of care and services outcome measures also showed significant improvement associated with culture change practices, including increased completion of advance care plans and improved quality of workers’ approach to residents. Various staff outcome measures also showed significant improvement associated with culture change, including improvements in staff turnover/retention, satisfaction/well-being/burnout, absenteeism, knowledge, and attitude. Additionally, studies have shown culture change to be associated with improvements in select organizational outcome measures including operations costs, occupancy rates, revenue/profits, and family satisfaction. Four of the 36 studies reported negative outcomes of culture change. These negative outcomes included increased resident fear/anxiety [28], increased resident incontinence, decreased resident engagement in activities, decreased family engagement [29,30], decreased resident well-being [31], and increased physical incidents [32]. Notably, negative outcomes often co-occurred with positive outcomes [27,28].

To address the limitations of previous culture change research, such as small sample sizes and limited geographic coverage, and to explain some of the previous equivocal findings from quality studies when the extent of culture change practice implementation was not considered or measured, we collaborated on a national study to understand whether nursing home introduction of culture change practices is associated with improved quality [33]. We identified 824 U.S. nursing homes that had implemented some culture change practices, and we classified them by level of culture change practice implementation (high versus low). In nursing homes with high levels of culture change practice implementation, the introduction of nursing home culture change was associated with significant improvements in some care processes (eg, decreased prevalence of restraints, tube feeding, and pressure ulcers; increased proportion of residents on bladder training programs) and improvements in some resident outcomes, including slightly fewer hospitalizations. Among nursing homes with lower levels of culture change practice implementation, the introduction of culture change was associated with fewer health-related and quality-of-life survey deficiencies, but also with a significant increase in the number of resident hospitalizations [33]. Conclusive evidence regarding the impact of nursing homes implementing specific culture change practices or a comprehensive array of culture change practices on resident outcomes and quality of life remains needed, but numerous benefits of culture change are apparent in the literature.

Diffusion of Culture Change Practices

As culture change is widely supported and shows promise for beneficial outcomes, culture change practices are increasingly being implemented in nursing homes nationally. In 2007, a Commonwealth Fund survey found 56% of directors of nursing in U.S. nursing homes reported any culture change implementation or leadership commitment to implementation, but only 5% reported that culture change had completely changed the way the nursing home cared for residents in all areas of the nursing home [34]. In contrast, by 2010, 85% of directors of nursing reported at least partial culture change implementation and 13% reported that culture change had completely changed the way the nursing home cared for residents in all areas [14]. In a more recent survey of nursing home administrators, 16% reported that culture change had completely changed the way the nursing home cared for residents in all areas [35].

Barriers to Culture Change Implementation

Although the growth of culture change in the nursing home industry in the past decade has been impressive, implementation of comprehensive culture change has lagged behind. This is because one notable feature of nursing home culture change is that it is a philosophy that consists of many related practices. As noted above, implementing culture change can involve changes to physical environments, resident-centered care practices, and staff empowerment. This means that facilities can choose to implement as many or as few changes as they would like, and research has shown that there has been a lot of variation in which culture change practices are implemented. For example, in previous research we found that facilities interested in attracting highly reimbursed Medicare rehabilitation patients were more likely to implement hotel-style changes to their physical environments than they were to implement resident-centered care practices or forms of staff empowerment [19]. Sterns and colleagues [36] found that facilities were more likely to implement less complex practices (eg, allowing residents to choose when they go to bed) than more complex practices (eg, involving staff and residents in organizational decision making). The authors suggest that differences in commitment of facility leaders to comprehensive culture change may have contributed to these differences.

Attributes of facility leaders and other aspects of organizational context have been shown to contribute to more and less successful culture change implementation. For example, Scalzi and colleagues [37] found that some important barriers to culture change implementation were not involving all staff in culture change activities and a lack of corporate level support for these efforts. Schuldheis [38] examined differences in organizational context and its role in culture change among 9 Oregon facilities; 3 facilities successfully implemented culture change practices and 6 facilities did not. Results showed that a facility’s existing organizational culture, attention to sustainability, management practices, and staff involvement were important to the success of the initiative. Similarly, Rosemond and colleagues [39] conducted a study involving 8 North Carolina nursing homes. They determined that unsuccessful culture change initiatives could be attributed to the organizations’ readiness for change, a lack of high quality management communications, and unfavorable perceptions of culture change by direct-care workers. A study conducted in 4 nursing homes by Munroe et al [40] found that formal culture change training provided by professional trainers produced better outcomes than informal “train the trainer” sessions provided by other facility managers. Bowers and colleagues [41] also found that unsuccessful implementation of the Green House model of culture change was likely related to a lack of training resources for staff. Similarly, after an in-depth ethnographic study of culture change implementation, Lopez [42] found that it was unrealistic to expect direct-care workers to perform their jobs in radically new ways without being provided with ongoing support from management.

Resistance to Change: A Key Barrier

Our own research sought to understand the barriers and challenges nursing home administrators faced when implementing culture change in their facilities and the strategies they used to overcome them. In interviews conducted with 64 administrators who had participated in a previous nationally representative survey about culture change implementation, administrators reported a wide variety of barriers, including old and outdated physical plants, the costs of some changes, and issues with unions [18]. A key barrier that administrators reported facing was resistance to change on the part of nursing facility staff, residents, and residents’ family members [43]. Administrators reported that residents were resistant to change primarily because they had been institutionalized in their thinking. In other words, nursing homes had essentially trained residents to expect things to be done at certain times and in certain ways. Resistance among staff reportedly included resistance to the overall concept of culture change and to specific culture change practices. Often, staff perceived that changes related to culture change implementation involved additional work or effort on their part without additional resources, but this was not the only reason for resistance. Most often staff, especially longer-term staff, simply were resistant to making any changes to their usual routines or duties.

This type of resistance to change among staff is not unique to culture change implementation and has long been a commonly cited barrier in the organizational change literature. For example, in a 1954 Harvard Business Review article, Lawrence [44] stated that resistance to change was “the most baffling and recalcitrant of the problems which business executives face.” Since that time, resistance to change has been extensively studied as have methods for overcoming such resistance.

Recommendations for Overcoming Resistance to Culture Change

In seminal work on employee resistance to change conducted shortly after World War II, Coch and French [45] challenged the concept that resistance to change was the result of flaws or inadequacies on the part of staff, which would make addressing resistance difficult. Instead, they proposed, and proved through experimental methods, that resistance arose primarily from the context within which the changes were taking place. In other words, they found that managers could ameliorate resistance to change through changes to management and leadership practices. In their experiment, resistance to change in a manufacturing plant was overcome when management effectively communicated to staff the reasons for the change and engaged staff in planning for the desired changes. Studies on the barriers and facilitators of culture change implementation in nursing facilities have similarly found that facility leaders can take steps to address, or even avoid, staff resistance to change.

In our own research, we have found that resistance to change is a common barrier faced by facility leaders. We also found that resistance to change was unique among barriers in that, although strategies used to address other types of barriers varied widely, administrators consistently reported using the same strategies to address and overcome resistance to change. These strategies all involved management and leadership activities, including education and training and improved communication. In addition, administrators discussed in detail the ways they tailored education and communication to their facility’s unique needs. They also indicated that these efforts should be ongoing, communication should be two-way, and that all staff should be included [43].

Good Communication

One important tool for avoiding or overcoming resistance to culture change that facility administrators reported was good communication. They reported that open and bidirectional communication fostered feedback about ongoing culture change efforts and encouraged engagement and buy-in from staff. They also suggested that it is important that this type of communication be ongoing. Good communication about culture change, in particular, included providing a strong rationale for the changes and involved getting input from staff before and during implementation [43].

These findings are similar to other studies of culture change which have found that culture change implementation should involve staff at all levels [37] and that facility leaders should follow through on the plans that have been communicated [39]. Interestingly, the importance of good and open communication has also been identified as important to other forms of nursing facility quality improvement [46].

Training and Education

The facility administrators we interviewed also reported providing education and training for staff about culture change in a variety of ways, including as part of regular in-service training and as a component of new employee orientation. The training materials used were often obtained from the leading culture change organizations. However, importantly, administrators reported tailoring these trainings to the specific needs of their employees or unique context of their facility. For example, administrators reported breaking up long training sessions into shorter segments provided over a longer period of time or organizing trainings to be provided to small groups on the units rather than in more didactic conference-style settings [43]. Administrators explained that providing training in this way was more palatable to staff and helped incorporate learning into everyday care.

Other studies of nursing home culture change have also found training and education to be important to implementation. For example, in a study of a labor-management partnership for culture change implementation, Leutz and colleagues [47] found training of staff from all disciplines by culture change experts to be an important element of successful implementation. Training topics included those that were very general, such as gerontology, and very specific, including person-centered care. Staff were paid for their time participating in training, which took place at their facilities to make participation easier. The trainings were also staggered over the course of several months, so that staff had time to use what they had learned between sessions and could discuss their experiences at the later sessions.

Munroe and colleagues [40] conducted a study of culture change training using pre-post test survey methods and found that formal training had more of an effect on staff than informal training. In the study, staff at 2 facilities received formal education from a consulting group while staff at 2 other facilities then received informal training from the staff of one of the formally trained facilities. An important conclusion of the authors was that the formal training did a better job than the informal training of helping facility leaders and managers view their relationships with staff differently. This suggests that facility leaders and managers may have to alter their management styles to create the supportive context within which culture change efforts can succeed [48].

Leadership Support

Good communication and training/education can be thought of as 2 examples of leadership support, and support from facility leaders and managers has been found, in multiple studies, to be critical to successful culture change efforts. For example, in a recent study of nursing facility culture change in the Netherlands, Snoeren and colleagues [49] found that facility managers can facilitate culture change implementation by supporting a variety of staff needs and promoting the facilities’ new desired values. Another study found that facilities with leaders who are supportive and foster staff flexibility, such as allowing staff to be creative in their problem-solving and have decentralized decision-making, were more likely to report having implemented culture change [24].

In a study focused specifically on facility leadership style and its relation to culture change implementation, Corazzini and colleagues [50] found an adaptive leadership style to be important to culture change implementation. Adaptive leadership styles are ones that acknowledge the importance of staff relationships and recognize that complex changes, like those often implemented in culture change efforts, require complex solutions that will likely evolve over time. These authors conclude that culture change implementation necessitates development of new normative values and behaviors and can, therefore, not be accomplished by simply generating new rules and procedures [50].

Of course, not all nursing facility leaders have the management skills needed to perform in these adaptive and flexible ways. Therefore, management training for facility leaders may be an important first step in a facility’s culture change efforts [51]. This type of training may help improve communication skills and allow facility leaders to perform in more adaptive and flexible ways to better meet the needs of their particular facility and staff. Research also suggests that culture change training for facility leaders may help them to form new and better relationships with staff [40], an important element of culture change.

Conclusion

Nursing home culture change aims to improve care quality and resident satisfaction through changes to physical environments, resident care practices, and staff empowerment. These include both relatively simple technical changes and more complex changes. Nursing home managers and leaders have reported a variety of barriers to implementing nursing home culture change. A common barrier cited is staff resistance to change. Many decades of research in the organizational change literature and more recent research on culture change implementation suggest steps that facility managers and leaders can take to avoid or overcome this resistance. These steps include providing management support, especially in the form of good communication and training and education.

Corresponding author: Denise A. Tyler, PhD, RTI International, 307 Waverly Oaks Rd., Waltham, MA 02452, [email protected].

Financial disclosures: None.

Take-Home Points

• SSIs after TJA pose a substantial burden on patients, surgeons, and the healthcare system.
• While different forms of preoperative skin preparation have shown varying outcomes after TJA, the importance of preoperative patient optimization (nutritional status, immune function, etc) cannot be overstated. 
• Intraoperative infection prevention measures include cutaneous preparation, gloving, body exhaust suits, surgical drapes, OR staff traffic and ventilation flow, and antibiotic-loaded cement. 
• Antibiotic prophylaxis for dental procedures in TJA patients continues to remain a controversial issue with conflicting recommendations.
• SSIs have considerable financial costs and require increased resource utilization. Given the significant economic burden associated with TJA infections, it is imperative for orthopedists to establish practical and cost-effective strategies to prevent these devastating complications.

Surgical-site infection (SSI), a potentially devastating complication of lower extremity total joint arthroplasty (TJA), is estimated to occur in 1% to 2.5% of cases annually.¹ Infection after TJA places a significant burden on patients, surgeons, and the healthcare system. Revision procedures that address infection after total hip arthroplasty (THA) are associated with more hospitalizations, more operations, longer hospital stay, and higher outpatient costs in comparison with primary THAs and revision surgeries for aseptic loosening.² If left untreated, a SSI can go deeper into the joint and develop into a periprosthetic infection, which can be disastrous and costly. A periprosthetic joint infection study that used 2001 to 2009 Nationwide Inpatient Sample (NIS) data found that the cost of revision procedures increased to $560 million from $320 million, and was projected to reach $1.62 billion by 2020.³ Furthermore, society incurs indirect costs as a result of patient disability and loss of wages and productivity.² Therefore, the issue of infection after TJA is even more crucial in our cost-conscious healthcare environment. 

Patient optimization, advances in surgical technique, sterile protocol, and operative procedures have been effective in reducing bacterial counts at incision sites and minimizing SSIs. As a result, infection rates have leveled off after rising for a decade.⁴ Although infection prevention modalities have their differences, routine use is fundamental and recommended by the Hospital Infection Control Practices Advisory Committee.⁵ Furthermore, both the US Centers for Disease Control and Prevention (CDC) and its Healthcare Infection Control Practices Advisory Committee^6,7 recently updated their SSI prevention guidelines by incorporating evidence-based methodology, an element missing from earlier recommendations.

The etiologies of postoperative SSIs have been discussed ad nauseam, but there are few reports summarizing the literature on infection prevention modalities. In this review, we identify and examine SSI prevention strategies as they relate to lower extremity TJA. Specifically, we discuss the literature on the preoperative, intraoperative, and postoperative actions that can be taken to reduce the incidence of SSIs after TJA. We also highlight the economic implications of SSIs that occur after TJA.

Methods

For this review, we performed a literature search with PubMed, EBSCOhost, and Scopus. We looked for reports published between the inception of each database and July 2016. Combinations of various search terms were used: surgical site, infection, total joint arthroplasty, knee, hip, preoperative, intraoperative, perioperative, postoperative, preparation, nutrition, ventilation, antibiotic, body exhaust suit, gloves, drain, costs, economic, and payment.

Our search identified 195 abstracts. Drs. Mistry and Chughtai reviewed these to determine which articles were relevant. For any uncertainties, consensus was reached with the help of Dr. Delanois. Of the 195 articles, 103 were potentially relevant, and 54 of the 103 were excluded for being not relevant to preventing SSIs after TJA or for being written in a language other than English. The references in the remaining articles were assessed, and those with potentially relevant titles were selected for abstract review. This step provided another 35 articles. After all exclusions, 48 articles remained. We discuss these in the context of preoperative, intraoperative, and postoperative measures and economic impact.

Results

Preoperative Measures

Skin Preparation. Preoperative skin preparation methods include standard washing and rinsing, antiseptic soaps, and iodine-based or chlorhexidine gluconate-based antiseptic showers or skin cloths. Iodine-based antiseptics are effective against a wide range of Gram-positive and Gram-negative bacteria, fungi, and viruses. These agents penetrate the cell wall, oxidize the microbial contents, and replace those contents with free iodine molecules.⁸ Iodophors are free iodine molecules associated with a polymer (eg, polyvinylpyrrolidone); the iodophor povidone-iodine is bactericidal.⁹ Chlorhexidine gluconate-based solutions are effective against many types of yeast, Gram-positive and Gram-negative bacteria, and a wide variety of viruses.⁹ Both solutions are useful. Patients with an allergy to iodine can use chlorhexidine. Table 1 summarizes the studies on preoperative measures for preventing SSIs.

There is no shortage of evidence of the efficacy of these antiseptics in minimizing the incidence of SSIs. Hayek and colleagues¹⁰ prospectively analyzed use of different preoperative skin preparation methods in 2015 patients. Six weeks after surgery, the infection rate was significantly lower with use of chlorhexidine than with use of an unmedicated bar of soap or placebo cloth (9% vs 11.7% and 12.8%, respectively; P < .05). In a study of 100 patients, Murray and colleagues¹¹ found the overall bacterial culture rate was significantly lower for those who used a 2% chlorhexidine gluconate cloth before shoulder surgery than for those who took a standard shower with soap (66% vs 94%; P = .0008). Darouiche and colleagues¹² found the overall SSI rate was significantly lower for 409 surgical patients prepared with chlorhexidine-alcohol than for 440 prepared with povidone-iodine (9.5% vs 16.1%; P = .004; relative risk [RR], 0.59; 95% confidence interval [CI], 0.41-0.85).

Chlorhexidine gluconate-impregnated cloths have also had promising results, which may be attributed to general ease of use and potentially improved patient adherence. Zywiel and colleagues¹³ reported no SSIs in 136 patients who used these cloths at home before total knee arthroplasty (TKA) and 21 SSIs (3.0%) in 711 patients who did not use the cloths. In a study of 2545 THA patients, Kapadia and colleagues¹⁴ noted a significantly lower incidence of SSIs with at-home preoperative use of chlorhexidine cloths than with only in-hospital perioperative skin preparation (0.5% vs 1.7%; P = .04). In 2293 TKAs, Johnson and colleagues¹⁵ similarly found a lower incidence of SSIs with at-home preoperative use of chlorhexidine cloths (0.6% vs 2.2%; P = .02). In another prospective, randomized trial, Kapadia and colleagues16 compared 275 patients who used chlorhexidine cloths the night before and the morning of lower extremity TJA surgery with 279 patients who underwent standard-of-care preparation (preadmission bathing with antibacterial soap and water). The chlorhexidine cohort had a lower overall incidence of infection (0.4% vs 2.9%; P = .049), and the standard-of-care cohort had a stronger association with infection (odds ratio [OR], 8.15; 95% CI, 1.01-65.6). 

Patient Optimization. Poor nutritional status may compromise immune function, potentially resulting in delayed healing, increased risk of infection, and, ultimately, negative postoperative outcomes. Malnutrition can be diagnosed on the basis of a prealbumin level of <15 mg/dL (normal, 15-30 mg/dL), a serum albumin level of <3.4 g/dL (normal, 3.4-5.4 g/dL), or a total lymphocyte count under 1200 cells/μL (normal, 3900-10,000 cells/μL).^17-19 Greene and colleagues¹⁸ found that patients with preoperative malnutrition had up to a 7-fold higher rate of infection after TJA. In a study of 135 THAs and TKAs, Alfargieny and colleagues²⁰ found preoperative serum albumin was the only nutritional biomarker predictive of SSI (P = .011). Furthermore, patients who take immunomodulating medications (eg, for inflammatory arthropathies) should temporarily discontinue them before surgery in order to lower their risk of infection.²¹ 

Smoking is well established as a major risk factor for poor outcomes after surgery. It is postulated that the vasoconstrictive effects of nicotine and the hypoxic effects of carbon monoxide contribute to poor wound healing.²² In a meta-analysis of 4 studies, Sørensen²³ found smokers were at increased risk for wound complications (OR, 2.27; 95% CI, 1.82-2.84), delayed wound healing and dehiscence (OR, 2.07; 95% CI, 1.53-2.81), and infection (OR, 1.79; 95% CI, 1.57-2.04). Moreover, smoking cessation decreased the incidence of SSIs (OR, 0.43; 95% CI, 0.21-0.85). A meta- analysis by Wong and colleagues²⁴ revealed an inflection point for improved outcomes in patients who abstained from smoking for at least 4 weeks before surgery. Risk of infection was lower for these patients than for current smokers (OR, 0.69; 95% CI, 0.56-0.84).

Other comorbidities contribute to SSIs as well. In their analysis of American College of Surgeons National Surgical Quality Improvement Program registry data on 25,235 patients who underwent primary and revision lower extremity TJA, Pugely and colleagues²⁵ found that, in the primary TJA cohort, body mass index (BMI) of >40 kg/m2 (OR, 1.9; 95% CI, 1.3-2.9), electrolyte disturbance (OR, 2.4; 95% CI, 1.0-6.0), and hypertension diagnosis (OR, 1.5; 95% CI, 1.1-2.0) increased the risk of SSI within 30 days. Furthermore, diabetes mellitus delays collagen synthesis, impairs lymphocyte function, and impairs wound healing, which may lead to poor recovery and higher risk of infection.²⁶ In a study of 167 TKAs performed in 115 patients with type 2 diabetes mellitus, Han and Kang²⁶ found that wound complications were 6 times more likely in those with hemoglobin A1c (HbA1c) levels higher than 8% than in those with lower HbA1c levels (OR, 6.07; 95% CI, 1.12-33.0). In a similar study of 462 patients with diabetes, Hwang and colleagues²⁷ found a higher likelihood of superficial SSIs in patients with HbA1c levels >8% (OR, 6.1; 95% CI, 1.6-23.4; P = .008). This association was also found in patients with a fasting blood glucose level of >200 mg/dL (OR, 9.2; 95% CI, 2.2-38.2; P = .038).

Methicillin-resistant Staphylococcus aureus (MRSA) is thought to account for 10% to 25% of all periprosthetic infections in the United States.28 Nasal colonization by this pathogen increases the risk for SSIs; however, decolonization protocols have proved useful in decreasing the rates of colonization. Moroski and colleagues²⁹ assessed the efficacy of a preoperative 5-day course of intranasal mupirocin in 289 primary or revision TJA patients. Before surgery, 12 patients had positive MRSA cultures, and 44 had positive methicillin-sensitive S aureus (MSSA) cultures. On day of surgery, a significant reduction in MRSA (P = .0073) and MSSA (P = .0341) colonization was noted. Rao and colleagues³⁰ found that the infection rate decreased from 2.7% to 1.2% in 2284 TJA patients treated with a decolonization protocol (P = .009). 

Intraoperative Measures

Cutaneous Preparation. The solutions used in perioperative skin preparation are similar to those used preoperatively: povidone-iodine, alcohol, and chlorhexidine. The efficacy of these preparations varies. Table 2 summarizes the studies on intraoperative measures for preventing SSIs.

The literature also highlights the importance of technique in incision-site preparation. In a prospective study, Morrison and colleagues³³ randomly assigned 600 primary TJA patients to either (1) use of alcohol and povidone-iodine before draping, with additional preparation with iodine povacrylex (DuraPrep) and isopropyl alcohol before application of the final drape (300-patient intervention group) or (2) only use of alcohol and povidone-iodine before draping (300-patient control group). At the final follow-up, the incidence of SSI was significantly lower in the intervention group than in the control group (1.8% vs 6.5%; P = .015). In another study that assessed perioperative skin preparation methods, Brown and colleagues34 found that airborne bacteria levels in operating rooms were >4 times higher with patients whose legs were prepared by a scrubbed, gowned leg-holder than with patients whose legs were prepared by an unscrubbed, ungowned leg-holder (P = .0001).

Hair Removal. Although removing hair from surgical sites is common practice, the literature advocating it varies. A large comprehensive review³⁵ revealed no increased risk of SSI with removing vs not removing hair (RR, 1.65; 95% CI, 0.85-3.19). On the other hand, some hair removal methods may affect the incidence of infection. For example, use of electric hair clippers is presumed to reduce the risk of SSIs, whereas traditional razors may compromise the epidermal barriers and create a pathway for bacterial colonization.^5,36,37 In the aforementioned review,³⁵ SSIs were more than twice as likely to occur with hair removed by shaving than with hair removed by electric clippers (RR, 2.02; 95% CI, 1.21-3.36). Cruse and Foord³⁸ found a higher rate of SSIs with hair removed by shaving than with hair removed by clipping (2.3% vs 1.7%). Most surgeons agree that, if given the choice, they would remove hair with electric clippers rather than razors.

Gloves. Almost all orthopedists double their gloves for TJA cases. Over several studies, the incidence of glove perforation during orthopedic procedures has ranged from 3.6% to 26%,^39-41 depending on the operating room personnel and glove layering studied. Orthopedists must know this startling finding, as surgical glove perforation is associated with an increase in the rate of SSIs, from 1.7% to 5.7%.³⁸ Carter and colleagues⁴² found the highest risk of glove perforation occurs when double-gloved attending surgeons, adult reconstruction fellows, and registered nurses initially assist during primary and revision TJA. In their study, outer and inner glove layers were perforated 2.5% of the time. All outer-layer perforations were noticed, but inner-layer perforations went unnoticed 81% of the time, which poses a potential hazard for both patients and healthcare personnel. In addition, there was a significant increase in the incidence of glove perforations for attending surgeons during revision TJA vs primary TJA (8.9% vs 3.7%; P = .04). This finding may be expected given the complexity of revision procedures, the presence of sharp bony and metal edges, and the longer operative times. Giving more attention to glove perforations during arthroplasties may mitigate the risk of SSI. As soon as a perforation is noticed, the glove should be removed and replaced.

Body Exhaust Suits. Early TJAs had infection rates approaching 10%.⁴³ Bacterial-laden particles shed from surgical staff were postulated to be the cause,^44,45 and this idea prompted the development of new technology, such as body exhaust suits, which have demonstrated up to a 20-fold reduction in airborne bacterial contamination and decreased incidence of deep infection, from 1% to 0.1%, as compared with conventional surgical attire.⁴⁶ However, the efficacy of these suits was recently challenged. Hooper and colleagues⁴⁷ assessed >88,000 TJA cases in the New Zealand Joint Registry and found a significant increase in early revision THA for deep infection with vs without use of body exhaust suits (0.186% vs 0.064%; P < .0001). The incidence of revision TKAs for deep infections with use of these suits was similar (0.243% vs 0.098%; P < .001). Many of the surgeons surveyed indicated their peripheral vision was limited by the suits, which may contribute to sterile field contamination. By contrast, Miner and colleagues⁴⁸ were unable to determine an increased risk of SSI with use of body exhaust suits (RR, 0.75; 95% CI, 0.34-1.62), though there was a trend toward more infections without suits. Moreover, these suits are effective in reducing mean air bacterial counts (P = .014), but it is not known if this method correlates with mean wound bacterial counts (r = –.011) and therefore increases the risk of SSI.⁴⁹

Surgical Drapes. Surgical draping, including cloths, iodine-impregnated materials, and woven or unwoven materials, is the standard of care worldwide. The particular draping technique usually varies by surgeon. Plastic drapes are better barriers than cloth drapes, as found in a study by Blom and colleagues⁵⁰: Bacterial growth rates were almost 10 times higher with use of wet woven cloth drapes than with plastic surgical drapes. These findings were supported in another, similar study by Blom and colleagues⁵¹: Wetting drapes with blood or normal saline enhanced bacterial penetration. In addition, wetting drapes with chlorhexidine or iodine reduced but did not eliminate bacterial penetration. Fairclough and colleagues⁵² emphasized that iodine-impregnated drapes reduced surgical-site bacterial contamination from 15% to 1.6%. However, a Cochrane review⁵³ found these drapes had no effect on the SSI rate (RR, 1.03; 95% CI, 0.06-1.66; P = .89), though the risk of infection was slightly higher with adhesive draping than with no drape (RR, 1.23; 95% CI, 1.02-1.48; P = .03).

Ventilation Flow. Laminar-airflow systems are widely used to prevent SSIs after TJA. Horizontal-flow and vertical-flow ventilation provides and maintains ultra-clean air in the operating room. Evans⁵⁴ found the bacterial counts in the air and the wound were lower with laminar airflow than without this airflow. The amount of airborne bacterial colony-forming units and dust large enough to carry bacteria was reduced to 1 or 2 particles more than 2 μm/m3 with use of a typical laminar- airflow system. In comparing 3922 TKA patients in laminar-airflow operating rooms with 4133 patients in conventional rooms, Lidwell and colleagues⁴⁶ found a significantly lower incidence of SSIs in patients in laminar-airflow operating rooms (0.6% vs 2.3%; P < .001).

Conversely, Miner and colleagues⁴⁸ did not find a lower risk of SSI with laminar-airflow systems (RR, 1.57; 95% CI, 0.75-3.31). In addition, in their analysis of >88,000 cases from the New Zealand Joint Registry, Hooper and colleagues⁴⁷ found that the incidence of early infections was higher with laminar-airflow systems than with standard airflow systems for both TKA (0.193% vs 0.100%; P = .019) and THA (0.148% vs 0.061%; P < .001). They postulated that vertically oriented airflow may have transmitted contaminated particles into the surgical sites. Additional evidence may be needed to resolve these conflicting findings and determine whether clean-air practices provide significant clinical benefit in the operating room.

Staff Traffic Volume. When staff enters or exits the operating room or makes extra movements during a procedure, airflow near the wound is disturbed and no longer able to remove sufficient airborne pathogens from the sterile field. The laminar- airflow pattern may be disrupted each time the operating room doors open and close, potentially allowing airborne pathogens to be introduced near the patient. Lynch and colleagues⁵⁵ found the operating room door opened almost 50 times per hour, and it took about 20 seconds to close each time. As a result, the door may remain open for up to 20 minutes per case, causing substantial airflow disruption and potentially ineffective removal of airborne bacterial particles. Similarly, Young and O’Regan⁵⁶ found the operating room door opened about 19 times per hour and took 20 seconds to close each time. The theater door was open an estimated 10.7% of each hour of sterile procedure. Presence of more staff also increases airborne bacterial counts. Pryor and Messmer⁵⁷ evaluated a cohort of 2864 patients to determine the effect of number of personnel in the operating theater on the incidence of SSIs. Infection rates were 6.27% with >17 different people entering the room and 1.52% with <9 different people entering the room. Restricting the number of people in the room may be one of the easiest and most efficient ways to prevent SSI.

Systemic Antibiotic Prophylaxis. Perioperative antibiotic use is vital in minimizing the risk of infection after TJA. The Surgical Care Improvement Project recommended beginning the first antimicrobial dose either within 60 minutes before surgical incision (for cephalosporin) or within 2 hours before incision (for vancomycin) and discontinuing the prophylactic antimicrobial agents within 24 hours after surgery ends.^58,59 However, Gorenoi and colleagues⁶⁰ were unable to recommend a way to select particular antibiotics, as they found no difference in the effectiveness of various antibiotic agents used in TKA. A systematic review by AlBuhairan and colleagues⁶¹ revealed that antibiotic prophylaxis (vs no prophylaxis) reduced the absolute risk of a SSI by 8% and the relative risk by 81% (P < 0.0001). These findings are supported by evidence of the efficacy of perioperative antibiotics in reducing the incidence of SSI.^62,63 Antibiotic regimens should be based on susceptibility and availability, depending on hospital prevalence of infections. Even more, patients should receive prophylaxis in a timely manner. Finally, bacteriostatic antibiotics (vancomycin) should not be used on their own for preoperative prophylaxis.

Antibiotic Cement. Antibiotic-loaded bone cement (ALBC), which locally releases antimicrobials in high concentration, is often used in revision joint arthroplasty, but use in primary joint arthroplasty remains controversial. In a study of THA patients, Parvizi and colleagues64 found infection rates of 1.2% with 2.3% with and without use of ALBC, respectively. Other studies have had opposing results. Namba and colleagues⁶⁵ evaluated 22,889 primary TKAs, 2030 (8.9%) of which used ALBC. The incidence of deep infection was significantly higher with ALBC than with regular bone cement (1.4% vs 0.7%; P = .002). In addition, a meta- analysis of >6500 primary TKA patients, by Zhou and colleagues,⁶⁶ revealed no significant difference in the incidence of deep SSIs with use of ALBC vs regular cement (1.32% vs 1.89%; RR, 0.75; 95% CI, 0.43-1.33; P = .33). More evidence is needed to determine the efficacy of ALBC in primary TJA. International Consensus Meeting on Periprosthetic Joint Infection participants recommended use of ALBC in high-risk patients, including patients who are obese or immunosuppressed or have diabetes or a prior history of infection.⁶⁷

Postoperative Measures

Antibiotic Prophylaxis. The American Academy of Orthopaedic Surgeons (AAOS) and the American Dental Association (ADA) have suggestions for antibiotic prophylaxis for patients at increased risk for infection. As of 2015, the ADA no longer recommends antibiotic prophylaxis for patients with prosthetic joint implants,68 whereas the AAOS considers all patients with TJA to be at risk.⁶⁹

Although recommendations exist, the actual risk of infection resulting from dental procedures and the role of antibiotic prophylaxis are not well defined. Berbari and colleagues⁷¹ found that antibiotic prophylaxis in high- or low-risk dental procedures did not decrease the risk of subsequent THA infection (OR, 0.9; 95% CI, 0.5-1.6) or TKA infection (OR, 1.2; 95% CI, 0.7-2.2). Moreover, the risk of infection was no higher for patients who had a prosthetic hip or knee and underwent a high- or low-risk dental procedure without antibiotic prophylaxis (OR, 0.8; 95% CI, 0.4-1.6) than for similar patients who did not undergo a dental procedure (OR, 0.6; 95% CI, 0.4-1.1). Some studies highlight the low level of evidence supporting antibiotic prophylaxis during dental procedures.^72,73 However, there is no evidence of adverse effects of antibiotic prophylaxis. Given the potential high risk of infection after such procedures, a more robust body of evidence is needed to reach consensus.

Evacuation Drain Management. Prolonged use of surgical evacuation drains may be a risk factor for SSI. Therefore, early drain removal is paramount. Higher infection rates with prolonged drain use have been found in patients with persistent wound drainage, including malnourished, obese, and over-anticoagulated patients. Patients with wounds persistently draining for >1 week should undergo superficial wound irrigation and débridement. Jaberi and colleagues⁷⁴ assessed 10,325 TJA patients and found that the majority of persistent drainage ceased within 1 week with use of less invasive measures, including oral antibiotics and local wound care. Furthermore, only 28% of patients with persistent drainage underwent surgical débridement. It is unclear if this practice alone is appropriate. Infection should always be suspected and treated aggressively, and cultures should be obtained from synovial fluid before antibiotics are started, unless there is an obvious superficial infection that does not require further work-up.⁶⁷

Economic Impact

SSIs remain a significant healthcare issue, and the social and financial costs are staggering. Without appropriate measures in place, these complications will place a larger burden on the healthcare system primarily as a result of longer hospital stays, multiple procedures, and increased resource utilization.⁷⁵ Given the risk of progression to prosthetic joint infection, early preventive interventions must be explored.

Improved patient selection may be an important factor in reducing SSIs. In an analysis of 8494 joint arthroplasties, Malinzak and colleagues⁸⁰ noted that patients with a BMI of >50 kg/m2 had an increased OR of infection of 21.3 compared to those with BMI <50 kg/m2. Wagner and colleagues⁸¹ analyzed 21,361 THAs and found that, for every BMI unit over 25 kg/m2, there was an 8% increased risk of joint infection (P < .001). Although it is unknown if there is an association between reduction in preoperative BMI and reduction in postoperative complication risk, it may still be worthwhile and cost-effective to modify this and similar risk factors before elective procedures.

Market forces are becoming a larger consideration in healthcare and are being driven by provider competition.⁸² Treatment outcomes, quality of care, and healthcare prices have gained attention as a means of estimating potential costs.⁸³ In 2011, the Centers for Medicare & Medicaid Services (CMS) advanced the Bundled Payments for Care Improvement (BPCI) initiative, which aimed to provide better coordinated care of higher quality and lower cost.⁸⁴ This led to development of the Comprehensive Care for Joint Replacement (CJR) program, which gives beneficiaries flexibility in choosing services and ensures that providers adhere to required standards. During its 5-year test period beginning in 2016, the CJR program is projected to save CMS $153 million.⁸⁴ Under this program, the institution where TJA is performed is responsible for all the costs of related care from time of surgery through 90 days after hospital discharge—which is known as an “episode of care.” If the cost incurred during an episode exceeds an established target cost (as determined by CMS), the hospital must repay Medicare the difference. Conversely, if the cost of an episode is less than the established target cost, the hospital is rewarded with the difference. Bundling payments for a single episode of care in this manner is thought to incentivize providers and hospitals to give patients more comprehensive and coordinated care. Given the substantial economic burden associated with joint arthroplasty infections, it is imperative for orthopedists to establish practical and cost-effective strategies that can prevent these disastrous complications.

Conclusion

SSIs are a devastating burden to patients, surgeons, and other healthcare providers. In recent years, new discoveries and innovations have helped mitigate the incidence of these complications of THA and TKA. However, the incidence of SSIs may rise with the increasing use of TJAs and with the development of new drug-resistant pathogens. In addition, the increasing number of TJAs performed on overweight and high-risk patients means the costs of postoperative infections will be substantial. With new reimbursement models in place, hospitals and providers are being held more accountable for the care they deliver during and after TJA. Consequently, more emphasis should be placed on techniques that are proved to minimize the incidence of SSIs.

Take-Home Points

• SSIs after TJA pose a substantial burden on patients, surgeons, and the healthcare system.
• While different forms of preoperative skin preparation have shown varying outcomes after TJA, the importance of preoperative patient optimization (nutritional status, immune function, etc) cannot be overstated. 
• Intraoperative infection prevention measures include cutaneous preparation, gloving, body exhaust suits, surgical drapes, OR staff traffic and ventilation flow, and antibiotic-loaded cement. 
• Antibiotic prophylaxis for dental procedures in TJA patients continues to remain a controversial issue with conflicting recommendations.
• SSIs have considerable financial costs and require increased resource utilization. Given the significant economic burden associated with TJA infections, it is imperative for orthopedists to establish practical and cost-effective strategies to prevent these devastating complications.

Surgical-site infection (SSI), a potentially devastating complication of lower extremity total joint arthroplasty (TJA), is estimated to occur in 1% to 2.5% of cases annually.¹ Infection after TJA places a significant burden on patients, surgeons, and the healthcare system. Revision procedures that address infection after total hip arthroplasty (THA) are associated with more hospitalizations, more operations, longer hospital stay, and higher outpatient costs in comparison with primary THAs and revision surgeries for aseptic loosening.² If left untreated, a SSI can go deeper into the joint and develop into a periprosthetic infection, which can be disastrous and costly. A periprosthetic joint infection study that used 2001 to 2009 Nationwide Inpatient Sample (NIS) data found that the cost of revision procedures increased to $560 million from $320 million, and was projected to reach $1.62 billion by 2020.³ Furthermore, society incurs indirect costs as a result of patient disability and loss of wages and productivity.² Therefore, the issue of infection after TJA is even more crucial in our cost-conscious healthcare environment. 

Patient optimization, advances in surgical technique, sterile protocol, and operative procedures have been effective in reducing bacterial counts at incision sites and minimizing SSIs. As a result, infection rates have leveled off after rising for a decade.⁴ Although infection prevention modalities have their differences, routine use is fundamental and recommended by the Hospital Infection Control Practices Advisory Committee.⁵ Furthermore, both the US Centers for Disease Control and Prevention (CDC) and its Healthcare Infection Control Practices Advisory Committee^6,7 recently updated their SSI prevention guidelines by incorporating evidence-based methodology, an element missing from earlier recommendations.

The etiologies of postoperative SSIs have been discussed ad nauseam, but there are few reports summarizing the literature on infection prevention modalities. In this review, we identify and examine SSI prevention strategies as they relate to lower extremity TJA. Specifically, we discuss the literature on the preoperative, intraoperative, and postoperative actions that can be taken to reduce the incidence of SSIs after TJA. We also highlight the economic implications of SSIs that occur after TJA.

Methods

For this review, we performed a literature search with PubMed, EBSCOhost, and Scopus. We looked for reports published between the inception of each database and July 2016. Combinations of various search terms were used: surgical site, infection, total joint arthroplasty, knee, hip, preoperative, intraoperative, perioperative, postoperative, preparation, nutrition, ventilation, antibiotic, body exhaust suit, gloves, drain, costs, economic, and payment.

Our search identified 195 abstracts. Drs. Mistry and Chughtai reviewed these to determine which articles were relevant. For any uncertainties, consensus was reached with the help of Dr. Delanois. Of the 195 articles, 103 were potentially relevant, and 54 of the 103 were excluded for being not relevant to preventing SSIs after TJA or for being written in a language other than English. The references in the remaining articles were assessed, and those with potentially relevant titles were selected for abstract review. This step provided another 35 articles. After all exclusions, 48 articles remained. We discuss these in the context of preoperative, intraoperative, and postoperative measures and economic impact.

Results

Preoperative Measures

Skin Preparation. Preoperative skin preparation methods include standard washing and rinsing, antiseptic soaps, and iodine-based or chlorhexidine gluconate-based antiseptic showers or skin cloths. Iodine-based antiseptics are effective against a wide range of Gram-positive and Gram-negative bacteria, fungi, and viruses. These agents penetrate the cell wall, oxidize the microbial contents, and replace those contents with free iodine molecules.⁸ Iodophors are free iodine molecules associated with a polymer (eg, polyvinylpyrrolidone); the iodophor povidone-iodine is bactericidal.⁹ Chlorhexidine gluconate-based solutions are effective against many types of yeast, Gram-positive and Gram-negative bacteria, and a wide variety of viruses.⁹ Both solutions are useful. Patients with an allergy to iodine can use chlorhexidine. Table 1 summarizes the studies on preoperative measures for preventing SSIs.

There is no shortage of evidence of the efficacy of these antiseptics in minimizing the incidence of SSIs. Hayek and colleagues¹⁰ prospectively analyzed use of different preoperative skin preparation methods in 2015 patients. Six weeks after surgery, the infection rate was significantly lower with use of chlorhexidine than with use of an unmedicated bar of soap or placebo cloth (9% vs 11.7% and 12.8%, respectively; P < .05). In a study of 100 patients, Murray and colleagues¹¹ found the overall bacterial culture rate was significantly lower for those who used a 2% chlorhexidine gluconate cloth before shoulder surgery than for those who took a standard shower with soap (66% vs 94%; P = .0008). Darouiche and colleagues¹² found the overall SSI rate was significantly lower for 409 surgical patients prepared with chlorhexidine-alcohol than for 440 prepared with povidone-iodine (9.5% vs 16.1%; P = .004; relative risk [RR], 0.59; 95% confidence interval [CI], 0.41-0.85).

Chlorhexidine gluconate-impregnated cloths have also had promising results, which may be attributed to general ease of use and potentially improved patient adherence. Zywiel and colleagues¹³ reported no SSIs in 136 patients who used these cloths at home before total knee arthroplasty (TKA) and 21 SSIs (3.0%) in 711 patients who did not use the cloths. In a study of 2545 THA patients, Kapadia and colleagues¹⁴ noted a significantly lower incidence of SSIs with at-home preoperative use of chlorhexidine cloths than with only in-hospital perioperative skin preparation (0.5% vs 1.7%; P = .04). In 2293 TKAs, Johnson and colleagues¹⁵ similarly found a lower incidence of SSIs with at-home preoperative use of chlorhexidine cloths (0.6% vs 2.2%; P = .02). In another prospective, randomized trial, Kapadia and colleagues16 compared 275 patients who used chlorhexidine cloths the night before and the morning of lower extremity TJA surgery with 279 patients who underwent standard-of-care preparation (preadmission bathing with antibacterial soap and water). The chlorhexidine cohort had a lower overall incidence of infection (0.4% vs 2.9%; P = .049), and the standard-of-care cohort had a stronger association with infection (odds ratio [OR], 8.15; 95% CI, 1.01-65.6). 

Patient Optimization. Poor nutritional status may compromise immune function, potentially resulting in delayed healing, increased risk of infection, and, ultimately, negative postoperative outcomes. Malnutrition can be diagnosed on the basis of a prealbumin level of <15 mg/dL (normal, 15-30 mg/dL), a serum albumin level of <3.4 g/dL (normal, 3.4-5.4 g/dL), or a total lymphocyte count under 1200 cells/μL (normal, 3900-10,000 cells/μL).^17-19 Greene and colleagues¹⁸ found that patients with preoperative malnutrition had up to a 7-fold higher rate of infection after TJA. In a study of 135 THAs and TKAs, Alfargieny and colleagues²⁰ found preoperative serum albumin was the only nutritional biomarker predictive of SSI (P = .011). Furthermore, patients who take immunomodulating medications (eg, for inflammatory arthropathies) should temporarily discontinue them before surgery in order to lower their risk of infection.²¹ 

Smoking is well established as a major risk factor for poor outcomes after surgery. It is postulated that the vasoconstrictive effects of nicotine and the hypoxic effects of carbon monoxide contribute to poor wound healing.²² In a meta-analysis of 4 studies, Sørensen²³ found smokers were at increased risk for wound complications (OR, 2.27; 95% CI, 1.82-2.84), delayed wound healing and dehiscence (OR, 2.07; 95% CI, 1.53-2.81), and infection (OR, 1.79; 95% CI, 1.57-2.04). Moreover, smoking cessation decreased the incidence of SSIs (OR, 0.43; 95% CI, 0.21-0.85). A meta- analysis by Wong and colleagues²⁴ revealed an inflection point for improved outcomes in patients who abstained from smoking for at least 4 weeks before surgery. Risk of infection was lower for these patients than for current smokers (OR, 0.69; 95% CI, 0.56-0.84).

Other comorbidities contribute to SSIs as well. In their analysis of American College of Surgeons National Surgical Quality Improvement Program registry data on 25,235 patients who underwent primary and revision lower extremity TJA, Pugely and colleagues²⁵ found that, in the primary TJA cohort, body mass index (BMI) of >40 kg/m2 (OR, 1.9; 95% CI, 1.3-2.9), electrolyte disturbance (OR, 2.4; 95% CI, 1.0-6.0), and hypertension diagnosis (OR, 1.5; 95% CI, 1.1-2.0) increased the risk of SSI within 30 days. Furthermore, diabetes mellitus delays collagen synthesis, impairs lymphocyte function, and impairs wound healing, which may lead to poor recovery and higher risk of infection.²⁶ In a study of 167 TKAs performed in 115 patients with type 2 diabetes mellitus, Han and Kang²⁶ found that wound complications were 6 times more likely in those with hemoglobin A1c (HbA1c) levels higher than 8% than in those with lower HbA1c levels (OR, 6.07; 95% CI, 1.12-33.0). In a similar study of 462 patients with diabetes, Hwang and colleagues²⁷ found a higher likelihood of superficial SSIs in patients with HbA1c levels >8% (OR, 6.1; 95% CI, 1.6-23.4; P = .008). This association was also found in patients with a fasting blood glucose level of >200 mg/dL (OR, 9.2; 95% CI, 2.2-38.2; P = .038).

Methicillin-resistant Staphylococcus aureus (MRSA) is thought to account for 10% to 25% of all periprosthetic infections in the United States.28 Nasal colonization by this pathogen increases the risk for SSIs; however, decolonization protocols have proved useful in decreasing the rates of colonization. Moroski and colleagues²⁹ assessed the efficacy of a preoperative 5-day course of intranasal mupirocin in 289 primary or revision TJA patients. Before surgery, 12 patients had positive MRSA cultures, and 44 had positive methicillin-sensitive S aureus (MSSA) cultures. On day of surgery, a significant reduction in MRSA (P = .0073) and MSSA (P = .0341) colonization was noted. Rao and colleagues³⁰ found that the infection rate decreased from 2.7% to 1.2% in 2284 TJA patients treated with a decolonization protocol (P = .009). 

Intraoperative Measures

Cutaneous Preparation. The solutions used in perioperative skin preparation are similar to those used preoperatively: povidone-iodine, alcohol, and chlorhexidine. The efficacy of these preparations varies. Table 2 summarizes the studies on intraoperative measures for preventing SSIs.

The literature also highlights the importance of technique in incision-site preparation. In a prospective study, Morrison and colleagues³³ randomly assigned 600 primary TJA patients to either (1) use of alcohol and povidone-iodine before draping, with additional preparation with iodine povacrylex (DuraPrep) and isopropyl alcohol before application of the final drape (300-patient intervention group) or (2) only use of alcohol and povidone-iodine before draping (300-patient control group). At the final follow-up, the incidence of SSI was significantly lower in the intervention group than in the control group (1.8% vs 6.5%; P = .015). In another study that assessed perioperative skin preparation methods, Brown and colleagues34 found that airborne bacteria levels in operating rooms were >4 times higher with patients whose legs were prepared by a scrubbed, gowned leg-holder than with patients whose legs were prepared by an unscrubbed, ungowned leg-holder (P = .0001).

Hair Removal. Although removing hair from surgical sites is common practice, the literature advocating it varies. A large comprehensive review³⁵ revealed no increased risk of SSI with removing vs not removing hair (RR, 1.65; 95% CI, 0.85-3.19). On the other hand, some hair removal methods may affect the incidence of infection. For example, use of electric hair clippers is presumed to reduce the risk of SSIs, whereas traditional razors may compromise the epidermal barriers and create a pathway for bacterial colonization.^5,36,37 In the aforementioned review,³⁵ SSIs were more than twice as likely to occur with hair removed by shaving than with hair removed by electric clippers (RR, 2.02; 95% CI, 1.21-3.36). Cruse and Foord³⁸ found a higher rate of SSIs with hair removed by shaving than with hair removed by clipping (2.3% vs 1.7%). Most surgeons agree that, if given the choice, they would remove hair with electric clippers rather than razors.

Gloves. Almost all orthopedists double their gloves for TJA cases. Over several studies, the incidence of glove perforation during orthopedic procedures has ranged from 3.6% to 26%,^39-41 depending on the operating room personnel and glove layering studied. Orthopedists must know this startling finding, as surgical glove perforation is associated with an increase in the rate of SSIs, from 1.7% to 5.7%.³⁸ Carter and colleagues⁴² found the highest risk of glove perforation occurs when double-gloved attending surgeons, adult reconstruction fellows, and registered nurses initially assist during primary and revision TJA. In their study, outer and inner glove layers were perforated 2.5% of the time. All outer-layer perforations were noticed, but inner-layer perforations went unnoticed 81% of the time, which poses a potential hazard for both patients and healthcare personnel. In addition, there was a significant increase in the incidence of glove perforations for attending surgeons during revision TJA vs primary TJA (8.9% vs 3.7%; P = .04). This finding may be expected given the complexity of revision procedures, the presence of sharp bony and metal edges, and the longer operative times. Giving more attention to glove perforations during arthroplasties may mitigate the risk of SSI. As soon as a perforation is noticed, the glove should be removed and replaced.

Body Exhaust Suits. Early TJAs had infection rates approaching 10%.⁴³ Bacterial-laden particles shed from surgical staff were postulated to be the cause,^44,45 and this idea prompted the development of new technology, such as body exhaust suits, which have demonstrated up to a 20-fold reduction in airborne bacterial contamination and decreased incidence of deep infection, from 1% to 0.1%, as compared with conventional surgical attire.⁴⁶ However, the efficacy of these suits was recently challenged. Hooper and colleagues⁴⁷ assessed >88,000 TJA cases in the New Zealand Joint Registry and found a significant increase in early revision THA for deep infection with vs without use of body exhaust suits (0.186% vs 0.064%; P < .0001). The incidence of revision TKAs for deep infections with use of these suits was similar (0.243% vs 0.098%; P < .001). Many of the surgeons surveyed indicated their peripheral vision was limited by the suits, which may contribute to sterile field contamination. By contrast, Miner and colleagues⁴⁸ were unable to determine an increased risk of SSI with use of body exhaust suits (RR, 0.75; 95% CI, 0.34-1.62), though there was a trend toward more infections without suits. Moreover, these suits are effective in reducing mean air bacterial counts (P = .014), but it is not known if this method correlates with mean wound bacterial counts (r = –.011) and therefore increases the risk of SSI.⁴⁹

Surgical Drapes. Surgical draping, including cloths, iodine-impregnated materials, and woven or unwoven materials, is the standard of care worldwide. The particular draping technique usually varies by surgeon. Plastic drapes are better barriers than cloth drapes, as found in a study by Blom and colleagues⁵⁰: Bacterial growth rates were almost 10 times higher with use of wet woven cloth drapes than with plastic surgical drapes. These findings were supported in another, similar study by Blom and colleagues⁵¹: Wetting drapes with blood or normal saline enhanced bacterial penetration. In addition, wetting drapes with chlorhexidine or iodine reduced but did not eliminate bacterial penetration. Fairclough and colleagues⁵² emphasized that iodine-impregnated drapes reduced surgical-site bacterial contamination from 15% to 1.6%. However, a Cochrane review⁵³ found these drapes had no effect on the SSI rate (RR, 1.03; 95% CI, 0.06-1.66; P = .89), though the risk of infection was slightly higher with adhesive draping than with no drape (RR, 1.23; 95% CI, 1.02-1.48; P = .03).

Ventilation Flow. Laminar-airflow systems are widely used to prevent SSIs after TJA. Horizontal-flow and vertical-flow ventilation provides and maintains ultra-clean air in the operating room. Evans⁵⁴ found the bacterial counts in the air and the wound were lower with laminar airflow than without this airflow. The amount of airborne bacterial colony-forming units and dust large enough to carry bacteria was reduced to 1 or 2 particles more than 2 μm/m3 with use of a typical laminar- airflow system. In comparing 3922 TKA patients in laminar-airflow operating rooms with 4133 patients in conventional rooms, Lidwell and colleagues⁴⁶ found a significantly lower incidence of SSIs in patients in laminar-airflow operating rooms (0.6% vs 2.3%; P < .001).

Conversely, Miner and colleagues⁴⁸ did not find a lower risk of SSI with laminar-airflow systems (RR, 1.57; 95% CI, 0.75-3.31). In addition, in their analysis of >88,000 cases from the New Zealand Joint Registry, Hooper and colleagues⁴⁷ found that the incidence of early infections was higher with laminar-airflow systems than with standard airflow systems for both TKA (0.193% vs 0.100%; P = .019) and THA (0.148% vs 0.061%; P < .001). They postulated that vertically oriented airflow may have transmitted contaminated particles into the surgical sites. Additional evidence may be needed to resolve these conflicting findings and determine whether clean-air practices provide significant clinical benefit in the operating room.

Staff Traffic Volume. When staff enters or exits the operating room or makes extra movements during a procedure, airflow near the wound is disturbed and no longer able to remove sufficient airborne pathogens from the sterile field. The laminar- airflow pattern may be disrupted each time the operating room doors open and close, potentially allowing airborne pathogens to be introduced near the patient. Lynch and colleagues⁵⁵ found the operating room door opened almost 50 times per hour, and it took about 20 seconds to close each time. As a result, the door may remain open for up to 20 minutes per case, causing substantial airflow disruption and potentially ineffective removal of airborne bacterial particles. Similarly, Young and O’Regan⁵⁶ found the operating room door opened about 19 times per hour and took 20 seconds to close each time. The theater door was open an estimated 10.7% of each hour of sterile procedure. Presence of more staff also increases airborne bacterial counts. Pryor and Messmer⁵⁷ evaluated a cohort of 2864 patients to determine the effect of number of personnel in the operating theater on the incidence of SSIs. Infection rates were 6.27% with >17 different people entering the room and 1.52% with <9 different people entering the room. Restricting the number of people in the room may be one of the easiest and most efficient ways to prevent SSI.

Systemic Antibiotic Prophylaxis. Perioperative antibiotic use is vital in minimizing the risk of infection after TJA. The Surgical Care Improvement Project recommended beginning the first antimicrobial dose either within 60 minutes before surgical incision (for cephalosporin) or within 2 hours before incision (for vancomycin) and discontinuing the prophylactic antimicrobial agents within 24 hours after surgery ends.^58,59 However, Gorenoi and colleagues⁶⁰ were unable to recommend a way to select particular antibiotics, as they found no difference in the effectiveness of various antibiotic agents used in TKA. A systematic review by AlBuhairan and colleagues⁶¹ revealed that antibiotic prophylaxis (vs no prophylaxis) reduced the absolute risk of a SSI by 8% and the relative risk by 81% (P < 0.0001). These findings are supported by evidence of the efficacy of perioperative antibiotics in reducing the incidence of SSI.^62,63 Antibiotic regimens should be based on susceptibility and availability, depending on hospital prevalence of infections. Even more, patients should receive prophylaxis in a timely manner. Finally, bacteriostatic antibiotics (vancomycin) should not be used on their own for preoperative prophylaxis.

Antibiotic Cement. Antibiotic-loaded bone cement (ALBC), which locally releases antimicrobials in high concentration, is often used in revision joint arthroplasty, but use in primary joint arthroplasty remains controversial. In a study of THA patients, Parvizi and colleagues64 found infection rates of 1.2% with 2.3% with and without use of ALBC, respectively. Other studies have had opposing results. Namba and colleagues⁶⁵ evaluated 22,889 primary TKAs, 2030 (8.9%) of which used ALBC. The incidence of deep infection was significantly higher with ALBC than with regular bone cement (1.4% vs 0.7%; P = .002). In addition, a meta- analysis of >6500 primary TKA patients, by Zhou and colleagues,⁶⁶ revealed no significant difference in the incidence of deep SSIs with use of ALBC vs regular cement (1.32% vs 1.89%; RR, 0.75; 95% CI, 0.43-1.33; P = .33). More evidence is needed to determine the efficacy of ALBC in primary TJA. International Consensus Meeting on Periprosthetic Joint Infection participants recommended use of ALBC in high-risk patients, including patients who are obese or immunosuppressed or have diabetes or a prior history of infection.⁶⁷

Postoperative Measures

Antibiotic Prophylaxis. The American Academy of Orthopaedic Surgeons (AAOS) and the American Dental Association (ADA) have suggestions for antibiotic prophylaxis for patients at increased risk for infection. As of 2015, the ADA no longer recommends antibiotic prophylaxis for patients with prosthetic joint implants,68 whereas the AAOS considers all patients with TJA to be at risk.⁶⁹

Although recommendations exist, the actual risk of infection resulting from dental procedures and the role of antibiotic prophylaxis are not well defined. Berbari and colleagues⁷¹ found that antibiotic prophylaxis in high- or low-risk dental procedures did not decrease the risk of subsequent THA infection (OR, 0.9; 95% CI, 0.5-1.6) or TKA infection (OR, 1.2; 95% CI, 0.7-2.2). Moreover, the risk of infection was no higher for patients who had a prosthetic hip or knee and underwent a high- or low-risk dental procedure without antibiotic prophylaxis (OR, 0.8; 95% CI, 0.4-1.6) than for similar patients who did not undergo a dental procedure (OR, 0.6; 95% CI, 0.4-1.1). Some studies highlight the low level of evidence supporting antibiotic prophylaxis during dental procedures.^72,73 However, there is no evidence of adverse effects of antibiotic prophylaxis. Given the potential high risk of infection after such procedures, a more robust body of evidence is needed to reach consensus.

Evacuation Drain Management. Prolonged use of surgical evacuation drains may be a risk factor for SSI. Therefore, early drain removal is paramount. Higher infection rates with prolonged drain use have been found in patients with persistent wound drainage, including malnourished, obese, and over-anticoagulated patients. Patients with wounds persistently draining for >1 week should undergo superficial wound irrigation and débridement. Jaberi and colleagues⁷⁴ assessed 10,325 TJA patients and found that the majority of persistent drainage ceased within 1 week with use of less invasive measures, including oral antibiotics and local wound care. Furthermore, only 28% of patients with persistent drainage underwent surgical débridement. It is unclear if this practice alone is appropriate. Infection should always be suspected and treated aggressively, and cultures should be obtained from synovial fluid before antibiotics are started, unless there is an obvious superficial infection that does not require further work-up.⁶⁷

Economic Impact

SSIs remain a significant healthcare issue, and the social and financial costs are staggering. Without appropriate measures in place, these complications will place a larger burden on the healthcare system primarily as a result of longer hospital stays, multiple procedures, and increased resource utilization.⁷⁵ Given the risk of progression to prosthetic joint infection, early preventive interventions must be explored.

Improved patient selection may be an important factor in reducing SSIs. In an analysis of 8494 joint arthroplasties, Malinzak and colleagues⁸⁰ noted that patients with a BMI of >50 kg/m2 had an increased OR of infection of 21.3 compared to those with BMI <50 kg/m2. Wagner and colleagues⁸¹ analyzed 21,361 THAs and found that, for every BMI unit over 25 kg/m2, there was an 8% increased risk of joint infection (P < .001). Although it is unknown if there is an association between reduction in preoperative BMI and reduction in postoperative complication risk, it may still be worthwhile and cost-effective to modify this and similar risk factors before elective procedures.

Market forces are becoming a larger consideration in healthcare and are being driven by provider competition.⁸² Treatment outcomes, quality of care, and healthcare prices have gained attention as a means of estimating potential costs.⁸³ In 2011, the Centers for Medicare & Medicaid Services (CMS) advanced the Bundled Payments for Care Improvement (BPCI) initiative, which aimed to provide better coordinated care of higher quality and lower cost.⁸⁴ This led to development of the Comprehensive Care for Joint Replacement (CJR) program, which gives beneficiaries flexibility in choosing services and ensures that providers adhere to required standards. During its 5-year test period beginning in 2016, the CJR program is projected to save CMS $153 million.⁸⁴ Under this program, the institution where TJA is performed is responsible for all the costs of related care from time of surgery through 90 days after hospital discharge—which is known as an “episode of care.” If the cost incurred during an episode exceeds an established target cost (as determined by CMS), the hospital must repay Medicare the difference. Conversely, if the cost of an episode is less than the established target cost, the hospital is rewarded with the difference. Bundling payments for a single episode of care in this manner is thought to incentivize providers and hospitals to give patients more comprehensive and coordinated care. Given the substantial economic burden associated with joint arthroplasty infections, it is imperative for orthopedists to establish practical and cost-effective strategies that can prevent these disastrous complications.

Conclusion

SSIs are a devastating burden to patients, surgeons, and other healthcare providers. In recent years, new discoveries and innovations have helped mitigate the incidence of these complications of THA and TKA. However, the incidence of SSIs may rise with the increasing use of TJAs and with the development of new drug-resistant pathogens. In addition, the increasing number of TJAs performed on overweight and high-risk patients means the costs of postoperative infections will be substantial. With new reimbursement models in place, hospitals and providers are being held more accountable for the care they deliver during and after TJA. Consequently, more emphasis should be placed on techniques that are proved to minimize the incidence of SSIs.

Take-Home Points

• SSIs after TJA pose a substantial burden on patients, surgeons, and the healthcare system.
• While different forms of preoperative skin preparation have shown varying outcomes after TJA, the importance of preoperative patient optimization (nutritional status, immune function, etc) cannot be overstated. 
• Intraoperative infection prevention measures include cutaneous preparation, gloving, body exhaust suits, surgical drapes, OR staff traffic and ventilation flow, and antibiotic-loaded cement. 
• Antibiotic prophylaxis for dental procedures in TJA patients continues to remain a controversial issue with conflicting recommendations.
• SSIs have considerable financial costs and require increased resource utilization. Given the significant economic burden associated with TJA infections, it is imperative for orthopedists to establish practical and cost-effective strategies to prevent these devastating complications.

Surgical-site infection (SSI), a potentially devastating complication of lower extremity total joint arthroplasty (TJA), is estimated to occur in 1% to 2.5% of cases annually.¹ Infection after TJA places a significant burden on patients, surgeons, and the healthcare system. Revision procedures that address infection after total hip arthroplasty (THA) are associated with more hospitalizations, more operations, longer hospital stay, and higher outpatient costs in comparison with primary THAs and revision surgeries for aseptic loosening.² If left untreated, a SSI can go deeper into the joint and develop into a periprosthetic infection, which can be disastrous and costly. A periprosthetic joint infection study that used 2001 to 2009 Nationwide Inpatient Sample (NIS) data found that the cost of revision procedures increased to $560 million from $320 million, and was projected to reach $1.62 billion by 2020.³ Furthermore, society incurs indirect costs as a result of patient disability and loss of wages and productivity.² Therefore, the issue of infection after TJA is even more crucial in our cost-conscious healthcare environment. 

Patient optimization, advances in surgical technique, sterile protocol, and operative procedures have been effective in reducing bacterial counts at incision sites and minimizing SSIs. As a result, infection rates have leveled off after rising for a decade.⁴ Although infection prevention modalities have their differences, routine use is fundamental and recommended by the Hospital Infection Control Practices Advisory Committee.⁵ Furthermore, both the US Centers for Disease Control and Prevention (CDC) and its Healthcare Infection Control Practices Advisory Committee^6,7 recently updated their SSI prevention guidelines by incorporating evidence-based methodology, an element missing from earlier recommendations.

The etiologies of postoperative SSIs have been discussed ad nauseam, but there are few reports summarizing the literature on infection prevention modalities. In this review, we identify and examine SSI prevention strategies as they relate to lower extremity TJA. Specifically, we discuss the literature on the preoperative, intraoperative, and postoperative actions that can be taken to reduce the incidence of SSIs after TJA. We also highlight the economic implications of SSIs that occur after TJA.

Methods

For this review, we performed a literature search with PubMed, EBSCOhost, and Scopus. We looked for reports published between the inception of each database and July 2016. Combinations of various search terms were used: surgical site, infection, total joint arthroplasty, knee, hip, preoperative, intraoperative, perioperative, postoperative, preparation, nutrition, ventilation, antibiotic, body exhaust suit, gloves, drain, costs, economic, and payment.

Our search identified 195 abstracts. Drs. Mistry and Chughtai reviewed these to determine which articles were relevant. For any uncertainties, consensus was reached with the help of Dr. Delanois. Of the 195 articles, 103 were potentially relevant, and 54 of the 103 were excluded for being not relevant to preventing SSIs after TJA or for being written in a language other than English. The references in the remaining articles were assessed, and those with potentially relevant titles were selected for abstract review. This step provided another 35 articles. After all exclusions, 48 articles remained. We discuss these in the context of preoperative, intraoperative, and postoperative measures and economic impact.

Results

Preoperative Measures

Skin Preparation. Preoperative skin preparation methods include standard washing and rinsing, antiseptic soaps, and iodine-based or chlorhexidine gluconate-based antiseptic showers or skin cloths. Iodine-based antiseptics are effective against a wide range of Gram-positive and Gram-negative bacteria, fungi, and viruses. These agents penetrate the cell wall, oxidize the microbial contents, and replace those contents with free iodine molecules.⁸ Iodophors are free iodine molecules associated with a polymer (eg, polyvinylpyrrolidone); the iodophor povidone-iodine is bactericidal.⁹ Chlorhexidine gluconate-based solutions are effective against many types of yeast, Gram-positive and Gram-negative bacteria, and a wide variety of viruses.⁹ Both solutions are useful. Patients with an allergy to iodine can use chlorhexidine. Table 1 summarizes the studies on preoperative measures for preventing SSIs.

There is no shortage of evidence of the efficacy of these antiseptics in minimizing the incidence of SSIs. Hayek and colleagues¹⁰ prospectively analyzed use of different preoperative skin preparation methods in 2015 patients. Six weeks after surgery, the infection rate was significantly lower with use of chlorhexidine than with use of an unmedicated bar of soap or placebo cloth (9% vs 11.7% and 12.8%, respectively; P < .05). In a study of 100 patients, Murray and colleagues¹¹ found the overall bacterial culture rate was significantly lower for those who used a 2% chlorhexidine gluconate cloth before shoulder surgery than for those who took a standard shower with soap (66% vs 94%; P = .0008). Darouiche and colleagues¹² found the overall SSI rate was significantly lower for 409 surgical patients prepared with chlorhexidine-alcohol than for 440 prepared with povidone-iodine (9.5% vs 16.1%; P = .004; relative risk [RR], 0.59; 95% confidence interval [CI], 0.41-0.85).

Chlorhexidine gluconate-impregnated cloths have also had promising results, which may be attributed to general ease of use and potentially improved patient adherence. Zywiel and colleagues¹³ reported no SSIs in 136 patients who used these cloths at home before total knee arthroplasty (TKA) and 21 SSIs (3.0%) in 711 patients who did not use the cloths. In a study of 2545 THA patients, Kapadia and colleagues¹⁴ noted a significantly lower incidence of SSIs with at-home preoperative use of chlorhexidine cloths than with only in-hospital perioperative skin preparation (0.5% vs 1.7%; P = .04). In 2293 TKAs, Johnson and colleagues¹⁵ similarly found a lower incidence of SSIs with at-home preoperative use of chlorhexidine cloths (0.6% vs 2.2%; P = .02). In another prospective, randomized trial, Kapadia and colleagues16 compared 275 patients who used chlorhexidine cloths the night before and the morning of lower extremity TJA surgery with 279 patients who underwent standard-of-care preparation (preadmission bathing with antibacterial soap and water). The chlorhexidine cohort had a lower overall incidence of infection (0.4% vs 2.9%; P = .049), and the standard-of-care cohort had a stronger association with infection (odds ratio [OR], 8.15; 95% CI, 1.01-65.6). 

Patient Optimization. Poor nutritional status may compromise immune function, potentially resulting in delayed healing, increased risk of infection, and, ultimately, negative postoperative outcomes. Malnutrition can be diagnosed on the basis of a prealbumin level of <15 mg/dL (normal, 15-30 mg/dL), a serum albumin level of <3.4 g/dL (normal, 3.4-5.4 g/dL), or a total lymphocyte count under 1200 cells/μL (normal, 3900-10,000 cells/μL).^17-19 Greene and colleagues¹⁸ found that patients with preoperative malnutrition had up to a 7-fold higher rate of infection after TJA. In a study of 135 THAs and TKAs, Alfargieny and colleagues²⁰ found preoperative serum albumin was the only nutritional biomarker predictive of SSI (P = .011). Furthermore, patients who take immunomodulating medications (eg, for inflammatory arthropathies) should temporarily discontinue them before surgery in order to lower their risk of infection.²¹ 

Smoking is well established as a major risk factor for poor outcomes after surgery. It is postulated that the vasoconstrictive effects of nicotine and the hypoxic effects of carbon monoxide contribute to poor wound healing.²² In a meta-analysis of 4 studies, Sørensen²³ found smokers were at increased risk for wound complications (OR, 2.27; 95% CI, 1.82-2.84), delayed wound healing and dehiscence (OR, 2.07; 95% CI, 1.53-2.81), and infection (OR, 1.79; 95% CI, 1.57-2.04). Moreover, smoking cessation decreased the incidence of SSIs (OR, 0.43; 95% CI, 0.21-0.85). A meta- analysis by Wong and colleagues²⁴ revealed an inflection point for improved outcomes in patients who abstained from smoking for at least 4 weeks before surgery. Risk of infection was lower for these patients than for current smokers (OR, 0.69; 95% CI, 0.56-0.84).

Other comorbidities contribute to SSIs as well. In their analysis of American College of Surgeons National Surgical Quality Improvement Program registry data on 25,235 patients who underwent primary and revision lower extremity TJA, Pugely and colleagues²⁵ found that, in the primary TJA cohort, body mass index (BMI) of >40 kg/m2 (OR, 1.9; 95% CI, 1.3-2.9), electrolyte disturbance (OR, 2.4; 95% CI, 1.0-6.0), and hypertension diagnosis (OR, 1.5; 95% CI, 1.1-2.0) increased the risk of SSI within 30 days. Furthermore, diabetes mellitus delays collagen synthesis, impairs lymphocyte function, and impairs wound healing, which may lead to poor recovery and higher risk of infection.²⁶ In a study of 167 TKAs performed in 115 patients with type 2 diabetes mellitus, Han and Kang²⁶ found that wound complications were 6 times more likely in those with hemoglobin A1c (HbA1c) levels higher than 8% than in those with lower HbA1c levels (OR, 6.07; 95% CI, 1.12-33.0). In a similar study of 462 patients with diabetes, Hwang and colleagues²⁷ found a higher likelihood of superficial SSIs in patients with HbA1c levels >8% (OR, 6.1; 95% CI, 1.6-23.4; P = .008). This association was also found in patients with a fasting blood glucose level of >200 mg/dL (OR, 9.2; 95% CI, 2.2-38.2; P = .038).

Methicillin-resistant Staphylococcus aureus (MRSA) is thought to account for 10% to 25% of all periprosthetic infections in the United States.28 Nasal colonization by this pathogen increases the risk for SSIs; however, decolonization protocols have proved useful in decreasing the rates of colonization. Moroski and colleagues²⁹ assessed the efficacy of a preoperative 5-day course of intranasal mupirocin in 289 primary or revision TJA patients. Before surgery, 12 patients had positive MRSA cultures, and 44 had positive methicillin-sensitive S aureus (MSSA) cultures. On day of surgery, a significant reduction in MRSA (P = .0073) and MSSA (P = .0341) colonization was noted. Rao and colleagues³⁰ found that the infection rate decreased from 2.7% to 1.2% in 2284 TJA patients treated with a decolonization protocol (P = .009). 

Intraoperative Measures

Cutaneous Preparation. The solutions used in perioperative skin preparation are similar to those used preoperatively: povidone-iodine, alcohol, and chlorhexidine. The efficacy of these preparations varies. Table 2 summarizes the studies on intraoperative measures for preventing SSIs.

The literature also highlights the importance of technique in incision-site preparation. In a prospective study, Morrison and colleagues³³ randomly assigned 600 primary TJA patients to either (1) use of alcohol and povidone-iodine before draping, with additional preparation with iodine povacrylex (DuraPrep) and isopropyl alcohol before application of the final drape (300-patient intervention group) or (2) only use of alcohol and povidone-iodine before draping (300-patient control group). At the final follow-up, the incidence of SSI was significantly lower in the intervention group than in the control group (1.8% vs 6.5%; P = .015). In another study that assessed perioperative skin preparation methods, Brown and colleagues34 found that airborne bacteria levels in operating rooms were >4 times higher with patients whose legs were prepared by a scrubbed, gowned leg-holder than with patients whose legs were prepared by an unscrubbed, ungowned leg-holder (P = .0001).

Hair Removal. Although removing hair from surgical sites is common practice, the literature advocating it varies. A large comprehensive review³⁵ revealed no increased risk of SSI with removing vs not removing hair (RR, 1.65; 95% CI, 0.85-3.19). On the other hand, some hair removal methods may affect the incidence of infection. For example, use of electric hair clippers is presumed to reduce the risk of SSIs, whereas traditional razors may compromise the epidermal barriers and create a pathway for bacterial colonization.^5,36,37 In the aforementioned review,³⁵ SSIs were more than twice as likely to occur with hair removed by shaving than with hair removed by electric clippers (RR, 2.02; 95% CI, 1.21-3.36). Cruse and Foord³⁸ found a higher rate of SSIs with hair removed by shaving than with hair removed by clipping (2.3% vs 1.7%). Most surgeons agree that, if given the choice, they would remove hair with electric clippers rather than razors.

Gloves. Almost all orthopedists double their gloves for TJA cases. Over several studies, the incidence of glove perforation during orthopedic procedures has ranged from 3.6% to 26%,^39-41 depending on the operating room personnel and glove layering studied. Orthopedists must know this startling finding, as surgical glove perforation is associated with an increase in the rate of SSIs, from 1.7% to 5.7%.³⁸ Carter and colleagues⁴² found the highest risk of glove perforation occurs when double-gloved attending surgeons, adult reconstruction fellows, and registered nurses initially assist during primary and revision TJA. In their study, outer and inner glove layers were perforated 2.5% of the time. All outer-layer perforations were noticed, but inner-layer perforations went unnoticed 81% of the time, which poses a potential hazard for both patients and healthcare personnel. In addition, there was a significant increase in the incidence of glove perforations for attending surgeons during revision TJA vs primary TJA (8.9% vs 3.7%; P = .04). This finding may be expected given the complexity of revision procedures, the presence of sharp bony and metal edges, and the longer operative times. Giving more attention to glove perforations during arthroplasties may mitigate the risk of SSI. As soon as a perforation is noticed, the glove should be removed and replaced.

Body Exhaust Suits. Early TJAs had infection rates approaching 10%.⁴³ Bacterial-laden particles shed from surgical staff were postulated to be the cause,^44,45 and this idea prompted the development of new technology, such as body exhaust suits, which have demonstrated up to a 20-fold reduction in airborne bacterial contamination and decreased incidence of deep infection, from 1% to 0.1%, as compared with conventional surgical attire.⁴⁶ However, the efficacy of these suits was recently challenged. Hooper and colleagues⁴⁷ assessed >88,000 TJA cases in the New Zealand Joint Registry and found a significant increase in early revision THA for deep infection with vs without use of body exhaust suits (0.186% vs 0.064%; P < .0001). The incidence of revision TKAs for deep infections with use of these suits was similar (0.243% vs 0.098%; P < .001). Many of the surgeons surveyed indicated their peripheral vision was limited by the suits, which may contribute to sterile field contamination. By contrast, Miner and colleagues⁴⁸ were unable to determine an increased risk of SSI with use of body exhaust suits (RR, 0.75; 95% CI, 0.34-1.62), though there was a trend toward more infections without suits. Moreover, these suits are effective in reducing mean air bacterial counts (P = .014), but it is not known if this method correlates with mean wound bacterial counts (r = –.011) and therefore increases the risk of SSI.⁴⁹

Surgical Drapes. Surgical draping, including cloths, iodine-impregnated materials, and woven or unwoven materials, is the standard of care worldwide. The particular draping technique usually varies by surgeon. Plastic drapes are better barriers than cloth drapes, as found in a study by Blom and colleagues⁵⁰: Bacterial growth rates were almost 10 times higher with use of wet woven cloth drapes than with plastic surgical drapes. These findings were supported in another, similar study by Blom and colleagues⁵¹: Wetting drapes with blood or normal saline enhanced bacterial penetration. In addition, wetting drapes with chlorhexidine or iodine reduced but did not eliminate bacterial penetration. Fairclough and colleagues⁵² emphasized that iodine-impregnated drapes reduced surgical-site bacterial contamination from 15% to 1.6%. However, a Cochrane review⁵³ found these drapes had no effect on the SSI rate (RR, 1.03; 95% CI, 0.06-1.66; P = .89), though the risk of infection was slightly higher with adhesive draping than with no drape (RR, 1.23; 95% CI, 1.02-1.48; P = .03).

Ventilation Flow. Laminar-airflow systems are widely used to prevent SSIs after TJA. Horizontal-flow and vertical-flow ventilation provides and maintains ultra-clean air in the operating room. Evans⁵⁴ found the bacterial counts in the air and the wound were lower with laminar airflow than without this airflow. The amount of airborne bacterial colony-forming units and dust large enough to carry bacteria was reduced to 1 or 2 particles more than 2 μm/m3 with use of a typical laminar- airflow system. In comparing 3922 TKA patients in laminar-airflow operating rooms with 4133 patients in conventional rooms, Lidwell and colleagues⁴⁶ found a significantly lower incidence of SSIs in patients in laminar-airflow operating rooms (0.6% vs 2.3%; P < .001).

Conversely, Miner and colleagues⁴⁸ did not find a lower risk of SSI with laminar-airflow systems (RR, 1.57; 95% CI, 0.75-3.31). In addition, in their analysis of >88,000 cases from the New Zealand Joint Registry, Hooper and colleagues⁴⁷ found that the incidence of early infections was higher with laminar-airflow systems than with standard airflow systems for both TKA (0.193% vs 0.100%; P = .019) and THA (0.148% vs 0.061%; P < .001). They postulated that vertically oriented airflow may have transmitted contaminated particles into the surgical sites. Additional evidence may be needed to resolve these conflicting findings and determine whether clean-air practices provide significant clinical benefit in the operating room.

Staff Traffic Volume. When staff enters or exits the operating room or makes extra movements during a procedure, airflow near the wound is disturbed and no longer able to remove sufficient airborne pathogens from the sterile field. The laminar- airflow pattern may be disrupted each time the operating room doors open and close, potentially allowing airborne pathogens to be introduced near the patient. Lynch and colleagues⁵⁵ found the operating room door opened almost 50 times per hour, and it took about 20 seconds to close each time. As a result, the door may remain open for up to 20 minutes per case, causing substantial airflow disruption and potentially ineffective removal of airborne bacterial particles. Similarly, Young and O’Regan⁵⁶ found the operating room door opened about 19 times per hour and took 20 seconds to close each time. The theater door was open an estimated 10.7% of each hour of sterile procedure. Presence of more staff also increases airborne bacterial counts. Pryor and Messmer⁵⁷ evaluated a cohort of 2864 patients to determine the effect of number of personnel in the operating theater on the incidence of SSIs. Infection rates were 6.27% with >17 different people entering the room and 1.52% with <9 different people entering the room. Restricting the number of people in the room may be one of the easiest and most efficient ways to prevent SSI.

Systemic Antibiotic Prophylaxis. Perioperative antibiotic use is vital in minimizing the risk of infection after TJA. The Surgical Care Improvement Project recommended beginning the first antimicrobial dose either within 60 minutes before surgical incision (for cephalosporin) or within 2 hours before incision (for vancomycin) and discontinuing the prophylactic antimicrobial agents within 24 hours after surgery ends.^58,59 However, Gorenoi and colleagues⁶⁰ were unable to recommend a way to select particular antibiotics, as they found no difference in the effectiveness of various antibiotic agents used in TKA. A systematic review by AlBuhairan and colleagues⁶¹ revealed that antibiotic prophylaxis (vs no prophylaxis) reduced the absolute risk of a SSI by 8% and the relative risk by 81% (P < 0.0001). These findings are supported by evidence of the efficacy of perioperative antibiotics in reducing the incidence of SSI.^62,63 Antibiotic regimens should be based on susceptibility and availability, depending on hospital prevalence of infections. Even more, patients should receive prophylaxis in a timely manner. Finally, bacteriostatic antibiotics (vancomycin) should not be used on their own for preoperative prophylaxis.

Antibiotic Cement. Antibiotic-loaded bone cement (ALBC), which locally releases antimicrobials in high concentration, is often used in revision joint arthroplasty, but use in primary joint arthroplasty remains controversial. In a study of THA patients, Parvizi and colleagues64 found infection rates of 1.2% with 2.3% with and without use of ALBC, respectively. Other studies have had opposing results. Namba and colleagues⁶⁵ evaluated 22,889 primary TKAs, 2030 (8.9%) of which used ALBC. The incidence of deep infection was significantly higher with ALBC than with regular bone cement (1.4% vs 0.7%; P = .002). In addition, a meta- analysis of >6500 primary TKA patients, by Zhou and colleagues,⁶⁶ revealed no significant difference in the incidence of deep SSIs with use of ALBC vs regular cement (1.32% vs 1.89%; RR, 0.75; 95% CI, 0.43-1.33; P = .33). More evidence is needed to determine the efficacy of ALBC in primary TJA. International Consensus Meeting on Periprosthetic Joint Infection participants recommended use of ALBC in high-risk patients, including patients who are obese or immunosuppressed or have diabetes or a prior history of infection.⁶⁷

Postoperative Measures

Antibiotic Prophylaxis. The American Academy of Orthopaedic Surgeons (AAOS) and the American Dental Association (ADA) have suggestions for antibiotic prophylaxis for patients at increased risk for infection. As of 2015, the ADA no longer recommends antibiotic prophylaxis for patients with prosthetic joint implants,68 whereas the AAOS considers all patients with TJA to be at risk.⁶⁹

Although recommendations exist, the actual risk of infection resulting from dental procedures and the role of antibiotic prophylaxis are not well defined. Berbari and colleagues⁷¹ found that antibiotic prophylaxis in high- or low-risk dental procedures did not decrease the risk of subsequent THA infection (OR, 0.9; 95% CI, 0.5-1.6) or TKA infection (OR, 1.2; 95% CI, 0.7-2.2). Moreover, the risk of infection was no higher for patients who had a prosthetic hip or knee and underwent a high- or low-risk dental procedure without antibiotic prophylaxis (OR, 0.8; 95% CI, 0.4-1.6) than for similar patients who did not undergo a dental procedure (OR, 0.6; 95% CI, 0.4-1.1). Some studies highlight the low level of evidence supporting antibiotic prophylaxis during dental procedures.^72,73 However, there is no evidence of adverse effects of antibiotic prophylaxis. Given the potential high risk of infection after such procedures, a more robust body of evidence is needed to reach consensus.

Evacuation Drain Management. Prolonged use of surgical evacuation drains may be a risk factor for SSI. Therefore, early drain removal is paramount. Higher infection rates with prolonged drain use have been found in patients with persistent wound drainage, including malnourished, obese, and over-anticoagulated patients. Patients with wounds persistently draining for >1 week should undergo superficial wound irrigation and débridement. Jaberi and colleagues⁷⁴ assessed 10,325 TJA patients and found that the majority of persistent drainage ceased within 1 week with use of less invasive measures, including oral antibiotics and local wound care. Furthermore, only 28% of patients with persistent drainage underwent surgical débridement. It is unclear if this practice alone is appropriate. Infection should always be suspected and treated aggressively, and cultures should be obtained from synovial fluid before antibiotics are started, unless there is an obvious superficial infection that does not require further work-up.⁶⁷

Economic Impact

SSIs remain a significant healthcare issue, and the social and financial costs are staggering. Without appropriate measures in place, these complications will place a larger burden on the healthcare system primarily as a result of longer hospital stays, multiple procedures, and increased resource utilization.⁷⁵ Given the risk of progression to prosthetic joint infection, early preventive interventions must be explored.

Improved patient selection may be an important factor in reducing SSIs. In an analysis of 8494 joint arthroplasties, Malinzak and colleagues⁸⁰ noted that patients with a BMI of >50 kg/m2 had an increased OR of infection of 21.3 compared to those with BMI <50 kg/m2. Wagner and colleagues⁸¹ analyzed 21,361 THAs and found that, for every BMI unit over 25 kg/m2, there was an 8% increased risk of joint infection (P < .001). Although it is unknown if there is an association between reduction in preoperative BMI and reduction in postoperative complication risk, it may still be worthwhile and cost-effective to modify this and similar risk factors before elective procedures.

Market forces are becoming a larger consideration in healthcare and are being driven by provider competition.⁸² Treatment outcomes, quality of care, and healthcare prices have gained attention as a means of estimating potential costs.⁸³ In 2011, the Centers for Medicare & Medicaid Services (CMS) advanced the Bundled Payments for Care Improvement (BPCI) initiative, which aimed to provide better coordinated care of higher quality and lower cost.⁸⁴ This led to development of the Comprehensive Care for Joint Replacement (CJR) program, which gives beneficiaries flexibility in choosing services and ensures that providers adhere to required standards. During its 5-year test period beginning in 2016, the CJR program is projected to save CMS $153 million.⁸⁴ Under this program, the institution where TJA is performed is responsible for all the costs of related care from time of surgery through 90 days after hospital discharge—which is known as an “episode of care.” If the cost incurred during an episode exceeds an established target cost (as determined by CMS), the hospital must repay Medicare the difference. Conversely, if the cost of an episode is less than the established target cost, the hospital is rewarded with the difference. Bundling payments for a single episode of care in this manner is thought to incentivize providers and hospitals to give patients more comprehensive and coordinated care. Given the substantial economic burden associated with joint arthroplasty infections, it is imperative for orthopedists to establish practical and cost-effective strategies that can prevent these disastrous complications.

Conclusion

SSIs are a devastating burden to patients, surgeons, and other healthcare providers. In recent years, new discoveries and innovations have helped mitigate the incidence of these complications of THA and TKA. However, the incidence of SSIs may rise with the increasing use of TJAs and with the development of new drug-resistant pathogens. In addition, the increasing number of TJAs performed on overweight and high-risk patients means the costs of postoperative infections will be substantial. With new reimbursement models in place, hospitals and providers are being held more accountable for the care they deliver during and after TJA. Consequently, more emphasis should be placed on techniques that are proved to minimize the incidence of SSIs.

IN THIS ARTICLE

• Patient history; what to ask
• Cardiovascular risk factors
• Disposition pathway
• Oral medications

Approximately one in three US adults, or about 75 million people, have high blood pressure (BP), which has been defined as a BP of 140/90 mm Hg or higher.¹ Unfortunately, only about half (54%) of those affected have their condition under optimal control.¹ From an epidemiologic standpoint, hypertension has the distinction of being the most common chronic condition in the US, affecting about 54% of persons ages 55 to 64 and about 73% of those 75 and older.^2,3 It is the number one reason patients schedule office visits with physicians; it accounts for the most prescriptions; and it is a major risk factor for heart disease and stroke, as well as a significant contributor to mortality throughout the world.⁴

HYPERTENSIVE URGENCY VS EMERGENCY

Hypertensive urgencies and emergencies account for approximately 27% of all medical emergencies and 2% to 3% of all annual visits to the emergency department (ED).⁵ Hypertensive urgency, or severe asymptomatic hypertension, is a common complaint in urgent care clinics and primary care offices as well. It is often defined as a systolic BP (SBP) of ≥ 160 mm Hg and/or a diastolic BP (DBP) ≥ 100 mm Hg with no associated end-organ damage.^5-7 Patients may experience hypertensive urgency if they have been noncompliant with their antihypertensive drug regimen; present with pain; have white-coat hypertension or anxiety; or use recreational drugs (eg, sympathomimetics).^5,8-10

Alternatively, hypertensive emergency, also known as hypertensive crisis, is generally defined as elevated BP > 180/120 mm Hg. Equally important, it is associated with signs, symptoms, or laboratory values indicative of target end-organ damage, such as cerebrovascular accident, myocardial infarction (MI), aortic dissection, acute left ventricular failure, acute pulmonary edema, acute renal failure, acute mental status changes (hypertensive encephalopathy), and eclampsia.^5,7,8,11,12

Determining appropriate management for patients with hypertensive urgency is controversial among clinicians. Practice patterns range from full screening and “rule-outs”—with prompt initiation of antihypertensive agents, regardless of whether the patient is symptomatic—to sending the patient home with minimal screening, laboratory testing, or treatment.

This article offers a guided approach to managing patients with hypertensive urgency in a logical fashion, based on risk stratification, thereby avoiding both extremes (extensive unnecessary workup or discharge without workup resulting in adverse outcomes). It is vital to differentiate between patients with hypertensive emergency, in which BP should be lowered in minutes, and patients with hypertensive urgency, in which BP can be lowered more slowly.¹²

PATHOPHYSIOLOGY

Normally, when BP increases, blood vessel diameter changes in response; this autoregulation serves to limit damage. However, when BP increases abruptly, the body’s ability to hemodynamically calibrate to such a rapid change is impeded, thus allowing for potential end-organ damage.^5,12 The increased vascular resistance observed in many patients with hypertension appears to be an autoregulatory process that helps to maintain a normal or viable level of tissue blood flow and organ perfusion despite the increased BP, rather than a primary cause of the hypertension.¹³

The exact physiology of hypertensive urgencies is not clearly understood, because of the multifactorial nature of the process. One leading theory is that circulating humoral vasoconstrictors cause an abrupt increase in systemic vascular resistance, which in turn causes mechanical shear stress to the endothelial wall. This endothelial damage promotes more vasoconstriction, platelet aggregation, and activation of the renin-angiotensin-aldosterone system, which thereby increases release of angiotensin II and various cytokines.¹⁴

HISTORY AND PHYSICAL

A detailed medical history is of utmost importance in distinguishing patients who present with asymptomatic hypertensive urgency from those experiencing a hypertensive emergency. In addition, obtain a full medication list, including any nutritional supplements or illicit drugs the patient may be taking. Question the patient regarding medication adherence; some may not be taking antihypertensive agents as prescribed or may have altered the dosing frequency in an effort to extend the duration of their prescription.^5,8 Table 1 lists pertinent questions to ask at presentation; the answers will dictate who needs further workup and possible admission as well as who will require screening for end-organ damage.⁷

The physical exam should focus primarily on a thorough cardiopulmonary and neurologic examination, as well as funduscopic examination, if needed. A complete set of vital signs should be recorded upon the patient’s arrival to the ED or clinic and should be repeated on the opposite arm for verification. Beginning with the eyes, conduct a thorough funduscopic examination to evaluate for papilledema or hemorrhages.⁵ During the cardiopulmonary exam, attention should be focused on signs of congestive heart failure and/or pulmonary edema, such as increased jugular vein distension, an S3 gallop, peripheral edema, and pulmonary rales. The neurologic exam is essential in evaluating for cerebrovascular accident, transient ischemic attack, or intracranial hemorrhage. A full cranial nerve examination is necessary, in addition to motor and sensory testing, at minimum.^5,9

RISK STRATIFICATION

According to the 2013 Task Force of the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC), several risk factors contribute to overall cardiovascular risk in asymptomatic patients presenting with severe hypertension (see Table 2).⁸ This report has been monumental in linking grades of hypertension directly to cardiovascular risk factors, but it differs from that recently published by the Eighth Joint National Committee (JNC 8), which offers evidence-based guidelines for the management of high BP in the general population of adults (with some modifications for individuals with diabetes or chronic kidney disease or of black ethnicity).¹⁵

According to the ESH/ESC study, patients with one or two risk factors who have grade 1 hypertension (SBP 140-159 mm Hg) are at moderate risk for cardiovascular disease (CVD) and patients with grade 2 (SBP 160-179 mm Hg) or grade 3 (SBP ≥ 180 mm Hg) hypertension are at moderate-to-high risk and high risk, respectively.⁸ Patients with three or more risk factors, or who already have end-organ damage, diabetes, or chronic kidney disease, enter the high-risk category for CVD even at grade 1 hypertension.⁸

These cardiovascular risk factors can and should be used as guidelines for deciding who needs further screening and who may have benign causes of severe hypertension (eg, white-coat hypertension, anxiety) that can be managed safely in an outpatient setting. In the author’s opinion, patients with known cardiovascular risk factors, those with signs or symptoms of end-organ damage, and those with test results suggestive of end-organ damage should have a more immediate treatment strategy initiated.

Numerous observational studies have shown a direct relationship between systemic hypertension and CVD risk in men and women of various ages, races, and ethnicities, regardless of other risk factors for CVD.¹² In patients with diabetes, uncontrolled hypertension is a strong predictor of cardiovascular morbidity and mortality and of progressive nephropathy leading to chronic kidney disease.⁸

SCREENING

Results from the following tests may provide useful clues in the workup of a patient with hypertensive urgency.

Basic metabolic panel. Many EDs and primary care offices offer point-of-care testing that can typically give a rapid (< 10 min) result of a basic metabolic panel. This useful, quick screening tool can identify renal failure due to chronic untreated hypertension, acute renal failure, or other disease states that cause electrolyte abnormalities such as hyperaldosteronism (hypertension with hypokalemia) or Cushing syndrome (hypertension with hypernatremia and hyperkalemia).⁷

Cardiac enzymes. Measurement of cardiac troponins (T or I) may provide confirmatory evidence of myocardial necrosis within two to three hours of suspected acute MI.^16,17 These tests are now available in most EDs and some clinics with point-of-care testing. A variety of current guidelines advocate repeat cardiac enzyme measurements at various time points, depending on results of initial testing and concomitant risk factors. These protocols vary by facility.

ECG. Obtaining an ECG is another quick, easy, and useful way to screen patients presenting with severe hypertensive urgency. Evidence of left ventricular hypertrophy suggests an increased risk for MI, stroke, heart failure, and sudden death.^7,18-20 The Cornell criteria of summing the R wave in aVL and the S wave in V₃, with a cutoff of 2.8 mV in men and 2.0 mV in women, has been shown to be the best predictor of future cardiovascular mortality.⁷ While an isolated finding of left ventricular hypertrophy on an ECG—in and of itself—may have limited value for an individual patient, this finding coupled with other risk factors may alter the provider’s assessment.

Chest radiograph. A chest radiograph can be helpful when used in conjunction with physical exam findings that suggest pulmonary edema and cardiomegaly.⁷ Widened mediastinum and tortuous aorta may also be evident on chest x-ray, necessitating further workup and imaging.

Urinalysis. In a patient presenting with asymptomatic hypertensive urgency, a urine dipstick result that shows new-onset proteinuria, while not definitive for diagnosis of nephrotic syndrome, may certainly prove helpful in the patient’s workup.^5,13

Urine drug screen. In patients without a history of hypertension who present with asymptomatic hypertensive urgency, the urine drug screen may ascertain exposure to cocaine, amphetamine, or phencyclidine.

Pregnancy test. A pregnancy test is essential for any female patient of childbearing age presenting to the ED, and a positive result may be concerning for preeclampsia in a hypertensive patient with no prior history of the condition.⁷

TREATMENT

Knowing who to treat and when is a vast area of debate among emergency and primary care providers. Patients with hypertension who have established risk factors are known to have worse outcomes than those who may be otherwise healthy. Some clinicians believe that patients presenting with hypertensive urgency should be discharged home without screening and/or treatment. However, because uncontrolled severe hypertension can lead to acute complications (eg, MI, cerebrovascular accident), in practice, many providers are unwilling to send the patient home without workup.¹² The patient’s condition must be viewed in the context of the entire disease spectrum, including risk factors.

The Figure offers a disposition pathway of recommendations based on risk stratification as well as screening tools for some of the less common causes of hypertensive urgency. Regardless of the results of screening tests or the decision to treat, affected patients require close primary care follow-up. Many of these patients may need further testing and careful management of their BP medication regimen.

How to treat

For patients with severe asymptomatic hypertension, if the history, physical, and screening tests do not show evidence of end-organ damage, BP can be controlled within 24 to 48 hours.^5,10,11,21 In adults with hypertensive urgency, the most reasonable goal is to reduce the BP to ≤ 160/100 mm Hg^5-7; however, the mean arterial pressure should not be lowered by more than 25% within the first two to three hours.¹³

Patients at high risk for imminent neurovascular, cardiovascular, renovascular, or pulmonary events should have their BP lowered over a period of hours, not minutes. In fact, there is evidence that rapid lowering of BP in asymptomatic patients may cause adverse outcomes.⁶ For example, in patients with acute ischemic stroke, increases in cerebral perfusion pressure promote an increase in vascular resistance—but decreasing the cerebral perfusion pressure abruptly will thereby decrease the cerebral blood flow, potentially causing cerebral ischemia or a worsening of the stroke.^9,14

Treatment options

A broad spectrum of therapeutic options has proven helpful in lowering BP over a short period of time, including oral captopril, clonidine, hydralazine, labetalol, and hydrochlorothiazide (see Table 3).^7,9,12,15 Nifedipine is contraindicated because of the abrupt and often unpredictable reduction in BP and associated myocardial ischemia, especially in patients with MI or left ventricular hypertrophy.^14,22,23 In cases of hypertensive urgency secondary to cocaine abuse, benzodiazepines would be the drug of choice and ß-blockers should be avoided due to the risk for coronary vasoconstriction.⁷

For patients with previously treated hypertension, the following options are reasonable: Increase the dose of the current antihypertensive medication; add another agent; reinstitute prior antihypertensive medications in nonadherent patients; or add a diuretic.

In patients with previously untreated hypertension, no clear evidence supports using one particular agent over another. However, initial treatment options that are generally considered safe include an ACE inhibitor, an angiotensin receptor blocker, a calcium channel blocker, or a thiazide diuretic.¹⁵ A few examples of medications within these categories include lisinopril (10 mg PO qd), losartan (50 mg PO qd), amlodipine (2.5 mg PO qd), or hydrochlorothiazide (25 mg PO qd).

Close follow-up is essential when an antihypertensive medication is started or reinstituted. Encourage the patient to reestablish care with their primary care provider (if you do not fill that role). You may need to refer the patient to a new provider or, in some cases, have the patient return to the ED for a repeat BP check.

CONCLUSION

The challenges of managing patients with hypertensive urgency are complicated by low follow-up rates with primary physicians, difficulty in obtaining referrals and follow-up for the patient, and hesitancy of providers to start patients on new BP medications. This article clarifies a well-defined algorithm for how to screen and risk-stratify patients who present to the ED or primary care office with hypertensive urgency.

IN THIS ARTICLE

• Patient history; what to ask
• Cardiovascular risk factors
• Disposition pathway
• Oral medications

Approximately one in three US adults, or about 75 million people, have high blood pressure (BP), which has been defined as a BP of 140/90 mm Hg or higher.¹ Unfortunately, only about half (54%) of those affected have their condition under optimal control.¹ From an epidemiologic standpoint, hypertension has the distinction of being the most common chronic condition in the US, affecting about 54% of persons ages 55 to 64 and about 73% of those 75 and older.^2,3 It is the number one reason patients schedule office visits with physicians; it accounts for the most prescriptions; and it is a major risk factor for heart disease and stroke, as well as a significant contributor to mortality throughout the world.⁴

HYPERTENSIVE URGENCY VS EMERGENCY

Hypertensive urgencies and emergencies account for approximately 27% of all medical emergencies and 2% to 3% of all annual visits to the emergency department (ED).⁵ Hypertensive urgency, or severe asymptomatic hypertension, is a common complaint in urgent care clinics and primary care offices as well. It is often defined as a systolic BP (SBP) of ≥ 160 mm Hg and/or a diastolic BP (DBP) ≥ 100 mm Hg with no associated end-organ damage.^5-7 Patients may experience hypertensive urgency if they have been noncompliant with their antihypertensive drug regimen; present with pain; have white-coat hypertension or anxiety; or use recreational drugs (eg, sympathomimetics).^5,8-10

Alternatively, hypertensive emergency, also known as hypertensive crisis, is generally defined as elevated BP > 180/120 mm Hg. Equally important, it is associated with signs, symptoms, or laboratory values indicative of target end-organ damage, such as cerebrovascular accident, myocardial infarction (MI), aortic dissection, acute left ventricular failure, acute pulmonary edema, acute renal failure, acute mental status changes (hypertensive encephalopathy), and eclampsia.^5,7,8,11,12

Determining appropriate management for patients with hypertensive urgency is controversial among clinicians. Practice patterns range from full screening and “rule-outs”—with prompt initiation of antihypertensive agents, regardless of whether the patient is symptomatic—to sending the patient home with minimal screening, laboratory testing, or treatment.

This article offers a guided approach to managing patients with hypertensive urgency in a logical fashion, based on risk stratification, thereby avoiding both extremes (extensive unnecessary workup or discharge without workup resulting in adverse outcomes). It is vital to differentiate between patients with hypertensive emergency, in which BP should be lowered in minutes, and patients with hypertensive urgency, in which BP can be lowered more slowly.¹²

PATHOPHYSIOLOGY

Normally, when BP increases, blood vessel diameter changes in response; this autoregulation serves to limit damage. However, when BP increases abruptly, the body’s ability to hemodynamically calibrate to such a rapid change is impeded, thus allowing for potential end-organ damage.^5,12 The increased vascular resistance observed in many patients with hypertension appears to be an autoregulatory process that helps to maintain a normal or viable level of tissue blood flow and organ perfusion despite the increased BP, rather than a primary cause of the hypertension.¹³

The exact physiology of hypertensive urgencies is not clearly understood, because of the multifactorial nature of the process. One leading theory is that circulating humoral vasoconstrictors cause an abrupt increase in systemic vascular resistance, which in turn causes mechanical shear stress to the endothelial wall. This endothelial damage promotes more vasoconstriction, platelet aggregation, and activation of the renin-angiotensin-aldosterone system, which thereby increases release of angiotensin II and various cytokines.¹⁴

HISTORY AND PHYSICAL

A detailed medical history is of utmost importance in distinguishing patients who present with asymptomatic hypertensive urgency from those experiencing a hypertensive emergency. In addition, obtain a full medication list, including any nutritional supplements or illicit drugs the patient may be taking. Question the patient regarding medication adherence; some may not be taking antihypertensive agents as prescribed or may have altered the dosing frequency in an effort to extend the duration of their prescription.^5,8 Table 1 lists pertinent questions to ask at presentation; the answers will dictate who needs further workup and possible admission as well as who will require screening for end-organ damage.⁷

The physical exam should focus primarily on a thorough cardiopulmonary and neurologic examination, as well as funduscopic examination, if needed. A complete set of vital signs should be recorded upon the patient’s arrival to the ED or clinic and should be repeated on the opposite arm for verification. Beginning with the eyes, conduct a thorough funduscopic examination to evaluate for papilledema or hemorrhages.⁵ During the cardiopulmonary exam, attention should be focused on signs of congestive heart failure and/or pulmonary edema, such as increased jugular vein distension, an S3 gallop, peripheral edema, and pulmonary rales. The neurologic exam is essential in evaluating for cerebrovascular accident, transient ischemic attack, or intracranial hemorrhage. A full cranial nerve examination is necessary, in addition to motor and sensory testing, at minimum.^5,9

RISK STRATIFICATION

According to the 2013 Task Force of the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC), several risk factors contribute to overall cardiovascular risk in asymptomatic patients presenting with severe hypertension (see Table 2).⁸ This report has been monumental in linking grades of hypertension directly to cardiovascular risk factors, but it differs from that recently published by the Eighth Joint National Committee (JNC 8), which offers evidence-based guidelines for the management of high BP in the general population of adults (with some modifications for individuals with diabetes or chronic kidney disease or of black ethnicity).¹⁵

According to the ESH/ESC study, patients with one or two risk factors who have grade 1 hypertension (SBP 140-159 mm Hg) are at moderate risk for cardiovascular disease (CVD) and patients with grade 2 (SBP 160-179 mm Hg) or grade 3 (SBP ≥ 180 mm Hg) hypertension are at moderate-to-high risk and high risk, respectively.⁸ Patients with three or more risk factors, or who already have end-organ damage, diabetes, or chronic kidney disease, enter the high-risk category for CVD even at grade 1 hypertension.⁸

These cardiovascular risk factors can and should be used as guidelines for deciding who needs further screening and who may have benign causes of severe hypertension (eg, white-coat hypertension, anxiety) that can be managed safely in an outpatient setting. In the author’s opinion, patients with known cardiovascular risk factors, those with signs or symptoms of end-organ damage, and those with test results suggestive of end-organ damage should have a more immediate treatment strategy initiated.

Numerous observational studies have shown a direct relationship between systemic hypertension and CVD risk in men and women of various ages, races, and ethnicities, regardless of other risk factors for CVD.¹² In patients with diabetes, uncontrolled hypertension is a strong predictor of cardiovascular morbidity and mortality and of progressive nephropathy leading to chronic kidney disease.⁸

SCREENING

Results from the following tests may provide useful clues in the workup of a patient with hypertensive urgency.

Basic metabolic panel. Many EDs and primary care offices offer point-of-care testing that can typically give a rapid (< 10 min) result of a basic metabolic panel. This useful, quick screening tool can identify renal failure due to chronic untreated hypertension, acute renal failure, or other disease states that cause electrolyte abnormalities such as hyperaldosteronism (hypertension with hypokalemia) or Cushing syndrome (hypertension with hypernatremia and hyperkalemia).⁷

Cardiac enzymes. Measurement of cardiac troponins (T or I) may provide confirmatory evidence of myocardial necrosis within two to three hours of suspected acute MI.^16,17 These tests are now available in most EDs and some clinics with point-of-care testing. A variety of current guidelines advocate repeat cardiac enzyme measurements at various time points, depending on results of initial testing and concomitant risk factors. These protocols vary by facility.

ECG. Obtaining an ECG is another quick, easy, and useful way to screen patients presenting with severe hypertensive urgency. Evidence of left ventricular hypertrophy suggests an increased risk for MI, stroke, heart failure, and sudden death.^7,18-20 The Cornell criteria of summing the R wave in aVL and the S wave in V₃, with a cutoff of 2.8 mV in men and 2.0 mV in women, has been shown to be the best predictor of future cardiovascular mortality.⁷ While an isolated finding of left ventricular hypertrophy on an ECG—in and of itself—may have limited value for an individual patient, this finding coupled with other risk factors may alter the provider’s assessment.

Chest radiograph. A chest radiograph can be helpful when used in conjunction with physical exam findings that suggest pulmonary edema and cardiomegaly.⁷ Widened mediastinum and tortuous aorta may also be evident on chest x-ray, necessitating further workup and imaging.

Urinalysis. In a patient presenting with asymptomatic hypertensive urgency, a urine dipstick result that shows new-onset proteinuria, while not definitive for diagnosis of nephrotic syndrome, may certainly prove helpful in the patient’s workup.^5,13

Urine drug screen. In patients without a history of hypertension who present with asymptomatic hypertensive urgency, the urine drug screen may ascertain exposure to cocaine, amphetamine, or phencyclidine.

Pregnancy test. A pregnancy test is essential for any female patient of childbearing age presenting to the ED, and a positive result may be concerning for preeclampsia in a hypertensive patient with no prior history of the condition.⁷

TREATMENT

Knowing who to treat and when is a vast area of debate among emergency and primary care providers. Patients with hypertension who have established risk factors are known to have worse outcomes than those who may be otherwise healthy. Some clinicians believe that patients presenting with hypertensive urgency should be discharged home without screening and/or treatment. However, because uncontrolled severe hypertension can lead to acute complications (eg, MI, cerebrovascular accident), in practice, many providers are unwilling to send the patient home without workup.¹² The patient’s condition must be viewed in the context of the entire disease spectrum, including risk factors.

The Figure offers a disposition pathway of recommendations based on risk stratification as well as screening tools for some of the less common causes of hypertensive urgency. Regardless of the results of screening tests or the decision to treat, affected patients require close primary care follow-up. Many of these patients may need further testing and careful management of their BP medication regimen.

How to treat

For patients with severe asymptomatic hypertension, if the history, physical, and screening tests do not show evidence of end-organ damage, BP can be controlled within 24 to 48 hours.^5,10,11,21 In adults with hypertensive urgency, the most reasonable goal is to reduce the BP to ≤ 160/100 mm Hg^5-7; however, the mean arterial pressure should not be lowered by more than 25% within the first two to three hours.¹³

Patients at high risk for imminent neurovascular, cardiovascular, renovascular, or pulmonary events should have their BP lowered over a period of hours, not minutes. In fact, there is evidence that rapid lowering of BP in asymptomatic patients may cause adverse outcomes.⁶ For example, in patients with acute ischemic stroke, increases in cerebral perfusion pressure promote an increase in vascular resistance—but decreasing the cerebral perfusion pressure abruptly will thereby decrease the cerebral blood flow, potentially causing cerebral ischemia or a worsening of the stroke.^9,14

Treatment options

A broad spectrum of therapeutic options has proven helpful in lowering BP over a short period of time, including oral captopril, clonidine, hydralazine, labetalol, and hydrochlorothiazide (see Table 3).^7,9,12,15 Nifedipine is contraindicated because of the abrupt and often unpredictable reduction in BP and associated myocardial ischemia, especially in patients with MI or left ventricular hypertrophy.^14,22,23 In cases of hypertensive urgency secondary to cocaine abuse, benzodiazepines would be the drug of choice and ß-blockers should be avoided due to the risk for coronary vasoconstriction.⁷

For patients with previously treated hypertension, the following options are reasonable: Increase the dose of the current antihypertensive medication; add another agent; reinstitute prior antihypertensive medications in nonadherent patients; or add a diuretic.

In patients with previously untreated hypertension, no clear evidence supports using one particular agent over another. However, initial treatment options that are generally considered safe include an ACE inhibitor, an angiotensin receptor blocker, a calcium channel blocker, or a thiazide diuretic.¹⁵ A few examples of medications within these categories include lisinopril (10 mg PO qd), losartan (50 mg PO qd), amlodipine (2.5 mg PO qd), or hydrochlorothiazide (25 mg PO qd).

Close follow-up is essential when an antihypertensive medication is started or reinstituted. Encourage the patient to reestablish care with their primary care provider (if you do not fill that role). You may need to refer the patient to a new provider or, in some cases, have the patient return to the ED for a repeat BP check.

CONCLUSION

The challenges of managing patients with hypertensive urgency are complicated by low follow-up rates with primary physicians, difficulty in obtaining referrals and follow-up for the patient, and hesitancy of providers to start patients on new BP medications. This article clarifies a well-defined algorithm for how to screen and risk-stratify patients who present to the ED or primary care office with hypertensive urgency.

IN THIS ARTICLE

• Patient history; what to ask
• Cardiovascular risk factors
• Disposition pathway
• Oral medications

Approximately one in three US adults, or about 75 million people, have high blood pressure (BP), which has been defined as a BP of 140/90 mm Hg or higher.¹ Unfortunately, only about half (54%) of those affected have their condition under optimal control.¹ From an epidemiologic standpoint, hypertension has the distinction of being the most common chronic condition in the US, affecting about 54% of persons ages 55 to 64 and about 73% of those 75 and older.^2,3 It is the number one reason patients schedule office visits with physicians; it accounts for the most prescriptions; and it is a major risk factor for heart disease and stroke, as well as a significant contributor to mortality throughout the world.⁴

HYPERTENSIVE URGENCY VS EMERGENCY

Hypertensive urgencies and emergencies account for approximately 27% of all medical emergencies and 2% to 3% of all annual visits to the emergency department (ED).⁵ Hypertensive urgency, or severe asymptomatic hypertension, is a common complaint in urgent care clinics and primary care offices as well. It is often defined as a systolic BP (SBP) of ≥ 160 mm Hg and/or a diastolic BP (DBP) ≥ 100 mm Hg with no associated end-organ damage.^5-7 Patients may experience hypertensive urgency if they have been noncompliant with their antihypertensive drug regimen; present with pain; have white-coat hypertension or anxiety; or use recreational drugs (eg, sympathomimetics).^5,8-10

Alternatively, hypertensive emergency, also known as hypertensive crisis, is generally defined as elevated BP > 180/120 mm Hg. Equally important, it is associated with signs, symptoms, or laboratory values indicative of target end-organ damage, such as cerebrovascular accident, myocardial infarction (MI), aortic dissection, acute left ventricular failure, acute pulmonary edema, acute renal failure, acute mental status changes (hypertensive encephalopathy), and eclampsia.^5,7,8,11,12

Determining appropriate management for patients with hypertensive urgency is controversial among clinicians. Practice patterns range from full screening and “rule-outs”—with prompt initiation of antihypertensive agents, regardless of whether the patient is symptomatic—to sending the patient home with minimal screening, laboratory testing, or treatment.

This article offers a guided approach to managing patients with hypertensive urgency in a logical fashion, based on risk stratification, thereby avoiding both extremes (extensive unnecessary workup or discharge without workup resulting in adverse outcomes). It is vital to differentiate between patients with hypertensive emergency, in which BP should be lowered in minutes, and patients with hypertensive urgency, in which BP can be lowered more slowly.¹²

PATHOPHYSIOLOGY

Normally, when BP increases, blood vessel diameter changes in response; this autoregulation serves to limit damage. However, when BP increases abruptly, the body’s ability to hemodynamically calibrate to such a rapid change is impeded, thus allowing for potential end-organ damage.^5,12 The increased vascular resistance observed in many patients with hypertension appears to be an autoregulatory process that helps to maintain a normal or viable level of tissue blood flow and organ perfusion despite the increased BP, rather than a primary cause of the hypertension.¹³

The exact physiology of hypertensive urgencies is not clearly understood, because of the multifactorial nature of the process. One leading theory is that circulating humoral vasoconstrictors cause an abrupt increase in systemic vascular resistance, which in turn causes mechanical shear stress to the endothelial wall. This endothelial damage promotes more vasoconstriction, platelet aggregation, and activation of the renin-angiotensin-aldosterone system, which thereby increases release of angiotensin II and various cytokines.¹⁴

HISTORY AND PHYSICAL

A detailed medical history is of utmost importance in distinguishing patients who present with asymptomatic hypertensive urgency from those experiencing a hypertensive emergency. In addition, obtain a full medication list, including any nutritional supplements or illicit drugs the patient may be taking. Question the patient regarding medication adherence; some may not be taking antihypertensive agents as prescribed or may have altered the dosing frequency in an effort to extend the duration of their prescription.^5,8 Table 1 lists pertinent questions to ask at presentation; the answers will dictate who needs further workup and possible admission as well as who will require screening for end-organ damage.⁷

The physical exam should focus primarily on a thorough cardiopulmonary and neurologic examination, as well as funduscopic examination, if needed. A complete set of vital signs should be recorded upon the patient’s arrival to the ED or clinic and should be repeated on the opposite arm for verification. Beginning with the eyes, conduct a thorough funduscopic examination to evaluate for papilledema or hemorrhages.⁵ During the cardiopulmonary exam, attention should be focused on signs of congestive heart failure and/or pulmonary edema, such as increased jugular vein distension, an S3 gallop, peripheral edema, and pulmonary rales. The neurologic exam is essential in evaluating for cerebrovascular accident, transient ischemic attack, or intracranial hemorrhage. A full cranial nerve examination is necessary, in addition to motor and sensory testing, at minimum.^5,9

RISK STRATIFICATION

According to the 2013 Task Force of the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC), several risk factors contribute to overall cardiovascular risk in asymptomatic patients presenting with severe hypertension (see Table 2).⁸ This report has been monumental in linking grades of hypertension directly to cardiovascular risk factors, but it differs from that recently published by the Eighth Joint National Committee (JNC 8), which offers evidence-based guidelines for the management of high BP in the general population of adults (with some modifications for individuals with diabetes or chronic kidney disease or of black ethnicity).¹⁵

According to the ESH/ESC study, patients with one or two risk factors who have grade 1 hypertension (SBP 140-159 mm Hg) are at moderate risk for cardiovascular disease (CVD) and patients with grade 2 (SBP 160-179 mm Hg) or grade 3 (SBP ≥ 180 mm Hg) hypertension are at moderate-to-high risk and high risk, respectively.⁸ Patients with three or more risk factors, or who already have end-organ damage, diabetes, or chronic kidney disease, enter the high-risk category for CVD even at grade 1 hypertension.⁸

These cardiovascular risk factors can and should be used as guidelines for deciding who needs further screening and who may have benign causes of severe hypertension (eg, white-coat hypertension, anxiety) that can be managed safely in an outpatient setting. In the author’s opinion, patients with known cardiovascular risk factors, those with signs or symptoms of end-organ damage, and those with test results suggestive of end-organ damage should have a more immediate treatment strategy initiated.

Numerous observational studies have shown a direct relationship between systemic hypertension and CVD risk in men and women of various ages, races, and ethnicities, regardless of other risk factors for CVD.¹² In patients with diabetes, uncontrolled hypertension is a strong predictor of cardiovascular morbidity and mortality and of progressive nephropathy leading to chronic kidney disease.⁸

SCREENING

Results from the following tests may provide useful clues in the workup of a patient with hypertensive urgency.

Basic metabolic panel. Many EDs and primary care offices offer point-of-care testing that can typically give a rapid (< 10 min) result of a basic metabolic panel. This useful, quick screening tool can identify renal failure due to chronic untreated hypertension, acute renal failure, or other disease states that cause electrolyte abnormalities such as hyperaldosteronism (hypertension with hypokalemia) or Cushing syndrome (hypertension with hypernatremia and hyperkalemia).⁷

Cardiac enzymes. Measurement of cardiac troponins (T or I) may provide confirmatory evidence of myocardial necrosis within two to three hours of suspected acute MI.^16,17 These tests are now available in most EDs and some clinics with point-of-care testing. A variety of current guidelines advocate repeat cardiac enzyme measurements at various time points, depending on results of initial testing and concomitant risk factors. These protocols vary by facility.

ECG. Obtaining an ECG is another quick, easy, and useful way to screen patients presenting with severe hypertensive urgency. Evidence of left ventricular hypertrophy suggests an increased risk for MI, stroke, heart failure, and sudden death.^7,18-20 The Cornell criteria of summing the R wave in aVL and the S wave in V₃, with a cutoff of 2.8 mV in men and 2.0 mV in women, has been shown to be the best predictor of future cardiovascular mortality.⁷ While an isolated finding of left ventricular hypertrophy on an ECG—in and of itself—may have limited value for an individual patient, this finding coupled with other risk factors may alter the provider’s assessment.

Chest radiograph. A chest radiograph can be helpful when used in conjunction with physical exam findings that suggest pulmonary edema and cardiomegaly.⁷ Widened mediastinum and tortuous aorta may also be evident on chest x-ray, necessitating further workup and imaging.

Urinalysis. In a patient presenting with asymptomatic hypertensive urgency, a urine dipstick result that shows new-onset proteinuria, while not definitive for diagnosis of nephrotic syndrome, may certainly prove helpful in the patient’s workup.^5,13

Urine drug screen. In patients without a history of hypertension who present with asymptomatic hypertensive urgency, the urine drug screen may ascertain exposure to cocaine, amphetamine, or phencyclidine.

Pregnancy test. A pregnancy test is essential for any female patient of childbearing age presenting to the ED, and a positive result may be concerning for preeclampsia in a hypertensive patient with no prior history of the condition.⁷

TREATMENT

Knowing who to treat and when is a vast area of debate among emergency and primary care providers. Patients with hypertension who have established risk factors are known to have worse outcomes than those who may be otherwise healthy. Some clinicians believe that patients presenting with hypertensive urgency should be discharged home without screening and/or treatment. However, because uncontrolled severe hypertension can lead to acute complications (eg, MI, cerebrovascular accident), in practice, many providers are unwilling to send the patient home without workup.¹² The patient’s condition must be viewed in the context of the entire disease spectrum, including risk factors.

The Figure offers a disposition pathway of recommendations based on risk stratification as well as screening tools for some of the less common causes of hypertensive urgency. Regardless of the results of screening tests or the decision to treat, affected patients require close primary care follow-up. Many of these patients may need further testing and careful management of their BP medication regimen.

How to treat

For patients with severe asymptomatic hypertension, if the history, physical, and screening tests do not show evidence of end-organ damage, BP can be controlled within 24 to 48 hours.^5,10,11,21 In adults with hypertensive urgency, the most reasonable goal is to reduce the BP to ≤ 160/100 mm Hg^5-7; however, the mean arterial pressure should not be lowered by more than 25% within the first two to three hours.¹³

Patients at high risk for imminent neurovascular, cardiovascular, renovascular, or pulmonary events should have their BP lowered over a period of hours, not minutes. In fact, there is evidence that rapid lowering of BP in asymptomatic patients may cause adverse outcomes.⁶ For example, in patients with acute ischemic stroke, increases in cerebral perfusion pressure promote an increase in vascular resistance—but decreasing the cerebral perfusion pressure abruptly will thereby decrease the cerebral blood flow, potentially causing cerebral ischemia or a worsening of the stroke.^9,14

Treatment options

A broad spectrum of therapeutic options has proven helpful in lowering BP over a short period of time, including oral captopril, clonidine, hydralazine, labetalol, and hydrochlorothiazide (see Table 3).^7,9,12,15 Nifedipine is contraindicated because of the abrupt and often unpredictable reduction in BP and associated myocardial ischemia, especially in patients with MI or left ventricular hypertrophy.^14,22,23 In cases of hypertensive urgency secondary to cocaine abuse, benzodiazepines would be the drug of choice and ß-blockers should be avoided due to the risk for coronary vasoconstriction.⁷

For patients with previously treated hypertension, the following options are reasonable: Increase the dose of the current antihypertensive medication; add another agent; reinstitute prior antihypertensive medications in nonadherent patients; or add a diuretic.

In patients with previously untreated hypertension, no clear evidence supports using one particular agent over another. However, initial treatment options that are generally considered safe include an ACE inhibitor, an angiotensin receptor blocker, a calcium channel blocker, or a thiazide diuretic.¹⁵ A few examples of medications within these categories include lisinopril (10 mg PO qd), losartan (50 mg PO qd), amlodipine (2.5 mg PO qd), or hydrochlorothiazide (25 mg PO qd).

Close follow-up is essential when an antihypertensive medication is started or reinstituted. Encourage the patient to reestablish care with their primary care provider (if you do not fill that role). You may need to refer the patient to a new provider or, in some cases, have the patient return to the ED for a repeat BP check.

CONCLUSION

The challenges of managing patients with hypertensive urgency are complicated by low follow-up rates with primary physicians, difficulty in obtaining referrals and follow-up for the patient, and hesitancy of providers to start patients on new BP medications. This article clarifies a well-defined algorithm for how to screen and risk-stratify patients who present to the ED or primary care office with hypertensive urgency.

Take-Home Points

• Systematic use of PROMs allows physicians to review data on pain, physical function, and psychological status to aid in clinical decision-making and best practices.
• PROMs should include both general outcome measures (VAS, SF-36, or EQ-5D) and reliable, valid, and responsive disease specific measures.
• PROM questionnaires should collect pertinent information while limiting the length to maximize patient compliance and reliability.
• PROMIS has been developed to standardize questionnaires, but generality for specific orthopedic procedures may result in less effective measures.
• PROMs can also be used for predictive modeling, which has the potential to help develop more cost-effective care and predict expected outcomes and recovery trajectories for individual patients.

Owing to their unique ability to recognize patients as stakeholders in their own healthcare, patient-reported outcome measures (PROMs) are becoming increasingly popular in the assessment of medical and surgical outcomes.¹ PROMs are an outcome measures subset in which patients complete questionnaires about their perceptions of their overall health status and specific health limitations. By systematically using PROMs before and after a clearly defined episode of care, clinicians can collect data on perceived pain level, physical function, and psychological status and use the data to validate use of surgical procedures and shape clinical decisions about best practices.^2-4 Although mortality and morbidity rates and other traditional measures are valuable in assessing outcomes, they do not represent or communicate the larger impact of an episode of care. As many orthopedic procedures are elective, and some are low-risk, the evaluation of changes in quality of life and self-reported functional improvement is an important addition to morbidity and mortality rates in capturing the true impact of a surgical procedure and recovery. The patient’s preoperative and postoperative perspectives on his or her health status have become important as well; our healthcare system has been placing more emphasis on patient-centered quality care.^2,5

Although PROMs have many benefits, implementation in an orthopedic surgery practice has its challenges. With so many PROMs available, selecting those that fit the patient population for a specialized orthopedic surgery practice can be difficult. In addition, although PROM data are essential for research and for measuring individual or institutional recovery trajectories for surgical procedures, in a busy practice getting patients to provide these data can be difficult.

PROMs are heavily used for outcomes assessment in the orthopedics literature, but there are few resources for orthopedic surgeons who want to implement PROMs in their practices. In this article, we review the literature on the challenges of effectively implementing PROMs in an orthopedic surgery practice.

PROM Selection Considerations

PROMs can be categorized as either generic or disease-specific,⁴ but together they are used to adequately capture the impact, both broad and local, of an orthopedic condition.

Generic Outcome Measures

Generic outcome measures apply to a range of subspecialties or anatomical regions, allowing for evaluation of a patient’s overall health or quality of life. The most widely accepted measure of pain is the visual analog scale (VAS). The VAS for pain quantifies the level of pain a patient experiences at a given time on a graphic sliding scale from 0 (no pain) to 10 (worst possible pain). The VAS is used in clinical evaluation of pain and in reported outcomes literature.^6,7

Many generic PROMs assess mental health status in addition to physical limitations. Poor preoperative mental health status has been recognized as a predictor of worse outcomes across a variety of orthopedic procedures.^8,9 Therefore, to assess the overall influence of an orthopedic condition, it is important to include at least 1 generic PROM that assesses mental health status before and after an episode of care. Generic PROMs commonly used in orthopedic surgery include the 36-Item Short Form Health Survey (SF-36), the shorter SF-12, the Veterans RAND 12-Item Health Survey (VR-12), the World Health Organization Disability Assessment Schedule (WHODAS), the European Quality of Life-5 Dimensions (EQ-5D) index, and the 10-item Patient-Reported Outcomes Measurement Information System Global Health (PROMIS-10) scale.^10-14

Some generic outcome measures (eg, the EQ-5D index) offer the “utility” calculation, which represents a preference for a patient’s desired health status. Such utilities allow for a measurement of quality of life, represented by quality-adjusted life years (QALY), which is a standardized measure of disease burden. Calculated QALY from measures such as the EQ-5D can be used in cost-effectiveness analyses of surgical interventions and have been used to validate use of procedures, particularly in arthroplasty.^15-17

Disease-Specific Outcome Measures

Likewise, there is a range of disease-specific PROMs validated for use in orthopedic surgery, and providers select PROMs that fit their scope of practice. In anatomical regions such as the knee, hip, and shoulder, disease-specific outcome measures vary significantly by subspecialty and patient population. When selecting disease-specific PROMs, providers must consider tools such as reliability, validity, responsiveness, and available population norms. One study used Evaluating Measures of Patient-Reported Outcomes (EMPRO) to assess the quality of a PROM in shoulders and concluded that the American Shoulder and Elbow Surgeons (ASES) index, the Simple Shoulder Test (SST), and the Oxford Shoulder Score (OSS) were all supported for use in practice.¹⁸ It is important to note that reliability, validity, and responsiveness of a PROM may vary with the diagnosis or the patient population studied. For example, the SST was found to be responsive in assessing rotator cuff injury but not as useful in assessing shoulder instability or arthritis.¹⁹ Variable responsiveness highlights the need for a diagnosis-based level of PROM customization. For example, patients who undergo a surgical intervention for shoulder instability are given a customized survey, which includes PROMs specific to their condition, such as the Western Ontario Shoulder Instability (WOSI) index.²⁰ For patients with knee instability, similar considerations apply; specific measures such as the Lysholm score and the Tenger Activity Scale capture the impact of injury in physically demanding activities.²¹ When selecting disease-specific PROMs, providers should consult articles like those by Davidson and Keating²² and Bent and colleagues,²³ who present provider-friendly tools that can be used to examine the effectiveness of a PROM, and provide additional background information on selecting disease-specific PROMs. For hip and knee arthroplasty subspecialties, the International Society of Arthroplasty Registries (ISAR) created a working group that determines best practices for PROM collection and identifies PROMs most commonly reported in arthroplasty.²⁴

Questionnaire Length Considerations

When PROMs are used in a practice, a balance must be struck between gathering enough information to determine functionality and limiting the patient burden of questionnaire length. A decision to use several PROMs all at once, at a single data collection point, can lengthen the questionnaire significantly. One study found that, with use of longer questionnaires, patients may lose interest, resulting in decreased reliability and compliance.²⁵ For example, providers who use the long (42-item) Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire to assess knee function are often limited in what other PROMs they may administer at the same time. Efforts to shorten this questionnaire while still capturing necessary information led to the development of the 7-item KOOS Jr, which was validated for use in knee arthroplasty and had its 7 items drawn from the original 42.²⁶ Similarly, the 40-item Hip Disability and Osteoarthritis Outcome Score (HOOS) questionnaire was shortened to the 6-item HOOS Jr, which was validated for use in hip arthroplasty,²⁷ and the generic SF-36 was shortened to the SF-12.¹¹ Providers trying to build an outcomes database while minimizing patient burden should consider using the shorter versions of these questionnaires but should also consider their validity, as KOOS Jr and HOOS Jr have been validated for use only in knee and hip arthroplasty and not in other knee and hip conditions.

PROM Data Collection Considerations

Comprehensive collection of longitudinal PROM data poses many challenges for providers and patients. For providers, the greatest challenges are infrastructure, technology, and the personnel needed to administer and store paper or electronic surveys. For patients, the most common survey completion barriers are questionnaire length, confusing or irrelevant content, and, in the case of some older adults, inability to complete surveys electronically.²⁵

Identifying a nonresponsive or noncompliant patient population is an important issue in collecting PROM data for research or other purposes. A study of factors associated with higher nonresponse rates in elective surgery patients (N = 135,474) found that noncompliance was higher for males, patients under age 55 years, nonwhites, patients in the lowest socioeconomic quintile, patients living alone, patients needing assistance in completing questionnaires, and patients who previously underwent surgery for their condition.²⁸ In a systematic review of methods that increased the response rates of postal and electronic surveys, Edwards and colleagues²⁹ found significantly higher odds of response for patients who were prenotified of the survey, given shorter questionnaires, or given a deadline for survey completion. Of note, response rates were lower when the word survey was used in the subject line of an email. 

PROM distribution has evolved with the rise of technological advances that allow for electronic survey distribution and data capture. Several studies have found that electronically administered PROMs have high response rates.^3,30,31 In a study of patients who underwent total hip arthroplasty, Rolfson and colleagues³² found that response rates were significantly higher for those who were surveyed on paper than for those surveyed over the internet. A randomized controlled study found that, compared with paper surveys, digital tablet surveys effectively and reliably collected PROM data; in addition, digital tablets provided instant data storage, and improved survey completion by requiring that all questions be answered before the survey could be submitted.33 However, age, race/ethnicity, and income disparities in technology use must be considered when administering internet-based follow-up surveys and analyzing data collected with web-based methods.³⁴ A study of total joint arthroplasty candidates found that several groups were less likely to complete electronic PROM questionnaires: patients over age 75 years, Hispanic or black patients, patients with Medicare or Medicaid, patients who previously underwent orthopedic surgery, patients undergoing revision total joint arthroplasty, patients with other comorbidities, and patients whose primary language was not English.³⁵ Providers interested in implementing PROMs must consider their patient population when selecting a method for survey distribution and follow-up. A study found that a majority of PROMs were written at a level many patients may not have understood, because of their literacy level or age; this lack of understanding created a barrier to compliance in many patient populations.³⁶

PROM Limitations and PROMIS Use

Use of PROMs has its limitations. The large variety of PROMs available for use in orthopedic surgery has led to several standardization initiatives. The National Institutes of Health funded the development of PROMIS, a person-centered measures database that evaluates and monitors the physical, social, and emotional health of adults and children.³⁷ The goal of PROMIS is to develop a standardized method of selecting PROMs, so that all medical disciplines and subspecialties can choose an applicable set of questions from the PROMIS question bank and use it in practice. Orthopedic surgery can use questions pertaining to physical functioning of the lower and upper extremities as well as quality of life and mental health. PROMIS physical function questions have been validated for use in several areas of orthopedic surgery.^38-40 A disadvantage of PROMIS is the overgenerality of its questions, which may not be as effective in capturing the implications of specific diagnoses. For example, it is difficult to use generalized questions to determine the implications of a diagnosis such as shoulder instability, which may affect only higher functioning activities or sports. More research on best PROM selection practices is needed in order to either standardize PROMs or move toward use of a single database such as PROMIS.

Future Directions in PROM Applications

PROMs are being used for research and patient engagement, but there are many other applications on the horizon. As already mentioned, predictive modeling is of particular interest. The existence of vast collaborative PROM databases that capture a diverse patient population introduces the possibility of creating models capable of predicting a patient outcome and enhancing shared decision-making.³ Predicting good or excellent patient outcomes for specific patient populations may allow elimination of certain postoperative visits, thereby creating more cost-effective care and reducing the burden of unnecessary clinic visits for both patients and physicians.

As with other healthcare areas, PROM data collection technology is rapidly advancing. Not only has electronic technology almost entirely replaced paper-and-pencil collection methods, but a new method of outcome data collection has been developed: computerized adaptive testing (CAT). CAT uses item-response theory to minimize the number of questions patients must answer in order for validated and reliable outcome scores to be calculated. According to multiple studies, CAT used across several questionnaires has reliably assessed PROMs while minimizing floor and ceiling effects, eliminating irrelevant questions, and shortening survey completion time.^41-43

Besides becoming more patient-friendly and accessible across multiple interfaces (mobile devices and computers), PROMs are also beginning to be integrated into the electronic medical record, allowing easier access to information during chart reviews. Use of statistical and predictive modeling, as described by Chang,³ could give PROMs a role in clinical decision-making. Informing patients of their expected outcome and recovery trajectory—based on demographics, comorbidities, preoperative functional status, and other factors—could influence their decision to undergo surgical intervention. As Halawi and colleagues⁴⁴ pointed out, it is important to discuss patient expectations before surgery, as unrealistic ones can negatively affect outcomes and lead to dissatisfaction. With clinicians having ready access to statistics and models in patient charts, we may see a transformation in clinical practices and surgical decision-making.

Conclusion

PROMs offer many ways to improve research and clinical care in orthopedic surgery. However, implementing PROMs in practice is not without challenges. Interested orthopedic surgeons should select the PROMs that are most appropriate—reliable, validated, and responsive to their patient population. Electronic distribution of PROM questionnaires is effective and allows data to be stored on entry, but orthopedic surgeons must consider their patient population to ensure accurate data capture and compliance in longitudinal surveys. Proper implementation of PROMs in a practice can allow clinicians to formulate expectations for postoperative recovery and set reasonable postoperative goals while engaging patients in improving quality of care.

Take-Home Points

• Systematic use of PROMs allows physicians to review data on pain, physical function, and psychological status to aid in clinical decision-making and best practices.
• PROMs should include both general outcome measures (VAS, SF-36, or EQ-5D) and reliable, valid, and responsive disease specific measures.
• PROM questionnaires should collect pertinent information while limiting the length to maximize patient compliance and reliability.
• PROMIS has been developed to standardize questionnaires, but generality for specific orthopedic procedures may result in less effective measures.
• PROMs can also be used for predictive modeling, which has the potential to help develop more cost-effective care and predict expected outcomes and recovery trajectories for individual patients.

Owing to their unique ability to recognize patients as stakeholders in their own healthcare, patient-reported outcome measures (PROMs) are becoming increasingly popular in the assessment of medical and surgical outcomes.¹ PROMs are an outcome measures subset in which patients complete questionnaires about their perceptions of their overall health status and specific health limitations. By systematically using PROMs before and after a clearly defined episode of care, clinicians can collect data on perceived pain level, physical function, and psychological status and use the data to validate use of surgical procedures and shape clinical decisions about best practices.^2-4 Although mortality and morbidity rates and other traditional measures are valuable in assessing outcomes, they do not represent or communicate the larger impact of an episode of care. As many orthopedic procedures are elective, and some are low-risk, the evaluation of changes in quality of life and self-reported functional improvement is an important addition to morbidity and mortality rates in capturing the true impact of a surgical procedure and recovery. The patient’s preoperative and postoperative perspectives on his or her health status have become important as well; our healthcare system has been placing more emphasis on patient-centered quality care.^2,5

Although PROMs have many benefits, implementation in an orthopedic surgery practice has its challenges. With so many PROMs available, selecting those that fit the patient population for a specialized orthopedic surgery practice can be difficult. In addition, although PROM data are essential for research and for measuring individual or institutional recovery trajectories for surgical procedures, in a busy practice getting patients to provide these data can be difficult.

PROMs are heavily used for outcomes assessment in the orthopedics literature, but there are few resources for orthopedic surgeons who want to implement PROMs in their practices. In this article, we review the literature on the challenges of effectively implementing PROMs in an orthopedic surgery practice.

PROM Selection Considerations

PROMs can be categorized as either generic or disease-specific,⁴ but together they are used to adequately capture the impact, both broad and local, of an orthopedic condition.

Generic Outcome Measures

Generic outcome measures apply to a range of subspecialties or anatomical regions, allowing for evaluation of a patient’s overall health or quality of life. The most widely accepted measure of pain is the visual analog scale (VAS). The VAS for pain quantifies the level of pain a patient experiences at a given time on a graphic sliding scale from 0 (no pain) to 10 (worst possible pain). The VAS is used in clinical evaluation of pain and in reported outcomes literature.^6,7

Many generic PROMs assess mental health status in addition to physical limitations. Poor preoperative mental health status has been recognized as a predictor of worse outcomes across a variety of orthopedic procedures.^8,9 Therefore, to assess the overall influence of an orthopedic condition, it is important to include at least 1 generic PROM that assesses mental health status before and after an episode of care. Generic PROMs commonly used in orthopedic surgery include the 36-Item Short Form Health Survey (SF-36), the shorter SF-12, the Veterans RAND 12-Item Health Survey (VR-12), the World Health Organization Disability Assessment Schedule (WHODAS), the European Quality of Life-5 Dimensions (EQ-5D) index, and the 10-item Patient-Reported Outcomes Measurement Information System Global Health (PROMIS-10) scale.^10-14

Some generic outcome measures (eg, the EQ-5D index) offer the “utility” calculation, which represents a preference for a patient’s desired health status. Such utilities allow for a measurement of quality of life, represented by quality-adjusted life years (QALY), which is a standardized measure of disease burden. Calculated QALY from measures such as the EQ-5D can be used in cost-effectiveness analyses of surgical interventions and have been used to validate use of procedures, particularly in arthroplasty.^15-17

Disease-Specific Outcome Measures

Likewise, there is a range of disease-specific PROMs validated for use in orthopedic surgery, and providers select PROMs that fit their scope of practice. In anatomical regions such as the knee, hip, and shoulder, disease-specific outcome measures vary significantly by subspecialty and patient population. When selecting disease-specific PROMs, providers must consider tools such as reliability, validity, responsiveness, and available population norms. One study used Evaluating Measures of Patient-Reported Outcomes (EMPRO) to assess the quality of a PROM in shoulders and concluded that the American Shoulder and Elbow Surgeons (ASES) index, the Simple Shoulder Test (SST), and the Oxford Shoulder Score (OSS) were all supported for use in practice.¹⁸ It is important to note that reliability, validity, and responsiveness of a PROM may vary with the diagnosis or the patient population studied. For example, the SST was found to be responsive in assessing rotator cuff injury but not as useful in assessing shoulder instability or arthritis.¹⁹ Variable responsiveness highlights the need for a diagnosis-based level of PROM customization. For example, patients who undergo a surgical intervention for shoulder instability are given a customized survey, which includes PROMs specific to their condition, such as the Western Ontario Shoulder Instability (WOSI) index.²⁰ For patients with knee instability, similar considerations apply; specific measures such as the Lysholm score and the Tenger Activity Scale capture the impact of injury in physically demanding activities.²¹ When selecting disease-specific PROMs, providers should consult articles like those by Davidson and Keating²² and Bent and colleagues,²³ who present provider-friendly tools that can be used to examine the effectiveness of a PROM, and provide additional background information on selecting disease-specific PROMs. For hip and knee arthroplasty subspecialties, the International Society of Arthroplasty Registries (ISAR) created a working group that determines best practices for PROM collection and identifies PROMs most commonly reported in arthroplasty.²⁴

Questionnaire Length Considerations

When PROMs are used in a practice, a balance must be struck between gathering enough information to determine functionality and limiting the patient burden of questionnaire length. A decision to use several PROMs all at once, at a single data collection point, can lengthen the questionnaire significantly. One study found that, with use of longer questionnaires, patients may lose interest, resulting in decreased reliability and compliance.²⁵ For example, providers who use the long (42-item) Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire to assess knee function are often limited in what other PROMs they may administer at the same time. Efforts to shorten this questionnaire while still capturing necessary information led to the development of the 7-item KOOS Jr, which was validated for use in knee arthroplasty and had its 7 items drawn from the original 42.²⁶ Similarly, the 40-item Hip Disability and Osteoarthritis Outcome Score (HOOS) questionnaire was shortened to the 6-item HOOS Jr, which was validated for use in hip arthroplasty,²⁷ and the generic SF-36 was shortened to the SF-12.¹¹ Providers trying to build an outcomes database while minimizing patient burden should consider using the shorter versions of these questionnaires but should also consider their validity, as KOOS Jr and HOOS Jr have been validated for use only in knee and hip arthroplasty and not in other knee and hip conditions.

PROM Data Collection Considerations

Comprehensive collection of longitudinal PROM data poses many challenges for providers and patients. For providers, the greatest challenges are infrastructure, technology, and the personnel needed to administer and store paper or electronic surveys. For patients, the most common survey completion barriers are questionnaire length, confusing or irrelevant content, and, in the case of some older adults, inability to complete surveys electronically.²⁵

Identifying a nonresponsive or noncompliant patient population is an important issue in collecting PROM data for research or other purposes. A study of factors associated with higher nonresponse rates in elective surgery patients (N = 135,474) found that noncompliance was higher for males, patients under age 55 years, nonwhites, patients in the lowest socioeconomic quintile, patients living alone, patients needing assistance in completing questionnaires, and patients who previously underwent surgery for their condition.²⁸ In a systematic review of methods that increased the response rates of postal and electronic surveys, Edwards and colleagues²⁹ found significantly higher odds of response for patients who were prenotified of the survey, given shorter questionnaires, or given a deadline for survey completion. Of note, response rates were lower when the word survey was used in the subject line of an email. 

PROM distribution has evolved with the rise of technological advances that allow for electronic survey distribution and data capture. Several studies have found that electronically administered PROMs have high response rates.^3,30,31 In a study of patients who underwent total hip arthroplasty, Rolfson and colleagues³² found that response rates were significantly higher for those who were surveyed on paper than for those surveyed over the internet. A randomized controlled study found that, compared with paper surveys, digital tablet surveys effectively and reliably collected PROM data; in addition, digital tablets provided instant data storage, and improved survey completion by requiring that all questions be answered before the survey could be submitted.33 However, age, race/ethnicity, and income disparities in technology use must be considered when administering internet-based follow-up surveys and analyzing data collected with web-based methods.³⁴ A study of total joint arthroplasty candidates found that several groups were less likely to complete electronic PROM questionnaires: patients over age 75 years, Hispanic or black patients, patients with Medicare or Medicaid, patients who previously underwent orthopedic surgery, patients undergoing revision total joint arthroplasty, patients with other comorbidities, and patients whose primary language was not English.³⁵ Providers interested in implementing PROMs must consider their patient population when selecting a method for survey distribution and follow-up. A study found that a majority of PROMs were written at a level many patients may not have understood, because of their literacy level or age; this lack of understanding created a barrier to compliance in many patient populations.³⁶

PROM Limitations and PROMIS Use

Use of PROMs has its limitations. The large variety of PROMs available for use in orthopedic surgery has led to several standardization initiatives. The National Institutes of Health funded the development of PROMIS, a person-centered measures database that evaluates and monitors the physical, social, and emotional health of adults and children.³⁷ The goal of PROMIS is to develop a standardized method of selecting PROMs, so that all medical disciplines and subspecialties can choose an applicable set of questions from the PROMIS question bank and use it in practice. Orthopedic surgery can use questions pertaining to physical functioning of the lower and upper extremities as well as quality of life and mental health. PROMIS physical function questions have been validated for use in several areas of orthopedic surgery.^38-40 A disadvantage of PROMIS is the overgenerality of its questions, which may not be as effective in capturing the implications of specific diagnoses. For example, it is difficult to use generalized questions to determine the implications of a diagnosis such as shoulder instability, which may affect only higher functioning activities or sports. More research on best PROM selection practices is needed in order to either standardize PROMs or move toward use of a single database such as PROMIS.

Future Directions in PROM Applications

PROMs are being used for research and patient engagement, but there are many other applications on the horizon. As already mentioned, predictive modeling is of particular interest. The existence of vast collaborative PROM databases that capture a diverse patient population introduces the possibility of creating models capable of predicting a patient outcome and enhancing shared decision-making.³ Predicting good or excellent patient outcomes for specific patient populations may allow elimination of certain postoperative visits, thereby creating more cost-effective care and reducing the burden of unnecessary clinic visits for both patients and physicians.

As with other healthcare areas, PROM data collection technology is rapidly advancing. Not only has electronic technology almost entirely replaced paper-and-pencil collection methods, but a new method of outcome data collection has been developed: computerized adaptive testing (CAT). CAT uses item-response theory to minimize the number of questions patients must answer in order for validated and reliable outcome scores to be calculated. According to multiple studies, CAT used across several questionnaires has reliably assessed PROMs while minimizing floor and ceiling effects, eliminating irrelevant questions, and shortening survey completion time.^41-43

Besides becoming more patient-friendly and accessible across multiple interfaces (mobile devices and computers), PROMs are also beginning to be integrated into the electronic medical record, allowing easier access to information during chart reviews. Use of statistical and predictive modeling, as described by Chang,³ could give PROMs a role in clinical decision-making. Informing patients of their expected outcome and recovery trajectory—based on demographics, comorbidities, preoperative functional status, and other factors—could influence their decision to undergo surgical intervention. As Halawi and colleagues⁴⁴ pointed out, it is important to discuss patient expectations before surgery, as unrealistic ones can negatively affect outcomes and lead to dissatisfaction. With clinicians having ready access to statistics and models in patient charts, we may see a transformation in clinical practices and surgical decision-making.

Conclusion

PROMs offer many ways to improve research and clinical care in orthopedic surgery. However, implementing PROMs in practice is not without challenges. Interested orthopedic surgeons should select the PROMs that are most appropriate—reliable, validated, and responsive to their patient population. Electronic distribution of PROM questionnaires is effective and allows data to be stored on entry, but orthopedic surgeons must consider their patient population to ensure accurate data capture and compliance in longitudinal surveys. Proper implementation of PROMs in a practice can allow clinicians to formulate expectations for postoperative recovery and set reasonable postoperative goals while engaging patients in improving quality of care.

Take-Home Points

• Systematic use of PROMs allows physicians to review data on pain, physical function, and psychological status to aid in clinical decision-making and best practices.
• PROMs should include both general outcome measures (VAS, SF-36, or EQ-5D) and reliable, valid, and responsive disease specific measures.
• PROM questionnaires should collect pertinent information while limiting the length to maximize patient compliance and reliability.
• PROMIS has been developed to standardize questionnaires, but generality for specific orthopedic procedures may result in less effective measures.
• PROMs can also be used for predictive modeling, which has the potential to help develop more cost-effective care and predict expected outcomes and recovery trajectories for individual patients.

Owing to their unique ability to recognize patients as stakeholders in their own healthcare, patient-reported outcome measures (PROMs) are becoming increasingly popular in the assessment of medical and surgical outcomes.¹ PROMs are an outcome measures subset in which patients complete questionnaires about their perceptions of their overall health status and specific health limitations. By systematically using PROMs before and after a clearly defined episode of care, clinicians can collect data on perceived pain level, physical function, and psychological status and use the data to validate use of surgical procedures and shape clinical decisions about best practices.^2-4 Although mortality and morbidity rates and other traditional measures are valuable in assessing outcomes, they do not represent or communicate the larger impact of an episode of care. As many orthopedic procedures are elective, and some are low-risk, the evaluation of changes in quality of life and self-reported functional improvement is an important addition to morbidity and mortality rates in capturing the true impact of a surgical procedure and recovery. The patient’s preoperative and postoperative perspectives on his or her health status have become important as well; our healthcare system has been placing more emphasis on patient-centered quality care.^2,5

Although PROMs have many benefits, implementation in an orthopedic surgery practice has its challenges. With so many PROMs available, selecting those that fit the patient population for a specialized orthopedic surgery practice can be difficult. In addition, although PROM data are essential for research and for measuring individual or institutional recovery trajectories for surgical procedures, in a busy practice getting patients to provide these data can be difficult.

PROMs are heavily used for outcomes assessment in the orthopedics literature, but there are few resources for orthopedic surgeons who want to implement PROMs in their practices. In this article, we review the literature on the challenges of effectively implementing PROMs in an orthopedic surgery practice.

PROM Selection Considerations

PROMs can be categorized as either generic or disease-specific,⁴ but together they are used to adequately capture the impact, both broad and local, of an orthopedic condition.

Generic Outcome Measures

Generic outcome measures apply to a range of subspecialties or anatomical regions, allowing for evaluation of a patient’s overall health or quality of life. The most widely accepted measure of pain is the visual analog scale (VAS). The VAS for pain quantifies the level of pain a patient experiences at a given time on a graphic sliding scale from 0 (no pain) to 10 (worst possible pain). The VAS is used in clinical evaluation of pain and in reported outcomes literature.^6,7

Many generic PROMs assess mental health status in addition to physical limitations. Poor preoperative mental health status has been recognized as a predictor of worse outcomes across a variety of orthopedic procedures.^8,9 Therefore, to assess the overall influence of an orthopedic condition, it is important to include at least 1 generic PROM that assesses mental health status before and after an episode of care. Generic PROMs commonly used in orthopedic surgery include the 36-Item Short Form Health Survey (SF-36), the shorter SF-12, the Veterans RAND 12-Item Health Survey (VR-12), the World Health Organization Disability Assessment Schedule (WHODAS), the European Quality of Life-5 Dimensions (EQ-5D) index, and the 10-item Patient-Reported Outcomes Measurement Information System Global Health (PROMIS-10) scale.^10-14

Some generic outcome measures (eg, the EQ-5D index) offer the “utility” calculation, which represents a preference for a patient’s desired health status. Such utilities allow for a measurement of quality of life, represented by quality-adjusted life years (QALY), which is a standardized measure of disease burden. Calculated QALY from measures such as the EQ-5D can be used in cost-effectiveness analyses of surgical interventions and have been used to validate use of procedures, particularly in arthroplasty.^15-17

Disease-Specific Outcome Measures

Likewise, there is a range of disease-specific PROMs validated for use in orthopedic surgery, and providers select PROMs that fit their scope of practice. In anatomical regions such as the knee, hip, and shoulder, disease-specific outcome measures vary significantly by subspecialty and patient population. When selecting disease-specific PROMs, providers must consider tools such as reliability, validity, responsiveness, and available population norms. One study used Evaluating Measures of Patient-Reported Outcomes (EMPRO) to assess the quality of a PROM in shoulders and concluded that the American Shoulder and Elbow Surgeons (ASES) index, the Simple Shoulder Test (SST), and the Oxford Shoulder Score (OSS) were all supported for use in practice.¹⁸ It is important to note that reliability, validity, and responsiveness of a PROM may vary with the diagnosis or the patient population studied. For example, the SST was found to be responsive in assessing rotator cuff injury but not as useful in assessing shoulder instability or arthritis.¹⁹ Variable responsiveness highlights the need for a diagnosis-based level of PROM customization. For example, patients who undergo a surgical intervention for shoulder instability are given a customized survey, which includes PROMs specific to their condition, such as the Western Ontario Shoulder Instability (WOSI) index.²⁰ For patients with knee instability, similar considerations apply; specific measures such as the Lysholm score and the Tenger Activity Scale capture the impact of injury in physically demanding activities.²¹ When selecting disease-specific PROMs, providers should consult articles like those by Davidson and Keating²² and Bent and colleagues,²³ who present provider-friendly tools that can be used to examine the effectiveness of a PROM, and provide additional background information on selecting disease-specific PROMs. For hip and knee arthroplasty subspecialties, the International Society of Arthroplasty Registries (ISAR) created a working group that determines best practices for PROM collection and identifies PROMs most commonly reported in arthroplasty.²⁴

Questionnaire Length Considerations

When PROMs are used in a practice, a balance must be struck between gathering enough information to determine functionality and limiting the patient burden of questionnaire length. A decision to use several PROMs all at once, at a single data collection point, can lengthen the questionnaire significantly. One study found that, with use of longer questionnaires, patients may lose interest, resulting in decreased reliability and compliance.²⁵ For example, providers who use the long (42-item) Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire to assess knee function are often limited in what other PROMs they may administer at the same time. Efforts to shorten this questionnaire while still capturing necessary information led to the development of the 7-item KOOS Jr, which was validated for use in knee arthroplasty and had its 7 items drawn from the original 42.²⁶ Similarly, the 40-item Hip Disability and Osteoarthritis Outcome Score (HOOS) questionnaire was shortened to the 6-item HOOS Jr, which was validated for use in hip arthroplasty,²⁷ and the generic SF-36 was shortened to the SF-12.¹¹ Providers trying to build an outcomes database while minimizing patient burden should consider using the shorter versions of these questionnaires but should also consider their validity, as KOOS Jr and HOOS Jr have been validated for use only in knee and hip arthroplasty and not in other knee and hip conditions.

PROM Data Collection Considerations

Comprehensive collection of longitudinal PROM data poses many challenges for providers and patients. For providers, the greatest challenges are infrastructure, technology, and the personnel needed to administer and store paper or electronic surveys. For patients, the most common survey completion barriers are questionnaire length, confusing or irrelevant content, and, in the case of some older adults, inability to complete surveys electronically.²⁵

Identifying a nonresponsive or noncompliant patient population is an important issue in collecting PROM data for research or other purposes. A study of factors associated with higher nonresponse rates in elective surgery patients (N = 135,474) found that noncompliance was higher for males, patients under age 55 years, nonwhites, patients in the lowest socioeconomic quintile, patients living alone, patients needing assistance in completing questionnaires, and patients who previously underwent surgery for their condition.²⁸ In a systematic review of methods that increased the response rates of postal and electronic surveys, Edwards and colleagues²⁹ found significantly higher odds of response for patients who were prenotified of the survey, given shorter questionnaires, or given a deadline for survey completion. Of note, response rates were lower when the word survey was used in the subject line of an email. 

PROM distribution has evolved with the rise of technological advances that allow for electronic survey distribution and data capture. Several studies have found that electronically administered PROMs have high response rates.^3,30,31 In a study of patients who underwent total hip arthroplasty, Rolfson and colleagues³² found that response rates were significantly higher for those who were surveyed on paper than for those surveyed over the internet. A randomized controlled study found that, compared with paper surveys, digital tablet surveys effectively and reliably collected PROM data; in addition, digital tablets provided instant data storage, and improved survey completion by requiring that all questions be answered before the survey could be submitted.33 However, age, race/ethnicity, and income disparities in technology use must be considered when administering internet-based follow-up surveys and analyzing data collected with web-based methods.³⁴ A study of total joint arthroplasty candidates found that several groups were less likely to complete electronic PROM questionnaires: patients over age 75 years, Hispanic or black patients, patients with Medicare or Medicaid, patients who previously underwent orthopedic surgery, patients undergoing revision total joint arthroplasty, patients with other comorbidities, and patients whose primary language was not English.³⁵ Providers interested in implementing PROMs must consider their patient population when selecting a method for survey distribution and follow-up. A study found that a majority of PROMs were written at a level many patients may not have understood, because of their literacy level or age; this lack of understanding created a barrier to compliance in many patient populations.³⁶

PROM Limitations and PROMIS Use

Use of PROMs has its limitations. The large variety of PROMs available for use in orthopedic surgery has led to several standardization initiatives. The National Institutes of Health funded the development of PROMIS, a person-centered measures database that evaluates and monitors the physical, social, and emotional health of adults and children.³⁷ The goal of PROMIS is to develop a standardized method of selecting PROMs, so that all medical disciplines and subspecialties can choose an applicable set of questions from the PROMIS question bank and use it in practice. Orthopedic surgery can use questions pertaining to physical functioning of the lower and upper extremities as well as quality of life and mental health. PROMIS physical function questions have been validated for use in several areas of orthopedic surgery.^38-40 A disadvantage of PROMIS is the overgenerality of its questions, which may not be as effective in capturing the implications of specific diagnoses. For example, it is difficult to use generalized questions to determine the implications of a diagnosis such as shoulder instability, which may affect only higher functioning activities or sports. More research on best PROM selection practices is needed in order to either standardize PROMs or move toward use of a single database such as PROMIS.

Future Directions in PROM Applications

PROMs are being used for research and patient engagement, but there are many other applications on the horizon. As already mentioned, predictive modeling is of particular interest. The existence of vast collaborative PROM databases that capture a diverse patient population introduces the possibility of creating models capable of predicting a patient outcome and enhancing shared decision-making.³ Predicting good or excellent patient outcomes for specific patient populations may allow elimination of certain postoperative visits, thereby creating more cost-effective care and reducing the burden of unnecessary clinic visits for both patients and physicians.

As with other healthcare areas, PROM data collection technology is rapidly advancing. Not only has electronic technology almost entirely replaced paper-and-pencil collection methods, but a new method of outcome data collection has been developed: computerized adaptive testing (CAT). CAT uses item-response theory to minimize the number of questions patients must answer in order for validated and reliable outcome scores to be calculated. According to multiple studies, CAT used across several questionnaires has reliably assessed PROMs while minimizing floor and ceiling effects, eliminating irrelevant questions, and shortening survey completion time.^41-43

Besides becoming more patient-friendly and accessible across multiple interfaces (mobile devices and computers), PROMs are also beginning to be integrated into the electronic medical record, allowing easier access to information during chart reviews. Use of statistical and predictive modeling, as described by Chang,³ could give PROMs a role in clinical decision-making. Informing patients of their expected outcome and recovery trajectory—based on demographics, comorbidities, preoperative functional status, and other factors—could influence their decision to undergo surgical intervention. As Halawi and colleagues⁴⁴ pointed out, it is important to discuss patient expectations before surgery, as unrealistic ones can negatively affect outcomes and lead to dissatisfaction. With clinicians having ready access to statistics and models in patient charts, we may see a transformation in clinical practices and surgical decision-making.

Conclusion

PROMs offer many ways to improve research and clinical care in orthopedic surgery. However, implementing PROMs in practice is not without challenges. Interested orthopedic surgeons should select the PROMs that are most appropriate—reliable, validated, and responsive to their patient population. Electronic distribution of PROM questionnaires is effective and allows data to be stored on entry, but orthopedic surgeons must consider their patient population to ensure accurate data capture and compliance in longitudinal surveys. Proper implementation of PROMs in a practice can allow clinicians to formulate expectations for postoperative recovery and set reasonable postoperative goals while engaging patients in improving quality of care.

Genital herpes is a common infection caused by herpes simplex virus type 1 (HSV-1) or herpes simplex virus type 2 (HSV-2). Although life-threatening health consequences of HSV infection after infancy are uncommon, women with genital herpes remain at risk for recurrent symptoms, which can be associated with significant physical and psychosocial distress. These patients also can transmit the disease to their partners and neonates, and have a 2- to 3-fold increased risk of HIV acquisition. In this article, we review the diagnosis and management of genital herpes in pregnant women.

CASE Asymptomatic pregnant patient tests positive for herpes

Sarah is a healthy 32-year-old (G1P0) presenting at 8 weeks’ gestation for her first prenatal visit. She requests HSV testing as she learned that genital herpes is common and it can be transmitted to the baby. You order the HSV-2 IgG assay from your laboratory, which performs the HerpeSelect HSV-2 enzyme immunoassay as the standard test. The test result is positive, with an index value of 2.2 (the manufacturer defines an index value >1.1 as positive). Repeat testing in 4 weeks returns positive results again, with an index value of 2.8.

The patient is distressed at this news. She has no history of genital lesions or symptoms consistent with genital herpes and is worried that her husband has been unfaithful. How would you manage this case?

How prevalent is HSV?

Genital herpes is a chronic viral infection transmitted through close contact with a person who is shedding the virus from genital or oral mucosa. In the United States, the National Health and Nutrition Examination Survey indicated an HSV-2 seroprevalence of 16% among persons aged 14 to 49 in 2005–2010, a decline from 21% in 1988–1991.¹ The prevalence among women is twice as high as among men, at 20% versus 11%, respectively. Among those with HSV-2, 87% are not aware that they are infected; they are at risk of infecting their partners, however.¹

In the same age group, the prevalence of HSV-1 is 54%.² The seroprevalence of HSV-1 in adolescents declined from 39% in 1999–2004 to 30% in 2005–2010, resulting in a high number of young people who are seronegative at the time of sexual debut. Concurrently, genital HSV-1 has emerged as a frequent cause of first-episode genital herpes, often associated with oral-genital contact during sexual debut.^2,3

When evaluating patients for possible genital herpes provide general educational messages regarding HSV infection and obtain a detailed medical and sexual history to determine the best diagnostic approach.

What are the clinical features of genital HSV infection?

The clinical manifestations of genital herpes vary according to whether the infection is primary, nonprimary first episode, or recurrent.

Primary infection. During primary infection,which occurs 4 to 12 days after sexual exposure and in the absence of pre-existing antibodies to HSV-1 or HSV-2, patients may experience genital and systemic symptoms (FIGURE and TABLE 1). Since this infection usually occurs in otherwise healthy people, for many, this is the most severe disease that they have experienced. However, most patients with primary infection develop mild, atypical, or completely asymptomatic presentation and are not diagnosed at the time of HSV acquisition. Whether primary infection is caused by HSV-1 or HSV-2 cannot be differentiated based on the clinical presentation alone.

Nonprimary first episode infection. In a nonprimary infection, newly acquired infection with HSV-1 or HSV-2 occurs in a person with pre-existing antibodies to the other virus. Almost always, this means new HSV-2 infection in a HSV-1 seropositive person, as prior HSV-2 infection appears to protect against HSV-1 acquisition. In general, the clinical presentation of nonprimary infection is somewhat milder and the rate of complications is lower, but clinically the overlap is great, and antibody tests are needed to define whether the patient has primary or nonprimary infection.⁴

Recurrent genital herpes infection occurs in most patients with genital herpes. The rate of recurrence is low in patients with genital HSV-1 and often high in patients with genital HSV-2 infection. The median number of recurrences is 1 in the first year of genital HSV-1 infection, and many patients will not have any recurrences following the first year. By contrast, in patients with genital HSV-2 infection, the median number of recurrences is 4, and a high rate of recurrences can continue for many years. Prodromal symptoms (localized irritation, paresthesias, and pruritus) can precede recurrences, which usually present with fewer lesions and last a shorter time than primary infection. Recurrent genital lesions tend to heal in approximately 5 to 10 days in the absence of antiviral treatment, and systemic symptoms are uncommon.⁵

Asymptomatic viral shedding. After resolution of a primary HSV infection, people shed the virus in the genital tract despite symptom absence. Asymptomatic shedding tends to be more frequent and prolonged with primary genital HSV-2 infection compared with HSV-1 infection.^6,7 The frequency of HSV shedding is highest in the first year of infection, and decreases subsequently.⁸ However, it is likely to persist intermittently for many years. Because the natural history is so strikingly different in genital HSV-1 versus HSV-2, identification of the viral type is important for prognostic information.

The first HSV episode does not necessarily indicate a new or recent infection—in about 25% of persons it represents the first recognized genital herpes episode. Additional serologic and virologic evaluation can be pursued to determine if the first episode represents a new infection.

Read about the diagnostic tests for genital HSV.

What diagnostic tests are available for genital herpes?

Most HSV infections are clinically silent. Therefore, laboratory tests are required to diagnose the infection. Even if symptoms are present, diagnoses based only on clinical presentation have a 20% false-positive rate. Always confirm diagnosis by laboratory assay.⁹ Furthermore, couples that are discordant for HSV-2 by history are often concordant by serologic assays, as the transmission already has occurred but was not recognized. In these cases, the direction of transmission cannot be determined, and stable couples often experience relief learning that they are not discordant.

Related article:
Effective treatment of recurrent bacterial vaginosis

Several laboratory tools for HSV diagnosis based on direct viral detection and antibody detection can be used in clinical settings (TABLE 2). Among patients with symptomatic genital herpes, a sample from the lesion can be used to confirm and identify viral type. Because polymerase chain reaction (PCR) is substantially more sensitive than viral culture and increasingly available it has emerged as the preferred test.⁹ Viral culture is highly specific (>99%), but sensitivity varies according to collection technique and stage of the lesions. (The test is less sensitive when lesions are healing.)^9,10 Antigen detection by immunofluorescence (direct fluorescent antibody) detects HSV from active lesions with high specificity, but sensitivity is low. Cytologic identification of infected cells (using Tzanck or Pap test) has limited utility for diagnosis due to low sensitivity and specificity.⁹

Type-specific antibodies to HSV develop during the first several weeks after acquisition and persist indefinitely.¹¹ Most accurate type-specific serologic tests are based on detection of glycoprotein G1 and glycoprotein G2 for HSV-1 and HSV-2, respectively.

HerpeSelect HSV-2 enzyme immunoassay (EIA) is one of the most commonly used tests in the United States. The manufacturer considers results with index values 1.1 or greater as showing HSV-2 infection. Unfortunately, low positive results, often with a defined index value of 1.1 to 3.5, are frequently false positive. These low positive values should be confirmed with another test, such as Western blot.⁹

Western blot has been considered the gold standard assay for HSV-1 and HSV-2 antibody detection; this test is available at the University of Washington in Seattle. When comparing the HSV-1 EIA and HSV-2 EIA with the Western blot assay in clinical practice, the estimated sensitivity and specificity are 70.2% and 91.6%, respectively, for HSV-1 and 91.9% and 57.4%, respectively, for HSV-2.¹²

HerpeSelect HSV-2 Immunoblot testing should not be considered as confirmatory because this assay detects the same antigen as the HSV-2 EIA. Serologic tests based on detection of HSV-IgM should not be used for diagnosis of genital herpes as IgM response can present during a new infection or HSV reactivation and because IgM responses are not type-specific. Clearly, more accurate commercial type-specific antibody tests are needed.

Specific HSV antibodies can take up to 12 weeks to develop. Therefore, repeat serologic testing for patients in whom initial HSV antibody results are negative yet recent genital herpes acquisition is suspected.¹¹ A confirmed positive HSV-2 antibody test indicates anogenital infection, even in a person who lacks genital symptoms. This finding became evident through a study of 53 HSV-2 seropositive patients who lacked a history of genital herpes. Patients were followed for 3 months, and all but 1 developed either virologic or clinical (or both) evidence of genital herpes.¹³

In the absence of genital or orolabial symptoms among individuals with positive HSV-1, serologic testing cannot distinguish anogenital from orolabial infection. Most of these infections may represent oral HSV-1 infection; however, given increasing occurrence of genital HSV-1 infection, this could also represent a genital infection.

What are the clinical uses of type-specific HSV serology?

Type-specific serologic tests are helpful in diagnosing patients with atypical or asymptomatic infection and managing the care of persons whose sex partners have genital herpes. Serologic testing can be useful to confirm a clinical diagnosis of HSV, to determine whether atypical lesions or symptoms are attributable to HSV, and as part of evaluation for sexually transmitted diseases in select patients. Screening for HSV-1 and HSV-2 in the general population is not supported by the Centers for Disease Control and Prevention (CDC) or the US Preventive Services Task Force (USPSTF) for several reasons^9,10:

• suboptimal performance of commercial HSV antibody tests
• low positive predictive value of these tests in low prevalence HSV settings
• lack of widely available confirmatory testing
• lack of cost-effectiveness
• potential for psychological harm.

Read about treating HSV infection during pregnancy.

Case Continued…

Because Sarah did not have a history of genital herpes, a serum sample was tested by the University of Washington Western blot. The results indicated that Sarah is seronegative for HSV-1 and HSV-2.

Sarah, who is now at 16 weeks’ gestation, returns for evaluation of new genital pain. On examination, she has several shallow ulcerations on the labia and bilateral tender inguinal adenopathy. Her husband recently had cold sores. She is anxious and would like to know if she has genital herpes and if her baby is at risk for HSV infection. You swab the base of a lesion for HSV PCR testing and start antiviral treatment.

Treating HSV infection during pregnancy

Women presenting with a new genital ulcer consistent with HSV should receive empiric antiviral treatment while awaiting confirmatory diagnostic laboratory testing, even during pregnancy. Antiviral therapy with acyclovir, valacyclovir, and famciclovir is the backbone of management of most symptomatic patients with herpes. Antiviral drugs can reduce signs and symptoms of first or recurrent genital herpes and can be used for daily suppressive therapy to prevent recurrences. These drugs do not eradicate the infection or alter the risk of frequency or severity after the drug is discontinued.

Antiviral advantages/disadvantages. Acyclovir is the least expensive drug, but valacyclovir is the most convenient therapy given its less frequent dosing. Acyclovir and valacyclovir are equally efficacious in treating first-episode genital herpes infection with respect to duration of viral shedding, time of healing, duration of pain, and time to symptom clearance. Two randomized clinical trials showed similar benefits of acyclovir and valacyclovir for suppressive therapy management of genital herpes.^14,15 Only 1 study compared the efficacy of famciclovir to valacyclovir for suppression and showed that valacyclovir was more effective.¹⁶ The cost of famciclovir is usually higher, and it has the least data on use in pregnant women. Acyclovir therapy can be safely used throughout pregnancy and during breastfeeding.⁹ Antiviral regimens for the treatment of genital HSV in pregnant and nonpregnant women recommended by the CDC are summarized in TABLE 3.¹⁷

Related article:
5 ways to reduce infection risk during pregnancy

Will your patient’s infant develop neonatal herpes infection?

Neonatal herpes is a potentially devastating infection that results from exposure to HSV from the maternal genital tract at vaginal delivery. Most cases occur in infants born to women who lack a history of genital herpes.¹⁸ In a large cohort study conducted in Washington State, isolation of HSV at the time of labor was strongly associated with vertical transmission (odds ratio [OR], 346).¹⁹ The risk of neonatal herpes increased among women shedding HSV-1 compared with HSV-2 (OR, 16.5). The highest risk of transmission to the neonate is in women who acquire genital herpes in a period close to the delivery (30% to 50% risk of transmission), compared with women with a prenatal history of herpes or who acquired herpes early in pregnancy (about 1% to 3% risk of transmission), most likely due to protective HSV-specific maternal antibodies and lower viral load during reactivation versus primary infection.¹⁸

Neonatal HSV-1 infection also has been reported in neonates born to women with primary HSV-1 gingivostomatitis during pregnancy; 70% of these women had oral clinical symptoms during the peripartum period.²⁰ Potential mechanisms are exposure to infected genital secretions, direct maternal hematogenous spread, or oral shedding from close contacts.

Although prenatal HSV screening is not recommended by the CDC or USPSTF, serologic testing could be helpful when identifying appropriate pregnancy management for women with a prior history of HSV infection. It also could be beneficial in identifying women without HSV to guide counseling prevention for HSV acquisition. In patients presenting with active genital lesions, viral-specific diagnostic evaluation should be obtained. In those with a history of laboratory confirmed genital herpes, no additional testing is warranted.

Preventing neonatal herpes

There are no prevention strategies for neonatal herpes in the United States, and the incidence of neonatal herpes has not changed in several decades.¹⁰ The current treatment guidelines focus on managing women who may be at risk for HSV acquisition during pregnancy and the management of genital lesions in women during pregnancy.^9,10,21

When the partner has HSV. Women who have no history of genital herpes or who are seronegative for HSV-2 should avoid intercourse during the third trimester with a partner known to have genital herpes.⁹ Those who have no history of orolabial herpes or who are seronegative for HSV-1 and have a seropositive partner should avoid receptive oral-genital contact and genital intercourse.⁹ Condoms can reduce but not eliminate the risk of HSV transmission; to effectively avoid genital herpes infection, abstinence is recommended.

When the patient has HSV. When managing the care of a pregnant woman with genital herpes evaluate for clinical symptoms and timing of infection or recurrence relative to time of delivery:

• Monitor women with a mild recurrence of HSV during the first 35 weeks of pregnancy without antiviral treatment, as most of the recurrent episodes of genital herpes are short.
• Consider antivirals for women with severe symptoms or multiple recurrences.
• Offer women with a history of genital lesions suppressive antiviral therapy at 36 weeks of gestation until delivery.²¹

In a meta-analysis of 7 randomized trials, 1,249 women with a history of genital herpes prior to or during pregnancy received prophylaxis with either acyclovir or valacyclovir versus placebo or no treatment at 36 weeks of gestation. Antiviral therapy reduced the risk of HSV recurrence at delivery (relative risk [RR], 0.28), cesarean delivery in those with recurrent genital herpes (RR, 0.3), and asymptomatic shedding at delivery (RR, 0.14).²² No data are available regarding the effectiveness of this approach to prevention of neonatal HSV, and case reports confirm neonatal HSV in infants born to women who received suppressive antiviral therapy at the end of pregnancy.²³

When cesarean delivery is warranted. At the time of delivery, ask all women about symptoms of genital herpes, including prodromal symptoms, and examine them for genital lesions. For women with active lesions or prodromal symptoms, offer cesarean delivery at the onset of labor or rupture of membranes—this recommendation is supported by the CDC and the American College of Obstetricians and Gynecologists.^9,21 The protective effect of cesarean delivery was evaluated in a large cohort study that found: among women who were shedding HSV at the time of delivery, neonates born by cesarean delivery were less likely to develop HSV infection compared with those born through vaginal delivery (1.2% vs 7.7%, respectively).¹⁹ Cesarean delivery is not indicated in patients with a history of HSV without clinical recurrence or prodrome at delivery, as such women have a very low risk of transmitting the infection to the neonate.²⁴

Avoid transcervical antepartum obstetric procedures to reduce the risk of placenta or membrane HSV infection; however, transabdominal invasive procedures can be performed safely, even in the presence of active genital lesions.²¹ Intrapartum procedures that can cause fetal skin disruption, such as use of fetal scalp electrode or forceps, are risk factors for HSV transmission and should be avoided in women with a history of genital herpes.

Related articles:
8 common questions about newborn circumcision

Case Resolved

Sarah’s genital lesion PCR results returned positive for HSV-1. She probably acquired the infection from oral-genital sex with her husband who likely has oral HSV-1, given the history of cold sores. You treat Sarah with acyclovir 400 mg 3 times per day for 7 days. At 36 weeks’ gestation, Sarah begins suppressive antiviral therapy until delivery. She spontaneously labors at 39 weeks’ gestation; at that time, she has no genital lesions and she delivers vaginally a healthy baby.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Genital herpes is a common infection caused by herpes simplex virus type 1 (HSV-1) or herpes simplex virus type 2 (HSV-2). Although life-threatening health consequences of HSV infection after infancy are uncommon, women with genital herpes remain at risk for recurrent symptoms, which can be associated with significant physical and psychosocial distress. These patients also can transmit the disease to their partners and neonates, and have a 2- to 3-fold increased risk of HIV acquisition. In this article, we review the diagnosis and management of genital herpes in pregnant women.

CASE Asymptomatic pregnant patient tests positive for herpes

Sarah is a healthy 32-year-old (G1P0) presenting at 8 weeks’ gestation for her first prenatal visit. She requests HSV testing as she learned that genital herpes is common and it can be transmitted to the baby. You order the HSV-2 IgG assay from your laboratory, which performs the HerpeSelect HSV-2 enzyme immunoassay as the standard test. The test result is positive, with an index value of 2.2 (the manufacturer defines an index value >1.1 as positive). Repeat testing in 4 weeks returns positive results again, with an index value of 2.8.

The patient is distressed at this news. She has no history of genital lesions or symptoms consistent with genital herpes and is worried that her husband has been unfaithful. How would you manage this case?

How prevalent is HSV?

Genital herpes is a chronic viral infection transmitted through close contact with a person who is shedding the virus from genital or oral mucosa. In the United States, the National Health and Nutrition Examination Survey indicated an HSV-2 seroprevalence of 16% among persons aged 14 to 49 in 2005–2010, a decline from 21% in 1988–1991.¹ The prevalence among women is twice as high as among men, at 20% versus 11%, respectively. Among those with HSV-2, 87% are not aware that they are infected; they are at risk of infecting their partners, however.¹

In the same age group, the prevalence of HSV-1 is 54%.² The seroprevalence of HSV-1 in adolescents declined from 39% in 1999–2004 to 30% in 2005–2010, resulting in a high number of young people who are seronegative at the time of sexual debut. Concurrently, genital HSV-1 has emerged as a frequent cause of first-episode genital herpes, often associated with oral-genital contact during sexual debut.^2,3

When evaluating patients for possible genital herpes provide general educational messages regarding HSV infection and obtain a detailed medical and sexual history to determine the best diagnostic approach.

What are the clinical features of genital HSV infection?

The clinical manifestations of genital herpes vary according to whether the infection is primary, nonprimary first episode, or recurrent.

Primary infection. During primary infection,which occurs 4 to 12 days after sexual exposure and in the absence of pre-existing antibodies to HSV-1 or HSV-2, patients may experience genital and systemic symptoms (FIGURE and TABLE 1). Since this infection usually occurs in otherwise healthy people, for many, this is the most severe disease that they have experienced. However, most patients with primary infection develop mild, atypical, or completely asymptomatic presentation and are not diagnosed at the time of HSV acquisition. Whether primary infection is caused by HSV-1 or HSV-2 cannot be differentiated based on the clinical presentation alone.

Nonprimary first episode infection. In a nonprimary infection, newly acquired infection with HSV-1 or HSV-2 occurs in a person with pre-existing antibodies to the other virus. Almost always, this means new HSV-2 infection in a HSV-1 seropositive person, as prior HSV-2 infection appears to protect against HSV-1 acquisition. In general, the clinical presentation of nonprimary infection is somewhat milder and the rate of complications is lower, but clinically the overlap is great, and antibody tests are needed to define whether the patient has primary or nonprimary infection.⁴

Recurrent genital herpes infection occurs in most patients with genital herpes. The rate of recurrence is low in patients with genital HSV-1 and often high in patients with genital HSV-2 infection. The median number of recurrences is 1 in the first year of genital HSV-1 infection, and many patients will not have any recurrences following the first year. By contrast, in patients with genital HSV-2 infection, the median number of recurrences is 4, and a high rate of recurrences can continue for many years. Prodromal symptoms (localized irritation, paresthesias, and pruritus) can precede recurrences, which usually present with fewer lesions and last a shorter time than primary infection. Recurrent genital lesions tend to heal in approximately 5 to 10 days in the absence of antiviral treatment, and systemic symptoms are uncommon.⁵

Asymptomatic viral shedding. After resolution of a primary HSV infection, people shed the virus in the genital tract despite symptom absence. Asymptomatic shedding tends to be more frequent and prolonged with primary genital HSV-2 infection compared with HSV-1 infection.^6,7 The frequency of HSV shedding is highest in the first year of infection, and decreases subsequently.⁸ However, it is likely to persist intermittently for many years. Because the natural history is so strikingly different in genital HSV-1 versus HSV-2, identification of the viral type is important for prognostic information.

The first HSV episode does not necessarily indicate a new or recent infection—in about 25% of persons it represents the first recognized genital herpes episode. Additional serologic and virologic evaluation can be pursued to determine if the first episode represents a new infection.

Read about the diagnostic tests for genital HSV.

What diagnostic tests are available for genital herpes?

Most HSV infections are clinically silent. Therefore, laboratory tests are required to diagnose the infection. Even if symptoms are present, diagnoses based only on clinical presentation have a 20% false-positive rate. Always confirm diagnosis by laboratory assay.⁹ Furthermore, couples that are discordant for HSV-2 by history are often concordant by serologic assays, as the transmission already has occurred but was not recognized. In these cases, the direction of transmission cannot be determined, and stable couples often experience relief learning that they are not discordant.

Related article:
Effective treatment of recurrent bacterial vaginosis

Several laboratory tools for HSV diagnosis based on direct viral detection and antibody detection can be used in clinical settings (TABLE 2). Among patients with symptomatic genital herpes, a sample from the lesion can be used to confirm and identify viral type. Because polymerase chain reaction (PCR) is substantially more sensitive than viral culture and increasingly available it has emerged as the preferred test.⁹ Viral culture is highly specific (>99%), but sensitivity varies according to collection technique and stage of the lesions. (The test is less sensitive when lesions are healing.)^9,10 Antigen detection by immunofluorescence (direct fluorescent antibody) detects HSV from active lesions with high specificity, but sensitivity is low. Cytologic identification of infected cells (using Tzanck or Pap test) has limited utility for diagnosis due to low sensitivity and specificity.⁹

Type-specific antibodies to HSV develop during the first several weeks after acquisition and persist indefinitely.¹¹ Most accurate type-specific serologic tests are based on detection of glycoprotein G1 and glycoprotein G2 for HSV-1 and HSV-2, respectively.

HerpeSelect HSV-2 enzyme immunoassay (EIA) is one of the most commonly used tests in the United States. The manufacturer considers results with index values 1.1 or greater as showing HSV-2 infection. Unfortunately, low positive results, often with a defined index value of 1.1 to 3.5, are frequently false positive. These low positive values should be confirmed with another test, such as Western blot.⁹

Western blot has been considered the gold standard assay for HSV-1 and HSV-2 antibody detection; this test is available at the University of Washington in Seattle. When comparing the HSV-1 EIA and HSV-2 EIA with the Western blot assay in clinical practice, the estimated sensitivity and specificity are 70.2% and 91.6%, respectively, for HSV-1 and 91.9% and 57.4%, respectively, for HSV-2.¹²

HerpeSelect HSV-2 Immunoblot testing should not be considered as confirmatory because this assay detects the same antigen as the HSV-2 EIA. Serologic tests based on detection of HSV-IgM should not be used for diagnosis of genital herpes as IgM response can present during a new infection or HSV reactivation and because IgM responses are not type-specific. Clearly, more accurate commercial type-specific antibody tests are needed.

Specific HSV antibodies can take up to 12 weeks to develop. Therefore, repeat serologic testing for patients in whom initial HSV antibody results are negative yet recent genital herpes acquisition is suspected.¹¹ A confirmed positive HSV-2 antibody test indicates anogenital infection, even in a person who lacks genital symptoms. This finding became evident through a study of 53 HSV-2 seropositive patients who lacked a history of genital herpes. Patients were followed for 3 months, and all but 1 developed either virologic or clinical (or both) evidence of genital herpes.¹³

In the absence of genital or orolabial symptoms among individuals with positive HSV-1, serologic testing cannot distinguish anogenital from orolabial infection. Most of these infections may represent oral HSV-1 infection; however, given increasing occurrence of genital HSV-1 infection, this could also represent a genital infection.

What are the clinical uses of type-specific HSV serology?

Type-specific serologic tests are helpful in diagnosing patients with atypical or asymptomatic infection and managing the care of persons whose sex partners have genital herpes. Serologic testing can be useful to confirm a clinical diagnosis of HSV, to determine whether atypical lesions or symptoms are attributable to HSV, and as part of evaluation for sexually transmitted diseases in select patients. Screening for HSV-1 and HSV-2 in the general population is not supported by the Centers for Disease Control and Prevention (CDC) or the US Preventive Services Task Force (USPSTF) for several reasons^9,10:

• suboptimal performance of commercial HSV antibody tests
• low positive predictive value of these tests in low prevalence HSV settings
• lack of widely available confirmatory testing
• lack of cost-effectiveness
• potential for psychological harm.

Read about treating HSV infection during pregnancy.

Case Continued…

Because Sarah did not have a history of genital herpes, a serum sample was tested by the University of Washington Western blot. The results indicated that Sarah is seronegative for HSV-1 and HSV-2.

Sarah, who is now at 16 weeks’ gestation, returns for evaluation of new genital pain. On examination, she has several shallow ulcerations on the labia and bilateral tender inguinal adenopathy. Her husband recently had cold sores. She is anxious and would like to know if she has genital herpes and if her baby is at risk for HSV infection. You swab the base of a lesion for HSV PCR testing and start antiviral treatment.

Treating HSV infection during pregnancy

Women presenting with a new genital ulcer consistent with HSV should receive empiric antiviral treatment while awaiting confirmatory diagnostic laboratory testing, even during pregnancy. Antiviral therapy with acyclovir, valacyclovir, and famciclovir is the backbone of management of most symptomatic patients with herpes. Antiviral drugs can reduce signs and symptoms of first or recurrent genital herpes and can be used for daily suppressive therapy to prevent recurrences. These drugs do not eradicate the infection or alter the risk of frequency or severity after the drug is discontinued.

Antiviral advantages/disadvantages. Acyclovir is the least expensive drug, but valacyclovir is the most convenient therapy given its less frequent dosing. Acyclovir and valacyclovir are equally efficacious in treating first-episode genital herpes infection with respect to duration of viral shedding, time of healing, duration of pain, and time to symptom clearance. Two randomized clinical trials showed similar benefits of acyclovir and valacyclovir for suppressive therapy management of genital herpes.^14,15 Only 1 study compared the efficacy of famciclovir to valacyclovir for suppression and showed that valacyclovir was more effective.¹⁶ The cost of famciclovir is usually higher, and it has the least data on use in pregnant women. Acyclovir therapy can be safely used throughout pregnancy and during breastfeeding.⁹ Antiviral regimens for the treatment of genital HSV in pregnant and nonpregnant women recommended by the CDC are summarized in TABLE 3.¹⁷

Related article:
5 ways to reduce infection risk during pregnancy

Will your patient’s infant develop neonatal herpes infection?

Neonatal herpes is a potentially devastating infection that results from exposure to HSV from the maternal genital tract at vaginal delivery. Most cases occur in infants born to women who lack a history of genital herpes.¹⁸ In a large cohort study conducted in Washington State, isolation of HSV at the time of labor was strongly associated with vertical transmission (odds ratio [OR], 346).¹⁹ The risk of neonatal herpes increased among women shedding HSV-1 compared with HSV-2 (OR, 16.5). The highest risk of transmission to the neonate is in women who acquire genital herpes in a period close to the delivery (30% to 50% risk of transmission), compared with women with a prenatal history of herpes or who acquired herpes early in pregnancy (about 1% to 3% risk of transmission), most likely due to protective HSV-specific maternal antibodies and lower viral load during reactivation versus primary infection.¹⁸

Neonatal HSV-1 infection also has been reported in neonates born to women with primary HSV-1 gingivostomatitis during pregnancy; 70% of these women had oral clinical symptoms during the peripartum period.²⁰ Potential mechanisms are exposure to infected genital secretions, direct maternal hematogenous spread, or oral shedding from close contacts.

Although prenatal HSV screening is not recommended by the CDC or USPSTF, serologic testing could be helpful when identifying appropriate pregnancy management for women with a prior history of HSV infection. It also could be beneficial in identifying women without HSV to guide counseling prevention for HSV acquisition. In patients presenting with active genital lesions, viral-specific diagnostic evaluation should be obtained. In those with a history of laboratory confirmed genital herpes, no additional testing is warranted.

Preventing neonatal herpes

There are no prevention strategies for neonatal herpes in the United States, and the incidence of neonatal herpes has not changed in several decades.¹⁰ The current treatment guidelines focus on managing women who may be at risk for HSV acquisition during pregnancy and the management of genital lesions in women during pregnancy.^9,10,21

When the partner has HSV. Women who have no history of genital herpes or who are seronegative for HSV-2 should avoid intercourse during the third trimester with a partner known to have genital herpes.⁹ Those who have no history of orolabial herpes or who are seronegative for HSV-1 and have a seropositive partner should avoid receptive oral-genital contact and genital intercourse.⁹ Condoms can reduce but not eliminate the risk of HSV transmission; to effectively avoid genital herpes infection, abstinence is recommended.

When the patient has HSV. When managing the care of a pregnant woman with genital herpes evaluate for clinical symptoms and timing of infection or recurrence relative to time of delivery:

• Monitor women with a mild recurrence of HSV during the first 35 weeks of pregnancy without antiviral treatment, as most of the recurrent episodes of genital herpes are short.
• Consider antivirals for women with severe symptoms or multiple recurrences.
• Offer women with a history of genital lesions suppressive antiviral therapy at 36 weeks of gestation until delivery.²¹

In a meta-analysis of 7 randomized trials, 1,249 women with a history of genital herpes prior to or during pregnancy received prophylaxis with either acyclovir or valacyclovir versus placebo or no treatment at 36 weeks of gestation. Antiviral therapy reduced the risk of HSV recurrence at delivery (relative risk [RR], 0.28), cesarean delivery in those with recurrent genital herpes (RR, 0.3), and asymptomatic shedding at delivery (RR, 0.14).²² No data are available regarding the effectiveness of this approach to prevention of neonatal HSV, and case reports confirm neonatal HSV in infants born to women who received suppressive antiviral therapy at the end of pregnancy.²³

When cesarean delivery is warranted. At the time of delivery, ask all women about symptoms of genital herpes, including prodromal symptoms, and examine them for genital lesions. For women with active lesions or prodromal symptoms, offer cesarean delivery at the onset of labor or rupture of membranes—this recommendation is supported by the CDC and the American College of Obstetricians and Gynecologists.^9,21 The protective effect of cesarean delivery was evaluated in a large cohort study that found: among women who were shedding HSV at the time of delivery, neonates born by cesarean delivery were less likely to develop HSV infection compared with those born through vaginal delivery (1.2% vs 7.7%, respectively).¹⁹ Cesarean delivery is not indicated in patients with a history of HSV without clinical recurrence or prodrome at delivery, as such women have a very low risk of transmitting the infection to the neonate.²⁴

Avoid transcervical antepartum obstetric procedures to reduce the risk of placenta or membrane HSV infection; however, transabdominal invasive procedures can be performed safely, even in the presence of active genital lesions.²¹ Intrapartum procedures that can cause fetal skin disruption, such as use of fetal scalp electrode or forceps, are risk factors for HSV transmission and should be avoided in women with a history of genital herpes.

Related articles:
8 common questions about newborn circumcision

Case Resolved

Sarah’s genital lesion PCR results returned positive for HSV-1. She probably acquired the infection from oral-genital sex with her husband who likely has oral HSV-1, given the history of cold sores. You treat Sarah with acyclovir 400 mg 3 times per day for 7 days. At 36 weeks’ gestation, Sarah begins suppressive antiviral therapy until delivery. She spontaneously labors at 39 weeks’ gestation; at that time, she has no genital lesions and she delivers vaginally a healthy baby.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Genital herpes is a common infection caused by herpes simplex virus type 1 (HSV-1) or herpes simplex virus type 2 (HSV-2). Although life-threatening health consequences of HSV infection after infancy are uncommon, women with genital herpes remain at risk for recurrent symptoms, which can be associated with significant physical and psychosocial distress. These patients also can transmit the disease to their partners and neonates, and have a 2- to 3-fold increased risk of HIV acquisition. In this article, we review the diagnosis and management of genital herpes in pregnant women.

CASE Asymptomatic pregnant patient tests positive for herpes

Sarah is a healthy 32-year-old (G1P0) presenting at 8 weeks’ gestation for her first prenatal visit. She requests HSV testing as she learned that genital herpes is common and it can be transmitted to the baby. You order the HSV-2 IgG assay from your laboratory, which performs the HerpeSelect HSV-2 enzyme immunoassay as the standard test. The test result is positive, with an index value of 2.2 (the manufacturer defines an index value >1.1 as positive). Repeat testing in 4 weeks returns positive results again, with an index value of 2.8.

The patient is distressed at this news. She has no history of genital lesions or symptoms consistent with genital herpes and is worried that her husband has been unfaithful. How would you manage this case?

How prevalent is HSV?

Genital herpes is a chronic viral infection transmitted through close contact with a person who is shedding the virus from genital or oral mucosa. In the United States, the National Health and Nutrition Examination Survey indicated an HSV-2 seroprevalence of 16% among persons aged 14 to 49 in 2005–2010, a decline from 21% in 1988–1991.¹ The prevalence among women is twice as high as among men, at 20% versus 11%, respectively. Among those with HSV-2, 87% are not aware that they are infected; they are at risk of infecting their partners, however.¹

In the same age group, the prevalence of HSV-1 is 54%.² The seroprevalence of HSV-1 in adolescents declined from 39% in 1999–2004 to 30% in 2005–2010, resulting in a high number of young people who are seronegative at the time of sexual debut. Concurrently, genital HSV-1 has emerged as a frequent cause of first-episode genital herpes, often associated with oral-genital contact during sexual debut.^2,3

When evaluating patients for possible genital herpes provide general educational messages regarding HSV infection and obtain a detailed medical and sexual history to determine the best diagnostic approach.

What are the clinical features of genital HSV infection?

The clinical manifestations of genital herpes vary according to whether the infection is primary, nonprimary first episode, or recurrent.

Primary infection. During primary infection,which occurs 4 to 12 days after sexual exposure and in the absence of pre-existing antibodies to HSV-1 or HSV-2, patients may experience genital and systemic symptoms (FIGURE and TABLE 1). Since this infection usually occurs in otherwise healthy people, for many, this is the most severe disease that they have experienced. However, most patients with primary infection develop mild, atypical, or completely asymptomatic presentation and are not diagnosed at the time of HSV acquisition. Whether primary infection is caused by HSV-1 or HSV-2 cannot be differentiated based on the clinical presentation alone.

Nonprimary first episode infection. In a nonprimary infection, newly acquired infection with HSV-1 or HSV-2 occurs in a person with pre-existing antibodies to the other virus. Almost always, this means new HSV-2 infection in a HSV-1 seropositive person, as prior HSV-2 infection appears to protect against HSV-1 acquisition. In general, the clinical presentation of nonprimary infection is somewhat milder and the rate of complications is lower, but clinically the overlap is great, and antibody tests are needed to define whether the patient has primary or nonprimary infection.⁴

Recurrent genital herpes infection occurs in most patients with genital herpes. The rate of recurrence is low in patients with genital HSV-1 and often high in patients with genital HSV-2 infection. The median number of recurrences is 1 in the first year of genital HSV-1 infection, and many patients will not have any recurrences following the first year. By contrast, in patients with genital HSV-2 infection, the median number of recurrences is 4, and a high rate of recurrences can continue for many years. Prodromal symptoms (localized irritation, paresthesias, and pruritus) can precede recurrences, which usually present with fewer lesions and last a shorter time than primary infection. Recurrent genital lesions tend to heal in approximately 5 to 10 days in the absence of antiviral treatment, and systemic symptoms are uncommon.⁵

Asymptomatic viral shedding. After resolution of a primary HSV infection, people shed the virus in the genital tract despite symptom absence. Asymptomatic shedding tends to be more frequent and prolonged with primary genital HSV-2 infection compared with HSV-1 infection.^6,7 The frequency of HSV shedding is highest in the first year of infection, and decreases subsequently.⁸ However, it is likely to persist intermittently for many years. Because the natural history is so strikingly different in genital HSV-1 versus HSV-2, identification of the viral type is important for prognostic information.

The first HSV episode does not necessarily indicate a new or recent infection—in about 25% of persons it represents the first recognized genital herpes episode. Additional serologic and virologic evaluation can be pursued to determine if the first episode represents a new infection.

Read about the diagnostic tests for genital HSV.

What diagnostic tests are available for genital herpes?

Most HSV infections are clinically silent. Therefore, laboratory tests are required to diagnose the infection. Even if symptoms are present, diagnoses based only on clinical presentation have a 20% false-positive rate. Always confirm diagnosis by laboratory assay.⁹ Furthermore, couples that are discordant for HSV-2 by history are often concordant by serologic assays, as the transmission already has occurred but was not recognized. In these cases, the direction of transmission cannot be determined, and stable couples often experience relief learning that they are not discordant.

Related article:
Effective treatment of recurrent bacterial vaginosis

Several laboratory tools for HSV diagnosis based on direct viral detection and antibody detection can be used in clinical settings (TABLE 2). Among patients with symptomatic genital herpes, a sample from the lesion can be used to confirm and identify viral type. Because polymerase chain reaction (PCR) is substantially more sensitive than viral culture and increasingly available it has emerged as the preferred test.⁹ Viral culture is highly specific (>99%), but sensitivity varies according to collection technique and stage of the lesions. (The test is less sensitive when lesions are healing.)^9,10 Antigen detection by immunofluorescence (direct fluorescent antibody) detects HSV from active lesions with high specificity, but sensitivity is low. Cytologic identification of infected cells (using Tzanck or Pap test) has limited utility for diagnosis due to low sensitivity and specificity.⁹

Type-specific antibodies to HSV develop during the first several weeks after acquisition and persist indefinitely.¹¹ Most accurate type-specific serologic tests are based on detection of glycoprotein G1 and glycoprotein G2 for HSV-1 and HSV-2, respectively.

HerpeSelect HSV-2 enzyme immunoassay (EIA) is one of the most commonly used tests in the United States. The manufacturer considers results with index values 1.1 or greater as showing HSV-2 infection. Unfortunately, low positive results, often with a defined index value of 1.1 to 3.5, are frequently false positive. These low positive values should be confirmed with another test, such as Western blot.⁹

Western blot has been considered the gold standard assay for HSV-1 and HSV-2 antibody detection; this test is available at the University of Washington in Seattle. When comparing the HSV-1 EIA and HSV-2 EIA with the Western blot assay in clinical practice, the estimated sensitivity and specificity are 70.2% and 91.6%, respectively, for HSV-1 and 91.9% and 57.4%, respectively, for HSV-2.¹²

HerpeSelect HSV-2 Immunoblot testing should not be considered as confirmatory because this assay detects the same antigen as the HSV-2 EIA. Serologic tests based on detection of HSV-IgM should not be used for diagnosis of genital herpes as IgM response can present during a new infection or HSV reactivation and because IgM responses are not type-specific. Clearly, more accurate commercial type-specific antibody tests are needed.

Specific HSV antibodies can take up to 12 weeks to develop. Therefore, repeat serologic testing for patients in whom initial HSV antibody results are negative yet recent genital herpes acquisition is suspected.¹¹ A confirmed positive HSV-2 antibody test indicates anogenital infection, even in a person who lacks genital symptoms. This finding became evident through a study of 53 HSV-2 seropositive patients who lacked a history of genital herpes. Patients were followed for 3 months, and all but 1 developed either virologic or clinical (or both) evidence of genital herpes.¹³

In the absence of genital or orolabial symptoms among individuals with positive HSV-1, serologic testing cannot distinguish anogenital from orolabial infection. Most of these infections may represent oral HSV-1 infection; however, given increasing occurrence of genital HSV-1 infection, this could also represent a genital infection.

What are the clinical uses of type-specific HSV serology?

Type-specific serologic tests are helpful in diagnosing patients with atypical or asymptomatic infection and managing the care of persons whose sex partners have genital herpes. Serologic testing can be useful to confirm a clinical diagnosis of HSV, to determine whether atypical lesions or symptoms are attributable to HSV, and as part of evaluation for sexually transmitted diseases in select patients. Screening for HSV-1 and HSV-2 in the general population is not supported by the Centers for Disease Control and Prevention (CDC) or the US Preventive Services Task Force (USPSTF) for several reasons^9,10:

• suboptimal performance of commercial HSV antibody tests
• low positive predictive value of these tests in low prevalence HSV settings
• lack of widely available confirmatory testing
• lack of cost-effectiveness
• potential for psychological harm.

Read about treating HSV infection during pregnancy.

Case Continued…

Because Sarah did not have a history of genital herpes, a serum sample was tested by the University of Washington Western blot. The results indicated that Sarah is seronegative for HSV-1 and HSV-2.

Sarah, who is now at 16 weeks’ gestation, returns for evaluation of new genital pain. On examination, she has several shallow ulcerations on the labia and bilateral tender inguinal adenopathy. Her husband recently had cold sores. She is anxious and would like to know if she has genital herpes and if her baby is at risk for HSV infection. You swab the base of a lesion for HSV PCR testing and start antiviral treatment.

Treating HSV infection during pregnancy

Women presenting with a new genital ulcer consistent with HSV should receive empiric antiviral treatment while awaiting confirmatory diagnostic laboratory testing, even during pregnancy. Antiviral therapy with acyclovir, valacyclovir, and famciclovir is the backbone of management of most symptomatic patients with herpes. Antiviral drugs can reduce signs and symptoms of first or recurrent genital herpes and can be used for daily suppressive therapy to prevent recurrences. These drugs do not eradicate the infection or alter the risk of frequency or severity after the drug is discontinued.

Antiviral advantages/disadvantages. Acyclovir is the least expensive drug, but valacyclovir is the most convenient therapy given its less frequent dosing. Acyclovir and valacyclovir are equally efficacious in treating first-episode genital herpes infection with respect to duration of viral shedding, time of healing, duration of pain, and time to symptom clearance. Two randomized clinical trials showed similar benefits of acyclovir and valacyclovir for suppressive therapy management of genital herpes.^14,15 Only 1 study compared the efficacy of famciclovir to valacyclovir for suppression and showed that valacyclovir was more effective.¹⁶ The cost of famciclovir is usually higher, and it has the least data on use in pregnant women. Acyclovir therapy can be safely used throughout pregnancy and during breastfeeding.⁹ Antiviral regimens for the treatment of genital HSV in pregnant and nonpregnant women recommended by the CDC are summarized in TABLE 3.¹⁷

Related article:
5 ways to reduce infection risk during pregnancy

Will your patient’s infant develop neonatal herpes infection?

Neonatal herpes is a potentially devastating infection that results from exposure to HSV from the maternal genital tract at vaginal delivery. Most cases occur in infants born to women who lack a history of genital herpes.¹⁸ In a large cohort study conducted in Washington State, isolation of HSV at the time of labor was strongly associated with vertical transmission (odds ratio [OR], 346).¹⁹ The risk of neonatal herpes increased among women shedding HSV-1 compared with HSV-2 (OR, 16.5). The highest risk of transmission to the neonate is in women who acquire genital herpes in a period close to the delivery (30% to 50% risk of transmission), compared with women with a prenatal history of herpes or who acquired herpes early in pregnancy (about 1% to 3% risk of transmission), most likely due to protective HSV-specific maternal antibodies and lower viral load during reactivation versus primary infection.¹⁸

Neonatal HSV-1 infection also has been reported in neonates born to women with primary HSV-1 gingivostomatitis during pregnancy; 70% of these women had oral clinical symptoms during the peripartum period.²⁰ Potential mechanisms are exposure to infected genital secretions, direct maternal hematogenous spread, or oral shedding from close contacts.

Although prenatal HSV screening is not recommended by the CDC or USPSTF, serologic testing could be helpful when identifying appropriate pregnancy management for women with a prior history of HSV infection. It also could be beneficial in identifying women without HSV to guide counseling prevention for HSV acquisition. In patients presenting with active genital lesions, viral-specific diagnostic evaluation should be obtained. In those with a history of laboratory confirmed genital herpes, no additional testing is warranted.

Preventing neonatal herpes

There are no prevention strategies for neonatal herpes in the United States, and the incidence of neonatal herpes has not changed in several decades.¹⁰ The current treatment guidelines focus on managing women who may be at risk for HSV acquisition during pregnancy and the management of genital lesions in women during pregnancy.^9,10,21

When the partner has HSV. Women who have no history of genital herpes or who are seronegative for HSV-2 should avoid intercourse during the third trimester with a partner known to have genital herpes.⁹ Those who have no history of orolabial herpes or who are seronegative for HSV-1 and have a seropositive partner should avoid receptive oral-genital contact and genital intercourse.⁹ Condoms can reduce but not eliminate the risk of HSV transmission; to effectively avoid genital herpes infection, abstinence is recommended.

When the patient has HSV. When managing the care of a pregnant woman with genital herpes evaluate for clinical symptoms and timing of infection or recurrence relative to time of delivery:

• Monitor women with a mild recurrence of HSV during the first 35 weeks of pregnancy without antiviral treatment, as most of the recurrent episodes of genital herpes are short.
• Consider antivirals for women with severe symptoms or multiple recurrences.
• Offer women with a history of genital lesions suppressive antiviral therapy at 36 weeks of gestation until delivery.²¹

In a meta-analysis of 7 randomized trials, 1,249 women with a history of genital herpes prior to or during pregnancy received prophylaxis with either acyclovir or valacyclovir versus placebo or no treatment at 36 weeks of gestation. Antiviral therapy reduced the risk of HSV recurrence at delivery (relative risk [RR], 0.28), cesarean delivery in those with recurrent genital herpes (RR, 0.3), and asymptomatic shedding at delivery (RR, 0.14).²² No data are available regarding the effectiveness of this approach to prevention of neonatal HSV, and case reports confirm neonatal HSV in infants born to women who received suppressive antiviral therapy at the end of pregnancy.²³

When cesarean delivery is warranted. At the time of delivery, ask all women about symptoms of genital herpes, including prodromal symptoms, and examine them for genital lesions. For women with active lesions or prodromal symptoms, offer cesarean delivery at the onset of labor or rupture of membranes—this recommendation is supported by the CDC and the American College of Obstetricians and Gynecologists.^9,21 The protective effect of cesarean delivery was evaluated in a large cohort study that found: among women who were shedding HSV at the time of delivery, neonates born by cesarean delivery were less likely to develop HSV infection compared with those born through vaginal delivery (1.2% vs 7.7%, respectively).¹⁹ Cesarean delivery is not indicated in patients with a history of HSV without clinical recurrence or prodrome at delivery, as such women have a very low risk of transmitting the infection to the neonate.²⁴

Avoid transcervical antepartum obstetric procedures to reduce the risk of placenta or membrane HSV infection; however, transabdominal invasive procedures can be performed safely, even in the presence of active genital lesions.²¹ Intrapartum procedures that can cause fetal skin disruption, such as use of fetal scalp electrode or forceps, are risk factors for HSV transmission and should be avoided in women with a history of genital herpes.

Related articles:
8 common questions about newborn circumcision

Case Resolved

Sarah’s genital lesion PCR results returned positive for HSV-1. She probably acquired the infection from oral-genital sex with her husband who likely has oral HSV-1, given the history of cold sores. You treat Sarah with acyclovir 400 mg 3 times per day for 7 days. At 36 weeks’ gestation, Sarah begins suppressive antiviral therapy until delivery. She spontaneously labors at 39 weeks’ gestation; at that time, she has no genital lesions and she delivers vaginally a healthy baby.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

From UConn Health, Farmington, CT.

Abstract

• Objective: To discuss the efficacy and generalizability of contingency management (CM) for the treatment of substance use disorders and design considerations for those considering implementing in clinical settings.
• Methods: Review of the literature.
• Results: CM is an efficacious treatment for substance abuse disorders that is widely generalizable across substance use disorders and patient characteristics. CM can be implemented in a number of treatment programs, including residential and outpatient settings, and it can be administered in both individual and group formats. Abstinence and attendance are the most commonly targeted behaviors in substance abuse treatment settings. Design features, including the selection of target behaviors, delivery methods, and reinforcers, are discussed. Schedule parameters, such as frequency, magnitude, immediacy, and escalation of reinforcement, are associated with overall impact of the CM program and are important considerations for those interested in tailoring CM protocols to their needs.
• Conclusion: CM is an efficacious option that is applicable to most substance abuse treatment patients. A number of demonstrations of real-world implementation have been published and suggest CM can be adapted with success to clinic settings. In adopting CM protocols, clinics should aim for those protocols with established efficacy; however, if adaptations are necessary, careful consideration should be given to modifications to minimize risks of undermining CM’s effects.

Key words: incentives; reinforcement; substance abuse treatment; dissemination; implementation.

Contingency management (CM) is a behavioral intervention that is efficacious in the treatment of substance use disorders (SUDs). CM uses a behavior analytic framework and applies principles of learning theory, particularly operant conditioning theory, to change client behavior(s) [1–5]. In basic terms, operant conditioning principles suggests that whether a behavior continues or not is a function of consequences [6]. Reinforced behaviors are more likely to occur in the future. Substance abuse can be viewed as a behavior maintained by the reinforcing effects of the drug itself [5], including the feel-good aspects of intoxication or relaxation and the amelioration of withdrawal symptoms. CM extends these same principles of to a treatment context, such that reinforcers for abstinent behavior are introduced to compete with the reinforcing effects of continued drug use [5].

In CM’s application to substance abuse treatment, drug-negative samples or treatment attendance are reinforced using tangible incentives with the goal of motivating continued abstinence and/or treatment engagement. When clients demonstrate these target behaviors, they earn incentives in the form of goods or services of value to the client, such as small electronics, gift cards, and toiletries. Despite the promising effects observed in research trials, real-world implementation efforts have not kept pace [7–9]. This review briefly discusses CM’s efficacy and highlights key features for professionals considering adopting this intervention. Demonstration efforts that illustrate how CM can be effectively implemented within the constraints and limitations of non-research, clinical settings are also presented.

Efficacy of CM

CM’s efficacy spans a number of SUDs, including cocaine, opioids, alcohol, nicotine, and marijuana [10–13], making it amenable for treatment of most SUD clinic populations. It generates larger effect sizes than other SUD treatments, including cognitive behavioral therapy [14], and it has been evaluated in a wide range of settings. Large-scale evaluations have been conducted in both intensive outpatient [15] and methadone maintenance [16] settings as part of the National Institute on Drug Abuse Clinical Trials Network, demonstrating consistent benefits of CM when added to treatment as usual. In the first of these 2 studies, Petry et al [15] randomized 415 stimulant users from 1 of 8 intensive outpatient clinics to treatment as usual or treatment as usual plus CM for alcohol and stimulant abstinence. CM participants submitted more substance-negative urine and breath samples, achieved continuous abstinence at significantly higher rates, and had longer treatment retention compared to those receiving treatment as usual. The parallel study [16] focused on stimulant use in clients from methadone maintenance clinics and found similar benefits of CM on stimulant abstinence. Beyond these settings, CM has been applied in a number of other contexts, including drop-in centers [17], vocational rehabilitation [18,19], job-skills training [20], and residential programs [21–23]. In addition, several group-based adaptations have been explored [17,24–27].

CM benefits most clients and generalizes across several demographic variables, including gender [28,29], race [30], housing status [31], and income levels [32–34]. Among clinical characteristics, CM is efficacious for those with co-occurring SUDs [35], other substance use [36], psychiatric disorders [37–39], medical problems [40–42], and history of transactional sex [43].

Design Considerations

Design features, including what behavior will be reinforced and how to do so, are among the first decision points for clinicians interested in implementing CM. One of the advantages of CM is that it has a high degree of flexibility in design, which means that it can be readily tailored to client populations and clinic needs. However, this flexibility can lead clinicians astray from the foundational principles of CM and unknowingly weaken the impact of the program. Below, some key considerations for CM protocol design are reviewed. For additional coverage of these topics, readers are referred to additional articles [1,2] or Petry’s comprehensive book on implementing CM [44]. In this review, published examples of CM’s application in real-world settings are presented, highlighting how CM has been adapted in these clinical efforts.

Target Behaviors

The selection of the target behavior will drive many of the subsequent program design decisions. As such, it is important to identify this feature early. Target behaviors must be achievable, objectively verifiable, and well defined. The most common CM targets are drug abstinence or therapy session attendance. CM has also been used to target other behaviors, such as medication adherence [45,46], treatment-related activities [47,48], and exercise [49–51]. Client self-report of behaviors or vaguely defined behaviors (eg, “good participation”) should be avoided. While some of the decisions related to CM protocols are flexible, the use of objectively verifiable target behaviors is a core feature that should not be neglected. If the behavior of interest cannot be objectively verified, an alternate behavior should be chosen.

Selection of the target behavior is often considered in hand with defining which population is eligible to participate in the CM program. Client characteristics are often forefront in this decision, but clinic-driven logistical issues or unmet needs may also play a role. A real-world example of this decision process is evident in the nationwide rollout of CM among the intensive outpatient programs within the Veterans Administration (VA). The VA identified a treatment need for those with stimulant use disorders, as this group did not have efficacious pharmacotherapy options available that targeted stimulant use. As such, the VA applied CM to patients with a focus on stimulant abstinence as the behavioral target [52]. For others, the decision may revolve around addressing underutilization of specific treatment resources (eg, outpatient groups, vocational rehabilitation) [53–56] or treatment needs among certain subgroups of clients, such as adolescents [57–59].

For abstinence targets, clinics would need to select one or more specific substances as the focus of the CM program. In general, targeting a single substance rather than multiple substances is more effective [10,13], is more straightforward for clients to understand, and allows more clients to access the reinforcers. Exposure to the reinforcers is necessary for CM to work; thus, setting a goal that is achievable for most clients should be a priority. Requiring abstinence from multiple substances means that some clients may never experience the reinforcer and thus cannot benefit from its effects at all. Some clinicians or administrators may initially have reservations about reinforcing single drug abstinence in the event that other drug use continues. However, targeting a single substance for reinforcement often results in reduced use of other substances [60]. Clinicians may find that this makes intuitive sense; a client with cocaine use disorder who is trying to maintain cocaine abstinence over a long period is likely to avoid using alcohol or other substances that might lead to relapse. For abstinence, objective verification through urine or breath specimens using tests that include validity checks is relatively straightforward.

Attendance is a popular target for clinics in part because it does not require additional staff time to collect specimen samples and it was the most commonly reported target behavior in samples of SUD providers who use incentives [61,62]. Objective verification of attendance is usually via a staff member, but expectations must be clear to both parties. Clinics should consider potential problems that may arise (eg, arriving late, leaving group early, excused absences) and carefully define and communicate expectations for the CM program. Piloting [19] the CM program with a small group of clients may be valuable in trouble-shooting challenges before wider implementation.

In a recent study [55], clients earned reinforcers for attending clinician-led group counseling sessions and/or the in-clinic patient-led Methadone Anonymous (MA) groups. This non-research, clinical effort addressed historically poor therapy attendance at the clinic, and attendance rates were compared before, during, and after the CM program. CM increased attendance to both groups in the short-term after implementation, but effects were more robust for the MA groups in which increased attendance persisted 3 months following the withdrawal of the contingencies. Overall effects of this program were modest, but they are notable given the use of an ultra-low cost approach.

Delivery Methods

The majority of CM studies used voucher or prize-based methods. Head-to-head comparisons suggest that they are comparable in efficacy [63–65], and each has advantages and disadvantages that may make one option more appealing for a given clinic. Voucher programs are generally straightforward to administer. Clients earn vouchers for each instance of the target behavior. The value of the vouchers typically increases with consecutive performance. The schedule used in the influential Higgins et al studies [66,67] started at $2.50 for the first cocaine-negative sample and increased by $0.50 for each subsequent consecutive cocaine-negative sample. Earned vouchers are exchanged for goods or services selected by the client, increasing the likelihood that the selected items will be highly desirable and allowing for a wide range of client preferences. Clients appear to prefer this approach when given a choice between set schedules or those that introduce an element of chance (ie, prize-based CM, discussed below) [68]. However, voucher programs can be costly (~$1000 per client over 12 weeks) and may require more staff time to fulfill individual requests for specific items. However, staff burden related to shopping can be reduced by limiting these individual requests and using an on-site stocked cabinet of goods similar to prize-CM programs.

Prize-based CM is similar but introduces probabilistic earnings and variability in prize magnitude. Rather than earning vouchers, clients earn draws from a fishbowl for each instance of the target behavior, again typically in an escalating manner. For example, a client may earn one draw from the fishbowl for the first cocaine-negative sample, 2 draws for the second consecutive negative sample, 3 draws for the third, and so on. A typical fishbowl is composed of 500 slips, some noting prizes and some having no prize value. Typically, half the slips in the bowl are non-monetary “good jobs.” The remaining half are small prizes worth about $1 in value (eg, food coupons, bus tokens, small toiletries), large prizes worth about $20 in value (eg, small electronics, gift certificates), and one slip is the jumbo prize worth about $100. When a client draws a winning slip, they select a prize from that category (ie, small, large, jumbo) from an onsite, stocked cabinet. Due to the probabilistic feature of prize-based CM, overall costs of the program can be substantially lower than typical voucher programs, with average maximum expected earnings ranging $250 t $450 per client over a 12-week treatment period [15,16,65,69]. Advantages of this method include potentially lower costs and minimal shopping demands (a once-monthly shopping trip to restock the cabinet will usually suffice) while maintaining comparable efficacy. Relative to voucher programs, prize-based CM involves additional administration time to allow for drawing slips from the fishbowl, which can be compounded when multiple clients want to draw at the same time such as in a group setting. Many of the group-based CM adaptations address this issue by limiting the number of clients who can draw for prizes in a given group or by limiting the number of draws per client [25,27,54].

Reinforcers

Regardless of whether selecting voucher or prize CM, reinforcers are critically important to the success of the program. Reinforcers must be desirable. One of the quickest ways to undermine a CM program is lack of variety or undesirable reinforcers. If stocking a cabinet with prizes onsite, care should be taken to have numerous options within each of the small and large prize categories that are appealing to a wide range of clients. Since a client who is consistently earning draws will choose prizes often, it is imperative to include enough variety so that even these clients find desirable items each time they select a prize. Clients should be asked regularly if they have suggestions for prizes; one program [54] found suggestion boxes useful for encouraging clients to voice their preferences. Donations can be solicited from local businesses to reduce costs [53], and low-cost but high-value options, such as clinic privileges, can also be explored. Petry [1,44] provides some suggestions of the latter, and Amass and Kamien [70] describe their successful strategies to fund and sustain a clinic-based CM program through community donations. Some clinics may already have tangible goods, such as gas or metro cards, that are offered to clients based on need rather than behavior [53]. These existing resources might be redirected to a CM program, in which these goods are contingent on abstinence or attendance, if appropriate.

Schedule Parameters

Once the target behavior, client population, and CM delivery methods are selected, the next step is to design the reinforcement schedule. The following schedule parameters apply to both voucher and prize-based CM systems. The more closely a clinical program adheres to the parameters of effective protocols, the more likely the program is to generate comparable outcomes. If there is a parameter or design feature that is incompatible with clinic needs, modifications can be introduced. However, each deviation away from the ideal has a chance of undermining the success of the CM program. Any changes and their potential impacts should considered carefully, and consultation with a CM expert may aid in the development of successful and efficacious clinic-based protocols. Of note, a meta-analysis [13] of CM studies found that researcher involvement in the planning and design of CM programs is associated with larger treatment effects. CM researchers are especially attuned to the potential impacts and pitfalls associated with modifying CM protocols, and they can be valuable resources for clinics interested in tailoring a CM program to their specific needs. Several examples of clinical demonstration projects that used researcher input are available [19,53,71].

Magnitude

Incentive magnitude was directly related to the size of treatment effects in a meta-analysis [11] of CM studies. Although not all studies find significant differences in outcomes related to magnitude [65,72], the bulk of evidence suggests magnitude is an important parameter and is related to effect size for both voucher [73–75] and prize-based CM [69,76] systems. Thus, although clinics may have restrictive budgets, severely undercutting the magnitude of rewards is not usually the solution as it can undermine treatment effects [76]. Donations can reduce overall costs [53,57,70], and other protocol features discussed below, such as capping the amount of reinforcement available, can reduce the overall magnitude available per patient.

Another approach, used in group-based CM, limits the number of patients who earn prizes per week [25,27]. For example, in a 2011 study by Petry et al, clients added slips with their name to a bowl for attendance and negative samples. Once all names were collected in the bowl, the group leader would pull a specified number of slips (eg, 3 slips per group). These individuals were eligible to draw from the prize bowl for prizes. This approach was associated with longer durations of consecutive abstinence and better treatment attendance relative to treatment as usual. However, clinics can control the overall program costs by limiting the number of patients eligible for prizes.

Frequency

Frequent reinforcement opportunities are ideal, and more frequent assessment is associated with larger treatment effects [10]. However, a number of factors, including which target behavior is selected and logistical issues specific to the clinic such as when groups meet, will play a role in determining the frequency of CM sessions. For abstinence targets, the substance targeted and type of test will largely determine the frequency of CM sessions. The goal would be to test at a frequency that would detect most or nearly all instances of use. For cocaine or opioids, this equates to testing 2 to 3 times weekly. Breath samples for alcohol or cigarette smoking would necessitate testing daily or multiple times per day to detect most instances of use because these tests have short windows of detection. CM protocols based on these breath tests have often had daily or twice daily CM sessions [77,78]; technological adaptations [77,79,80] or residential settings [21,23] may reduce burden to the client for assessment of these substances. Tapering the number of breath tests over time or transitioning from daily breath tests to once or twice weekly urine testing after abstinence is established is another approach [81,82].

Marijuana, on the other hand, poses difficulties because it is detectable in urine samples for up to 2 weeks following use. If relying solely on urine results for reinforcement, clients may not test negative for several days or weeks after last use, resulting in a delay of reinforcement. To address this issue, some CM programs targeting marijuana abstinence initially reinforce attendance in the first 2 weeks and then transition to reinforcing marijuana-negative drug samples for the remainder of the treatment period [48].

In general, more frequent CM sessions can translate to higher costs; however, infrequent reinforcement (ie, less than weekly) is not as effective [45]. In real-world applications, clinics often need to balance feasibility and costs with the ideal CM schedule. In abstinence-based CM, this compromise may result in a testing schedule that may not capture all instances of use. For example, while thrice-weekly testing may be ideal for cocaine or opioids, a twice-weekly schedule may be selected because it lowers costs and is more consistent with clinic schedules.

Immediacy

In general, clinics should aim to deliver reinforcement as immediately as possible, as delays between the target behavior and reinforcement are associated with decreased treatment effects [10,11,83]. For drug abstinence, onsite urine testing systems that provide immediate results are preferred over sending samples for laboratory testing. Clinics that do not have access to or who cannot afford specimen testing that allows onsite collection and immediate results might consider other options for target behaviors, such as attendance.

Immediacy of reinforcement is also important when targeting attendance. One clinic [53] implemented a program that offered a $50 incentive if clients attended 1 month of group therapy sessions. This approach was not effective and no clients earned the incentive for several months. After consultation, the clinic revised the incentive program to a daily drawing for attendance using the fishbowl method, thereby decreasing the delay between the behavior and its consequence. This example illustrates not only problems with delayed reinforcement but also the common mistake of setting expectations for the target behavior too high. Attending a month of group therapy sessions is a high bar that few patients will achieve, resulting in a system that mostly rewards those already doing well [19]. In contrast, attending a single group session in order to earn reinforcers is a reachable goal and increases the likelihood that more clients are exposed to the reinforcers. These small steps (ie, attending a single group or submitting a single drug negative urine) encourage initiation of the behavior(s) targeted. Other features, such as escalation (discussed next), aim to sustain the behavior over time.

Escalation

Escalation involves increasing the amount of reinforcement for each consecutive target behavior. In the voucher programs, the amount earned per negative sample may increase for each consecutive negative sample (eg, $2.50 for the first negative sample, $3.00 for the second, $3.50 for the third, and so on). For prize-based programs, the number of draws escalates with consecutive performance (eg, 1 draw for the first group attended, 2 draws for the second, 3 for the third, and so on). Protocols that include escalation generate larger effects than those that have a set, flat incentive amount even when total costs are the same across comparison conditions [73].

Escalating schedules usually include a reset feature. Following a positive or refused sample or unexcused absence, the amount earned for the next negative sample is reduced to the initial amount and begins escalating anew with consecutive negative samples. Some schedules allow for a rapid reset in which after a specified period of time or consecutive performance, the value jumps to the value achieved when the relapse occurred [66].

Despite its consistent inclusion in CM protocols from randomized clinical trials, our data [61] suggest that more than half of providers using incentives in treatment as part of a clinical effort do not use escalating reinforcers. Escalating schedules require more careful tracking of client progress, possibly contributing to lower uptake of this design feature in clinical practice. Development of simple tracking forms can minimize this challenge.

Another drawback of escalation pertaining to prize-based CM is that escalating schedules can affect the duration of CM sessions when clients are drawing a large number of slips each session and escalation can increase costs of the overall program. Capping the number of draws will help mitigate both issues. For example, once a client reaches 10 draws for group attendance, they continue earning 10 draws for each consecutive session attended with no further escalation.

Putting It All Together

CM sessions can be conducted as stand-alone sessions or incorporated into group or individual therapy sessions. Many clinicians will find the latter approach sets a positive tone for the therapy session given CM's focus on what the client is doing well. Starting the treatment session with the CM component often naturally leads into a discussion of relevant therapeutic issues, such as effective coping, slips, or triggers. The CM session length can be variable, but it is typically under 10 minutes. Thus, the CM component need not dominate the clinical session or content. CM sessions for abstinence are scheduled according to a set schedule (eg, Mondays and Thursdays) and often coincide with other treatment aspects (eg, before or after group therapy on Mondays and Thursdays). CM sessions for attendance also generally follow a set schedule (eg, client expected to attend Monday and Wednesday group therapy sessions). The duration of the CM protocol can also vary, with most clinical trials ranging from 12 to 24 weeks. Very short durations are unlikely to produce lasting behavior change, particularly with complex behaviors such as abstinence. Petry [44] recommends no less than 8 weeks duration and a maximum duration of 24 weeks.

As discussed, CM offers many opportunities for tailoring to optimize its fit within the existing structure of clinics. However, this flexibility must be viewed together with an understanding of the principles that impact CM's efficacy. Specific recommendations for CM protocol development will depend on the behavior targeted, the delivery methods, and format (eg, individual versus group settings). For these reasons, consultation with a CM expert is ideal. However, some general guidelines for developing a CM program that incorporate the principles discussed above include an 8- to 12-week program that (1) provides sufficient magnitude to compete with the behavior you are attempting to change, (2) offers frequent opportunities for reinforcement (eg, 2-3 times/wk for opioids or stimulant abstinence, 1-2 times/week for attendance targets; not less than weekly for most behaviors), (3) delivers the reinforcement immediately or very close in time with the behavior (eg, reinforce attendance at the beginning of the group, use onsite urine testing and reinforce immediately after testing), and (4) incorporates escalating and reset features into the schedule.

Clinician Training and Supervision

Training in CM is an important part of the implementation process. Studies [62,84–87] have identified a number of perceived barriers to and negative beliefs about CM, including philosophical and logistical concerns. Tangible incentives, the core of most CM protocols, are generally viewed less favorably than social or nonspecified incentives [84,86,87]. Philosophical concerns relate to CM’s inability to address the underlying causes of addiction, that it does not address multiple behaviors, and that it may undermine internal motivation for sobriety [62,84]. An additional objection relates to paying someone to do what they should do on their own [86]. Logistical and practical concerns often represent implementation barriers such as costs and access to training and supervision, but they also reflect concern for what happens when contingencies are withdrawn, that clients may sell or trade prizes for drugs, and worries that CM’s evidence does not generalize to clinic populations [62].

Many of these beliefs reflect a limited understanding of CM, and addressing these misperceptions is a first step toward reducing resistance to implementation efforts. For example, a substantial body of literature points to CM’s wide generalizability across a range of characteristics, clients that sell or trade prizes for drugs are likely to disrupt their chain of negative samples or attendance, and most studies do not find negative impacts of CM on intrinsic motivation [88–90]. Fortunately, CM training appears to be an effective way to address negative beliefs. In the VA implementation effort [52], training workshops decreased perceived barriers and increased positive impressions of CM [91]. In other training efforts, brief educational materials were effective in changing perceptions of CM’s efficacy [92].

Beyond initial training, supervision of CM delivery is likely to be necessary [93,94]. Clinician skill in delivering CM is related to client outcomes [93,95] and relatively simple adherence measures are available for monitoring [96,97]. However, the best methods for training and supervision of CM have yet to be established. The VA initiative was developed in consultation with CM experts and employed ongoing phone consultation following initial training workshops [52,91]. This approach represented significant investment by the VA toward staff training and CM protocol development that may not be achievable for individual clinics. As attention to CM’s dissemination and implementation has grown, some free resources have been developed. Promoting Awareness of Motivational Incentives (PAMI; www.bettertxoutcomes.org/bettertxoutcomes/PAMI.html) is a collaborative initiative sponsored by the National Institute of Drug Abuse and the Substance Abuse and Mental Health Services Administration. It offers free resources and training materials.

Conclusion

Overall, CM is a highly efficacious treatment for SUDs that generalizes to most clients. Despite a robust evidence base, CM’s implementation in clinical settings lags behind other empirically supported treatments [92]. At least in part, CM’s costs, which include not only staff training and adherence monitoring (as with other treatments), but also costs of the incentives themselves, may contribute to slow uptake in clinical settings. Clinics often do not have the resources available for CM within their operating budgets. However, a growing number of projects [19,52,53,55–57,70,71] illustrate CM implementation within routine clinical care, and increased revenue from improved attendance to treatment groups may be one mechanism through which to fund a CM program [54,56,57]. These projects are valuable not only for demonstrating that CM can be efficacious outside the research setting, but also for highlighting how implementation barriers can be overcome. Continued efforts of this nature are likely to be particularly valuable for clinicians and administrators considering adopting CM within clinical settings.

From UConn Health, Farmington, CT.

Abstract

• Objective: To discuss the efficacy and generalizability of contingency management (CM) for the treatment of substance use disorders and design considerations for those considering implementing in clinical settings.
• Methods: Review of the literature.
• Results: CM is an efficacious treatment for substance abuse disorders that is widely generalizable across substance use disorders and patient characteristics. CM can be implemented in a number of treatment programs, including residential and outpatient settings, and it can be administered in both individual and group formats. Abstinence and attendance are the most commonly targeted behaviors in substance abuse treatment settings. Design features, including the selection of target behaviors, delivery methods, and reinforcers, are discussed. Schedule parameters, such as frequency, magnitude, immediacy, and escalation of reinforcement, are associated with overall impact of the CM program and are important considerations for those interested in tailoring CM protocols to their needs.
• Conclusion: CM is an efficacious option that is applicable to most substance abuse treatment patients. A number of demonstrations of real-world implementation have been published and suggest CM can be adapted with success to clinic settings. In adopting CM protocols, clinics should aim for those protocols with established efficacy; however, if adaptations are necessary, careful consideration should be given to modifications to minimize risks of undermining CM’s effects.

Key words: incentives; reinforcement; substance abuse treatment; dissemination; implementation.

Contingency management (CM) is a behavioral intervention that is efficacious in the treatment of substance use disorders (SUDs). CM uses a behavior analytic framework and applies principles of learning theory, particularly operant conditioning theory, to change client behavior(s) [1–5]. In basic terms, operant conditioning principles suggests that whether a behavior continues or not is a function of consequences [6]. Reinforced behaviors are more likely to occur in the future. Substance abuse can be viewed as a behavior maintained by the reinforcing effects of the drug itself [5], including the feel-good aspects of intoxication or relaxation and the amelioration of withdrawal symptoms. CM extends these same principles of to a treatment context, such that reinforcers for abstinent behavior are introduced to compete with the reinforcing effects of continued drug use [5].

In CM’s application to substance abuse treatment, drug-negative samples or treatment attendance are reinforced using tangible incentives with the goal of motivating continued abstinence and/or treatment engagement. When clients demonstrate these target behaviors, they earn incentives in the form of goods or services of value to the client, such as small electronics, gift cards, and toiletries. Despite the promising effects observed in research trials, real-world implementation efforts have not kept pace [7–9]. This review briefly discusses CM’s efficacy and highlights key features for professionals considering adopting this intervention. Demonstration efforts that illustrate how CM can be effectively implemented within the constraints and limitations of non-research, clinical settings are also presented.

Efficacy of CM

CM’s efficacy spans a number of SUDs, including cocaine, opioids, alcohol, nicotine, and marijuana [10–13], making it amenable for treatment of most SUD clinic populations. It generates larger effect sizes than other SUD treatments, including cognitive behavioral therapy [14], and it has been evaluated in a wide range of settings. Large-scale evaluations have been conducted in both intensive outpatient [15] and methadone maintenance [16] settings as part of the National Institute on Drug Abuse Clinical Trials Network, demonstrating consistent benefits of CM when added to treatment as usual. In the first of these 2 studies, Petry et al [15] randomized 415 stimulant users from 1 of 8 intensive outpatient clinics to treatment as usual or treatment as usual plus CM for alcohol and stimulant abstinence. CM participants submitted more substance-negative urine and breath samples, achieved continuous abstinence at significantly higher rates, and had longer treatment retention compared to those receiving treatment as usual. The parallel study [16] focused on stimulant use in clients from methadone maintenance clinics and found similar benefits of CM on stimulant abstinence. Beyond these settings, CM has been applied in a number of other contexts, including drop-in centers [17], vocational rehabilitation [18,19], job-skills training [20], and residential programs [21–23]. In addition, several group-based adaptations have been explored [17,24–27].

CM benefits most clients and generalizes across several demographic variables, including gender [28,29], race [30], housing status [31], and income levels [32–34]. Among clinical characteristics, CM is efficacious for those with co-occurring SUDs [35], other substance use [36], psychiatric disorders [37–39], medical problems [40–42], and history of transactional sex [43].

Design Considerations

Design features, including what behavior will be reinforced and how to do so, are among the first decision points for clinicians interested in implementing CM. One of the advantages of CM is that it has a high degree of flexibility in design, which means that it can be readily tailored to client populations and clinic needs. However, this flexibility can lead clinicians astray from the foundational principles of CM and unknowingly weaken the impact of the program. Below, some key considerations for CM protocol design are reviewed. For additional coverage of these topics, readers are referred to additional articles [1,2] or Petry’s comprehensive book on implementing CM [44]. In this review, published examples of CM’s application in real-world settings are presented, highlighting how CM has been adapted in these clinical efforts.

Target Behaviors

The selection of the target behavior will drive many of the subsequent program design decisions. As such, it is important to identify this feature early. Target behaviors must be achievable, objectively verifiable, and well defined. The most common CM targets are drug abstinence or therapy session attendance. CM has also been used to target other behaviors, such as medication adherence [45,46], treatment-related activities [47,48], and exercise [49–51]. Client self-report of behaviors or vaguely defined behaviors (eg, “good participation”) should be avoided. While some of the decisions related to CM protocols are flexible, the use of objectively verifiable target behaviors is a core feature that should not be neglected. If the behavior of interest cannot be objectively verified, an alternate behavior should be chosen.

Selection of the target behavior is often considered in hand with defining which population is eligible to participate in the CM program. Client characteristics are often forefront in this decision, but clinic-driven logistical issues or unmet needs may also play a role. A real-world example of this decision process is evident in the nationwide rollout of CM among the intensive outpatient programs within the Veterans Administration (VA). The VA identified a treatment need for those with stimulant use disorders, as this group did not have efficacious pharmacotherapy options available that targeted stimulant use. As such, the VA applied CM to patients with a focus on stimulant abstinence as the behavioral target [52]. For others, the decision may revolve around addressing underutilization of specific treatment resources (eg, outpatient groups, vocational rehabilitation) [53–56] or treatment needs among certain subgroups of clients, such as adolescents [57–59].

For abstinence targets, clinics would need to select one or more specific substances as the focus of the CM program. In general, targeting a single substance rather than multiple substances is more effective [10,13], is more straightforward for clients to understand, and allows more clients to access the reinforcers. Exposure to the reinforcers is necessary for CM to work; thus, setting a goal that is achievable for most clients should be a priority. Requiring abstinence from multiple substances means that some clients may never experience the reinforcer and thus cannot benefit from its effects at all. Some clinicians or administrators may initially have reservations about reinforcing single drug abstinence in the event that other drug use continues. However, targeting a single substance for reinforcement often results in reduced use of other substances [60]. Clinicians may find that this makes intuitive sense; a client with cocaine use disorder who is trying to maintain cocaine abstinence over a long period is likely to avoid using alcohol or other substances that might lead to relapse. For abstinence, objective verification through urine or breath specimens using tests that include validity checks is relatively straightforward.

Attendance is a popular target for clinics in part because it does not require additional staff time to collect specimen samples and it was the most commonly reported target behavior in samples of SUD providers who use incentives [61,62]. Objective verification of attendance is usually via a staff member, but expectations must be clear to both parties. Clinics should consider potential problems that may arise (eg, arriving late, leaving group early, excused absences) and carefully define and communicate expectations for the CM program. Piloting [19] the CM program with a small group of clients may be valuable in trouble-shooting challenges before wider implementation.

In a recent study [55], clients earned reinforcers for attending clinician-led group counseling sessions and/or the in-clinic patient-led Methadone Anonymous (MA) groups. This non-research, clinical effort addressed historically poor therapy attendance at the clinic, and attendance rates were compared before, during, and after the CM program. CM increased attendance to both groups in the short-term after implementation, but effects were more robust for the MA groups in which increased attendance persisted 3 months following the withdrawal of the contingencies. Overall effects of this program were modest, but they are notable given the use of an ultra-low cost approach.

Delivery Methods

The majority of CM studies used voucher or prize-based methods. Head-to-head comparisons suggest that they are comparable in efficacy [63–65], and each has advantages and disadvantages that may make one option more appealing for a given clinic. Voucher programs are generally straightforward to administer. Clients earn vouchers for each instance of the target behavior. The value of the vouchers typically increases with consecutive performance. The schedule used in the influential Higgins et al studies [66,67] started at $2.50 for the first cocaine-negative sample and increased by $0.50 for each subsequent consecutive cocaine-negative sample. Earned vouchers are exchanged for goods or services selected by the client, increasing the likelihood that the selected items will be highly desirable and allowing for a wide range of client preferences. Clients appear to prefer this approach when given a choice between set schedules or those that introduce an element of chance (ie, prize-based CM, discussed below) [68]. However, voucher programs can be costly (~$1000 per client over 12 weeks) and may require more staff time to fulfill individual requests for specific items. However, staff burden related to shopping can be reduced by limiting these individual requests and using an on-site stocked cabinet of goods similar to prize-CM programs.

Prize-based CM is similar but introduces probabilistic earnings and variability in prize magnitude. Rather than earning vouchers, clients earn draws from a fishbowl for each instance of the target behavior, again typically in an escalating manner. For example, a client may earn one draw from the fishbowl for the first cocaine-negative sample, 2 draws for the second consecutive negative sample, 3 draws for the third, and so on. A typical fishbowl is composed of 500 slips, some noting prizes and some having no prize value. Typically, half the slips in the bowl are non-monetary “good jobs.” The remaining half are small prizes worth about $1 in value (eg, food coupons, bus tokens, small toiletries), large prizes worth about $20 in value (eg, small electronics, gift certificates), and one slip is the jumbo prize worth about $100. When a client draws a winning slip, they select a prize from that category (ie, small, large, jumbo) from an onsite, stocked cabinet. Due to the probabilistic feature of prize-based CM, overall costs of the program can be substantially lower than typical voucher programs, with average maximum expected earnings ranging $250 t $450 per client over a 12-week treatment period [15,16,65,69]. Advantages of this method include potentially lower costs and minimal shopping demands (a once-monthly shopping trip to restock the cabinet will usually suffice) while maintaining comparable efficacy. Relative to voucher programs, prize-based CM involves additional administration time to allow for drawing slips from the fishbowl, which can be compounded when multiple clients want to draw at the same time such as in a group setting. Many of the group-based CM adaptations address this issue by limiting the number of clients who can draw for prizes in a given group or by limiting the number of draws per client [25,27,54].

Reinforcers

Regardless of whether selecting voucher or prize CM, reinforcers are critically important to the success of the program. Reinforcers must be desirable. One of the quickest ways to undermine a CM program is lack of variety or undesirable reinforcers. If stocking a cabinet with prizes onsite, care should be taken to have numerous options within each of the small and large prize categories that are appealing to a wide range of clients. Since a client who is consistently earning draws will choose prizes often, it is imperative to include enough variety so that even these clients find desirable items each time they select a prize. Clients should be asked regularly if they have suggestions for prizes; one program [54] found suggestion boxes useful for encouraging clients to voice their preferences. Donations can be solicited from local businesses to reduce costs [53], and low-cost but high-value options, such as clinic privileges, can also be explored. Petry [1,44] provides some suggestions of the latter, and Amass and Kamien [70] describe their successful strategies to fund and sustain a clinic-based CM program through community donations. Some clinics may already have tangible goods, such as gas or metro cards, that are offered to clients based on need rather than behavior [53]. These existing resources might be redirected to a CM program, in which these goods are contingent on abstinence or attendance, if appropriate.

Schedule Parameters

Once the target behavior, client population, and CM delivery methods are selected, the next step is to design the reinforcement schedule. The following schedule parameters apply to both voucher and prize-based CM systems. The more closely a clinical program adheres to the parameters of effective protocols, the more likely the program is to generate comparable outcomes. If there is a parameter or design feature that is incompatible with clinic needs, modifications can be introduced. However, each deviation away from the ideal has a chance of undermining the success of the CM program. Any changes and their potential impacts should considered carefully, and consultation with a CM expert may aid in the development of successful and efficacious clinic-based protocols. Of note, a meta-analysis [13] of CM studies found that researcher involvement in the planning and design of CM programs is associated with larger treatment effects. CM researchers are especially attuned to the potential impacts and pitfalls associated with modifying CM protocols, and they can be valuable resources for clinics interested in tailoring a CM program to their specific needs. Several examples of clinical demonstration projects that used researcher input are available [19,53,71].

Magnitude

Incentive magnitude was directly related to the size of treatment effects in a meta-analysis [11] of CM studies. Although not all studies find significant differences in outcomes related to magnitude [65,72], the bulk of evidence suggests magnitude is an important parameter and is related to effect size for both voucher [73–75] and prize-based CM [69,76] systems. Thus, although clinics may have restrictive budgets, severely undercutting the magnitude of rewards is not usually the solution as it can undermine treatment effects [76]. Donations can reduce overall costs [53,57,70], and other protocol features discussed below, such as capping the amount of reinforcement available, can reduce the overall magnitude available per patient.

Another approach, used in group-based CM, limits the number of patients who earn prizes per week [25,27]. For example, in a 2011 study by Petry et al, clients added slips with their name to a bowl for attendance and negative samples. Once all names were collected in the bowl, the group leader would pull a specified number of slips (eg, 3 slips per group). These individuals were eligible to draw from the prize bowl for prizes. This approach was associated with longer durations of consecutive abstinence and better treatment attendance relative to treatment as usual. However, clinics can control the overall program costs by limiting the number of patients eligible for prizes.

Frequency

Frequent reinforcement opportunities are ideal, and more frequent assessment is associated with larger treatment effects [10]. However, a number of factors, including which target behavior is selected and logistical issues specific to the clinic such as when groups meet, will play a role in determining the frequency of CM sessions. For abstinence targets, the substance targeted and type of test will largely determine the frequency of CM sessions. The goal would be to test at a frequency that would detect most or nearly all instances of use. For cocaine or opioids, this equates to testing 2 to 3 times weekly. Breath samples for alcohol or cigarette smoking would necessitate testing daily or multiple times per day to detect most instances of use because these tests have short windows of detection. CM protocols based on these breath tests have often had daily or twice daily CM sessions [77,78]; technological adaptations [77,79,80] or residential settings [21,23] may reduce burden to the client for assessment of these substances. Tapering the number of breath tests over time or transitioning from daily breath tests to once or twice weekly urine testing after abstinence is established is another approach [81,82].

Marijuana, on the other hand, poses difficulties because it is detectable in urine samples for up to 2 weeks following use. If relying solely on urine results for reinforcement, clients may not test negative for several days or weeks after last use, resulting in a delay of reinforcement. To address this issue, some CM programs targeting marijuana abstinence initially reinforce attendance in the first 2 weeks and then transition to reinforcing marijuana-negative drug samples for the remainder of the treatment period [48].

In general, more frequent CM sessions can translate to higher costs; however, infrequent reinforcement (ie, less than weekly) is not as effective [45]. In real-world applications, clinics often need to balance feasibility and costs with the ideal CM schedule. In abstinence-based CM, this compromise may result in a testing schedule that may not capture all instances of use. For example, while thrice-weekly testing may be ideal for cocaine or opioids, a twice-weekly schedule may be selected because it lowers costs and is more consistent with clinic schedules.

Immediacy

In general, clinics should aim to deliver reinforcement as immediately as possible, as delays between the target behavior and reinforcement are associated with decreased treatment effects [10,11,83]. For drug abstinence, onsite urine testing systems that provide immediate results are preferred over sending samples for laboratory testing. Clinics that do not have access to or who cannot afford specimen testing that allows onsite collection and immediate results might consider other options for target behaviors, such as attendance.

Immediacy of reinforcement is also important when targeting attendance. One clinic [53] implemented a program that offered a $50 incentive if clients attended 1 month of group therapy sessions. This approach was not effective and no clients earned the incentive for several months. After consultation, the clinic revised the incentive program to a daily drawing for attendance using the fishbowl method, thereby decreasing the delay between the behavior and its consequence. This example illustrates not only problems with delayed reinforcement but also the common mistake of setting expectations for the target behavior too high. Attending a month of group therapy sessions is a high bar that few patients will achieve, resulting in a system that mostly rewards those already doing well [19]. In contrast, attending a single group session in order to earn reinforcers is a reachable goal and increases the likelihood that more clients are exposed to the reinforcers. These small steps (ie, attending a single group or submitting a single drug negative urine) encourage initiation of the behavior(s) targeted. Other features, such as escalation (discussed next), aim to sustain the behavior over time.

Escalation

Escalation involves increasing the amount of reinforcement for each consecutive target behavior. In the voucher programs, the amount earned per negative sample may increase for each consecutive negative sample (eg, $2.50 for the first negative sample, $3.00 for the second, $3.50 for the third, and so on). For prize-based programs, the number of draws escalates with consecutive performance (eg, 1 draw for the first group attended, 2 draws for the second, 3 for the third, and so on). Protocols that include escalation generate larger effects than those that have a set, flat incentive amount even when total costs are the same across comparison conditions [73].

Escalating schedules usually include a reset feature. Following a positive or refused sample or unexcused absence, the amount earned for the next negative sample is reduced to the initial amount and begins escalating anew with consecutive negative samples. Some schedules allow for a rapid reset in which after a specified period of time or consecutive performance, the value jumps to the value achieved when the relapse occurred [66].

Despite its consistent inclusion in CM protocols from randomized clinical trials, our data [61] suggest that more than half of providers using incentives in treatment as part of a clinical effort do not use escalating reinforcers. Escalating schedules require more careful tracking of client progress, possibly contributing to lower uptake of this design feature in clinical practice. Development of simple tracking forms can minimize this challenge.

Another drawback of escalation pertaining to prize-based CM is that escalating schedules can affect the duration of CM sessions when clients are drawing a large number of slips each session and escalation can increase costs of the overall program. Capping the number of draws will help mitigate both issues. For example, once a client reaches 10 draws for group attendance, they continue earning 10 draws for each consecutive session attended with no further escalation.

Putting It All Together

CM sessions can be conducted as stand-alone sessions or incorporated into group or individual therapy sessions. Many clinicians will find the latter approach sets a positive tone for the therapy session given CM's focus on what the client is doing well. Starting the treatment session with the CM component often naturally leads into a discussion of relevant therapeutic issues, such as effective coping, slips, or triggers. The CM session length can be variable, but it is typically under 10 minutes. Thus, the CM component need not dominate the clinical session or content. CM sessions for abstinence are scheduled according to a set schedule (eg, Mondays and Thursdays) and often coincide with other treatment aspects (eg, before or after group therapy on Mondays and Thursdays). CM sessions for attendance also generally follow a set schedule (eg, client expected to attend Monday and Wednesday group therapy sessions). The duration of the CM protocol can also vary, with most clinical trials ranging from 12 to 24 weeks. Very short durations are unlikely to produce lasting behavior change, particularly with complex behaviors such as abstinence. Petry [44] recommends no less than 8 weeks duration and a maximum duration of 24 weeks.

As discussed, CM offers many opportunities for tailoring to optimize its fit within the existing structure of clinics. However, this flexibility must be viewed together with an understanding of the principles that impact CM's efficacy. Specific recommendations for CM protocol development will depend on the behavior targeted, the delivery methods, and format (eg, individual versus group settings). For these reasons, consultation with a CM expert is ideal. However, some general guidelines for developing a CM program that incorporate the principles discussed above include an 8- to 12-week program that (1) provides sufficient magnitude to compete with the behavior you are attempting to change, (2) offers frequent opportunities for reinforcement (eg, 2-3 times/wk for opioids or stimulant abstinence, 1-2 times/week for attendance targets; not less than weekly for most behaviors), (3) delivers the reinforcement immediately or very close in time with the behavior (eg, reinforce attendance at the beginning of the group, use onsite urine testing and reinforce immediately after testing), and (4) incorporates escalating and reset features into the schedule.

Clinician Training and Supervision

Training in CM is an important part of the implementation process. Studies [62,84–87] have identified a number of perceived barriers to and negative beliefs about CM, including philosophical and logistical concerns. Tangible incentives, the core of most CM protocols, are generally viewed less favorably than social or nonspecified incentives [84,86,87]. Philosophical concerns relate to CM’s inability to address the underlying causes of addiction, that it does not address multiple behaviors, and that it may undermine internal motivation for sobriety [62,84]. An additional objection relates to paying someone to do what they should do on their own [86]. Logistical and practical concerns often represent implementation barriers such as costs and access to training and supervision, but they also reflect concern for what happens when contingencies are withdrawn, that clients may sell or trade prizes for drugs, and worries that CM’s evidence does not generalize to clinic populations [62].

Many of these beliefs reflect a limited understanding of CM, and addressing these misperceptions is a first step toward reducing resistance to implementation efforts. For example, a substantial body of literature points to CM’s wide generalizability across a range of characteristics, clients that sell or trade prizes for drugs are likely to disrupt their chain of negative samples or attendance, and most studies do not find negative impacts of CM on intrinsic motivation [88–90]. Fortunately, CM training appears to be an effective way to address negative beliefs. In the VA implementation effort [52], training workshops decreased perceived barriers and increased positive impressions of CM [91]. In other training efforts, brief educational materials were effective in changing perceptions of CM’s efficacy [92].

Beyond initial training, supervision of CM delivery is likely to be necessary [93,94]. Clinician skill in delivering CM is related to client outcomes [93,95] and relatively simple adherence measures are available for monitoring [96,97]. However, the best methods for training and supervision of CM have yet to be established. The VA initiative was developed in consultation with CM experts and employed ongoing phone consultation following initial training workshops [52,91]. This approach represented significant investment by the VA toward staff training and CM protocol development that may not be achievable for individual clinics. As attention to CM’s dissemination and implementation has grown, some free resources have been developed. Promoting Awareness of Motivational Incentives (PAMI; www.bettertxoutcomes.org/bettertxoutcomes/PAMI.html) is a collaborative initiative sponsored by the National Institute of Drug Abuse and the Substance Abuse and Mental Health Services Administration. It offers free resources and training materials.

Conclusion

Overall, CM is a highly efficacious treatment for SUDs that generalizes to most clients. Despite a robust evidence base, CM’s implementation in clinical settings lags behind other empirically supported treatments [92]. At least in part, CM’s costs, which include not only staff training and adherence monitoring (as with other treatments), but also costs of the incentives themselves, may contribute to slow uptake in clinical settings. Clinics often do not have the resources available for CM within their operating budgets. However, a growing number of projects [19,52,53,55–57,70,71] illustrate CM implementation within routine clinical care, and increased revenue from improved attendance to treatment groups may be one mechanism through which to fund a CM program [54,56,57]. These projects are valuable not only for demonstrating that CM can be efficacious outside the research setting, but also for highlighting how implementation barriers can be overcome. Continued efforts of this nature are likely to be particularly valuable for clinicians and administrators considering adopting CM within clinical settings.

From UConn Health, Farmington, CT.

Abstract

• Objective: To discuss the efficacy and generalizability of contingency management (CM) for the treatment of substance use disorders and design considerations for those considering implementing in clinical settings.
• Methods: Review of the literature.
• Results: CM is an efficacious treatment for substance abuse disorders that is widely generalizable across substance use disorders and patient characteristics. CM can be implemented in a number of treatment programs, including residential and outpatient settings, and it can be administered in both individual and group formats. Abstinence and attendance are the most commonly targeted behaviors in substance abuse treatment settings. Design features, including the selection of target behaviors, delivery methods, and reinforcers, are discussed. Schedule parameters, such as frequency, magnitude, immediacy, and escalation of reinforcement, are associated with overall impact of the CM program and are important considerations for those interested in tailoring CM protocols to their needs.
• Conclusion: CM is an efficacious option that is applicable to most substance abuse treatment patients. A number of demonstrations of real-world implementation have been published and suggest CM can be adapted with success to clinic settings. In adopting CM protocols, clinics should aim for those protocols with established efficacy; however, if adaptations are necessary, careful consideration should be given to modifications to minimize risks of undermining CM’s effects.

Key words: incentives; reinforcement; substance abuse treatment; dissemination; implementation.

Contingency management (CM) is a behavioral intervention that is efficacious in the treatment of substance use disorders (SUDs). CM uses a behavior analytic framework and applies principles of learning theory, particularly operant conditioning theory, to change client behavior(s) [1–5]. In basic terms, operant conditioning principles suggests that whether a behavior continues or not is a function of consequences [6]. Reinforced behaviors are more likely to occur in the future. Substance abuse can be viewed as a behavior maintained by the reinforcing effects of the drug itself [5], including the feel-good aspects of intoxication or relaxation and the amelioration of withdrawal symptoms. CM extends these same principles of to a treatment context, such that reinforcers for abstinent behavior are introduced to compete with the reinforcing effects of continued drug use [5].

In CM’s application to substance abuse treatment, drug-negative samples or treatment attendance are reinforced using tangible incentives with the goal of motivating continued abstinence and/or treatment engagement. When clients demonstrate these target behaviors, they earn incentives in the form of goods or services of value to the client, such as small electronics, gift cards, and toiletries. Despite the promising effects observed in research trials, real-world implementation efforts have not kept pace [7–9]. This review briefly discusses CM’s efficacy and highlights key features for professionals considering adopting this intervention. Demonstration efforts that illustrate how CM can be effectively implemented within the constraints and limitations of non-research, clinical settings are also presented.

Efficacy of CM

CM’s efficacy spans a number of SUDs, including cocaine, opioids, alcohol, nicotine, and marijuana [10–13], making it amenable for treatment of most SUD clinic populations. It generates larger effect sizes than other SUD treatments, including cognitive behavioral therapy [14], and it has been evaluated in a wide range of settings. Large-scale evaluations have been conducted in both intensive outpatient [15] and methadone maintenance [16] settings as part of the National Institute on Drug Abuse Clinical Trials Network, demonstrating consistent benefits of CM when added to treatment as usual. In the first of these 2 studies, Petry et al [15] randomized 415 stimulant users from 1 of 8 intensive outpatient clinics to treatment as usual or treatment as usual plus CM for alcohol and stimulant abstinence. CM participants submitted more substance-negative urine and breath samples, achieved continuous abstinence at significantly higher rates, and had longer treatment retention compared to those receiving treatment as usual. The parallel study [16] focused on stimulant use in clients from methadone maintenance clinics and found similar benefits of CM on stimulant abstinence. Beyond these settings, CM has been applied in a number of other contexts, including drop-in centers [17], vocational rehabilitation [18,19], job-skills training [20], and residential programs [21–23]. In addition, several group-based adaptations have been explored [17,24–27].

CM benefits most clients and generalizes across several demographic variables, including gender [28,29], race [30], housing status [31], and income levels [32–34]. Among clinical characteristics, CM is efficacious for those with co-occurring SUDs [35], other substance use [36], psychiatric disorders [37–39], medical problems [40–42], and history of transactional sex [43].

Design Considerations

Design features, including what behavior will be reinforced and how to do so, are among the first decision points for clinicians interested in implementing CM. One of the advantages of CM is that it has a high degree of flexibility in design, which means that it can be readily tailored to client populations and clinic needs. However, this flexibility can lead clinicians astray from the foundational principles of CM and unknowingly weaken the impact of the program. Below, some key considerations for CM protocol design are reviewed. For additional coverage of these topics, readers are referred to additional articles [1,2] or Petry’s comprehensive book on implementing CM [44]. In this review, published examples of CM’s application in real-world settings are presented, highlighting how CM has been adapted in these clinical efforts.

Target Behaviors

The selection of the target behavior will drive many of the subsequent program design decisions. As such, it is important to identify this feature early. Target behaviors must be achievable, objectively verifiable, and well defined. The most common CM targets are drug abstinence or therapy session attendance. CM has also been used to target other behaviors, such as medication adherence [45,46], treatment-related activities [47,48], and exercise [49–51]. Client self-report of behaviors or vaguely defined behaviors (eg, “good participation”) should be avoided. While some of the decisions related to CM protocols are flexible, the use of objectively verifiable target behaviors is a core feature that should not be neglected. If the behavior of interest cannot be objectively verified, an alternate behavior should be chosen.

Selection of the target behavior is often considered in hand with defining which population is eligible to participate in the CM program. Client characteristics are often forefront in this decision, but clinic-driven logistical issues or unmet needs may also play a role. A real-world example of this decision process is evident in the nationwide rollout of CM among the intensive outpatient programs within the Veterans Administration (VA). The VA identified a treatment need for those with stimulant use disorders, as this group did not have efficacious pharmacotherapy options available that targeted stimulant use. As such, the VA applied CM to patients with a focus on stimulant abstinence as the behavioral target [52]. For others, the decision may revolve around addressing underutilization of specific treatment resources (eg, outpatient groups, vocational rehabilitation) [53–56] or treatment needs among certain subgroups of clients, such as adolescents [57–59].

For abstinence targets, clinics would need to select one or more specific substances as the focus of the CM program. In general, targeting a single substance rather than multiple substances is more effective [10,13], is more straightforward for clients to understand, and allows more clients to access the reinforcers. Exposure to the reinforcers is necessary for CM to work; thus, setting a goal that is achievable for most clients should be a priority. Requiring abstinence from multiple substances means that some clients may never experience the reinforcer and thus cannot benefit from its effects at all. Some clinicians or administrators may initially have reservations about reinforcing single drug abstinence in the event that other drug use continues. However, targeting a single substance for reinforcement often results in reduced use of other substances [60]. Clinicians may find that this makes intuitive sense; a client with cocaine use disorder who is trying to maintain cocaine abstinence over a long period is likely to avoid using alcohol or other substances that might lead to relapse. For abstinence, objective verification through urine or breath specimens using tests that include validity checks is relatively straightforward.

Attendance is a popular target for clinics in part because it does not require additional staff time to collect specimen samples and it was the most commonly reported target behavior in samples of SUD providers who use incentives [61,62]. Objective verification of attendance is usually via a staff member, but expectations must be clear to both parties. Clinics should consider potential problems that may arise (eg, arriving late, leaving group early, excused absences) and carefully define and communicate expectations for the CM program. Piloting [19] the CM program with a small group of clients may be valuable in trouble-shooting challenges before wider implementation.

In a recent study [55], clients earned reinforcers for attending clinician-led group counseling sessions and/or the in-clinic patient-led Methadone Anonymous (MA) groups. This non-research, clinical effort addressed historically poor therapy attendance at the clinic, and attendance rates were compared before, during, and after the CM program. CM increased attendance to both groups in the short-term after implementation, but effects were more robust for the MA groups in which increased attendance persisted 3 months following the withdrawal of the contingencies. Overall effects of this program were modest, but they are notable given the use of an ultra-low cost approach.

Delivery Methods

The majority of CM studies used voucher or prize-based methods. Head-to-head comparisons suggest that they are comparable in efficacy [63–65], and each has advantages and disadvantages that may make one option more appealing for a given clinic. Voucher programs are generally straightforward to administer. Clients earn vouchers for each instance of the target behavior. The value of the vouchers typically increases with consecutive performance. The schedule used in the influential Higgins et al studies [66,67] started at $2.50 for the first cocaine-negative sample and increased by $0.50 for each subsequent consecutive cocaine-negative sample. Earned vouchers are exchanged for goods or services selected by the client, increasing the likelihood that the selected items will be highly desirable and allowing for a wide range of client preferences. Clients appear to prefer this approach when given a choice between set schedules or those that introduce an element of chance (ie, prize-based CM, discussed below) [68]. However, voucher programs can be costly (~$1000 per client over 12 weeks) and may require more staff time to fulfill individual requests for specific items. However, staff burden related to shopping can be reduced by limiting these individual requests and using an on-site stocked cabinet of goods similar to prize-CM programs.

Prize-based CM is similar but introduces probabilistic earnings and variability in prize magnitude. Rather than earning vouchers, clients earn draws from a fishbowl for each instance of the target behavior, again typically in an escalating manner. For example, a client may earn one draw from the fishbowl for the first cocaine-negative sample, 2 draws for the second consecutive negative sample, 3 draws for the third, and so on. A typical fishbowl is composed of 500 slips, some noting prizes and some having no prize value. Typically, half the slips in the bowl are non-monetary “good jobs.” The remaining half are small prizes worth about $1 in value (eg, food coupons, bus tokens, small toiletries), large prizes worth about $20 in value (eg, small electronics, gift certificates), and one slip is the jumbo prize worth about $100. When a client draws a winning slip, they select a prize from that category (ie, small, large, jumbo) from an onsite, stocked cabinet. Due to the probabilistic feature of prize-based CM, overall costs of the program can be substantially lower than typical voucher programs, with average maximum expected earnings ranging $250 t $450 per client over a 12-week treatment period [15,16,65,69]. Advantages of this method include potentially lower costs and minimal shopping demands (a once-monthly shopping trip to restock the cabinet will usually suffice) while maintaining comparable efficacy. Relative to voucher programs, prize-based CM involves additional administration time to allow for drawing slips from the fishbowl, which can be compounded when multiple clients want to draw at the same time such as in a group setting. Many of the group-based CM adaptations address this issue by limiting the number of clients who can draw for prizes in a given group or by limiting the number of draws per client [25,27,54].

Reinforcers

Regardless of whether selecting voucher or prize CM, reinforcers are critically important to the success of the program. Reinforcers must be desirable. One of the quickest ways to undermine a CM program is lack of variety or undesirable reinforcers. If stocking a cabinet with prizes onsite, care should be taken to have numerous options within each of the small and large prize categories that are appealing to a wide range of clients. Since a client who is consistently earning draws will choose prizes often, it is imperative to include enough variety so that even these clients find desirable items each time they select a prize. Clients should be asked regularly if they have suggestions for prizes; one program [54] found suggestion boxes useful for encouraging clients to voice their preferences. Donations can be solicited from local businesses to reduce costs [53], and low-cost but high-value options, such as clinic privileges, can also be explored. Petry [1,44] provides some suggestions of the latter, and Amass and Kamien [70] describe their successful strategies to fund and sustain a clinic-based CM program through community donations. Some clinics may already have tangible goods, such as gas or metro cards, that are offered to clients based on need rather than behavior [53]. These existing resources might be redirected to a CM program, in which these goods are contingent on abstinence or attendance, if appropriate.

Schedule Parameters

Once the target behavior, client population, and CM delivery methods are selected, the next step is to design the reinforcement schedule. The following schedule parameters apply to both voucher and prize-based CM systems. The more closely a clinical program adheres to the parameters of effective protocols, the more likely the program is to generate comparable outcomes. If there is a parameter or design feature that is incompatible with clinic needs, modifications can be introduced. However, each deviation away from the ideal has a chance of undermining the success of the CM program. Any changes and their potential impacts should considered carefully, and consultation with a CM expert may aid in the development of successful and efficacious clinic-based protocols. Of note, a meta-analysis [13] of CM studies found that researcher involvement in the planning and design of CM programs is associated with larger treatment effects. CM researchers are especially attuned to the potential impacts and pitfalls associated with modifying CM protocols, and they can be valuable resources for clinics interested in tailoring a CM program to their specific needs. Several examples of clinical demonstration projects that used researcher input are available [19,53,71].

Magnitude

Incentive magnitude was directly related to the size of treatment effects in a meta-analysis [11] of CM studies. Although not all studies find significant differences in outcomes related to magnitude [65,72], the bulk of evidence suggests magnitude is an important parameter and is related to effect size for both voucher [73–75] and prize-based CM [69,76] systems. Thus, although clinics may have restrictive budgets, severely undercutting the magnitude of rewards is not usually the solution as it can undermine treatment effects [76]. Donations can reduce overall costs [53,57,70], and other protocol features discussed below, such as capping the amount of reinforcement available, can reduce the overall magnitude available per patient.

Another approach, used in group-based CM, limits the number of patients who earn prizes per week [25,27]. For example, in a 2011 study by Petry et al, clients added slips with their name to a bowl for attendance and negative samples. Once all names were collected in the bowl, the group leader would pull a specified number of slips (eg, 3 slips per group). These individuals were eligible to draw from the prize bowl for prizes. This approach was associated with longer durations of consecutive abstinence and better treatment attendance relative to treatment as usual. However, clinics can control the overall program costs by limiting the number of patients eligible for prizes.

Frequency

Frequent reinforcement opportunities are ideal, and more frequent assessment is associated with larger treatment effects [10]. However, a number of factors, including which target behavior is selected and logistical issues specific to the clinic such as when groups meet, will play a role in determining the frequency of CM sessions. For abstinence targets, the substance targeted and type of test will largely determine the frequency of CM sessions. The goal would be to test at a frequency that would detect most or nearly all instances of use. For cocaine or opioids, this equates to testing 2 to 3 times weekly. Breath samples for alcohol or cigarette smoking would necessitate testing daily or multiple times per day to detect most instances of use because these tests have short windows of detection. CM protocols based on these breath tests have often had daily or twice daily CM sessions [77,78]; technological adaptations [77,79,80] or residential settings [21,23] may reduce burden to the client for assessment of these substances. Tapering the number of breath tests over time or transitioning from daily breath tests to once or twice weekly urine testing after abstinence is established is another approach [81,82].

Marijuana, on the other hand, poses difficulties because it is detectable in urine samples for up to 2 weeks following use. If relying solely on urine results for reinforcement, clients may not test negative for several days or weeks after last use, resulting in a delay of reinforcement. To address this issue, some CM programs targeting marijuana abstinence initially reinforce attendance in the first 2 weeks and then transition to reinforcing marijuana-negative drug samples for the remainder of the treatment period [48].

In general, more frequent CM sessions can translate to higher costs; however, infrequent reinforcement (ie, less than weekly) is not as effective [45]. In real-world applications, clinics often need to balance feasibility and costs with the ideal CM schedule. In abstinence-based CM, this compromise may result in a testing schedule that may not capture all instances of use. For example, while thrice-weekly testing may be ideal for cocaine or opioids, a twice-weekly schedule may be selected because it lowers costs and is more consistent with clinic schedules.

Immediacy

In general, clinics should aim to deliver reinforcement as immediately as possible, as delays between the target behavior and reinforcement are associated with decreased treatment effects [10,11,83]. For drug abstinence, onsite urine testing systems that provide immediate results are preferred over sending samples for laboratory testing. Clinics that do not have access to or who cannot afford specimen testing that allows onsite collection and immediate results might consider other options for target behaviors, such as attendance.

Immediacy of reinforcement is also important when targeting attendance. One clinic [53] implemented a program that offered a $50 incentive if clients attended 1 month of group therapy sessions. This approach was not effective and no clients earned the incentive for several months. After consultation, the clinic revised the incentive program to a daily drawing for attendance using the fishbowl method, thereby decreasing the delay between the behavior and its consequence. This example illustrates not only problems with delayed reinforcement but also the common mistake of setting expectations for the target behavior too high. Attending a month of group therapy sessions is a high bar that few patients will achieve, resulting in a system that mostly rewards those already doing well [19]. In contrast, attending a single group session in order to earn reinforcers is a reachable goal and increases the likelihood that more clients are exposed to the reinforcers. These small steps (ie, attending a single group or submitting a single drug negative urine) encourage initiation of the behavior(s) targeted. Other features, such as escalation (discussed next), aim to sustain the behavior over time.

Escalation

Escalation involves increasing the amount of reinforcement for each consecutive target behavior. In the voucher programs, the amount earned per negative sample may increase for each consecutive negative sample (eg, $2.50 for the first negative sample, $3.00 for the second, $3.50 for the third, and so on). For prize-based programs, the number of draws escalates with consecutive performance (eg, 1 draw for the first group attended, 2 draws for the second, 3 for the third, and so on). Protocols that include escalation generate larger effects than those that have a set, flat incentive amount even when total costs are the same across comparison conditions [73].

Escalating schedules usually include a reset feature. Following a positive or refused sample or unexcused absence, the amount earned for the next negative sample is reduced to the initial amount and begins escalating anew with consecutive negative samples. Some schedules allow for a rapid reset in which after a specified period of time or consecutive performance, the value jumps to the value achieved when the relapse occurred [66].

Despite its consistent inclusion in CM protocols from randomized clinical trials, our data [61] suggest that more than half of providers using incentives in treatment as part of a clinical effort do not use escalating reinforcers. Escalating schedules require more careful tracking of client progress, possibly contributing to lower uptake of this design feature in clinical practice. Development of simple tracking forms can minimize this challenge.

Another drawback of escalation pertaining to prize-based CM is that escalating schedules can affect the duration of CM sessions when clients are drawing a large number of slips each session and escalation can increase costs of the overall program. Capping the number of draws will help mitigate both issues. For example, once a client reaches 10 draws for group attendance, they continue earning 10 draws for each consecutive session attended with no further escalation.

Putting It All Together

CM sessions can be conducted as stand-alone sessions or incorporated into group or individual therapy sessions. Many clinicians will find the latter approach sets a positive tone for the therapy session given CM's focus on what the client is doing well. Starting the treatment session with the CM component often naturally leads into a discussion of relevant therapeutic issues, such as effective coping, slips, or triggers. The CM session length can be variable, but it is typically under 10 minutes. Thus, the CM component need not dominate the clinical session or content. CM sessions for abstinence are scheduled according to a set schedule (eg, Mondays and Thursdays) and often coincide with other treatment aspects (eg, before or after group therapy on Mondays and Thursdays). CM sessions for attendance also generally follow a set schedule (eg, client expected to attend Monday and Wednesday group therapy sessions). The duration of the CM protocol can also vary, with most clinical trials ranging from 12 to 24 weeks. Very short durations are unlikely to produce lasting behavior change, particularly with complex behaviors such as abstinence. Petry [44] recommends no less than 8 weeks duration and a maximum duration of 24 weeks.

As discussed, CM offers many opportunities for tailoring to optimize its fit within the existing structure of clinics. However, this flexibility must be viewed together with an understanding of the principles that impact CM's efficacy. Specific recommendations for CM protocol development will depend on the behavior targeted, the delivery methods, and format (eg, individual versus group settings). For these reasons, consultation with a CM expert is ideal. However, some general guidelines for developing a CM program that incorporate the principles discussed above include an 8- to 12-week program that (1) provides sufficient magnitude to compete with the behavior you are attempting to change, (2) offers frequent opportunities for reinforcement (eg, 2-3 times/wk for opioids or stimulant abstinence, 1-2 times/week for attendance targets; not less than weekly for most behaviors), (3) delivers the reinforcement immediately or very close in time with the behavior (eg, reinforce attendance at the beginning of the group, use onsite urine testing and reinforce immediately after testing), and (4) incorporates escalating and reset features into the schedule.

Clinician Training and Supervision

Training in CM is an important part of the implementation process. Studies [62,84–87] have identified a number of perceived barriers to and negative beliefs about CM, including philosophical and logistical concerns. Tangible incentives, the core of most CM protocols, are generally viewed less favorably than social or nonspecified incentives [84,86,87]. Philosophical concerns relate to CM’s inability to address the underlying causes of addiction, that it does not address multiple behaviors, and that it may undermine internal motivation for sobriety [62,84]. An additional objection relates to paying someone to do what they should do on their own [86]. Logistical and practical concerns often represent implementation barriers such as costs and access to training and supervision, but they also reflect concern for what happens when contingencies are withdrawn, that clients may sell or trade prizes for drugs, and worries that CM’s evidence does not generalize to clinic populations [62].

Many of these beliefs reflect a limited understanding of CM, and addressing these misperceptions is a first step toward reducing resistance to implementation efforts. For example, a substantial body of literature points to CM’s wide generalizability across a range of characteristics, clients that sell or trade prizes for drugs are likely to disrupt their chain of negative samples or attendance, and most studies do not find negative impacts of CM on intrinsic motivation [88–90]. Fortunately, CM training appears to be an effective way to address negative beliefs. In the VA implementation effort [52], training workshops decreased perceived barriers and increased positive impressions of CM [91]. In other training efforts, brief educational materials were effective in changing perceptions of CM’s efficacy [92].

Beyond initial training, supervision of CM delivery is likely to be necessary [93,94]. Clinician skill in delivering CM is related to client outcomes [93,95] and relatively simple adherence measures are available for monitoring [96,97]. However, the best methods for training and supervision of CM have yet to be established. The VA initiative was developed in consultation with CM experts and employed ongoing phone consultation following initial training workshops [52,91]. This approach represented significant investment by the VA toward staff training and CM protocol development that may not be achievable for individual clinics. As attention to CM’s dissemination and implementation has grown, some free resources have been developed. Promoting Awareness of Motivational Incentives (PAMI; www.bettertxoutcomes.org/bettertxoutcomes/PAMI.html) is a collaborative initiative sponsored by the National Institute of Drug Abuse and the Substance Abuse and Mental Health Services Administration. It offers free resources and training materials.

Conclusion

Overall, CM is a highly efficacious treatment for SUDs that generalizes to most clients. Despite a robust evidence base, CM’s implementation in clinical settings lags behind other empirically supported treatments [92]. At least in part, CM’s costs, which include not only staff training and adherence monitoring (as with other treatments), but also costs of the incentives themselves, may contribute to slow uptake in clinical settings. Clinics often do not have the resources available for CM within their operating budgets. However, a growing number of projects [19,52,53,55–57,70,71] illustrate CM implementation within routine clinical care, and increased revenue from improved attendance to treatment groups may be one mechanism through which to fund a CM program [54,56,57]. These projects are valuable not only for demonstrating that CM can be efficacious outside the research setting, but also for highlighting how implementation barriers can be overcome. Continued efforts of this nature are likely to be particularly valuable for clinicians and administrators considering adopting CM within clinical settings.

Case 1 Lola, 28, has a history of muscular aches and joint pain throughout her body, fatigue, and mental fogginess. A rheumatologist diagnosed fibromyalgia, but Lola just moved to your town and is establishing care. She is feeling desperate because her pain has worsened and the medication previously prescribed (gabapentin 300 mg tid) is no longer working. She asks to try oxycodone.

Case 2 Matt is a 59-year-old truck driver with severe hip osteoarthritis (OA). His orthopedist recommended against hip replacement at this time because of his young age and a heart condition that makes him high risk. His pain makes sitting for long periods very difficult. He presents to you for help because he is worried he will be unable to continue working.

Case 3 Keith is a 56-year-old construction worker who has been experiencing back pain for many years. The pain has become more debilitating over time; it is now constant, and Keith can hardly make it through his work day. He has been getting hydrocodone/acetaminophen from urgent care centers and emergency departments, but he isn’t sure it is helping and is coming to you to assume his pain management.

Chronic pain (defined as > 3 mo in duration) is a complex, heterogeneous condition affecting an estimated 116 million US adults.¹ Much of the management of chronic pain occurs in primary care settings, placing family practice providers (FPPs) on the frontlines of two epidemics: that of chronic pain and that of the abuse and misuse of opioid pain medications.

To improve communication about the risks and benefits of opioid therapy and the safety and effectiveness of pain treatments in general, many professional organizations, health care institutions, and recently the CDC, have published guidelines on the use of opioids for nonmalignant chronic pain.² With these guidelines in mind—and in light of the latest evidence—we propose the following paradigm for the treatment of chronic pain. A critical aspect is determining the underlying pathophysiology of a patient’s pain in order to develop a well-rounded, multimodal, evidence-based treatment plan. Detailed here is the application of this approach to the treatment of three common diagnoses: fibromyalgia, osteoarthritis, and low back pain.

LOOK TO THE CENTRAL AND PERIPHERAL NERVOUS SYSTEM

Acute pain begins with activation of peripheral nociceptors at the site of injury. This causes depolarization up the spinal cord and through the brain stem to higher cortical centers where the pain is perceived and localized. Descending neural pathways transport both excitatory and inhibitory information from the brain to the periphery via the spinal cord, which either increases or decreases the perception of pain.³

When damage/injury doesn’t correlate with the perception of pain

Until recently, it was assumed that chronic pain worked much the same way as acute pain and was caused by ongoing nociceptive input in the periphery, but research has shown us that the central nervous system (CNS) can play a large role in the modulation of nociception. This new understanding comes from the lack of evidence pointing to any pain state in which the degree of nociceptive input correlates with the degree of pain experienced.

For most patients with chronic pain, regardless of their diagnosis, there is some degree of alteration in the processing of nociceptive signals by the CNS contributing to the experience of pain.⁴ This alteration is thought to result from peripheral nociceptive signaling persisting past the point of tissue healing, leading to a hypersensitivity of nerve fibers, which then continue to respond to low, or absent, sensory stimuli.

Central sensitization is when this hypersensitivity develops in the superficial, deep, and ventral cord nerves. When this happens, pain is often accompanied by systemic symptoms such as fatigue and slowed cognitive processing, often with little to no actual stimulation of the peripheral nociceptors.³

Table 1 lists the possible mechanisms of pain, which can be broken down into four categories: peripheral nociceptive (inflammatory or mechanical), peripheral neuropathic (underlying damage to a peripheral nerve), central (when the CNS is the primary entity involved in maintaining the pain), or any combination of the three.⁴

As pain becomes chronic, multiple mechanisms overlap

It is important to remember that for any single pain diagnosis, there is likely to be—at least initially—a principle underlying mechanism generating the pain. But as the pain becomes chronic, an overlap of multiple mechanisms develops, with central sensitization often playing a more dominant role than peripheral stimulation (regardless of the diagnosis).

For example, in a patient with rheumatoid arthritis (RA), peripheral nociceptive input (in the form of inflammation) is likely the initial mechanism at work, but as time goes on, central processing becomes more involved. The patient may then begin to experience pain that is disproportionate to what is generally expected with RA and may develop other somatic symptoms. The diagnosis then becomes pain primarily related to RA with central sensitization, and both need to be addressed in a treatment plan. In rheumatic conditions, comorbid fibromyalgia (indicative of central sensitization) is thought to occur in 15% to 30% of patients.⁵

FPPs can utilize the underlying mechanisms to cut across diagnostic labels and tailor treatments to those that are most likely to be effective. For a patient with more prominent peripheral involvement, a procedural intervention such as injections or surgery alone may suffice, whereas a broader approach including psychotherapy, medications, exercise, and other lifestyle interventions may be necessary for a patient with pain caused predominantly by central sensitization.

Addressing both peripheral and central components is essential. One prospective, observational cohort study of more than 600 patients scheduled for unilateral total knee or total hip arthroplasty found that patients with a higher degree of centralization of pain (measured by widespread pain index and modified fibromyalgia screening scales) were less likely to report improvement in the affected body part and in overall body pain following surgery.^6,7

There is a high degree of overlap among many of the chronic pain syndromes (fibromyalgia, irritable bowel syndrome, interstitial cystitis, chronic headaches) that have been found to have a central sensitization component.⁸ Providers of primary care are aptly positioned to recognize central sensitization as the underlying pathology and target treatment effectively.

TAILOR TREATMENT TO THE UNDERLYING MECHANISMS OF PAIN

As with any chronic condition, a thorough workup (complete with history, physical exam, and diagnostic testing, as appropriate) is indicated. In the setting of chronic pain, it’s important to identify the primary mechanism, as well as secondary factors that may contribute to the patient’s pain, before developing your treatment plan. These secondary factors may include co-occurring affect disorders, a history of trauma, poor sleep, and tobacco use.^9-12 A history of trauma, for example, co-exists with many pain syndromes. For these patients, central sensitization is responsible for much of their pain. As a result, traditional cognitive behavioral therapy (CBT) may not be the best option because of its focus on accepting pain as a chronic diagnosis; more trauma-focused treatments, such as those dealing in emotional awareness and understanding of the CNS’s role in chronic pain, need to be considered.¹³

Three common conditions. Below we present evidence-based treatment approaches for conditions typically associated with each of the major mechanisms of chronic pain: fibromyalgia (central sensitization), OA (peripheral nociceptive), and low back pain (mixed pain state).

Fibromyalgia: a case of central sensitization

Fibromyalgia is a hallmark diagnosis for patients in whom central sensitization is the dominant cause of pain. They usually present with widespread, diffuse pain and somatic symptoms such as fatigue, memory difficulties, and poor sleep quality.⁸ When explaining the pain mechanism to patients, it may be useful to use the analogy of a volume control dial that is stuck in the “high” position and can’t be turned down.

Genes, the environment, and neurotransmitters play a role. The origin of the pain amplification process is believed to be multifactorial.

Genetic factors are thought to contribute to a predisposition for amplification. To date, five sets of genes have been implicated in increased sensitivity to pain leading to increased risk of the development of chronic pain during a patient’s lifetime.^14-19

Environmental factors (eg, early life trauma, physical trauma especially to the trunk, certain infections such as Lyme disease and Epstein-Barr virus, and emotional stress) may trigger or exacerbate symptoms.⁸ Of note: Only about 5% to 10% of people who experience these triggers actually develop a chronic pain state, while the rest regain their baseline health.⁴ This raises the question of whether there is a point during an acute pain episode in which one can intervene and prevent the acute pain from becoming chronic in those at higher risk.⁴

Imbalances of neurotransmitters (high glutamate; low norepinephrine, serotonin, and gamma-aminobutyric acid [GABA]) play a role in central amplification.^20-22 These substances not only affect sensory transmission, but also control levels of alertness, sleep, mood, and memory.

The diagnostic criteria for fibromyalgia were modified in 2011 to remove the tender point examination and to add somatic symptoms.⁶ These criteria can be useful in the clinical setting in identifying not only fibromyalgia itself but also the degree of “fibromyalgianess” a patient has, which is an indicator of how large a role the centralization process plays in the maintenance of chronic pain.^23,24

Treatment: multimodal and patient empowering. Evidence-based treatment options for fibromyalgia, as well as other conditions for which there is a high degree of centralized pain, can be found in Table 2.^25-36 Multimodal treatment, with an emphasis on patient knowledge and empowerment, is generally thought to be the most beneficial.^25,37 Treatment should almost always include CBT and exercise/activity therapies, which have high degrees of efficacy with few adverse effects.^26,29

In terms of medication, centrally-acting agents (tricyclic antidepressants, serotonin norepinephrine reuptake inhibitors [SNRIs], and alpha 2 delta ligands) are the most effective. There is little to no data showing benefit from anti-inflammatories or opioids in the setting of fibromyalgia. There is some data to suggest that combination therapy, for example with an SNRI (milnacipran) and an alpha 2 delta ligand (pregabalin), may provide more benefit than treating with pregabalin alone.³⁸

Complementary and alternative therapies (eg, yoga, chiropractic care, acupuncture, massage) are being studied more, and while evidence is only preliminary in terms of efficacy, there is increasing emphasis being placed on the need for patients with chronic pain to shift their treatment expectations to greater acceptance of pain and the need for ongoing self-care.²⁸

OA: an example of peripheral nociceptive pain

OA is a condition long thought to be characterized by damage to the cartilage and bone; however, as with many other pain diagnoses, there is frequently little correlation between damage seen on radiographs and the amount of pain that patients experience.

One study analyzed data on almost 7,000 patients from the National Health and Nutrition Examination Survey (NHANES I) and found that between 30% and 50% of OA patients with moderate to severe radiographic changes were asymptomatic, and 10% of those with moderate to severe pain had normal radiographs or only mild changes.³⁹ Research is showing that many factors may contribute to this discrepancy, including the typical “wear and tear” of the disease, subacute levels of inflammation that can lead to peripheral sensitization, and, in some patients, a centralized pain component.⁴⁰ The patients with more centralized pain often have pain that is disproportionate to radiographic evidence, as well as more somatic symptoms, such as fatigue, sleep disturbance, and memory issues.⁴¹

Treatment should be multimodal and include interventions targeted at halting the progression of damage as well as palliation of pain. All treatment plans for OA should also include exercise, weight reduction, and self-management, in addition to pharmacologic interventions, to reduce both the micro-inflammation and the centralized pain component (when present). Intra-articular injections of various types have been studied with some having more efficacy in pain reduction and functional improvement than others.^42-45 See Table 3 for a summary of evidence-based treatment options.^42-61

Low back pain: a mixed pain state

Low back pain (LBP) has been recognized as a mixed pain state for quite some time. While some patients may experience purely nociceptive and/or neuropathic pain, most cases are nonspecific, with patients experiencing varying degrees of nociceptive (myofascial LBP), neuropathic (lumbar radiculopathy), and central sensitization pain.^62,63 Evidence for centralized pain is demonstrated in studies showing hyperalgesia, augmented central pain processing, involvement of the emotional brain, and delayed recovery influenced by poor coping strategies.^64-67

When developing a treatment plan for a patient with chronic LBP, remember that the pain derives from a complex combination of pathophysiologic contributors. Identifying where a patient lies on the pain centralization spectrum can help you tailor treatment.

In one study of 548 patients presenting to a tertiary pain clinic with primary spine pain diagnoses, 42% met diagnostic criteria for fibromyalgia.⁶⁸ Compared to criteria-negative patients, these patients tended to be younger, unemployed, and receiving compensation; they had greater pain intensity, pain interference, and used stronger words to describe their neuropathic pain, as well as having higher levels of depression/anxiety and a lower level of physical function.

Because LBP is a condition with high prevalence and associated disability, many clinical boards have created guidelines for management. These guidelines tend to vary in the strength of evidence used, and the extent to which they are followed in clinical practice remains largely unknown. Recommendations frequently discourage the use of ultrasound/electrotherapy, but many encourage short-term use of medications, supervised exercise therapy, CBT, and multidisciplinary treatment.

Guidelines tend to differ most widely with regard to recommendations for spinal manipulation and specific drug therapies.⁶⁹ The classes of drugs that may be most useful when centralized pain is present include the SNRIs and the alpha 2 delta calcium channel ligands.⁴ See Table 4 for a summary of evidence-based treatment options.^70-89

Case 1 Lola is started on amitriptyline 25 mg at bedtime, which improves her fatigue and cognitive symptoms. During monthly office visits, her FPP educates her about the pathophysiology of fibromyalgia and uses motivational interviewing to get her slowly moving and increasing her activity level. She is weaned off the gabapentin previously prescribed, as her symptoms stabilize and improve.

Case 2 Matt is sent for a steroid injection, which decreases his pain temporarily. During this time, he begins physical therapy; slowly, with increased movement, his function improves. A trial of duloxetine provides pain relief; that combined with intermittent NSAIDs has allowed Matt to maintain his function and his job.

Case 3 Because Keith was only taking the narcotics intermittently and wasn’t certain they were helping, CBT was sufficient to wean him off the medication without any worsening of his pain in the process. By participating in physical therapy, he has learned how to perform certain tasks at his job without pain or injury. He uses NSAIDs as needed for pain.

The authors thank Drs. Daniel Clauw (University of Michigan, Ann Arbor) and Martha Rumschlag (Providence Family Medicine Residency Program, Southfield, Michigan), for their valuable contributions to this article.

Case 1 Lola, 28, has a history of muscular aches and joint pain throughout her body, fatigue, and mental fogginess. A rheumatologist diagnosed fibromyalgia, but Lola just moved to your town and is establishing care. She is feeling desperate because her pain has worsened and the medication previously prescribed (gabapentin 300 mg tid) is no longer working. She asks to try oxycodone.

Case 2 Matt is a 59-year-old truck driver with severe hip osteoarthritis (OA). His orthopedist recommended against hip replacement at this time because of his young age and a heart condition that makes him high risk. His pain makes sitting for long periods very difficult. He presents to you for help because he is worried he will be unable to continue working.

Case 3 Keith is a 56-year-old construction worker who has been experiencing back pain for many years. The pain has become more debilitating over time; it is now constant, and Keith can hardly make it through his work day. He has been getting hydrocodone/acetaminophen from urgent care centers and emergency departments, but he isn’t sure it is helping and is coming to you to assume his pain management.

Chronic pain (defined as > 3 mo in duration) is a complex, heterogeneous condition affecting an estimated 116 million US adults.¹ Much of the management of chronic pain occurs in primary care settings, placing family practice providers (FPPs) on the frontlines of two epidemics: that of chronic pain and that of the abuse and misuse of opioid pain medications.

To improve communication about the risks and benefits of opioid therapy and the safety and effectiveness of pain treatments in general, many professional organizations, health care institutions, and recently the CDC, have published guidelines on the use of opioids for nonmalignant chronic pain.² With these guidelines in mind—and in light of the latest evidence—we propose the following paradigm for the treatment of chronic pain. A critical aspect is determining the underlying pathophysiology of a patient’s pain in order to develop a well-rounded, multimodal, evidence-based treatment plan. Detailed here is the application of this approach to the treatment of three common diagnoses: fibromyalgia, osteoarthritis, and low back pain.

LOOK TO THE CENTRAL AND PERIPHERAL NERVOUS SYSTEM

Acute pain begins with activation of peripheral nociceptors at the site of injury. This causes depolarization up the spinal cord and through the brain stem to higher cortical centers where the pain is perceived and localized. Descending neural pathways transport both excitatory and inhibitory information from the brain to the periphery via the spinal cord, which either increases or decreases the perception of pain.³

When damage/injury doesn’t correlate with the perception of pain

Until recently, it was assumed that chronic pain worked much the same way as acute pain and was caused by ongoing nociceptive input in the periphery, but research has shown us that the central nervous system (CNS) can play a large role in the modulation of nociception. This new understanding comes from the lack of evidence pointing to any pain state in which the degree of nociceptive input correlates with the degree of pain experienced.

For most patients with chronic pain, regardless of their diagnosis, there is some degree of alteration in the processing of nociceptive signals by the CNS contributing to the experience of pain.⁴ This alteration is thought to result from peripheral nociceptive signaling persisting past the point of tissue healing, leading to a hypersensitivity of nerve fibers, which then continue to respond to low, or absent, sensory stimuli.

Central sensitization is when this hypersensitivity develops in the superficial, deep, and ventral cord nerves. When this happens, pain is often accompanied by systemic symptoms such as fatigue and slowed cognitive processing, often with little to no actual stimulation of the peripheral nociceptors.³

Table 1 lists the possible mechanisms of pain, which can be broken down into four categories: peripheral nociceptive (inflammatory or mechanical), peripheral neuropathic (underlying damage to a peripheral nerve), central (when the CNS is the primary entity involved in maintaining the pain), or any combination of the three.⁴

As pain becomes chronic, multiple mechanisms overlap

It is important to remember that for any single pain diagnosis, there is likely to be—at least initially—a principle underlying mechanism generating the pain. But as the pain becomes chronic, an overlap of multiple mechanisms develops, with central sensitization often playing a more dominant role than peripheral stimulation (regardless of the diagnosis).

For example, in a patient with rheumatoid arthritis (RA), peripheral nociceptive input (in the form of inflammation) is likely the initial mechanism at work, but as time goes on, central processing becomes more involved. The patient may then begin to experience pain that is disproportionate to what is generally expected with RA and may develop other somatic symptoms. The diagnosis then becomes pain primarily related to RA with central sensitization, and both need to be addressed in a treatment plan. In rheumatic conditions, comorbid fibromyalgia (indicative of central sensitization) is thought to occur in 15% to 30% of patients.⁵

FPPs can utilize the underlying mechanisms to cut across diagnostic labels and tailor treatments to those that are most likely to be effective. For a patient with more prominent peripheral involvement, a procedural intervention such as injections or surgery alone may suffice, whereas a broader approach including psychotherapy, medications, exercise, and other lifestyle interventions may be necessary for a patient with pain caused predominantly by central sensitization.

Addressing both peripheral and central components is essential. One prospective, observational cohort study of more than 600 patients scheduled for unilateral total knee or total hip arthroplasty found that patients with a higher degree of centralization of pain (measured by widespread pain index and modified fibromyalgia screening scales) were less likely to report improvement in the affected body part and in overall body pain following surgery.^6,7

There is a high degree of overlap among many of the chronic pain syndromes (fibromyalgia, irritable bowel syndrome, interstitial cystitis, chronic headaches) that have been found to have a central sensitization component.⁸ Providers of primary care are aptly positioned to recognize central sensitization as the underlying pathology and target treatment effectively.

TAILOR TREATMENT TO THE UNDERLYING MECHANISMS OF PAIN

As with any chronic condition, a thorough workup (complete with history, physical exam, and diagnostic testing, as appropriate) is indicated. In the setting of chronic pain, it’s important to identify the primary mechanism, as well as secondary factors that may contribute to the patient’s pain, before developing your treatment plan. These secondary factors may include co-occurring affect disorders, a history of trauma, poor sleep, and tobacco use.^9-12 A history of trauma, for example, co-exists with many pain syndromes. For these patients, central sensitization is responsible for much of their pain. As a result, traditional cognitive behavioral therapy (CBT) may not be the best option because of its focus on accepting pain as a chronic diagnosis; more trauma-focused treatments, such as those dealing in emotional awareness and understanding of the CNS’s role in chronic pain, need to be considered.¹³

Three common conditions. Below we present evidence-based treatment approaches for conditions typically associated with each of the major mechanisms of chronic pain: fibromyalgia (central sensitization), OA (peripheral nociceptive), and low back pain (mixed pain state).

Fibromyalgia: a case of central sensitization

Fibromyalgia is a hallmark diagnosis for patients in whom central sensitization is the dominant cause of pain. They usually present with widespread, diffuse pain and somatic symptoms such as fatigue, memory difficulties, and poor sleep quality.⁸ When explaining the pain mechanism to patients, it may be useful to use the analogy of a volume control dial that is stuck in the “high” position and can’t be turned down.

Genes, the environment, and neurotransmitters play a role. The origin of the pain amplification process is believed to be multifactorial.

Genetic factors are thought to contribute to a predisposition for amplification. To date, five sets of genes have been implicated in increased sensitivity to pain leading to increased risk of the development of chronic pain during a patient’s lifetime.^14-19

Environmental factors (eg, early life trauma, physical trauma especially to the trunk, certain infections such as Lyme disease and Epstein-Barr virus, and emotional stress) may trigger or exacerbate symptoms.⁸ Of note: Only about 5% to 10% of people who experience these triggers actually develop a chronic pain state, while the rest regain their baseline health.⁴ This raises the question of whether there is a point during an acute pain episode in which one can intervene and prevent the acute pain from becoming chronic in those at higher risk.⁴

Imbalances of neurotransmitters (high glutamate; low norepinephrine, serotonin, and gamma-aminobutyric acid [GABA]) play a role in central amplification.^20-22 These substances not only affect sensory transmission, but also control levels of alertness, sleep, mood, and memory.

The diagnostic criteria for fibromyalgia were modified in 2011 to remove the tender point examination and to add somatic symptoms.⁶ These criteria can be useful in the clinical setting in identifying not only fibromyalgia itself but also the degree of “fibromyalgianess” a patient has, which is an indicator of how large a role the centralization process plays in the maintenance of chronic pain.^23,24

Treatment: multimodal and patient empowering. Evidence-based treatment options for fibromyalgia, as well as other conditions for which there is a high degree of centralized pain, can be found in Table 2.^25-36 Multimodal treatment, with an emphasis on patient knowledge and empowerment, is generally thought to be the most beneficial.^25,37 Treatment should almost always include CBT and exercise/activity therapies, which have high degrees of efficacy with few adverse effects.^26,29

In terms of medication, centrally-acting agents (tricyclic antidepressants, serotonin norepinephrine reuptake inhibitors [SNRIs], and alpha 2 delta ligands) are the most effective. There is little to no data showing benefit from anti-inflammatories or opioids in the setting of fibromyalgia. There is some data to suggest that combination therapy, for example with an SNRI (milnacipran) and an alpha 2 delta ligand (pregabalin), may provide more benefit than treating with pregabalin alone.³⁸

Complementary and alternative therapies (eg, yoga, chiropractic care, acupuncture, massage) are being studied more, and while evidence is only preliminary in terms of efficacy, there is increasing emphasis being placed on the need for patients with chronic pain to shift their treatment expectations to greater acceptance of pain and the need for ongoing self-care.²⁸

OA: an example of peripheral nociceptive pain

OA is a condition long thought to be characterized by damage to the cartilage and bone; however, as with many other pain diagnoses, there is frequently little correlation between damage seen on radiographs and the amount of pain that patients experience.

One study analyzed data on almost 7,000 patients from the National Health and Nutrition Examination Survey (NHANES I) and found that between 30% and 50% of OA patients with moderate to severe radiographic changes were asymptomatic, and 10% of those with moderate to severe pain had normal radiographs or only mild changes.³⁹ Research is showing that many factors may contribute to this discrepancy, including the typical “wear and tear” of the disease, subacute levels of inflammation that can lead to peripheral sensitization, and, in some patients, a centralized pain component.⁴⁰ The patients with more centralized pain often have pain that is disproportionate to radiographic evidence, as well as more somatic symptoms, such as fatigue, sleep disturbance, and memory issues.⁴¹

Treatment should be multimodal and include interventions targeted at halting the progression of damage as well as palliation of pain. All treatment plans for OA should also include exercise, weight reduction, and self-management, in addition to pharmacologic interventions, to reduce both the micro-inflammation and the centralized pain component (when present). Intra-articular injections of various types have been studied with some having more efficacy in pain reduction and functional improvement than others.^42-45 See Table 3 for a summary of evidence-based treatment options.^42-61

Low back pain: a mixed pain state

Low back pain (LBP) has been recognized as a mixed pain state for quite some time. While some patients may experience purely nociceptive and/or neuropathic pain, most cases are nonspecific, with patients experiencing varying degrees of nociceptive (myofascial LBP), neuropathic (lumbar radiculopathy), and central sensitization pain.^62,63 Evidence for centralized pain is demonstrated in studies showing hyperalgesia, augmented central pain processing, involvement of the emotional brain, and delayed recovery influenced by poor coping strategies.^64-67

When developing a treatment plan for a patient with chronic LBP, remember that the pain derives from a complex combination of pathophysiologic contributors. Identifying where a patient lies on the pain centralization spectrum can help you tailor treatment.

In one study of 548 patients presenting to a tertiary pain clinic with primary spine pain diagnoses, 42% met diagnostic criteria for fibromyalgia.⁶⁸ Compared to criteria-negative patients, these patients tended to be younger, unemployed, and receiving compensation; they had greater pain intensity, pain interference, and used stronger words to describe their neuropathic pain, as well as having higher levels of depression/anxiety and a lower level of physical function.

Because LBP is a condition with high prevalence and associated disability, many clinical boards have created guidelines for management. These guidelines tend to vary in the strength of evidence used, and the extent to which they are followed in clinical practice remains largely unknown. Recommendations frequently discourage the use of ultrasound/electrotherapy, but many encourage short-term use of medications, supervised exercise therapy, CBT, and multidisciplinary treatment.

Guidelines tend to differ most widely with regard to recommendations for spinal manipulation and specific drug therapies.⁶⁹ The classes of drugs that may be most useful when centralized pain is present include the SNRIs and the alpha 2 delta calcium channel ligands.⁴ See Table 4 for a summary of evidence-based treatment options.^70-89

Case 1 Lola is started on amitriptyline 25 mg at bedtime, which improves her fatigue and cognitive symptoms. During monthly office visits, her FPP educates her about the pathophysiology of fibromyalgia and uses motivational interviewing to get her slowly moving and increasing her activity level. She is weaned off the gabapentin previously prescribed, as her symptoms stabilize and improve.

Case 2 Matt is sent for a steroid injection, which decreases his pain temporarily. During this time, he begins physical therapy; slowly, with increased movement, his function improves. A trial of duloxetine provides pain relief; that combined with intermittent NSAIDs has allowed Matt to maintain his function and his job.

Case 3 Because Keith was only taking the narcotics intermittently and wasn’t certain they were helping, CBT was sufficient to wean him off the medication without any worsening of his pain in the process. By participating in physical therapy, he has learned how to perform certain tasks at his job without pain or injury. He uses NSAIDs as needed for pain.

The authors thank Drs. Daniel Clauw (University of Michigan, Ann Arbor) and Martha Rumschlag (Providence Family Medicine Residency Program, Southfield, Michigan), for their valuable contributions to this article.

Case 1 Lola, 28, has a history of muscular aches and joint pain throughout her body, fatigue, and mental fogginess. A rheumatologist diagnosed fibromyalgia, but Lola just moved to your town and is establishing care. She is feeling desperate because her pain has worsened and the medication previously prescribed (gabapentin 300 mg tid) is no longer working. She asks to try oxycodone.

Case 2 Matt is a 59-year-old truck driver with severe hip osteoarthritis (OA). His orthopedist recommended against hip replacement at this time because of his young age and a heart condition that makes him high risk. His pain makes sitting for long periods very difficult. He presents to you for help because he is worried he will be unable to continue working.

Case 3 Keith is a 56-year-old construction worker who has been experiencing back pain for many years. The pain has become more debilitating over time; it is now constant, and Keith can hardly make it through his work day. He has been getting hydrocodone/acetaminophen from urgent care centers and emergency departments, but he isn’t sure it is helping and is coming to you to assume his pain management.

Chronic pain (defined as > 3 mo in duration) is a complex, heterogeneous condition affecting an estimated 116 million US adults.¹ Much of the management of chronic pain occurs in primary care settings, placing family practice providers (FPPs) on the frontlines of two epidemics: that of chronic pain and that of the abuse and misuse of opioid pain medications.

To improve communication about the risks and benefits of opioid therapy and the safety and effectiveness of pain treatments in general, many professional organizations, health care institutions, and recently the CDC, have published guidelines on the use of opioids for nonmalignant chronic pain.² With these guidelines in mind—and in light of the latest evidence—we propose the following paradigm for the treatment of chronic pain. A critical aspect is determining the underlying pathophysiology of a patient’s pain in order to develop a well-rounded, multimodal, evidence-based treatment plan. Detailed here is the application of this approach to the treatment of three common diagnoses: fibromyalgia, osteoarthritis, and low back pain.

LOOK TO THE CENTRAL AND PERIPHERAL NERVOUS SYSTEM

Acute pain begins with activation of peripheral nociceptors at the site of injury. This causes depolarization up the spinal cord and through the brain stem to higher cortical centers where the pain is perceived and localized. Descending neural pathways transport both excitatory and inhibitory information from the brain to the periphery via the spinal cord, which either increases or decreases the perception of pain.³

When damage/injury doesn’t correlate with the perception of pain

Until recently, it was assumed that chronic pain worked much the same way as acute pain and was caused by ongoing nociceptive input in the periphery, but research has shown us that the central nervous system (CNS) can play a large role in the modulation of nociception. This new understanding comes from the lack of evidence pointing to any pain state in which the degree of nociceptive input correlates with the degree of pain experienced.

For most patients with chronic pain, regardless of their diagnosis, there is some degree of alteration in the processing of nociceptive signals by the CNS contributing to the experience of pain.⁴ This alteration is thought to result from peripheral nociceptive signaling persisting past the point of tissue healing, leading to a hypersensitivity of nerve fibers, which then continue to respond to low, or absent, sensory stimuli.

Central sensitization is when this hypersensitivity develops in the superficial, deep, and ventral cord nerves. When this happens, pain is often accompanied by systemic symptoms such as fatigue and slowed cognitive processing, often with little to no actual stimulation of the peripheral nociceptors.³

Table 1 lists the possible mechanisms of pain, which can be broken down into four categories: peripheral nociceptive (inflammatory or mechanical), peripheral neuropathic (underlying damage to a peripheral nerve), central (when the CNS is the primary entity involved in maintaining the pain), or any combination of the three.⁴

As pain becomes chronic, multiple mechanisms overlap

It is important to remember that for any single pain diagnosis, there is likely to be—at least initially—a principle underlying mechanism generating the pain. But as the pain becomes chronic, an overlap of multiple mechanisms develops, with central sensitization often playing a more dominant role than peripheral stimulation (regardless of the diagnosis).

For example, in a patient with rheumatoid arthritis (RA), peripheral nociceptive input (in the form of inflammation) is likely the initial mechanism at work, but as time goes on, central processing becomes more involved. The patient may then begin to experience pain that is disproportionate to what is generally expected with RA and may develop other somatic symptoms. The diagnosis then becomes pain primarily related to RA with central sensitization, and both need to be addressed in a treatment plan. In rheumatic conditions, comorbid fibromyalgia (indicative of central sensitization) is thought to occur in 15% to 30% of patients.⁵

FPPs can utilize the underlying mechanisms to cut across diagnostic labels and tailor treatments to those that are most likely to be effective. For a patient with more prominent peripheral involvement, a procedural intervention such as injections or surgery alone may suffice, whereas a broader approach including psychotherapy, medications, exercise, and other lifestyle interventions may be necessary for a patient with pain caused predominantly by central sensitization.

Addressing both peripheral and central components is essential. One prospective, observational cohort study of more than 600 patients scheduled for unilateral total knee or total hip arthroplasty found that patients with a higher degree of centralization of pain (measured by widespread pain index and modified fibromyalgia screening scales) were less likely to report improvement in the affected body part and in overall body pain following surgery.^6,7

There is a high degree of overlap among many of the chronic pain syndromes (fibromyalgia, irritable bowel syndrome, interstitial cystitis, chronic headaches) that have been found to have a central sensitization component.⁸ Providers of primary care are aptly positioned to recognize central sensitization as the underlying pathology and target treatment effectively.

TAILOR TREATMENT TO THE UNDERLYING MECHANISMS OF PAIN

As with any chronic condition, a thorough workup (complete with history, physical exam, and diagnostic testing, as appropriate) is indicated. In the setting of chronic pain, it’s important to identify the primary mechanism, as well as secondary factors that may contribute to the patient’s pain, before developing your treatment plan. These secondary factors may include co-occurring affect disorders, a history of trauma, poor sleep, and tobacco use.^9-12 A history of trauma, for example, co-exists with many pain syndromes. For these patients, central sensitization is responsible for much of their pain. As a result, traditional cognitive behavioral therapy (CBT) may not be the best option because of its focus on accepting pain as a chronic diagnosis; more trauma-focused treatments, such as those dealing in emotional awareness and understanding of the CNS’s role in chronic pain, need to be considered.¹³

Three common conditions. Below we present evidence-based treatment approaches for conditions typically associated with each of the major mechanisms of chronic pain: fibromyalgia (central sensitization), OA (peripheral nociceptive), and low back pain (mixed pain state).

Fibromyalgia: a case of central sensitization

Fibromyalgia is a hallmark diagnosis for patients in whom central sensitization is the dominant cause of pain. They usually present with widespread, diffuse pain and somatic symptoms such as fatigue, memory difficulties, and poor sleep quality.⁸ When explaining the pain mechanism to patients, it may be useful to use the analogy of a volume control dial that is stuck in the “high” position and can’t be turned down.

Genes, the environment, and neurotransmitters play a role. The origin of the pain amplification process is believed to be multifactorial.

Genetic factors are thought to contribute to a predisposition for amplification. To date, five sets of genes have been implicated in increased sensitivity to pain leading to increased risk of the development of chronic pain during a patient’s lifetime.^14-19

Environmental factors (eg, early life trauma, physical trauma especially to the trunk, certain infections such as Lyme disease and Epstein-Barr virus, and emotional stress) may trigger or exacerbate symptoms.⁸ Of note: Only about 5% to 10% of people who experience these triggers actually develop a chronic pain state, while the rest regain their baseline health.⁴ This raises the question of whether there is a point during an acute pain episode in which one can intervene and prevent the acute pain from becoming chronic in those at higher risk.⁴

Imbalances of neurotransmitters (high glutamate; low norepinephrine, serotonin, and gamma-aminobutyric acid [GABA]) play a role in central amplification.^20-22 These substances not only affect sensory transmission, but also control levels of alertness, sleep, mood, and memory.

The diagnostic criteria for fibromyalgia were modified in 2011 to remove the tender point examination and to add somatic symptoms.⁶ These criteria can be useful in the clinical setting in identifying not only fibromyalgia itself but also the degree of “fibromyalgianess” a patient has, which is an indicator of how large a role the centralization process plays in the maintenance of chronic pain.^23,24

Treatment: multimodal and patient empowering. Evidence-based treatment options for fibromyalgia, as well as other conditions for which there is a high degree of centralized pain, can be found in Table 2.^25-36 Multimodal treatment, with an emphasis on patient knowledge and empowerment, is generally thought to be the most beneficial.^25,37 Treatment should almost always include CBT and exercise/activity therapies, which have high degrees of efficacy with few adverse effects.^26,29

In terms of medication, centrally-acting agents (tricyclic antidepressants, serotonin norepinephrine reuptake inhibitors [SNRIs], and alpha 2 delta ligands) are the most effective. There is little to no data showing benefit from anti-inflammatories or opioids in the setting of fibromyalgia. There is some data to suggest that combination therapy, for example with an SNRI (milnacipran) and an alpha 2 delta ligand (pregabalin), may provide more benefit than treating with pregabalin alone.³⁸

Complementary and alternative therapies (eg, yoga, chiropractic care, acupuncture, massage) are being studied more, and while evidence is only preliminary in terms of efficacy, there is increasing emphasis being placed on the need for patients with chronic pain to shift their treatment expectations to greater acceptance of pain and the need for ongoing self-care.²⁸

OA: an example of peripheral nociceptive pain

OA is a condition long thought to be characterized by damage to the cartilage and bone; however, as with many other pain diagnoses, there is frequently little correlation between damage seen on radiographs and the amount of pain that patients experience.

One study analyzed data on almost 7,000 patients from the National Health and Nutrition Examination Survey (NHANES I) and found that between 30% and 50% of OA patients with moderate to severe radiographic changes were asymptomatic, and 10% of those with moderate to severe pain had normal radiographs or only mild changes.³⁹ Research is showing that many factors may contribute to this discrepancy, including the typical “wear and tear” of the disease, subacute levels of inflammation that can lead to peripheral sensitization, and, in some patients, a centralized pain component.⁴⁰ The patients with more centralized pain often have pain that is disproportionate to radiographic evidence, as well as more somatic symptoms, such as fatigue, sleep disturbance, and memory issues.⁴¹

Treatment should be multimodal and include interventions targeted at halting the progression of damage as well as palliation of pain. All treatment plans for OA should also include exercise, weight reduction, and self-management, in addition to pharmacologic interventions, to reduce both the micro-inflammation and the centralized pain component (when present). Intra-articular injections of various types have been studied with some having more efficacy in pain reduction and functional improvement than others.^42-45 See Table 3 for a summary of evidence-based treatment options.^42-61

Low back pain: a mixed pain state

Low back pain (LBP) has been recognized as a mixed pain state for quite some time. While some patients may experience purely nociceptive and/or neuropathic pain, most cases are nonspecific, with patients experiencing varying degrees of nociceptive (myofascial LBP), neuropathic (lumbar radiculopathy), and central sensitization pain.^62,63 Evidence for centralized pain is demonstrated in studies showing hyperalgesia, augmented central pain processing, involvement of the emotional brain, and delayed recovery influenced by poor coping strategies.^64-67

When developing a treatment plan for a patient with chronic LBP, remember that the pain derives from a complex combination of pathophysiologic contributors. Identifying where a patient lies on the pain centralization spectrum can help you tailor treatment.

In one study of 548 patients presenting to a tertiary pain clinic with primary spine pain diagnoses, 42% met diagnostic criteria for fibromyalgia.⁶⁸ Compared to criteria-negative patients, these patients tended to be younger, unemployed, and receiving compensation; they had greater pain intensity, pain interference, and used stronger words to describe their neuropathic pain, as well as having higher levels of depression/anxiety and a lower level of physical function.

Because LBP is a condition with high prevalence and associated disability, many clinical boards have created guidelines for management. These guidelines tend to vary in the strength of evidence used, and the extent to which they are followed in clinical practice remains largely unknown. Recommendations frequently discourage the use of ultrasound/electrotherapy, but many encourage short-term use of medications, supervised exercise therapy, CBT, and multidisciplinary treatment.

Guidelines tend to differ most widely with regard to recommendations for spinal manipulation and specific drug therapies.⁶⁹ The classes of drugs that may be most useful when centralized pain is present include the SNRIs and the alpha 2 delta calcium channel ligands.⁴ See Table 4 for a summary of evidence-based treatment options.^70-89

Case 1 Lola is started on amitriptyline 25 mg at bedtime, which improves her fatigue and cognitive symptoms. During monthly office visits, her FPP educates her about the pathophysiology of fibromyalgia and uses motivational interviewing to get her slowly moving and increasing her activity level. She is weaned off the gabapentin previously prescribed, as her symptoms stabilize and improve.

Case 2 Matt is sent for a steroid injection, which decreases his pain temporarily. During this time, he begins physical therapy; slowly, with increased movement, his function improves. A trial of duloxetine provides pain relief; that combined with intermittent NSAIDs has allowed Matt to maintain his function and his job.

Case 3 Because Keith was only taking the narcotics intermittently and wasn’t certain they were helping, CBT was sufficient to wean him off the medication without any worsening of his pain in the process. By participating in physical therapy, he has learned how to perform certain tasks at his job without pain or injury. He uses NSAIDs as needed for pain.

The authors thank Drs. Daniel Clauw (University of Michigan, Ann Arbor) and Martha Rumschlag (Providence Family Medicine Residency Program, Southfield, Michigan), for their valuable contributions to this article.

IN THIS ARTICLE

• Diagnostic tests
• Complications of PID
• CDC treatment regimens

Pelvic inflammatory disease (PID) is an ascending polymicrobial infection of the female upper reproductive tract that primarily affects sexually active women ages 15 to 29. Around 5% of sexually active women in the United States were treated for PID from 2011-2013.¹ The rates and severity of PID have declined in North America and Western Europe due to overall decrease in sexually transmitted infection (STI) rates, improved screening initiatives for Chlamydia trachomatis, better treatment compliance secondary to increased access to antibiotics, and diagnostic tests with higher sensitivity.² Despite this rate reduction, PID remains a major public health concern given the significant long-term complications, which include infertility, ectopic pregnancy, and chronic pelvic pain.³

EPIDEMIOLOGY AND PATHOGENESIS

PID is caused by sexually transmitted bacteria or enteric organisms that have spread to internal reproductive organs. Historically, the two most common pathogens identified in cases of PID have been Chlamydia trachomatis and Neisseria gonorrhoeae; however, the decline in rates of gonorrhea has led to a diminished role for N gonorrhoeae (though it continues to be associated with more severe cases).^4,5

More recent studies have suggested a shift in the causative organisms; less than half of women diagnosed with acute PID test positive for either N gonorrhoeae or C trachomatis.⁶ Emerging infectious agents associated with PID include Mycoplasma genitalium, Gardnerella vaginalis, and bacterial vaginosis–associated bacteria.^5,7,8-10

RISK FACTORS

Women ages 15 to 25 are at an increased risk for PID. The high prevalence in this age group may be attributable to high-risk behaviors, including a high number of sexual partners, high frequency of new sexual partners, and engagement in sexual intercourse without condoms.¹¹

Taking an accurate sexual history is imperative. Clinicians should maintain a high level of suspicion for PID in women with a history of the disease, as 25% will experience recurrence.¹²

Clinicians should not be deterred from screening for STIs and cervical cancer in women who report having sex with other women. In addition, transgender patients should be assessed for STIs and HIV-related risks based on current anatomy sexual practices.¹³

PHYSICAL EXAM

While some cases of PID are asymptomatic, the typical presentation includes bilateral abdominal pain and/or pelvic pain, with onset during or shortly after menses. The pain often worsens with movement and coitus. Associated signs and symptoms include abnormal uterine bleeding or vaginal discharge; dysuria; fever and chills; frequent urination; lower back pain; and nausea and/or vomiting.^14,15

All females suspected of having PID should undergo both a bimanual exam and a speculum exam. On bimanual examination, adnexal tenderness has the highest sensitivity (93% to 95.5%) for ruling out acute PID, whereas on speculum exam, purulent endocervical discharge has the highest specificity (93%).^16,17 Bimanual exam findings suggestive of PID include cervical motion tenderness, uterine tenderness, and/or adnexal tenderness. Suggestive speculum exam findings include abnormal discoloration or texture of the cervix and/or endocervical mucopurulent discharge.^5,16,17

One cardinal rule that should not be overlooked is that all females of reproductive age who present with abdominal pain and/or pelvic pain should take a pregnancy test to rule out ectopic pregnancy and any other pregnancy-related complications.

DIAGNOSIS

The diagnosis of PID relies on clinical judgement and a high index of suspicion.^5,18 The CDC’s diagnostic criteria for acute PID include

• Sexually active female AND
• Pelvic or lower abdominal pain AND
• Cervical motion tenderness OR uterine tenderness OR adnexal tenderness.⁵

Additional findings that support the diagnosis include

• Abnormal cervical mucopurulent discharge or cervical friability
• Abundant white blood cells (WBCs) on saline microscopy of vaginal fluid
• Elevated C-reactive protein
• Elevated erythrocyte sedimentation rate
• Laboratory documentation of infection with C trachomatis or N gonorrhea
• Oral temperature > 101°F.^5,18

The CDC notes that the first two findings (mucopurulent discharge and evidence of WBCs on microscopy) occur in most women with PID; in their absence, the diagnosis is unlikely and other sources of pain should be considered.⁵ The differential for PID includes acute appendicitis; adhesions; carcinoid tumor; cholecystitis; ectopic pregnancy; endometriosis; inflammatory bowel disease; and ovarian cyst.¹⁹

Given the variability in presentation, clinicians may find it useful to perform further diagnostic testing. There are additional laboratory tests that may be ordered for patients with a suspected diagnosis of PID (see Table 1).

TREATMENT

According to the CDC’s 2015 treatment guidelines for PID, a negative endocervical exam and negative microbial screening do not rule out an upper reproductive tract infection. Therefore, all sexually active women who present with lower abdominal pain and/or pelvic pain and have evidence of cervical motion, uterine, or adnexal tenderness on bimanual exam should be treated immediately.⁵

Treatment guidelines are outlined in Table 2. The polymicrobial nature of PID requires gram-negative antibiotic coverage, such as doxycycline plus a second/third-generation cephalosporin.⁵ Clinicians should note that cefoxitin, a second-generation cephalosporin, is recommended as firstline therapy for inpatients, as it has better anaerobic coverage than ceftriaxone.¹⁹ A targeted change in antibiotic coverage—such as inclusion of a macrolide and/or metronidazole—might be necessary if a causative organism is identified by culture.⁷

Treatment is indicated for all patients with a presumptive diagnosis of PID regardless of symptoms or exam findings, as PID may be asymptomatic and long-term sequelae (eg, infertility, ectopic pregnancy) are often irreversible. At-risk patients include sexually active adolescents, women with multiple sexual partners, women with a history of STI, those whose sexual partner has an STI, and women living in communities with a high prevalence of disease.^20,21

Women being treated for PID should be advised to abstain from sexual intercourse until symptoms have resolved, treatment is completed, and any sexual partners have been treated as well. It is essential to emphasize to patients (and their partners) the importance of compliance to treatment regimens and the risk for PID co-infection and reinfection, as recurrence leads to an increase in long-term complications.⁵

Treatment of sexual partners. The CDC instructs that a woman’s most recent partner should be treated if she had sexual intercourse within 60 days of onset of symptoms or diagnosis. Furthermore, men who have had sexual contact with a woman who has PID in the 60 days prior to onset of her symptoms should be evaluated, tested, and treated for chlamydia and gonorrhea, regardless of the etiology of PID or the pathogens isolated from the woman.⁵

Admission criteria. Hospitalization should be based on provider judgment despite patient age. The suggested admission criteria include surgical emergency (eg, appendicitis), tubo-ovarian abscess, pregnancy, severe illness, nausea and vomiting, high fever, inability to follow or tolerate an outpatient oral regimen, and lack of clinical response to oral antimicrobial therapy.⁵

Follow-up care. Clinical improvement (ie, reduction in abdominal, uterine, adnexal, and cervical motion tenderness) should occur within 72 hours of antimicrobial therapy initiation. If it does not, hospital admission or adjustment in antimicrobial regimen should be considered, as well as additional diagnostic testing (eg, laparoscopy). In addition, all women with chlamydial- or gonococcal-related PID should return in three months for surveillance testing.²²

COMPLICATIONS

Long-term complications—including infertility, chronic pelvic pain, and ectopic pregnancy—may occur, even when there has been a clinical response to adequate treatment. Data from the PID Evaluation and Clinical Health (PEACH) study were analyzed to assess long-term sequelae at seven years postdiagnosis and treatment. The researchers found that about 21% of women experienced recurrent PID, 19% developed infertility, and 42% reported chronic pelvic pain.³ Other research has also shown that repeat episodes of PID and delayed treatment increase the risk for long-term complications.^23,24

SCREENING AND PREVENTION

Ten percent of women with an untreated STI will go on to develop PID.⁴ It is imperative to educate patients on the dangers and consequences of STIs when they become sexually active. Adolescents benefit the most from preventive education; this group is twice as likely as any other age group to be diagnosed with PID due to their inclination toward risky sexual behavior. Additionally, younger women tend to have a more friable cervix, increasing their risk for infection.^25,26 Providers should promote safe sexual practices, such as condom use and less frequent partner exchange, in order to reduce STI exposure.

In 2015, the rate of reported cases of C trachomatis was 645.5 per 100,000 females, and of N gonorrheae, 107.2 per 100,000 females.²³ The United States Preventive Services Task Force and the CDC recommend annual screening for chlamydia and gonorrhea in all sexually active women younger than 25, as well as sexually active women ages 25 and older who are considered at increased risk.⁵

CONCLUSION

PID is often difficult to diagnose, since patients may be asymptomatic or present with vague symptoms. Clinicians should maintain a high level of suspicion for PID in adolescent females due to the high incidence of STI exposure in this population. The best way to prevent long-term complications of PID is to prevent the first episode of PID and/or first exposure to STIs. Therefore, clinicians should be proactive in offering STI screenings to all sexually active patients younger than 25 who request care, regardless of their chief complaint, and educating patients on the potential long-term effects of PID and STIs.

IN THIS ARTICLE

• Diagnostic tests
• Complications of PID
• CDC treatment regimens

Pelvic inflammatory disease (PID) is an ascending polymicrobial infection of the female upper reproductive tract that primarily affects sexually active women ages 15 to 29. Around 5% of sexually active women in the United States were treated for PID from 2011-2013.¹ The rates and severity of PID have declined in North America and Western Europe due to overall decrease in sexually transmitted infection (STI) rates, improved screening initiatives for Chlamydia trachomatis, better treatment compliance secondary to increased access to antibiotics, and diagnostic tests with higher sensitivity.² Despite this rate reduction, PID remains a major public health concern given the significant long-term complications, which include infertility, ectopic pregnancy, and chronic pelvic pain.³

EPIDEMIOLOGY AND PATHOGENESIS

PID is caused by sexually transmitted bacteria or enteric organisms that have spread to internal reproductive organs. Historically, the two most common pathogens identified in cases of PID have been Chlamydia trachomatis and Neisseria gonorrhoeae; however, the decline in rates of gonorrhea has led to a diminished role for N gonorrhoeae (though it continues to be associated with more severe cases).^4,5

More recent studies have suggested a shift in the causative organisms; less than half of women diagnosed with acute PID test positive for either N gonorrhoeae or C trachomatis.⁶ Emerging infectious agents associated with PID include Mycoplasma genitalium, Gardnerella vaginalis, and bacterial vaginosis–associated bacteria.^5,7,8-10

RISK FACTORS

Women ages 15 to 25 are at an increased risk for PID. The high prevalence in this age group may be attributable to high-risk behaviors, including a high number of sexual partners, high frequency of new sexual partners, and engagement in sexual intercourse without condoms.¹¹

Taking an accurate sexual history is imperative. Clinicians should maintain a high level of suspicion for PID in women with a history of the disease, as 25% will experience recurrence.¹²

Clinicians should not be deterred from screening for STIs and cervical cancer in women who report having sex with other women. In addition, transgender patients should be assessed for STIs and HIV-related risks based on current anatomy sexual practices.¹³

PHYSICAL EXAM

While some cases of PID are asymptomatic, the typical presentation includes bilateral abdominal pain and/or pelvic pain, with onset during or shortly after menses. The pain often worsens with movement and coitus. Associated signs and symptoms include abnormal uterine bleeding or vaginal discharge; dysuria; fever and chills; frequent urination; lower back pain; and nausea and/or vomiting.^14,15

All females suspected of having PID should undergo both a bimanual exam and a speculum exam. On bimanual examination, adnexal tenderness has the highest sensitivity (93% to 95.5%) for ruling out acute PID, whereas on speculum exam, purulent endocervical discharge has the highest specificity (93%).^16,17 Bimanual exam findings suggestive of PID include cervical motion tenderness, uterine tenderness, and/or adnexal tenderness. Suggestive speculum exam findings include abnormal discoloration or texture of the cervix and/or endocervical mucopurulent discharge.^5,16,17

One cardinal rule that should not be overlooked is that all females of reproductive age who present with abdominal pain and/or pelvic pain should take a pregnancy test to rule out ectopic pregnancy and any other pregnancy-related complications.

DIAGNOSIS

The diagnosis of PID relies on clinical judgement and a high index of suspicion.^5,18 The CDC’s diagnostic criteria for acute PID include

• Sexually active female AND
• Pelvic or lower abdominal pain AND
• Cervical motion tenderness OR uterine tenderness OR adnexal tenderness.⁵

Additional findings that support the diagnosis include

• Abnormal cervical mucopurulent discharge or cervical friability
• Abundant white blood cells (WBCs) on saline microscopy of vaginal fluid
• Elevated C-reactive protein
• Elevated erythrocyte sedimentation rate
• Laboratory documentation of infection with C trachomatis or N gonorrhea
• Oral temperature > 101°F.^5,18

The CDC notes that the first two findings (mucopurulent discharge and evidence of WBCs on microscopy) occur in most women with PID; in their absence, the diagnosis is unlikely and other sources of pain should be considered.⁵ The differential for PID includes acute appendicitis; adhesions; carcinoid tumor; cholecystitis; ectopic pregnancy; endometriosis; inflammatory bowel disease; and ovarian cyst.¹⁹

Given the variability in presentation, clinicians may find it useful to perform further diagnostic testing. There are additional laboratory tests that may be ordered for patients with a suspected diagnosis of PID (see Table 1).

TREATMENT

According to the CDC’s 2015 treatment guidelines for PID, a negative endocervical exam and negative microbial screening do not rule out an upper reproductive tract infection. Therefore, all sexually active women who present with lower abdominal pain and/or pelvic pain and have evidence of cervical motion, uterine, or adnexal tenderness on bimanual exam should be treated immediately.⁵

Treatment guidelines are outlined in Table 2. The polymicrobial nature of PID requires gram-negative antibiotic coverage, such as doxycycline plus a second/third-generation cephalosporin.⁵ Clinicians should note that cefoxitin, a second-generation cephalosporin, is recommended as firstline therapy for inpatients, as it has better anaerobic coverage than ceftriaxone.¹⁹ A targeted change in antibiotic coverage—such as inclusion of a macrolide and/or metronidazole—might be necessary if a causative organism is identified by culture.⁷

Treatment is indicated for all patients with a presumptive diagnosis of PID regardless of symptoms or exam findings, as PID may be asymptomatic and long-term sequelae (eg, infertility, ectopic pregnancy) are often irreversible. At-risk patients include sexually active adolescents, women with multiple sexual partners, women with a history of STI, those whose sexual partner has an STI, and women living in communities with a high prevalence of disease.^20,21

Women being treated for PID should be advised to abstain from sexual intercourse until symptoms have resolved, treatment is completed, and any sexual partners have been treated as well. It is essential to emphasize to patients (and their partners) the importance of compliance to treatment regimens and the risk for PID co-infection and reinfection, as recurrence leads to an increase in long-term complications.⁵

Treatment of sexual partners. The CDC instructs that a woman’s most recent partner should be treated if she had sexual intercourse within 60 days of onset of symptoms or diagnosis. Furthermore, men who have had sexual contact with a woman who has PID in the 60 days prior to onset of her symptoms should be evaluated, tested, and treated for chlamydia and gonorrhea, regardless of the etiology of PID or the pathogens isolated from the woman.⁵

Admission criteria. Hospitalization should be based on provider judgment despite patient age. The suggested admission criteria include surgical emergency (eg, appendicitis), tubo-ovarian abscess, pregnancy, severe illness, nausea and vomiting, high fever, inability to follow or tolerate an outpatient oral regimen, and lack of clinical response to oral antimicrobial therapy.⁵

Follow-up care. Clinical improvement (ie, reduction in abdominal, uterine, adnexal, and cervical motion tenderness) should occur within 72 hours of antimicrobial therapy initiation. If it does not, hospital admission or adjustment in antimicrobial regimen should be considered, as well as additional diagnostic testing (eg, laparoscopy). In addition, all women with chlamydial- or gonococcal-related PID should return in three months for surveillance testing.²²

COMPLICATIONS

Long-term complications—including infertility, chronic pelvic pain, and ectopic pregnancy—may occur, even when there has been a clinical response to adequate treatment. Data from the PID Evaluation and Clinical Health (PEACH) study were analyzed to assess long-term sequelae at seven years postdiagnosis and treatment. The researchers found that about 21% of women experienced recurrent PID, 19% developed infertility, and 42% reported chronic pelvic pain.³ Other research has also shown that repeat episodes of PID and delayed treatment increase the risk for long-term complications.^23,24

SCREENING AND PREVENTION

Ten percent of women with an untreated STI will go on to develop PID.⁴ It is imperative to educate patients on the dangers and consequences of STIs when they become sexually active. Adolescents benefit the most from preventive education; this group is twice as likely as any other age group to be diagnosed with PID due to their inclination toward risky sexual behavior. Additionally, younger women tend to have a more friable cervix, increasing their risk for infection.^25,26 Providers should promote safe sexual practices, such as condom use and less frequent partner exchange, in order to reduce STI exposure.

In 2015, the rate of reported cases of C trachomatis was 645.5 per 100,000 females, and of N gonorrheae, 107.2 per 100,000 females.²³ The United States Preventive Services Task Force and the CDC recommend annual screening for chlamydia and gonorrhea in all sexually active women younger than 25, as well as sexually active women ages 25 and older who are considered at increased risk.⁵

CONCLUSION

PID is often difficult to diagnose, since patients may be asymptomatic or present with vague symptoms. Clinicians should maintain a high level of suspicion for PID in adolescent females due to the high incidence of STI exposure in this population. The best way to prevent long-term complications of PID is to prevent the first episode of PID and/or first exposure to STIs. Therefore, clinicians should be proactive in offering STI screenings to all sexually active patients younger than 25 who request care, regardless of their chief complaint, and educating patients on the potential long-term effects of PID and STIs.

IN THIS ARTICLE

• Diagnostic tests
• Complications of PID
• CDC treatment regimens

Pelvic inflammatory disease (PID) is an ascending polymicrobial infection of the female upper reproductive tract that primarily affects sexually active women ages 15 to 29. Around 5% of sexually active women in the United States were treated for PID from 2011-2013.¹ The rates and severity of PID have declined in North America and Western Europe due to overall decrease in sexually transmitted infection (STI) rates, improved screening initiatives for Chlamydia trachomatis, better treatment compliance secondary to increased access to antibiotics, and diagnostic tests with higher sensitivity.² Despite this rate reduction, PID remains a major public health concern given the significant long-term complications, which include infertility, ectopic pregnancy, and chronic pelvic pain.³

EPIDEMIOLOGY AND PATHOGENESIS

PID is caused by sexually transmitted bacteria or enteric organisms that have spread to internal reproductive organs. Historically, the two most common pathogens identified in cases of PID have been Chlamydia trachomatis and Neisseria gonorrhoeae; however, the decline in rates of gonorrhea has led to a diminished role for N gonorrhoeae (though it continues to be associated with more severe cases).^4,5

More recent studies have suggested a shift in the causative organisms; less than half of women diagnosed with acute PID test positive for either N gonorrhoeae or C trachomatis.⁶ Emerging infectious agents associated with PID include Mycoplasma genitalium, Gardnerella vaginalis, and bacterial vaginosis–associated bacteria.^5,7,8-10

RISK FACTORS

Women ages 15 to 25 are at an increased risk for PID. The high prevalence in this age group may be attributable to high-risk behaviors, including a high number of sexual partners, high frequency of new sexual partners, and engagement in sexual intercourse without condoms.¹¹

Taking an accurate sexual history is imperative. Clinicians should maintain a high level of suspicion for PID in women with a history of the disease, as 25% will experience recurrence.¹²

Clinicians should not be deterred from screening for STIs and cervical cancer in women who report having sex with other women. In addition, transgender patients should be assessed for STIs and HIV-related risks based on current anatomy sexual practices.¹³

PHYSICAL EXAM

While some cases of PID are asymptomatic, the typical presentation includes bilateral abdominal pain and/or pelvic pain, with onset during or shortly after menses. The pain often worsens with movement and coitus. Associated signs and symptoms include abnormal uterine bleeding or vaginal discharge; dysuria; fever and chills; frequent urination; lower back pain; and nausea and/or vomiting.^14,15

All females suspected of having PID should undergo both a bimanual exam and a speculum exam. On bimanual examination, adnexal tenderness has the highest sensitivity (93% to 95.5%) for ruling out acute PID, whereas on speculum exam, purulent endocervical discharge has the highest specificity (93%).^16,17 Bimanual exam findings suggestive of PID include cervical motion tenderness, uterine tenderness, and/or adnexal tenderness. Suggestive speculum exam findings include abnormal discoloration or texture of the cervix and/or endocervical mucopurulent discharge.^5,16,17

One cardinal rule that should not be overlooked is that all females of reproductive age who present with abdominal pain and/or pelvic pain should take a pregnancy test to rule out ectopic pregnancy and any other pregnancy-related complications.

DIAGNOSIS

The diagnosis of PID relies on clinical judgement and a high index of suspicion.^5,18 The CDC’s diagnostic criteria for acute PID include

• Sexually active female AND
• Pelvic or lower abdominal pain AND
• Cervical motion tenderness OR uterine tenderness OR adnexal tenderness.⁵

Additional findings that support the diagnosis include

• Abnormal cervical mucopurulent discharge or cervical friability
• Abundant white blood cells (WBCs) on saline microscopy of vaginal fluid
• Elevated C-reactive protein
• Elevated erythrocyte sedimentation rate
• Laboratory documentation of infection with C trachomatis or N gonorrhea
• Oral temperature > 101°F.^5,18

The CDC notes that the first two findings (mucopurulent discharge and evidence of WBCs on microscopy) occur in most women with PID; in their absence, the diagnosis is unlikely and other sources of pain should be considered.⁵ The differential for PID includes acute appendicitis; adhesions; carcinoid tumor; cholecystitis; ectopic pregnancy; endometriosis; inflammatory bowel disease; and ovarian cyst.¹⁹

Given the variability in presentation, clinicians may find it useful to perform further diagnostic testing. There are additional laboratory tests that may be ordered for patients with a suspected diagnosis of PID (see Table 1).

TREATMENT

According to the CDC’s 2015 treatment guidelines for PID, a negative endocervical exam and negative microbial screening do not rule out an upper reproductive tract infection. Therefore, all sexually active women who present with lower abdominal pain and/or pelvic pain and have evidence of cervical motion, uterine, or adnexal tenderness on bimanual exam should be treated immediately.⁵

Treatment guidelines are outlined in Table 2. The polymicrobial nature of PID requires gram-negative antibiotic coverage, such as doxycycline plus a second/third-generation cephalosporin.⁵ Clinicians should note that cefoxitin, a second-generation cephalosporin, is recommended as firstline therapy for inpatients, as it has better anaerobic coverage than ceftriaxone.¹⁹ A targeted change in antibiotic coverage—such as inclusion of a macrolide and/or metronidazole—might be necessary if a causative organism is identified by culture.⁷

Treatment is indicated for all patients with a presumptive diagnosis of PID regardless of symptoms or exam findings, as PID may be asymptomatic and long-term sequelae (eg, infertility, ectopic pregnancy) are often irreversible. At-risk patients include sexually active adolescents, women with multiple sexual partners, women with a history of STI, those whose sexual partner has an STI, and women living in communities with a high prevalence of disease.^20,21

Women being treated for PID should be advised to abstain from sexual intercourse until symptoms have resolved, treatment is completed, and any sexual partners have been treated as well. It is essential to emphasize to patients (and their partners) the importance of compliance to treatment regimens and the risk for PID co-infection and reinfection, as recurrence leads to an increase in long-term complications.⁵

Treatment of sexual partners. The CDC instructs that a woman’s most recent partner should be treated if she had sexual intercourse within 60 days of onset of symptoms or diagnosis. Furthermore, men who have had sexual contact with a woman who has PID in the 60 days prior to onset of her symptoms should be evaluated, tested, and treated for chlamydia and gonorrhea, regardless of the etiology of PID or the pathogens isolated from the woman.⁵

Admission criteria. Hospitalization should be based on provider judgment despite patient age. The suggested admission criteria include surgical emergency (eg, appendicitis), tubo-ovarian abscess, pregnancy, severe illness, nausea and vomiting, high fever, inability to follow or tolerate an outpatient oral regimen, and lack of clinical response to oral antimicrobial therapy.⁵

Follow-up care. Clinical improvement (ie, reduction in abdominal, uterine, adnexal, and cervical motion tenderness) should occur within 72 hours of antimicrobial therapy initiation. If it does not, hospital admission or adjustment in antimicrobial regimen should be considered, as well as additional diagnostic testing (eg, laparoscopy). In addition, all women with chlamydial- or gonococcal-related PID should return in three months for surveillance testing.²²