Clinical Review

From the Department of Preventive Medicine and Environmental Health, University of Kentucky College of Public Health, Lexington, KY.

Abstract

• Objective: To review the classification, epidemiology, clinical presentation, and evaluation of patients with chronic obstructive pulmonary disease (COPD).
• Methods: Review of the literature.
• Results: While smoking remains the most important risk factor for COPD in much of the developed world, other risk factors, including genetic factors and occupational or environmental exposures, remain important. COPD is the third leading cause of death in the United States. In 2011, 13.7 million adults aged ≥ 25 years were diagnosed with COPD in the United States, and as many as 12 million adults may have COPD that is undiagnosed. In 2010, COPD was responsible for an estimated 10.3 million physician office visits and 1.5 million emergency room visits and was estimated to be the second leading cause of disability-adjusted life years lost among the US population. COPD has primary, secondary, and tertiary prevention strategies. The treatment of COPD has improved in recent years, with new therapies improving patient quality of life.
• Conclusion: COPD remains a serious public health problem that is often underdiagnosed, particularly in its early stages.

Key words: Chronic obstructive pulmonary disease; epidemiology; mortality; smoking; evaluation.

Chronic obstructive pulmonary disease (COPD) is characterized by fixed airflow obstruction with breathing-related symptoms, such as chronic cough, exertional dyspnea, expectoration, and wheeze [1]. These symptoms may occur in conjunction with airway hyperresponsiveness and overlap with other chronic diseases such as asthma. Although COPD is a nonspecific term referring to a set of conditions that develop progressively as a result of a number of different disease processes, it most commonly refers to chronic bronchitis and emphysema. These conditions can be present with or without significant physical impairment. Despite being a very common disease and the third leading cause of death in the United States [2], COPD often is a silent and unrecognized disease, particularly in its early phases [3], and may go untreated.

In this article, we review the classification, epidemiology, clinical presentation, and assessment of patients with COPD.

Definition and Classification

Several different definitions have existed for COPD [4–8]. The Global Initiative for Chronic Obstructive Lung Disease (GOLD), an international collaboration of leading experts in COPD launched in the late 90s with a goal to develop evidence-based recommendations for diagnosis and management of COPD [4], currently defines COPD as “a common, preventable and treatable disease that is characterized by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases” [4].

Severity of COPD has typically been determined using the degree of lung function impairment, although the wisdom of this approach has been questioned, 

Previous definitions of COPD differentiated between chronic bronchitis, asthma, and emphysema, acknowledging that there is frequently overlap between these disease entities [12,13]. The GOLD definition of COPD does not differentiate between chronic bronchitis and emphysema but does note that although asthma and COPD can coexist [4], the largely reversible airflow limitation in asthma merits different therapeutic approaches than the largely irreversible airflow limitation of COPD. The overlap of asthma and COPD in a significant proportion of patients has been the focus of recent work [14].

Epidemiology

Prevalence of COPD

The Behavioral Risk Factor Surveillance System (BRFSS) is an ongoing national random-digit-dialed telephone survey of landline and cellphone households designed to measure behavioral risk factors for the noninstitutionalized adult population of the US [15]. An affirmative response to the following question was defined as physician-diagnosed COPD: “Have you ever been told by a doctor or other health professional that you have chronic obstructive pulmonary disease (COPD), emphysema, or bronchitis?”[16]. Based on 2011 BRFSS survey, 13.7 million adults aged ≥ 25 years were estimated to have a self-reported physician diagnosis of COPD in the United States. The greatest age-adjusted prevalence was found to be clustered along the Ohio River Valley and the southern states [16].

The National Health Interview Survey (NHIS) is an annually conducted, nationally representative survey of the civilian noninstitutionalized population aged 18 years and older. A positive response to one or both of the following questions was used to define COPD: “Have you ever been told by a doctor or other health professional that you had emphysema?” and “During the past 12 months, have you been told by a doctor or other health professional that you had chronic bronchitis?” Age-adjusted COPD prevalence estimates showed significant interyear variation during 1999–2011 period, and were higher in women than in men with the highest prevalence noted in 2001 for both genders [16].

The NHIS estimates for COPD have 2 important limitations. First, these estimates depend on the proper recognition and diagnosis of COPD by both the study participants and their health care providers. This would tend to bias the estimates toward counting fewer cases than actually exist. A bias in the opposite direction, however, is that the term chronic bronchitis in this survey is not precisely defined and could be interpreted as recurrent episodes of acute bronchitis. The finding that “chronic bronchitis” has been reported in 3% to 4% of children supports the presence of this potential bias. The second limitation is that this survey is not able to validate, through physiologic evaluation, whether airway obstruction is present or absent.

These limitations were addressed, in part, by separate nationally representative US surveys that include an examination component, such as the National Health and Nutrition Examination Surveys (NHANES) [17]. An analysis of these data from 1988–1994 and 2007–2012 [18] demonstrated that over 70% of people with evidence of obstruction (based on an FEV₁/FVC < 70%) did not have a diagnosis of lung disease (COPD or asthma). In addition, people with evidence of obstruction had a higher risk of mortality whether or not they had diagnosed lung disease [18].

Evaluation of “reversibility” of the airway obstruction requires the administration of bronchodilator, which is not a part of most population-based studies. A subset of participants in the NHANES 2007–2012 survey received a bronchodilator, with a decrease in the estimated prevalence of obstruction from 20.9% to 14.0% [19]. However, a closer look at similar data from a study where all people got a bronchodilator reveal that only a small proportion of people with “reversibility” actually had a significant response to the bronchodilator [20]. In a clinic-based study of subjects with COPD who were aged 69 years and older, 31% demonstrated reversibility, defined as a 15% improvement (from baseline) in FVC and FEV₁ following administration of an inhaled bronchodilator [21]. In this study, subjects with more severe obstruction were more likely to have reversibility but would also be more likely to continue to have diminished lung function after maximum improvement was obtained, thus being classified as having “partial reversibility.”

The presence of significant reversibility or partial reversibility in patients with COPD [15] and nonreversible airflow obstruction in asthma patients [22] demonstrates that these diseases can coexist or, alternatively, that there is overlap and imprecision in the ways that these diseases are clinically diagnosed.

Morbidity and Mortality

COPD is a leading cause of disease morbidity and mortality in the United States. The National Center for Health Statistics (NCHS) conducts ongoing surveillance of several health indicators nationally. The NCHS collects physician office visit data using the National Ambulatory Medical Care Survey [23], emergency department visit data and hospital outpatient data using the National Hospital Ambulatory Medical Care Survey [24], hospitalization data using the National Hospital Discharge Survey [25], and death data using the mortality component of the National Vital Statistics System [26]. The following data include the number and rate of COPD events in adults in the United States (using International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM], codes 490, 491, 492 and 496) in these data sets for the most recent years available.

In 2010, COPD was responsible for an estimated 10.3 million physician office visits, with a resulting age-adjusted rate of 494.8 per 10,000 US civilian population [16]. COPD was also responsible for an estimated 1.5 million emergency room visits, with a resulting age-adjusted rate of 72 visits per 10,000 population [16].

COPD is a leading cause of hospitalization in US adults, particularly in older populations. In 2010, almost 699,000 hospitalizations, were attributed to COPD. The age-adjusted rate of COPD hospitalizations (as the primary cause of hospitalization) was 32.2 per 10,000 population in 2010 [16].

Deaths due to or associated with COPD have not significantly changed since 1999. While the age-adjusted death rate among men declined during 1999–2010 (P = 0.001), the rate among women has not changed significantly (P = 0.127). In 2010, 63, 778 men and 69, 797 women aged ≥ 25 years died of COPD [26]. One of the limitations of using the mortality component of the National Vital Statistics System is that it is based on the underlying cause of death as reported on the death certificate; however, many decedents with COPD listed on the death certificate have their death attributed to another cause [27]. The significance of COPD as a contributor to death is undefined when it is present with diseases more likely to be attributed as the underlying cause of death, such as myocardial infarction or lung cancer [28].

COPD is a very costly disease, with estimated direct medical costs in 2004 of $20.9 billion. The estimated indirect costs related to morbidity (loss of work time and productivity) and premature mortality is an additional $16.3 billion, for a total of $37.2 billion [29]. Because COPD may be present but not listed as the underlying cause of death or the primary reason for hospitalization, these cited estimates may underestimate the true cost of COPD. For example, in another analysis of COPD costs in the US, the total for 2010 was estimated at $32.1 billion [30], but could be up to $100 billion [31] depending on the assumptions surrounding comorbid disease.

Another manifestation of the importance of COPD is its effect on the burden of disease in a population determined using disability-adjusted life-years (DALYs). DALYs for a disease or condition are calculated as the sum of the years of life lost due to premature mortality in the population and the years of life lost due to disability [32]. In 2010, COPD was estimated to be the second leading cause of DALYs lost among the North American population [33]. Worldwide, COPD is expected to move up from being the twelfth leading cause of DALYs lost in 1990 to the fifth leading cause in 2020 [34].

Gender Differences

Smoking-related diseases such as COPD and lung cancer are continuing to increase among women in the United States [35,36], while they have plateaued or are decreasing among men [27,37]. Some evidence has emerged that compared with men at a similar level of tobacco smoking, women may be more likely to develop COPD [38] or that the severity of COPD in women may be increased [39–41].

In the Lung Health Study, which evaluated patients with mild COPD, more women than men demonstrated increased airway responsiveness, although this difference was thought to be related to airway caliber rather than gender [42]. Adult women are more likely to both develop and die of asthma than are men [43–45]. In NHANES III, whereas women reported more physician-diagnosed COPD and asthma than men, men and women had similar rates of decreased lung function, and a similar proportion of both men and women with low lung function had undiagnosed lung disease [3]. The current evidence is inadequate to determine whether women who smoke are more likely to develop COPD or have more severe COPD than men, although this question is being studied by various groups.

Risk Factors and Etiology

Smoking is the dominant risk factor for the development and progression of COPD; however, not all smokers develop COPD, and COPD does occur in persons who have never smoked [1], suggesting that other factors are important in the etiology of COPD. Alpha1-antitrypsin deficiency is an important cause of COPD in a very small percentage of cases [46]. Other undefined genetic factors certainly play an important role in COPD development [38]. The role of infections in both the development and progression of COPD is receiving increased attention, including the role of adenoviral infections in emphysema [47–49].

Occupational and environmental exposures to various pollutants (eg, particulate matter, agricultural dusts) are also important factors in the development of COPD [50,51]. Exposure to indoor air pollutants such as smoke from solid biomass fuels is a major risk factor for COPD especially among women and children in low- and middle-income countries [52,53]. Occupational exposure to fumes and dusts remains an important cause for COPD globally [53,54]. Exposure to outdoor air pollution is associated with a risk of development of COPD as well as exacerbation of the existing disease [53,55].

Clinical Presentation

COPD is heterogeneous in its presentation. Based on data from NHANES III, 44% of patients with severe airflow limitation (FEV₁ < 50% of predicted) may not report symptoms [3]. Among patients with severe airflow limitation who do report symptoms, the symptoms reported most frequently include wheezing (64%) and shortness of breath (65%).

In recent years, COPD has been increasingly recognized as a systemic illness, with effects on nutritional status, muscle wasting, and depression [56–58]. A large proportion of patients probably have components of chronic bronchitis, asthma, and emphysema occurring together. Although some of this overlap may be related to misdiagnosis, some of it may be a measure of the presence of airflow limitation reversibility, as described above. Better defining individuals in these groups may ultimately help tailor better interventions.

Some of the barriers to COPD diagnosis and subsequent treatment often include insufficient knowledge and awareness about COPD especially among primary care physicians, misdiagnosis of COPD as other respiratory diseases such asthma, as well as patient-related barriers involving lack of awareness of early symptoms of COPD and considering them to be related to aging or smoking [59].

Evaluation

The evaluation of a patient with suspected COPD is oriented toward establishing the correct diagnosis and, once this has occurred, determining the extent of the impairment such that therapy can be appropriately targeted.

Components in the evaluation of COPD are listed in Table 3. Every patient with suspected COPD should undergo a thorough history and physical examination. The history should pay particular attention to the following: exposure to risk factors; past history of asthma or allergic disease; family history of COPD; presence of comorbid diseases; effect of disease on the patient’s life, including ability to work and mental health status; and possibilities for reducing risk factors, especially smoking cessation [4]. The physical examination is rarely diagnostic in COPD because most physical abnormalities do not occur until the advanced stages of the disease. Physical examination findings in 

Pulmonary function testing is a critical part of the evaluation of suspected COPD. Whereas most patients with COPD can be managed by a primary care physician, patients with moderate or severe COPD should be evaluated by a specialist [4].

Once the diagnosis of moderate or severe COPD has been established, further testing, including chest radiograph, arterial blood gas determination, screening for α1-antitrypsin deficiency, 6-minute walk testing or exercise oxymetry may be indicated based on the patient’s history and/or clinical findings. Data from computed tomography scans are useful in some advanced cases.

Prognosis of COPD is often influenced by presence of various comorbidities including extrapulmonary, such as osteoporosis, metabolic syndrome, and depression that may be seen as parts of multimorbidity associated with aging [60,61]. Therefore, it is advised to look for comorbidities in COPD patients with any severity of airflow obstruction and treat them accordingly [4].

Therapy for COPD targets reducing risk factors, improving symptoms, and decreasing the risk of exacerbations [10]. Interventions include smoking cessation, vaccinations, decreasing exposures to occupational and environmental pollutants, pulmonary rehabilitation, bronchodilators, and corticosteroids. Select patients with advanced COPD may benefit from other interventions, such as surgical reduction of lung size, lung transplant, the phosphodiesterase inhibitor roflumilast and chronic treatment with antibiotics such as macrolides.

Conclusion

COPD is a common disease that is a leading cause of morbidity and mortality, both in the United States and worldwide. Most cases of COPD are attributable to smoking. Although its incidence among men has plateaued, it continues to increase among women. COPD, particularly in its early stages, is under-diagnosed in the United States. An increased awareness among physicians of the prevalence of mild COPD and the importance of spirometry in diagnosing the disease is important in combating the disease.

Corresponding author: David M. Mannino, MD, Department of Preventive Medicine and Environmental Health, University of Kentucky College of Public Health, 111 Washington Avenue, Lexington, KY 40536, [email protected].

 Financial disclosures: Dr. Mannino has received fees from GlaxoSmithKline, Novartis, AstraZeneca, Sunovion, and Boehringer Ingelheim for advisory board services.

From the Department of Preventive Medicine and Environmental Health, University of Kentucky College of Public Health, Lexington, KY.

Abstract

• Objective: To review the classification, epidemiology, clinical presentation, and evaluation of patients with chronic obstructive pulmonary disease (COPD).
• Methods: Review of the literature.
• Results: While smoking remains the most important risk factor for COPD in much of the developed world, other risk factors, including genetic factors and occupational or environmental exposures, remain important. COPD is the third leading cause of death in the United States. In 2011, 13.7 million adults aged ≥ 25 years were diagnosed with COPD in the United States, and as many as 12 million adults may have COPD that is undiagnosed. In 2010, COPD was responsible for an estimated 10.3 million physician office visits and 1.5 million emergency room visits and was estimated to be the second leading cause of disability-adjusted life years lost among the US population. COPD has primary, secondary, and tertiary prevention strategies. The treatment of COPD has improved in recent years, with new therapies improving patient quality of life.
• Conclusion: COPD remains a serious public health problem that is often underdiagnosed, particularly in its early stages.

Key words: Chronic obstructive pulmonary disease; epidemiology; mortality; smoking; evaluation.

Chronic obstructive pulmonary disease (COPD) is characterized by fixed airflow obstruction with breathing-related symptoms, such as chronic cough, exertional dyspnea, expectoration, and wheeze [1]. These symptoms may occur in conjunction with airway hyperresponsiveness and overlap with other chronic diseases such as asthma. Although COPD is a nonspecific term referring to a set of conditions that develop progressively as a result of a number of different disease processes, it most commonly refers to chronic bronchitis and emphysema. These conditions can be present with or without significant physical impairment. Despite being a very common disease and the third leading cause of death in the United States [2], COPD often is a silent and unrecognized disease, particularly in its early phases [3], and may go untreated.

In this article, we review the classification, epidemiology, clinical presentation, and assessment of patients with COPD.

Definition and Classification

Several different definitions have existed for COPD [4–8]. The Global Initiative for Chronic Obstructive Lung Disease (GOLD), an international collaboration of leading experts in COPD launched in the late 90s with a goal to develop evidence-based recommendations for diagnosis and management of COPD [4], currently defines COPD as “a common, preventable and treatable disease that is characterized by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases” [4].

Severity of COPD has typically been determined using the degree of lung function impairment, although the wisdom of this approach has been questioned, 

Previous definitions of COPD differentiated between chronic bronchitis, asthma, and emphysema, acknowledging that there is frequently overlap between these disease entities [12,13]. The GOLD definition of COPD does not differentiate between chronic bronchitis and emphysema but does note that although asthma and COPD can coexist [4], the largely reversible airflow limitation in asthma merits different therapeutic approaches than the largely irreversible airflow limitation of COPD. The overlap of asthma and COPD in a significant proportion of patients has been the focus of recent work [14].

Epidemiology

Prevalence of COPD

The Behavioral Risk Factor Surveillance System (BRFSS) is an ongoing national random-digit-dialed telephone survey of landline and cellphone households designed to measure behavioral risk factors for the noninstitutionalized adult population of the US [15]. An affirmative response to the following question was defined as physician-diagnosed COPD: “Have you ever been told by a doctor or other health professional that you have chronic obstructive pulmonary disease (COPD), emphysema, or bronchitis?”[16]. Based on 2011 BRFSS survey, 13.7 million adults aged ≥ 25 years were estimated to have a self-reported physician diagnosis of COPD in the United States. The greatest age-adjusted prevalence was found to be clustered along the Ohio River Valley and the southern states [16].

The National Health Interview Survey (NHIS) is an annually conducted, nationally representative survey of the civilian noninstitutionalized population aged 18 years and older. A positive response to one or both of the following questions was used to define COPD: “Have you ever been told by a doctor or other health professional that you had emphysema?” and “During the past 12 months, have you been told by a doctor or other health professional that you had chronic bronchitis?” Age-adjusted COPD prevalence estimates showed significant interyear variation during 1999–2011 period, and were higher in women than in men with the highest prevalence noted in 2001 for both genders [16].

The NHIS estimates for COPD have 2 important limitations. First, these estimates depend on the proper recognition and diagnosis of COPD by both the study participants and their health care providers. This would tend to bias the estimates toward counting fewer cases than actually exist. A bias in the opposite direction, however, is that the term chronic bronchitis in this survey is not precisely defined and could be interpreted as recurrent episodes of acute bronchitis. The finding that “chronic bronchitis” has been reported in 3% to 4% of children supports the presence of this potential bias. The second limitation is that this survey is not able to validate, through physiologic evaluation, whether airway obstruction is present or absent.

These limitations were addressed, in part, by separate nationally representative US surveys that include an examination component, such as the National Health and Nutrition Examination Surveys (NHANES) [17]. An analysis of these data from 1988–1994 and 2007–2012 [18] demonstrated that over 70% of people with evidence of obstruction (based on an FEV₁/FVC < 70%) did not have a diagnosis of lung disease (COPD or asthma). In addition, people with evidence of obstruction had a higher risk of mortality whether or not they had diagnosed lung disease [18].

Evaluation of “reversibility” of the airway obstruction requires the administration of bronchodilator, which is not a part of most population-based studies. A subset of participants in the NHANES 2007–2012 survey received a bronchodilator, with a decrease in the estimated prevalence of obstruction from 20.9% to 14.0% [19]. However, a closer look at similar data from a study where all people got a bronchodilator reveal that only a small proportion of people with “reversibility” actually had a significant response to the bronchodilator [20]. In a clinic-based study of subjects with COPD who were aged 69 years and older, 31% demonstrated reversibility, defined as a 15% improvement (from baseline) in FVC and FEV₁ following administration of an inhaled bronchodilator [21]. In this study, subjects with more severe obstruction were more likely to have reversibility but would also be more likely to continue to have diminished lung function after maximum improvement was obtained, thus being classified as having “partial reversibility.”

The presence of significant reversibility or partial reversibility in patients with COPD [15] and nonreversible airflow obstruction in asthma patients [22] demonstrates that these diseases can coexist or, alternatively, that there is overlap and imprecision in the ways that these diseases are clinically diagnosed.

Morbidity and Mortality

COPD is a leading cause of disease morbidity and mortality in the United States. The National Center for Health Statistics (NCHS) conducts ongoing surveillance of several health indicators nationally. The NCHS collects physician office visit data using the National Ambulatory Medical Care Survey [23], emergency department visit data and hospital outpatient data using the National Hospital Ambulatory Medical Care Survey [24], hospitalization data using the National Hospital Discharge Survey [25], and death data using the mortality component of the National Vital Statistics System [26]. The following data include the number and rate of COPD events in adults in the United States (using International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM], codes 490, 491, 492 and 496) in these data sets for the most recent years available.

In 2010, COPD was responsible for an estimated 10.3 million physician office visits, with a resulting age-adjusted rate of 494.8 per 10,000 US civilian population [16]. COPD was also responsible for an estimated 1.5 million emergency room visits, with a resulting age-adjusted rate of 72 visits per 10,000 population [16].

COPD is a leading cause of hospitalization in US adults, particularly in older populations. In 2010, almost 699,000 hospitalizations, were attributed to COPD. The age-adjusted rate of COPD hospitalizations (as the primary cause of hospitalization) was 32.2 per 10,000 population in 2010 [16].

Deaths due to or associated with COPD have not significantly changed since 1999. While the age-adjusted death rate among men declined during 1999–2010 (P = 0.001), the rate among women has not changed significantly (P = 0.127). In 2010, 63, 778 men and 69, 797 women aged ≥ 25 years died of COPD [26]. One of the limitations of using the mortality component of the National Vital Statistics System is that it is based on the underlying cause of death as reported on the death certificate; however, many decedents with COPD listed on the death certificate have their death attributed to another cause [27]. The significance of COPD as a contributor to death is undefined when it is present with diseases more likely to be attributed as the underlying cause of death, such as myocardial infarction or lung cancer [28].

COPD is a very costly disease, with estimated direct medical costs in 2004 of $20.9 billion. The estimated indirect costs related to morbidity (loss of work time and productivity) and premature mortality is an additional $16.3 billion, for a total of $37.2 billion [29]. Because COPD may be present but not listed as the underlying cause of death or the primary reason for hospitalization, these cited estimates may underestimate the true cost of COPD. For example, in another analysis of COPD costs in the US, the total for 2010 was estimated at $32.1 billion [30], but could be up to $100 billion [31] depending on the assumptions surrounding comorbid disease.

Another manifestation of the importance of COPD is its effect on the burden of disease in a population determined using disability-adjusted life-years (DALYs). DALYs for a disease or condition are calculated as the sum of the years of life lost due to premature mortality in the population and the years of life lost due to disability [32]. In 2010, COPD was estimated to be the second leading cause of DALYs lost among the North American population [33]. Worldwide, COPD is expected to move up from being the twelfth leading cause of DALYs lost in 1990 to the fifth leading cause in 2020 [34].

Gender Differences

Smoking-related diseases such as COPD and lung cancer are continuing to increase among women in the United States [35,36], while they have plateaued or are decreasing among men [27,37]. Some evidence has emerged that compared with men at a similar level of tobacco smoking, women may be more likely to develop COPD [38] or that the severity of COPD in women may be increased [39–41].

In the Lung Health Study, which evaluated patients with mild COPD, more women than men demonstrated increased airway responsiveness, although this difference was thought to be related to airway caliber rather than gender [42]. Adult women are more likely to both develop and die of asthma than are men [43–45]. In NHANES III, whereas women reported more physician-diagnosed COPD and asthma than men, men and women had similar rates of decreased lung function, and a similar proportion of both men and women with low lung function had undiagnosed lung disease [3]. The current evidence is inadequate to determine whether women who smoke are more likely to develop COPD or have more severe COPD than men, although this question is being studied by various groups.

Risk Factors and Etiology

Smoking is the dominant risk factor for the development and progression of COPD; however, not all smokers develop COPD, and COPD does occur in persons who have never smoked [1], suggesting that other factors are important in the etiology of COPD. Alpha1-antitrypsin deficiency is an important cause of COPD in a very small percentage of cases [46]. Other undefined genetic factors certainly play an important role in COPD development [38]. The role of infections in both the development and progression of COPD is receiving increased attention, including the role of adenoviral infections in emphysema [47–49].

Occupational and environmental exposures to various pollutants (eg, particulate matter, agricultural dusts) are also important factors in the development of COPD [50,51]. Exposure to indoor air pollutants such as smoke from solid biomass fuels is a major risk factor for COPD especially among women and children in low- and middle-income countries [52,53]. Occupational exposure to fumes and dusts remains an important cause for COPD globally [53,54]. Exposure to outdoor air pollution is associated with a risk of development of COPD as well as exacerbation of the existing disease [53,55].

Clinical Presentation

COPD is heterogeneous in its presentation. Based on data from NHANES III, 44% of patients with severe airflow limitation (FEV₁ < 50% of predicted) may not report symptoms [3]. Among patients with severe airflow limitation who do report symptoms, the symptoms reported most frequently include wheezing (64%) and shortness of breath (65%).

In recent years, COPD has been increasingly recognized as a systemic illness, with effects on nutritional status, muscle wasting, and depression [56–58]. A large proportion of patients probably have components of chronic bronchitis, asthma, and emphysema occurring together. Although some of this overlap may be related to misdiagnosis, some of it may be a measure of the presence of airflow limitation reversibility, as described above. Better defining individuals in these groups may ultimately help tailor better interventions.

Some of the barriers to COPD diagnosis and subsequent treatment often include insufficient knowledge and awareness about COPD especially among primary care physicians, misdiagnosis of COPD as other respiratory diseases such asthma, as well as patient-related barriers involving lack of awareness of early symptoms of COPD and considering them to be related to aging or smoking [59].

Evaluation

The evaluation of a patient with suspected COPD is oriented toward establishing the correct diagnosis and, once this has occurred, determining the extent of the impairment such that therapy can be appropriately targeted.

Components in the evaluation of COPD are listed in Table 3. Every patient with suspected COPD should undergo a thorough history and physical examination. The history should pay particular attention to the following: exposure to risk factors; past history of asthma or allergic disease; family history of COPD; presence of comorbid diseases; effect of disease on the patient’s life, including ability to work and mental health status; and possibilities for reducing risk factors, especially smoking cessation [4]. The physical examination is rarely diagnostic in COPD because most physical abnormalities do not occur until the advanced stages of the disease. Physical examination findings in 

Pulmonary function testing is a critical part of the evaluation of suspected COPD. Whereas most patients with COPD can be managed by a primary care physician, patients with moderate or severe COPD should be evaluated by a specialist [4].

Once the diagnosis of moderate or severe COPD has been established, further testing, including chest radiograph, arterial blood gas determination, screening for α1-antitrypsin deficiency, 6-minute walk testing or exercise oxymetry may be indicated based on the patient’s history and/or clinical findings. Data from computed tomography scans are useful in some advanced cases.

Prognosis of COPD is often influenced by presence of various comorbidities including extrapulmonary, such as osteoporosis, metabolic syndrome, and depression that may be seen as parts of multimorbidity associated with aging [60,61]. Therefore, it is advised to look for comorbidities in COPD patients with any severity of airflow obstruction and treat them accordingly [4].

Therapy for COPD targets reducing risk factors, improving symptoms, and decreasing the risk of exacerbations [10]. Interventions include smoking cessation, vaccinations, decreasing exposures to occupational and environmental pollutants, pulmonary rehabilitation, bronchodilators, and corticosteroids. Select patients with advanced COPD may benefit from other interventions, such as surgical reduction of lung size, lung transplant, the phosphodiesterase inhibitor roflumilast and chronic treatment with antibiotics such as macrolides.

Conclusion

COPD is a common disease that is a leading cause of morbidity and mortality, both in the United States and worldwide. Most cases of COPD are attributable to smoking. Although its incidence among men has plateaued, it continues to increase among women. COPD, particularly in its early stages, is under-diagnosed in the United States. An increased awareness among physicians of the prevalence of mild COPD and the importance of spirometry in diagnosing the disease is important in combating the disease.

Corresponding author: David M. Mannino, MD, Department of Preventive Medicine and Environmental Health, University of Kentucky College of Public Health, 111 Washington Avenue, Lexington, KY 40536, [email protected].

 Financial disclosures: Dr. Mannino has received fees from GlaxoSmithKline, Novartis, AstraZeneca, Sunovion, and Boehringer Ingelheim for advisory board services.

From the Department of Preventive Medicine and Environmental Health, University of Kentucky College of Public Health, Lexington, KY.

Abstract

• Objective: To review the classification, epidemiology, clinical presentation, and evaluation of patients with chronic obstructive pulmonary disease (COPD).
• Methods: Review of the literature.
• Results: While smoking remains the most important risk factor for COPD in much of the developed world, other risk factors, including genetic factors and occupational or environmental exposures, remain important. COPD is the third leading cause of death in the United States. In 2011, 13.7 million adults aged ≥ 25 years were diagnosed with COPD in the United States, and as many as 12 million adults may have COPD that is undiagnosed. In 2010, COPD was responsible for an estimated 10.3 million physician office visits and 1.5 million emergency room visits and was estimated to be the second leading cause of disability-adjusted life years lost among the US population. COPD has primary, secondary, and tertiary prevention strategies. The treatment of COPD has improved in recent years, with new therapies improving patient quality of life.
• Conclusion: COPD remains a serious public health problem that is often underdiagnosed, particularly in its early stages.

Key words: Chronic obstructive pulmonary disease; epidemiology; mortality; smoking; evaluation.

Chronic obstructive pulmonary disease (COPD) is characterized by fixed airflow obstruction with breathing-related symptoms, such as chronic cough, exertional dyspnea, expectoration, and wheeze [1]. These symptoms may occur in conjunction with airway hyperresponsiveness and overlap with other chronic diseases such as asthma. Although COPD is a nonspecific term referring to a set of conditions that develop progressively as a result of a number of different disease processes, it most commonly refers to chronic bronchitis and emphysema. These conditions can be present with or without significant physical impairment. Despite being a very common disease and the third leading cause of death in the United States [2], COPD often is a silent and unrecognized disease, particularly in its early phases [3], and may go untreated.

In this article, we review the classification, epidemiology, clinical presentation, and assessment of patients with COPD.

Definition and Classification

Several different definitions have existed for COPD [4–8]. The Global Initiative for Chronic Obstructive Lung Disease (GOLD), an international collaboration of leading experts in COPD launched in the late 90s with a goal to develop evidence-based recommendations for diagnosis and management of COPD [4], currently defines COPD as “a common, preventable and treatable disease that is characterized by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases” [4].

Severity of COPD has typically been determined using the degree of lung function impairment, although the wisdom of this approach has been questioned, 

Previous definitions of COPD differentiated between chronic bronchitis, asthma, and emphysema, acknowledging that there is frequently overlap between these disease entities [12,13]. The GOLD definition of COPD does not differentiate between chronic bronchitis and emphysema but does note that although asthma and COPD can coexist [4], the largely reversible airflow limitation in asthma merits different therapeutic approaches than the largely irreversible airflow limitation of COPD. The overlap of asthma and COPD in a significant proportion of patients has been the focus of recent work [14].

Epidemiology

Prevalence of COPD

The Behavioral Risk Factor Surveillance System (BRFSS) is an ongoing national random-digit-dialed telephone survey of landline and cellphone households designed to measure behavioral risk factors for the noninstitutionalized adult population of the US [15]. An affirmative response to the following question was defined as physician-diagnosed COPD: “Have you ever been told by a doctor or other health professional that you have chronic obstructive pulmonary disease (COPD), emphysema, or bronchitis?”[16]. Based on 2011 BRFSS survey, 13.7 million adults aged ≥ 25 years were estimated to have a self-reported physician diagnosis of COPD in the United States. The greatest age-adjusted prevalence was found to be clustered along the Ohio River Valley and the southern states [16].

The National Health Interview Survey (NHIS) is an annually conducted, nationally representative survey of the civilian noninstitutionalized population aged 18 years and older. A positive response to one or both of the following questions was used to define COPD: “Have you ever been told by a doctor or other health professional that you had emphysema?” and “During the past 12 months, have you been told by a doctor or other health professional that you had chronic bronchitis?” Age-adjusted COPD prevalence estimates showed significant interyear variation during 1999–2011 period, and were higher in women than in men with the highest prevalence noted in 2001 for both genders [16].

The NHIS estimates for COPD have 2 important limitations. First, these estimates depend on the proper recognition and diagnosis of COPD by both the study participants and their health care providers. This would tend to bias the estimates toward counting fewer cases than actually exist. A bias in the opposite direction, however, is that the term chronic bronchitis in this survey is not precisely defined and could be interpreted as recurrent episodes of acute bronchitis. The finding that “chronic bronchitis” has been reported in 3% to 4% of children supports the presence of this potential bias. The second limitation is that this survey is not able to validate, through physiologic evaluation, whether airway obstruction is present or absent.

These limitations were addressed, in part, by separate nationally representative US surveys that include an examination component, such as the National Health and Nutrition Examination Surveys (NHANES) [17]. An analysis of these data from 1988–1994 and 2007–2012 [18] demonstrated that over 70% of people with evidence of obstruction (based on an FEV₁/FVC < 70%) did not have a diagnosis of lung disease (COPD or asthma). In addition, people with evidence of obstruction had a higher risk of mortality whether or not they had diagnosed lung disease [18].

Evaluation of “reversibility” of the airway obstruction requires the administration of bronchodilator, which is not a part of most population-based studies. A subset of participants in the NHANES 2007–2012 survey received a bronchodilator, with a decrease in the estimated prevalence of obstruction from 20.9% to 14.0% [19]. However, a closer look at similar data from a study where all people got a bronchodilator reveal that only a small proportion of people with “reversibility” actually had a significant response to the bronchodilator [20]. In a clinic-based study of subjects with COPD who were aged 69 years and older, 31% demonstrated reversibility, defined as a 15% improvement (from baseline) in FVC and FEV₁ following administration of an inhaled bronchodilator [21]. In this study, subjects with more severe obstruction were more likely to have reversibility but would also be more likely to continue to have diminished lung function after maximum improvement was obtained, thus being classified as having “partial reversibility.”

The presence of significant reversibility or partial reversibility in patients with COPD [15] and nonreversible airflow obstruction in asthma patients [22] demonstrates that these diseases can coexist or, alternatively, that there is overlap and imprecision in the ways that these diseases are clinically diagnosed.

Morbidity and Mortality

COPD is a leading cause of disease morbidity and mortality in the United States. The National Center for Health Statistics (NCHS) conducts ongoing surveillance of several health indicators nationally. The NCHS collects physician office visit data using the National Ambulatory Medical Care Survey [23], emergency department visit data and hospital outpatient data using the National Hospital Ambulatory Medical Care Survey [24], hospitalization data using the National Hospital Discharge Survey [25], and death data using the mortality component of the National Vital Statistics System [26]. The following data include the number and rate of COPD events in adults in the United States (using International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM], codes 490, 491, 492 and 496) in these data sets for the most recent years available.

In 2010, COPD was responsible for an estimated 10.3 million physician office visits, with a resulting age-adjusted rate of 494.8 per 10,000 US civilian population [16]. COPD was also responsible for an estimated 1.5 million emergency room visits, with a resulting age-adjusted rate of 72 visits per 10,000 population [16].

COPD is a leading cause of hospitalization in US adults, particularly in older populations. In 2010, almost 699,000 hospitalizations, were attributed to COPD. The age-adjusted rate of COPD hospitalizations (as the primary cause of hospitalization) was 32.2 per 10,000 population in 2010 [16].

Deaths due to or associated with COPD have not significantly changed since 1999. While the age-adjusted death rate among men declined during 1999–2010 (P = 0.001), the rate among women has not changed significantly (P = 0.127). In 2010, 63, 778 men and 69, 797 women aged ≥ 25 years died of COPD [26]. One of the limitations of using the mortality component of the National Vital Statistics System is that it is based on the underlying cause of death as reported on the death certificate; however, many decedents with COPD listed on the death certificate have their death attributed to another cause [27]. The significance of COPD as a contributor to death is undefined when it is present with diseases more likely to be attributed as the underlying cause of death, such as myocardial infarction or lung cancer [28].

COPD is a very costly disease, with estimated direct medical costs in 2004 of $20.9 billion. The estimated indirect costs related to morbidity (loss of work time and productivity) and premature mortality is an additional $16.3 billion, for a total of $37.2 billion [29]. Because COPD may be present but not listed as the underlying cause of death or the primary reason for hospitalization, these cited estimates may underestimate the true cost of COPD. For example, in another analysis of COPD costs in the US, the total for 2010 was estimated at $32.1 billion [30], but could be up to $100 billion [31] depending on the assumptions surrounding comorbid disease.

Another manifestation of the importance of COPD is its effect on the burden of disease in a population determined using disability-adjusted life-years (DALYs). DALYs for a disease or condition are calculated as the sum of the years of life lost due to premature mortality in the population and the years of life lost due to disability [32]. In 2010, COPD was estimated to be the second leading cause of DALYs lost among the North American population [33]. Worldwide, COPD is expected to move up from being the twelfth leading cause of DALYs lost in 1990 to the fifth leading cause in 2020 [34].

Gender Differences

Smoking-related diseases such as COPD and lung cancer are continuing to increase among women in the United States [35,36], while they have plateaued or are decreasing among men [27,37]. Some evidence has emerged that compared with men at a similar level of tobacco smoking, women may be more likely to develop COPD [38] or that the severity of COPD in women may be increased [39–41].

In the Lung Health Study, which evaluated patients with mild COPD, more women than men demonstrated increased airway responsiveness, although this difference was thought to be related to airway caliber rather than gender [42]. Adult women are more likely to both develop and die of asthma than are men [43–45]. In NHANES III, whereas women reported more physician-diagnosed COPD and asthma than men, men and women had similar rates of decreased lung function, and a similar proportion of both men and women with low lung function had undiagnosed lung disease [3]. The current evidence is inadequate to determine whether women who smoke are more likely to develop COPD or have more severe COPD than men, although this question is being studied by various groups.

Risk Factors and Etiology

Smoking is the dominant risk factor for the development and progression of COPD; however, not all smokers develop COPD, and COPD does occur in persons who have never smoked [1], suggesting that other factors are important in the etiology of COPD. Alpha1-antitrypsin deficiency is an important cause of COPD in a very small percentage of cases [46]. Other undefined genetic factors certainly play an important role in COPD development [38]. The role of infections in both the development and progression of COPD is receiving increased attention, including the role of adenoviral infections in emphysema [47–49].

Occupational and environmental exposures to various pollutants (eg, particulate matter, agricultural dusts) are also important factors in the development of COPD [50,51]. Exposure to indoor air pollutants such as smoke from solid biomass fuels is a major risk factor for COPD especially among women and children in low- and middle-income countries [52,53]. Occupational exposure to fumes and dusts remains an important cause for COPD globally [53,54]. Exposure to outdoor air pollution is associated with a risk of development of COPD as well as exacerbation of the existing disease [53,55].

Clinical Presentation

COPD is heterogeneous in its presentation. Based on data from NHANES III, 44% of patients with severe airflow limitation (FEV₁ < 50% of predicted) may not report symptoms [3]. Among patients with severe airflow limitation who do report symptoms, the symptoms reported most frequently include wheezing (64%) and shortness of breath (65%).

In recent years, COPD has been increasingly recognized as a systemic illness, with effects on nutritional status, muscle wasting, and depression [56–58]. A large proportion of patients probably have components of chronic bronchitis, asthma, and emphysema occurring together. Although some of this overlap may be related to misdiagnosis, some of it may be a measure of the presence of airflow limitation reversibility, as described above. Better defining individuals in these groups may ultimately help tailor better interventions.

Some of the barriers to COPD diagnosis and subsequent treatment often include insufficient knowledge and awareness about COPD especially among primary care physicians, misdiagnosis of COPD as other respiratory diseases such asthma, as well as patient-related barriers involving lack of awareness of early symptoms of COPD and considering them to be related to aging or smoking [59].

Evaluation

The evaluation of a patient with suspected COPD is oriented toward establishing the correct diagnosis and, once this has occurred, determining the extent of the impairment such that therapy can be appropriately targeted.

Components in the evaluation of COPD are listed in Table 3. Every patient with suspected COPD should undergo a thorough history and physical examination. The history should pay particular attention to the following: exposure to risk factors; past history of asthma or allergic disease; family history of COPD; presence of comorbid diseases; effect of disease on the patient’s life, including ability to work and mental health status; and possibilities for reducing risk factors, especially smoking cessation [4]. The physical examination is rarely diagnostic in COPD because most physical abnormalities do not occur until the advanced stages of the disease. Physical examination findings in 

Pulmonary function testing is a critical part of the evaluation of suspected COPD. Whereas most patients with COPD can be managed by a primary care physician, patients with moderate or severe COPD should be evaluated by a specialist [4].

Once the diagnosis of moderate or severe COPD has been established, further testing, including chest radiograph, arterial blood gas determination, screening for α1-antitrypsin deficiency, 6-minute walk testing or exercise oxymetry may be indicated based on the patient’s history and/or clinical findings. Data from computed tomography scans are useful in some advanced cases.

Prognosis of COPD is often influenced by presence of various comorbidities including extrapulmonary, such as osteoporosis, metabolic syndrome, and depression that may be seen as parts of multimorbidity associated with aging [60,61]. Therefore, it is advised to look for comorbidities in COPD patients with any severity of airflow obstruction and treat them accordingly [4].

Therapy for COPD targets reducing risk factors, improving symptoms, and decreasing the risk of exacerbations [10]. Interventions include smoking cessation, vaccinations, decreasing exposures to occupational and environmental pollutants, pulmonary rehabilitation, bronchodilators, and corticosteroids. Select patients with advanced COPD may benefit from other interventions, such as surgical reduction of lung size, lung transplant, the phosphodiesterase inhibitor roflumilast and chronic treatment with antibiotics such as macrolides.

Conclusion

COPD is a common disease that is a leading cause of morbidity and mortality, both in the United States and worldwide. Most cases of COPD are attributable to smoking. Although its incidence among men has plateaued, it continues to increase among women. COPD, particularly in its early stages, is under-diagnosed in the United States. An increased awareness among physicians of the prevalence of mild COPD and the importance of spirometry in diagnosing the disease is important in combating the disease.

Corresponding author: David M. Mannino, MD, Department of Preventive Medicine and Environmental Health, University of Kentucky College of Public Health, 111 Washington Avenue, Lexington, KY 40536, [email protected].

 Financial disclosures: Dr. Mannino has received fees from GlaxoSmithKline, Novartis, AstraZeneca, Sunovion, and Boehringer Ingelheim for advisory board services.

From the Primary Care Institute, Gainesville, FL.

Abstract

• Objective: To provide primary care practitioners with the knowledge required to identify and address older adult suicide risk in their practice.
• Methods: Review of the literature and good clinical practices.
• Results: Primary care practitioners play an important role in older adult suicide prevention and must have knowledge about older adult suicide risk, including risk factors and warning signs in this age-group. Practitioners also must appropriately screen for and manage suicide risk. Older adults, particularly older men, are at high risk for suicide, though they may be less likely to report suicide ideation. Additionally, older adults frequently see primary care practitioners within a month prior to death by suicide. A number of older adult–specific risk factors are reviewed, and appropriate screening and intervention for the primary care setting are discussed.
• Conclusion: Primary care practitioners are uniquely qualified to address a broad range of potential risk factors and should be prepared to identify risk factors and warning signs for older adult suicide, ask appropriate questions to screen for suicide risk, and intervene to prevent suicide.

Key words: suicide; older adults; risk factors; screening; safety planning.

Primary care practitioners play an important role in older adult suicide prevention and have a responsibility to identify and address suicide risk among older adults. To do so, practitioners must understand the problem of older adult suicide, recognize risk factors for suicide in older adults, screen for suicide risk, and appropriately assess and manage suicide risk. Primary care practitioners may face challenges in completing these tasks; the goal of this article is to assist practitioners in addressing these challenges.

Suicide in Older Adults

The United States has recently seen increases in suicide rates across the lifespan; from 1999 to 2014, the suicide rate rose by 24% across all ages [3]. Among both men and women aged 65 to 74, the suicide rate increased in this time period [3]. The high suicide rate among older adults is particularly important to address given the increasing numbers of older adults in the United States. By 2050, the older adult population in the United States is expected to reach 88.5 million, more than double the older adult population in 2010 [4]. Additionally, the generation that is currently aging into older adulthood has historically had higher rates of suicide across their lifespan [5]. Given that suicide rates also increase in older adulthood for men, the coming decades may evidence even higher rates of suicide among older adults than previously and it is critical that older adult suicide prevention becomes a public health priority.

It is also essential to discuss other suicide-related outcomes among older adults, including suicide attempts and suicide ideation. This is critical particularly because the ratio of suicide attempts to deaths by suicide in this age-group is 4 to 1 [1]. This is in contrast to the ratio of attempts to deaths across all ages, which is 25 suicide attempts per death by suicide [1]. This means that suicide prevention must occur before a first suicide attempt is made; suicide attempts cannot be used a marker of elevated suicide risk in older adults or an indication that intervention is needed. Intervention is required prior to suicide risk becoming elevated to the point of a suicide attempt.

It is also critical to recognize that despite the fact that suicide rates rise with age, reports of suicide ideation decrease with age [7,8]. Across all ages, 3.9% of Americans report past-year suicide ideation; however, only 2.7% of older adults report thoughts of suicide [9]. The discrepancy with the increasing rates of death by suicide with age suggest that suicide risk, and thereby opportunities for intervention, may be missed in this age-group [10].

However, older adults may be more willing to report death ideation, as research has found that over 15% of older adults endorse death ideation [11–13]. Death ideation is a desire for death without a specific desire to end one’s own life, and is an important suicide-related outcome, as older adults with death ideation appear the same as those with suicide ideation in terms of depression, hopelessness, and history of suicidal behavior [14]. Additionally, older adults with death ideation had more hospitalizations, more outpatient visits, and more medical issues than older adults with suicide ideation [15]. Therefore, death ideation should be taken as seriously as suicide ideation in older adults [14]. In sum, the high rates of death by suicide, the likelihood of death on a first or early suicide attempt, and the discrepancy between decreasing reports of suicide ideation and increasing rates of death by suicide among older adults indicate that older adult suicide is an important public health problem.

Suicide Prevention Strategies

Many suicide prevention strategies to date have focused on indicated prevention, which concentrates on individuals already identified at high risk (eg, those with suicide ideation or who have made a suicide attempt) [16]. However, because older adults may not report suicide ideation or survive a first suicide attempt, indicated prevention is likely not enough to be effective in older adult suicide prevention. A multilevel suicide prevention strategy [17] is required to prevent older adult suicide [18]. Older adult suicide prevention must include indicated prevention but must also include selective and universal prevention [16]. Selective prevention focuses on groups who may be at risk for suicide (eg, individuals with depression, older adults) and universal prevention focuses on the entire population (eg, interventions to reduce mental health stigma) [16]. To prevent older adult suicide, crisis intervention is critical, but suicide prevention efforts upstream of the development of a suicidal crisis are also essential.

The Importance of Primary Care

Research indicates that primary care is one of the best settings in which to engage in older adult suicide prevention [18]. Older adults are significantly less likely to receive specialty mental health care than younger adults, even when they have depressive symptoms [19]. Additionally, among older adults who died by suicide, 58% had contact with a primary care provider within a month of their deaths, compared to only 11% who had contact with a mental health specialist [20]. Among older adults who died by suicide, 67% saw any provider in the 4 weeks prior to their death [21]. Approximately 10% of older adults saw an outpatient mental health provider, 11% saw a primary care physician for a mental health issue, and 40% saw a primary care physician for a non-mental health issue [21]. Therefore, because older adults are less likely to receive specialty mental health treatment and so often seen a primary care practitioner prior to death by suicide, primary care may be the ideal place for older adult suicide risk to be detected and addressed, especially as many older adults visit primary care without a mental health presenting concern prior to their death by suicide.

Additionally, older adults may be more likely to disclose suicide ideation to primary care practitioners, with whom they are more familiar, than physicians in other settings (eg, emergency departments). Research has shown that familiarity with a primary care physician significantly increases the likelihood of patient disclosure of psychosocial issues to the physician [22]. Primary care providers also have a critical role as care coordinators; many older adults also see specialty physicians and use the emergency department. In fact, older adults are more likely to use the emergency department than younger adults, but emergency departments are not equipped to navigate the complex care needs of this population [23]. Primary care practitioners are important in ensuring that health issues of older adults are addressed by coordinating with specialists, hospitals (eg, inpatient stays, emergency department visits, surgery) and other health services (eg, home health care, physical therapy). Approximately 35% of older adults in the United States experience a lack of care coordination [24], which can negatively impact their health and leave issues such as suicide ideation unaddressed. Primary care practitioners may be critical in screening for mental health issues and suicide risk during even routine visits because of their familiarity with patients, and also play an important role in coordinating care for older adults to improve well-being and to ensure that critical issues, such as suicide ideation, are appropriately addressed.

Primary care practitioners can also be key in upstream prevention. Primary care practitioners are in a unique role to address risk factors for suicide prior to the development of a suicidal crisis. Because older adults frequently see primary care practitioners, such practitioners may have more opportunities to identify risk factors (eg, chronic pain, depression). Primary care practitioners are also trained to treat a broad range of conditions, providing the skills to address many different risk factors.

Finally, primary care is a setting in which screening for depression and suicide ideation among older adults is recommended. The US Preventive Services Task Force recommends screening for depression in all adults and older adults and provides recommended screening instruments, some of which include questions about self-harm or suicide risk [25]. However, this same group has concluded that there is insufficient evidence to support a recommendation for suicide risk screening [26]. Despite this, the Joint Commission recently released an alert that recommends screening for suicide risk in all settings, including primary care [27]. The Joint Commission requirement for ambulatory care that is relevant to suicide is PC.04.01.01: The organization has a process that addresses the patient’s need for continuing care, treatment, or services after discharge or transfer; behavioral health settings have additional suicide-specific requirements. The recommendations, though, go far beyond this requirement for primary care. The Joint Commission specifically notes that primary care clinicians play an important role in detecting suicide ideation and recommends that primary care practitioners review each patient’s history for suicide risk factors, screen all patients for suicide risk, review screenings before patients leave appointments, and take appropriate actions to address suicide risk when needed [27]. Further details are available in the Joint Commission’s Sentinel Event Alert titled, “Detecting and treating suicide ideation in all settings” [27]. Given these recommendations, primary care is an important setting in which to identify and address suicide risk.

Risk Factors for Older Adult Suicide

Numerous reviews exist that cover many risk factors for suicide in older adults [18,28]. This article will focus briefly on risk factors that are likely to be recognized and potentially addressed by primary care practitioners. Risk factors that apply across the lifespan can be recalled through a mnemonic: IS PATH WARM [29]. These risk factors include suicide Ideation, Substance abuse, Purposelessness, Anxiety (including agitation and poor sleep), feeling Trapped, Hopelessness, social Withdrawal, Anger or rage, Recklessness (ie, engaging in risky activities), and Mood changes. The National Suicide Prevention Lifeline also includes being in unbearable physical pain, perceiving one’s self as a burden to others, and seeking revenge on others as risk factors [30]. More specific to older adults, Conwell notes 5 categories or domains of risk factors with strong research support: psychiatric symptoms, somatic illness, functional impairment, social integration, and personality traits and coping [18,31].

Affective or mood disorders, particularly depression and depressive symptoms, are some of the most well-studied and strongest risk factors for older adult suicide [31]; 71% to 97% of all older adults who die by suicide have psychiatric illnesses [28]. Mood disorders, including major depressive episodes, are most consistently linked to older adult suicide risk; there is evidence as well for anxiety disorders and substance abuse disorders as risk factors, though it is somewhat mixed [28]. Therefore, screening for depression, anxiety, and substance abuse may be key to recognizing potential suicide risk. However, depression and anxiety do not present similarly in younger and older adults [32,33]. Depressive symptoms in older adults may be more somatic (eg, agitation, gastrointestinal symptoms) [32] and may reflect more anhedonia than mood changes [33]. Anxiety in older adults tends to be reported as stress or tension, whereas younger adults report feeling anxious or worried [33]. Additionally, substance abuse is often underrecognized, underdiagnosed, and undertreated in older adults [34]. Proactive screening for substance abuse is important as it may not interfere with work or other obligations in older adults, and therefore substance abuse may not be identified by older adults or others in their lives.

Physical illness may also be a risk factor for suicide [28,31]. Numerous diagnoses have been linked to suicide risk, including cancers, neurodegenerative diseases (eg, amyotrophic lateral sclerosis, Huntington disease), spinal cord injury, cardiovascular disease, and pulmonary disease [28,35]. However, overall illness burden (ie, number of chronic illnesses) [28] and self-perceived health [36] appear to be stronger risk factors than any specific illness. Additionally, authors have suggested that illness itself may not be a particularly strong risk factor, but the effect of illness on depressive symptoms [35], functioning, pain, or hopelessness due to the potential for decline over time [28] may increase suicide risk in older adults. Pain itself has been identified as a risk factor for suicide, as have perceptions of burden to others, hopelessness, and functional impairment [28].

In terms of functional impairment, research has shown that impairment in completing instrumental activities of daily living is associated with higher risk for death by suicide, and cognitive impairment may also be associated with elevated suicide risk [28]. However, there are some discrepant findings regarding the role of dementia in suicide risk, which may reflect medical and psychiatric comorbidities, as well as different stages of dementia or levels of cognitive impairment (eg, hopelessness about cognitive decline may increase suicide risk shortly after diagnosis, whereas lack of insight may decrease risk later in the course of the illness) [37]. Related to functional or cognitive impairment is perceived burdensomeness (ie, the perception that one is a liability or burden to others, to the point that others would be better off if one was gone) [38], which may also be associated with suicide risk in older adults [39,40]. Researchers have found that the interaction between perceived burdensomeness and thwarted belongingness (ie, a belief that one lacks reciprocal caring relationships and does not belong) identified older adults who were likely experiencing suicide ideation but did not report it [41]. These findings indicate that perceived burdensomeness and thwarted belongingness may be key in identifying older adults at risk for suicide.

Thwarted belongingness has also been linked to suicide ideation in older adults [41]. In fact, studies suggest that social integration is especially important for reducing suicide risk in this population [28,31,42]. A larger social network, living with others, and being active in the community are each protective against suicide [28]. Bereavement, which can reduce social connectedness and acts as a significant life stressor, is also an important risk factor [31]. Retirement may also reduce social connectedness, and employment changes have been identified as a suicide risk factor for older adults [28]. Retirement has been linked to risk for death by suicide in this population [43], and may not only serve to reduce social connectedness, but for some older adults may also be a significant role loss or loss of sense of purpose that can influence suicide risk.

Finally, rigid personality traits or coping styles are a risk factor for suicide among older adults [28,31]. As older adults face potential losses, health changes, and functional decline, effective positive coping strategies and flexibility are key to maintaining well-being. If older adults are unable to flexibly cope with these challenges, their risk for suicide increases [28].

In addition to risk factors, which confer suicide risk but do not necessarily suggest that an older adult is thinking about suicide, warning signs exist that indicate that suicide risk is imminent. These include suicidal communication (ie, talking or writing about suicide), seeking access to means, and making preparations for suicide (eg, ensuring a will is in place, giving away prized possessions). One important note is that discussing and preparing for death may be developmentally appropriate for older adults, particularly those with chronic illnesses; however, such appropriate preparation is critically different from talking about suicide or a desire for death.

Additionally, a lack of planning for the future may be a warning sign. For example, older adults who decline to schedule medical follow-up or do not wish to refill needed prescriptions may be exhibiting warning signs that should be addressed. Similarly, not following needed medical regimens (eg, an older adult with diabetes no longer taking insulin) is also a warning sign. Other, potentially more subtle warning signs may include significant changes in mood, sleep, or social interactions. Older adults may become agitated and sleep less when they are considering suicide, or may feel more at ease after they have made the decision to die by suicide and their sleep or mood may improve. Withdrawing from valued others may also be a warning sign. Finally, recent major changes (eg, loss of a spouse, moving to an assisted living facility) may be triggers for suicide risk and can serve as warning signs themselves.

Specific Screening Strategies

Given the numerous risk factors and warning signs for older adult suicide, as well as the time limitations that primary care practitioners face [44,45], it would be impractical to comprehensively assess each older adult who presents at a primary care practice. Therefore, more specific screening is necessary. Most importantly, every older adult should be screened for suicide ideation and death ideation at every visit. Screening at every visit is critical because suicide ideation may develop at any point. Previous research has included screening of over 29,000 older adults in 11 primary care settings for suicide ideation, risk of alcohol misuse, and mental health disorders [15], suggesting that suicide risk screening is feasible. Other studies have also successfully used widespread screening for depression and suicide ideation among older adults in primary care [46–48]. Additionally, in an emergency department setting, universal suicide risk screening has been associated with significantly improved risk detection [49], indicating that improved screening may be beneficial in identifying suicide risk. Importantly, asking about suicide does not cause thoughts of suicide [50]. Additionally, it is a myth that those who talk about suicide ideation will not act on these thoughts [51].

When primary care practitioners inquire about suicide ideation, they should also ask about death ideation; though some may believe that death ideation is not as significant in terms of suicide risk as suicide ideation, recall that research has not found differences in previous suicide attempts or current hopelessness among older adults with death ideation versus suicide ideation [14]. Therefore, screening for death ideation should be completed as part of every suicide risk screening.

Screening can take many forms. Screening may be oral; asking an older adult if he or she is having thoughts of suicide or is experiencing a desire to die is a brief, 2-question screening that may provide valuable information (eg, “Are you having thoughts about your own death or wanting to die?”, “Are you having thoughts of killing yourself or thinking about suicide?”). This screening may be conducted by medical assistants, nurses, care managers, or physicians, with the patient’s responses documented. Importantly, a standard procedure should be implemented to ensure older adults are consistently asked about suicide risk at each visit, but do not feel inundated by such questions from numerous staff.

If verbal questions are asked, they must be asked appropriately. Euphemisms or indirect language should not be used during a screening; older adults should be directly asked about thoughts of death and suicide, not simply asked questions such as, “Have you ever had thoughts of harming or hurting yourself?” A question like this does not adequately assess current suicide risk, as it does not assess current thoughts, nor does it specifically inquire about suicide ideation (ie, killing one’s self). It is also important to phrase questions in a manner that invites honest responses and conveys an openness to listening. For example, asking, “You’re not thinking about suicide, are you?” suggests that the practitioner wants the older adult to say no and is not comfortable with the older adult endorsing suicide ideation. Open questions that allow endorsement or denial (eg, “Are you having thoughts of killing yourself?”) imply that the practitioner is receptive to either an endorsement or denial of suicide ideation.

Alternatively, a written screening can be used; older adults may complete a questionnaire prior to their appointment or while waiting to see their practitioner. Such an assessment may be a brief screening (eg, using similar yes/no questions to an oral screening), or may be a standardized measure. For example, the Geriatric Suicide Ideation Scale [52] is a 31-item self-report measure that provides scores for suicide ideation, death ideation, loss of personal and social worth, and perceived meaning in life. Though there are not standard cutoffs that suggest high versus low suicide risk, responses can be reviewed to identify whether older adults are reporting suicide ideation or death ideation, and can also be compared to norms (ie, average scores) from other older adults [52]. This measure also has the benefit of 2 subscales that do not specifically require reporting thoughts of suicide or death (ie, loss of personal and social worth, perceived meaning in life), which may give practitioners an indication of an older adult’s suicide risk even if the older adult is not comfortable disclosing suicide ideation, as has been shown in previous research [7,8].

Similarly, the Geriatric Depression Scale, which has a validated 15-item version [53], does not directly ask about suicide ideation but has a 5-item subscale that has been found to be highly correlated with reported suicide ideation [54]. When administered to older adult primary care patients, this subscale was an effective measure of suicide ideation; a score of ≥ 1 was the best cutoff for determining whether an older adult reported suicide ideation [55].

Additionally, as noted previously, the interaction between perceived burdensomeness and thwarted belongingness may identify older adults who are potentially experiencing, but not reporting, suicide ideation [41]. The Interpersonal Needs Questionnaire [56] is the validated assessment for both perceived burdensomeness and thwarted belongingness. Perceived burdensomeness is assessed via 6 self-report items, and thwarted belongingness is assessed via 9 self-report items on this measure [56]. There are not specific cutoffs that determine high versus low perceived burdensomeness or thwarted belongingness, but older adults’ responses can provide information about their experiences of these constructs. Administration of the Interpersonal Needs Questionnaire can provide information about potential risk for suicide among older adults who may otherwise deny thoughts of suicide or death.

If the screening for suicide ideation or death ideation is positive (ie, the older adult endorses thoughts of suicide or death), the treating primary care practitioner must then follow up with additional questions to determine current level of suicide risk. To make this determination, at a minimum, follow-up questions should focus on whether the older adult has any intent to die by suicide (eg, “Do you have any intent to act on your thoughts of suicide?”), as well as whether he or she has a plan to die by suicide (eg, “Have you begun formulating a plan to die by suicide?”). When asking about a plan, it is important to determine how specific the plan is. For example, an older adult with a specific method identified and date selected to implement the plan is at much higher risk than an older adult with a relatively vague idea. It is also critical to assess for the older adult’s access to means for suicide. If an older adult has a specific plan and has the capability to carry out the plan (eg, plans to overdose on prescription medication and has large quantities of medication or high-lethality medication at home), he or she is more likely to die by suicide than an older adult who does not have access to means (eg, only has small quantities of low-lethality medication available). A general assessment of risk factors and previous suicidal behavior (ie, any previous suicide attempts) also informs decisions about level of risk and interventions.

After a screening or assessment is completed, a risk determination must be made and documented. Acute suicide risk can be categorized as low, moderate, or high. It is not appropriate to say that there is “no” suicide risk present. Low risk occurs when there is no current suicide ideation, no plan to die by suicide, and no intent to act on suicidal thoughts, especially when the patient has no history of suicidal behavior and few risk factors [57]. Moderate risk is evident when there is current suicide ideation, but no specific plan to die by suicide or intent to act on suicidal thoughts. There are likely warning signs or risk factors, which may include previous suicidal behaviors, present in moderate suicide risk [57]. High risk is indicated by current suicide ideation with plan to die by suicide and suicidal intent. There are significant warning signs and risk factors present; there may also be a recent suicide attempt, though this is not a requirement for a high risk determination [57]. Undetermined suicide risk occurs when a practitioner cannot accurately assess risk, but concern regarding suicide is present; this is primarily used when a patient refuses to answer questions about suicide. Undetermined risk should be treated as at least moderate risk. Because research shows that death ideation has similar outcomes to suicide ideation in older adults [14], death ideation should also be factored into determinations of suicide risk; reports of death ideation may indicate low or moderate risk in older adults, dependent upon other risk factors, suicidal intent, and plan.

After a risk determination is made, it must be documented in the medical record. The level of risk and rationale for that determination must be included [58]. Stating only the level of risk without a rationale (ie, the older adult’s responses to questions) is not adequate, and documenting only the older adult’s responses without a determination of risk is also not sufficient. Finally, it is critical to document the intervention that occurred or steps taken after the level of risk was determined.

Critically, stating only that there was no indication of suicide risk is inadequate. For example, documenting “No evidence of suicide risk” is not appropriate. This documentation does not indicate that the older adult was specifically asked about suicide ideation, death ideation, suicidal intent, or plan to die by suicide. It also does not indicate a level of suicide risk. Examples of appropriate documentation include:

 Patient was asked about suicide risk. She denied current suicide ideation but reported death ideation. She denied any current suicidal intent or plan. She also denied any previous suicide attempts. Therefore, acute suicide risk was deemed to be low. Provided patient with wallet card about the National Suicide Prevention Lifeline. Also called the Friendship Line while in the room with the patient to connect her with services. Finally, provided a brief list of local mental health professionals to patient; the patient reported she would like to see Dr. Smith. Called and left a message for Dr. Smith with referral information with patient during appointment.

Patient was asked about suicide risk. He reported both death ideation and suicide ideation. He also reported a nonspecific plan (ie, causing a single-vehicle motor vehicle accident, with no specific plan for the motor vehicle accident or timeframe) and denied any intent to act on his thoughts of suicide. He reported one previous suicide attempt, at age 22, by overdose on over-the-counter medication. He reported that this attempt did not require medical attention. Therefore, acute suicide risk was determined to be moderate. Patient was introduced to the behavioral health specialist, who met with the patient during the appointment to conduct further assessment and intervention.

Specific Intervention Strategies

Despite the fact that the pace of the primary care setting often does not allow for time-intensive intervention, there are ways to address suicide risk in this setting. Importantly, no-suicide contracts should not be used at any time [59,60]. No-suicide contracts are documents that patients who are experiencing suicide ideation are required to sign that state that they will not die by suicide while under the care of the practitioner. These contracts have no evidence of effectiveness, and some researchers argue that they may in fact damage the relationship with patients and serve the practitioner’s needs more than the patient’s needs [59].

One of the best options for older adults at low acute suicide risk is to provide resources and referrals. The National Suicide Prevention Lifeline can be reached at 1-800-273-TALK (8255); trained counselors are available to speak to patients at all times. Wallet cards with information about the National Suicide Prevention Lifeline are available at no charge from the US Substance Abuse and Mental Health Services Administration online store. The Friendship Line is another service available free to adults ages 60 and older, 24 hours per day, 7 days per week; this line can be reached at 1-800-971-0016. The Friendship Line, which is managed by the Institute on Aging, also provides outreach calls to older adults who may be isolated or lonely, increasing connectedness and potentially reducing suicide risk.

Having a ready list of local mental health professionals with expertise in geriatrics and suicide risk to provide to the patient is also beneficial. Recall, though, that older adults are less likely to seek out and receive mental health services [19]; therefore, connecting the patient with resources or referrals during the appointment is critical. If the practitioner does not have time to do this, having a medical assistant or other staff member that the patient knows engage in this step may be appropriate. For example, the patient can call the Friendship Line or National Suicide Prevention Lifeline while in the room with the practitioner, which may reduce anxiety or stigma about doing so and connect the patient with services. Similarly, calling a local mental health professional to make a referral during the appointment may increase the likelihood that the older adult will follow up on the referral.

The most ideal method of intervention for moderate or high acute suicide risk is a warm handoff to a behavioral or mental health specialist. As primary care and behavioral health become more integrated and financially viable as reimbursement through the Centers for Medicare and Medicaid Services improves [61], it is becoming increasingly likely that such a specialist will be on-site and available. Research has found that collaborative care in primary care reduces suicide risk in older adults [46–48,62]. Mental health specialists can conduct more comprehensive assessments and spend more time intervening to reduce suicide risk among older adults with death or suicide ideation. If an on-site behavioral health specialist is not available, older adults at high suicide risk may need to be referred to an emergency department for further evaluation and follow-up. Each state has its own laws and procedures regarding this process, which should be incorporated into a practice’s procedures for addressing high suicide risk. The procedure often involves ensuring that the older adult is accompanied at all times (ie, not left alone in a room), alerting emergency services (usually via phone call to an emergency line, such as 911), and completion of paperwork by a practitioner asserting that the patient is a danger to self. Police or other emergency personnel are then responsible for transporting the patient for further evaluation and determination of whether hospitalization is required.

If more time is available, either via the treating primary care practitioner or other patient care staff in the office, other brief interventions may be beneficial. First, means safety discussions are critical, particularly for older adults with plans for suicide or access to highly lethal means. In such discussions, patients are encouraged to restrict access to the methods that they may use to die by suicide. Plans for restricting access are developed, and when possible, a support person is enlisted to ensure that the plans are carried out. For example, if an older adult has access to firearms (eg, keeps a loaded weapon in his or her nightstand), he or she is encouraged to restrict his or her access to it. Ideally, this is through removing the weapon from the home, either permanently or until suicide risk reduces (eg, giving it to a friend, turning it over to police), but more safe storage may also be an option if the older adult is not willing to remove the weapon from the home. This may mean using a gun lock or storing the weapon in a gun safe, storing ammunition separately from an unloaded weapon, removing the firing pin, or otherwise disassembling the weapon. Means safety counseling has been shown to be effective in reducing suicide rates [63] and is acceptable to patients [64]. Studies indicate that over 90% of individuals who make a suicide attempt and survive do not go on to die by suicide [65]; therefore, reducing access to highly lethal means during a suicidal crisis may be key in reducing suicide rates. Though an in-depth review of means safety counseling is outside the scope of this article, readers are directed to Bryan, Stone, and Rudd’s article for a practical overview of means safety discussions [66].

Second, safety planning is a brief intervention that may be beneficial in the primary care setting [67,68]. The goal of a safety plan is to create an individualized plan to remain safe during a suicidal crisis. Means safety discussion is the last of 6 steps in the safety plan [68]. The first 5 steps include identifying warning signs, using internal coping strategies, social connectedness as distraction, social support for the crisis, and professionals that can be used as resources. When patients can identify specific, individualized warning signs that occur prior to a crisis, they can then use strategies to cope and prevent the crisis from worsening. Coping strategies that are encouraged are first internal (ie, those that can be done without relying on anyone else), such as exercise or journaling. If those do not improve the patient’s mood, then he or she is encouraged to use people or social settings as a distraction (eg, people watching at the mall, calling an acquaintance to chat), and if he or she is still feeling bad, encouraged to get social support for the crisis (eg, calling a family member to discuss the crisis and get support). Finally, if all of these steps are not effective, the older adult is encouraged to reach out to professional supports, such as a mental health provider, the National Suicide Prevention Lifeline, or 911 (or go to an emergency room). Readers are encouraged to review Stanley and Brown’s articles for comprehensive details about safety planning as an intervention [67,68]. Additionally, an article with specific adaptations for safety planning with older adults is forthcoming [69].

Conclusion

Older adults, particularly older men, are at high risk for suicide [1,2], and primary care practitioners are a critical component of older adult suicide prevention. Older adults frequently see primary care practitioners within a month prior to death by suicide [20,21]; primary care practitioners are uniquely qualified to address a broad range of potential risk factors, and may have more interactions and familiarity with older adults at risk for suicide than other medical professionals [20–22]. Primary care practitioners should be prepared to identify risk factors and warning signs for older adult suicide, ask appropriate questions to screen for suicide risk, and intervene to prevent suicide. Screening can consist of standardized written questionnaires or oral questioning, and interventions may include providing resources and referrals, discussions about means safety, safety planning, and handoff to a mental health specialist. Interventions for suicide risk are likely feasible and acceptable in primary care [46–48]. Primary care practitioners have an important role to play in older adult suicide prevention, and must be prepared to interact with older adults who may be at risk for suicide.

Corresponding author: Danielle R. Jahn, PhD, Primary Care Institute, 605 NE 1st St, Gainesville, FL 32605, [email protected].

Financial disclosures: None reported.

From the Primary Care Institute, Gainesville, FL.

Abstract

• Objective: To provide primary care practitioners with the knowledge required to identify and address older adult suicide risk in their practice.
• Methods: Review of the literature and good clinical practices.
• Results: Primary care practitioners play an important role in older adult suicide prevention and must have knowledge about older adult suicide risk, including risk factors and warning signs in this age-group. Practitioners also must appropriately screen for and manage suicide risk. Older adults, particularly older men, are at high risk for suicide, though they may be less likely to report suicide ideation. Additionally, older adults frequently see primary care practitioners within a month prior to death by suicide. A number of older adult–specific risk factors are reviewed, and appropriate screening and intervention for the primary care setting are discussed.
• Conclusion: Primary care practitioners are uniquely qualified to address a broad range of potential risk factors and should be prepared to identify risk factors and warning signs for older adult suicide, ask appropriate questions to screen for suicide risk, and intervene to prevent suicide.

Key words: suicide; older adults; risk factors; screening; safety planning.

Primary care practitioners play an important role in older adult suicide prevention and have a responsibility to identify and address suicide risk among older adults. To do so, practitioners must understand the problem of older adult suicide, recognize risk factors for suicide in older adults, screen for suicide risk, and appropriately assess and manage suicide risk. Primary care practitioners may face challenges in completing these tasks; the goal of this article is to assist practitioners in addressing these challenges.

Suicide in Older Adults

The United States has recently seen increases in suicide rates across the lifespan; from 1999 to 2014, the suicide rate rose by 24% across all ages [3]. Among both men and women aged 65 to 74, the suicide rate increased in this time period [3]. The high suicide rate among older adults is particularly important to address given the increasing numbers of older adults in the United States. By 2050, the older adult population in the United States is expected to reach 88.5 million, more than double the older adult population in 2010 [4]. Additionally, the generation that is currently aging into older adulthood has historically had higher rates of suicide across their lifespan [5]. Given that suicide rates also increase in older adulthood for men, the coming decades may evidence even higher rates of suicide among older adults than previously and it is critical that older adult suicide prevention becomes a public health priority.

It is also essential to discuss other suicide-related outcomes among older adults, including suicide attempts and suicide ideation. This is critical particularly because the ratio of suicide attempts to deaths by suicide in this age-group is 4 to 1 [1]. This is in contrast to the ratio of attempts to deaths across all ages, which is 25 suicide attempts per death by suicide [1]. This means that suicide prevention must occur before a first suicide attempt is made; suicide attempts cannot be used a marker of elevated suicide risk in older adults or an indication that intervention is needed. Intervention is required prior to suicide risk becoming elevated to the point of a suicide attempt.

It is also critical to recognize that despite the fact that suicide rates rise with age, reports of suicide ideation decrease with age [7,8]. Across all ages, 3.9% of Americans report past-year suicide ideation; however, only 2.7% of older adults report thoughts of suicide [9]. The discrepancy with the increasing rates of death by suicide with age suggest that suicide risk, and thereby opportunities for intervention, may be missed in this age-group [10].

However, older adults may be more willing to report death ideation, as research has found that over 15% of older adults endorse death ideation [11–13]. Death ideation is a desire for death without a specific desire to end one’s own life, and is an important suicide-related outcome, as older adults with death ideation appear the same as those with suicide ideation in terms of depression, hopelessness, and history of suicidal behavior [14]. Additionally, older adults with death ideation had more hospitalizations, more outpatient visits, and more medical issues than older adults with suicide ideation [15]. Therefore, death ideation should be taken as seriously as suicide ideation in older adults [14]. In sum, the high rates of death by suicide, the likelihood of death on a first or early suicide attempt, and the discrepancy between decreasing reports of suicide ideation and increasing rates of death by suicide among older adults indicate that older adult suicide is an important public health problem.

Suicide Prevention Strategies

Many suicide prevention strategies to date have focused on indicated prevention, which concentrates on individuals already identified at high risk (eg, those with suicide ideation or who have made a suicide attempt) [16]. However, because older adults may not report suicide ideation or survive a first suicide attempt, indicated prevention is likely not enough to be effective in older adult suicide prevention. A multilevel suicide prevention strategy [17] is required to prevent older adult suicide [18]. Older adult suicide prevention must include indicated prevention but must also include selective and universal prevention [16]. Selective prevention focuses on groups who may be at risk for suicide (eg, individuals with depression, older adults) and universal prevention focuses on the entire population (eg, interventions to reduce mental health stigma) [16]. To prevent older adult suicide, crisis intervention is critical, but suicide prevention efforts upstream of the development of a suicidal crisis are also essential.

The Importance of Primary Care

Research indicates that primary care is one of the best settings in which to engage in older adult suicide prevention [18]. Older adults are significantly less likely to receive specialty mental health care than younger adults, even when they have depressive symptoms [19]. Additionally, among older adults who died by suicide, 58% had contact with a primary care provider within a month of their deaths, compared to only 11% who had contact with a mental health specialist [20]. Among older adults who died by suicide, 67% saw any provider in the 4 weeks prior to their death [21]. Approximately 10% of older adults saw an outpatient mental health provider, 11% saw a primary care physician for a mental health issue, and 40% saw a primary care physician for a non-mental health issue [21]. Therefore, because older adults are less likely to receive specialty mental health treatment and so often seen a primary care practitioner prior to death by suicide, primary care may be the ideal place for older adult suicide risk to be detected and addressed, especially as many older adults visit primary care without a mental health presenting concern prior to their death by suicide.

Additionally, older adults may be more likely to disclose suicide ideation to primary care practitioners, with whom they are more familiar, than physicians in other settings (eg, emergency departments). Research has shown that familiarity with a primary care physician significantly increases the likelihood of patient disclosure of psychosocial issues to the physician [22]. Primary care providers also have a critical role as care coordinators; many older adults also see specialty physicians and use the emergency department. In fact, older adults are more likely to use the emergency department than younger adults, but emergency departments are not equipped to navigate the complex care needs of this population [23]. Primary care practitioners are important in ensuring that health issues of older adults are addressed by coordinating with specialists, hospitals (eg, inpatient stays, emergency department visits, surgery) and other health services (eg, home health care, physical therapy). Approximately 35% of older adults in the United States experience a lack of care coordination [24], which can negatively impact their health and leave issues such as suicide ideation unaddressed. Primary care practitioners may be critical in screening for mental health issues and suicide risk during even routine visits because of their familiarity with patients, and also play an important role in coordinating care for older adults to improve well-being and to ensure that critical issues, such as suicide ideation, are appropriately addressed.

Primary care practitioners can also be key in upstream prevention. Primary care practitioners are in a unique role to address risk factors for suicide prior to the development of a suicidal crisis. Because older adults frequently see primary care practitioners, such practitioners may have more opportunities to identify risk factors (eg, chronic pain, depression). Primary care practitioners are also trained to treat a broad range of conditions, providing the skills to address many different risk factors.

Finally, primary care is a setting in which screening for depression and suicide ideation among older adults is recommended. The US Preventive Services Task Force recommends screening for depression in all adults and older adults and provides recommended screening instruments, some of which include questions about self-harm or suicide risk [25]. However, this same group has concluded that there is insufficient evidence to support a recommendation for suicide risk screening [26]. Despite this, the Joint Commission recently released an alert that recommends screening for suicide risk in all settings, including primary care [27]. The Joint Commission requirement for ambulatory care that is relevant to suicide is PC.04.01.01: The organization has a process that addresses the patient’s need for continuing care, treatment, or services after discharge or transfer; behavioral health settings have additional suicide-specific requirements. The recommendations, though, go far beyond this requirement for primary care. The Joint Commission specifically notes that primary care clinicians play an important role in detecting suicide ideation and recommends that primary care practitioners review each patient’s history for suicide risk factors, screen all patients for suicide risk, review screenings before patients leave appointments, and take appropriate actions to address suicide risk when needed [27]. Further details are available in the Joint Commission’s Sentinel Event Alert titled, “Detecting and treating suicide ideation in all settings” [27]. Given these recommendations, primary care is an important setting in which to identify and address suicide risk.

Risk Factors for Older Adult Suicide

Numerous reviews exist that cover many risk factors for suicide in older adults [18,28]. This article will focus briefly on risk factors that are likely to be recognized and potentially addressed by primary care practitioners. Risk factors that apply across the lifespan can be recalled through a mnemonic: IS PATH WARM [29]. These risk factors include suicide Ideation, Substance abuse, Purposelessness, Anxiety (including agitation and poor sleep), feeling Trapped, Hopelessness, social Withdrawal, Anger or rage, Recklessness (ie, engaging in risky activities), and Mood changes. The National Suicide Prevention Lifeline also includes being in unbearable physical pain, perceiving one’s self as a burden to others, and seeking revenge on others as risk factors [30]. More specific to older adults, Conwell notes 5 categories or domains of risk factors with strong research support: psychiatric symptoms, somatic illness, functional impairment, social integration, and personality traits and coping [18,31].

Affective or mood disorders, particularly depression and depressive symptoms, are some of the most well-studied and strongest risk factors for older adult suicide [31]; 71% to 97% of all older adults who die by suicide have psychiatric illnesses [28]. Mood disorders, including major depressive episodes, are most consistently linked to older adult suicide risk; there is evidence as well for anxiety disorders and substance abuse disorders as risk factors, though it is somewhat mixed [28]. Therefore, screening for depression, anxiety, and substance abuse may be key to recognizing potential suicide risk. However, depression and anxiety do not present similarly in younger and older adults [32,33]. Depressive symptoms in older adults may be more somatic (eg, agitation, gastrointestinal symptoms) [32] and may reflect more anhedonia than mood changes [33]. Anxiety in older adults tends to be reported as stress or tension, whereas younger adults report feeling anxious or worried [33]. Additionally, substance abuse is often underrecognized, underdiagnosed, and undertreated in older adults [34]. Proactive screening for substance abuse is important as it may not interfere with work or other obligations in older adults, and therefore substance abuse may not be identified by older adults or others in their lives.

Physical illness may also be a risk factor for suicide [28,31]. Numerous diagnoses have been linked to suicide risk, including cancers, neurodegenerative diseases (eg, amyotrophic lateral sclerosis, Huntington disease), spinal cord injury, cardiovascular disease, and pulmonary disease [28,35]. However, overall illness burden (ie, number of chronic illnesses) [28] and self-perceived health [36] appear to be stronger risk factors than any specific illness. Additionally, authors have suggested that illness itself may not be a particularly strong risk factor, but the effect of illness on depressive symptoms [35], functioning, pain, or hopelessness due to the potential for decline over time [28] may increase suicide risk in older adults. Pain itself has been identified as a risk factor for suicide, as have perceptions of burden to others, hopelessness, and functional impairment [28].

In terms of functional impairment, research has shown that impairment in completing instrumental activities of daily living is associated with higher risk for death by suicide, and cognitive impairment may also be associated with elevated suicide risk [28]. However, there are some discrepant findings regarding the role of dementia in suicide risk, which may reflect medical and psychiatric comorbidities, as well as different stages of dementia or levels of cognitive impairment (eg, hopelessness about cognitive decline may increase suicide risk shortly after diagnosis, whereas lack of insight may decrease risk later in the course of the illness) [37]. Related to functional or cognitive impairment is perceived burdensomeness (ie, the perception that one is a liability or burden to others, to the point that others would be better off if one was gone) [38], which may also be associated with suicide risk in older adults [39,40]. Researchers have found that the interaction between perceived burdensomeness and thwarted belongingness (ie, a belief that one lacks reciprocal caring relationships and does not belong) identified older adults who were likely experiencing suicide ideation but did not report it [41]. These findings indicate that perceived burdensomeness and thwarted belongingness may be key in identifying older adults at risk for suicide.

Thwarted belongingness has also been linked to suicide ideation in older adults [41]. In fact, studies suggest that social integration is especially important for reducing suicide risk in this population [28,31,42]. A larger social network, living with others, and being active in the community are each protective against suicide [28]. Bereavement, which can reduce social connectedness and acts as a significant life stressor, is also an important risk factor [31]. Retirement may also reduce social connectedness, and employment changes have been identified as a suicide risk factor for older adults [28]. Retirement has been linked to risk for death by suicide in this population [43], and may not only serve to reduce social connectedness, but for some older adults may also be a significant role loss or loss of sense of purpose that can influence suicide risk.

Finally, rigid personality traits or coping styles are a risk factor for suicide among older adults [28,31]. As older adults face potential losses, health changes, and functional decline, effective positive coping strategies and flexibility are key to maintaining well-being. If older adults are unable to flexibly cope with these challenges, their risk for suicide increases [28].

In addition to risk factors, which confer suicide risk but do not necessarily suggest that an older adult is thinking about suicide, warning signs exist that indicate that suicide risk is imminent. These include suicidal communication (ie, talking or writing about suicide), seeking access to means, and making preparations for suicide (eg, ensuring a will is in place, giving away prized possessions). One important note is that discussing and preparing for death may be developmentally appropriate for older adults, particularly those with chronic illnesses; however, such appropriate preparation is critically different from talking about suicide or a desire for death.

Additionally, a lack of planning for the future may be a warning sign. For example, older adults who decline to schedule medical follow-up or do not wish to refill needed prescriptions may be exhibiting warning signs that should be addressed. Similarly, not following needed medical regimens (eg, an older adult with diabetes no longer taking insulin) is also a warning sign. Other, potentially more subtle warning signs may include significant changes in mood, sleep, or social interactions. Older adults may become agitated and sleep less when they are considering suicide, or may feel more at ease after they have made the decision to die by suicide and their sleep or mood may improve. Withdrawing from valued others may also be a warning sign. Finally, recent major changes (eg, loss of a spouse, moving to an assisted living facility) may be triggers for suicide risk and can serve as warning signs themselves.

Specific Screening Strategies

Given the numerous risk factors and warning signs for older adult suicide, as well as the time limitations that primary care practitioners face [44,45], it would be impractical to comprehensively assess each older adult who presents at a primary care practice. Therefore, more specific screening is necessary. Most importantly, every older adult should be screened for suicide ideation and death ideation at every visit. Screening at every visit is critical because suicide ideation may develop at any point. Previous research has included screening of over 29,000 older adults in 11 primary care settings for suicide ideation, risk of alcohol misuse, and mental health disorders [15], suggesting that suicide risk screening is feasible. Other studies have also successfully used widespread screening for depression and suicide ideation among older adults in primary care [46–48]. Additionally, in an emergency department setting, universal suicide risk screening has been associated with significantly improved risk detection [49], indicating that improved screening may be beneficial in identifying suicide risk. Importantly, asking about suicide does not cause thoughts of suicide [50]. Additionally, it is a myth that those who talk about suicide ideation will not act on these thoughts [51].

When primary care practitioners inquire about suicide ideation, they should also ask about death ideation; though some may believe that death ideation is not as significant in terms of suicide risk as suicide ideation, recall that research has not found differences in previous suicide attempts or current hopelessness among older adults with death ideation versus suicide ideation [14]. Therefore, screening for death ideation should be completed as part of every suicide risk screening.

Screening can take many forms. Screening may be oral; asking an older adult if he or she is having thoughts of suicide or is experiencing a desire to die is a brief, 2-question screening that may provide valuable information (eg, “Are you having thoughts about your own death or wanting to die?”, “Are you having thoughts of killing yourself or thinking about suicide?”). This screening may be conducted by medical assistants, nurses, care managers, or physicians, with the patient’s responses documented. Importantly, a standard procedure should be implemented to ensure older adults are consistently asked about suicide risk at each visit, but do not feel inundated by such questions from numerous staff.

If verbal questions are asked, they must be asked appropriately. Euphemisms or indirect language should not be used during a screening; older adults should be directly asked about thoughts of death and suicide, not simply asked questions such as, “Have you ever had thoughts of harming or hurting yourself?” A question like this does not adequately assess current suicide risk, as it does not assess current thoughts, nor does it specifically inquire about suicide ideation (ie, killing one’s self). It is also important to phrase questions in a manner that invites honest responses and conveys an openness to listening. For example, asking, “You’re not thinking about suicide, are you?” suggests that the practitioner wants the older adult to say no and is not comfortable with the older adult endorsing suicide ideation. Open questions that allow endorsement or denial (eg, “Are you having thoughts of killing yourself?”) imply that the practitioner is receptive to either an endorsement or denial of suicide ideation.

Alternatively, a written screening can be used; older adults may complete a questionnaire prior to their appointment or while waiting to see their practitioner. Such an assessment may be a brief screening (eg, using similar yes/no questions to an oral screening), or may be a standardized measure. For example, the Geriatric Suicide Ideation Scale [52] is a 31-item self-report measure that provides scores for suicide ideation, death ideation, loss of personal and social worth, and perceived meaning in life. Though there are not standard cutoffs that suggest high versus low suicide risk, responses can be reviewed to identify whether older adults are reporting suicide ideation or death ideation, and can also be compared to norms (ie, average scores) from other older adults [52]. This measure also has the benefit of 2 subscales that do not specifically require reporting thoughts of suicide or death (ie, loss of personal and social worth, perceived meaning in life), which may give practitioners an indication of an older adult’s suicide risk even if the older adult is not comfortable disclosing suicide ideation, as has been shown in previous research [7,8].

Similarly, the Geriatric Depression Scale, which has a validated 15-item version [53], does not directly ask about suicide ideation but has a 5-item subscale that has been found to be highly correlated with reported suicide ideation [54]. When administered to older adult primary care patients, this subscale was an effective measure of suicide ideation; a score of ≥ 1 was the best cutoff for determining whether an older adult reported suicide ideation [55].

Additionally, as noted previously, the interaction between perceived burdensomeness and thwarted belongingness may identify older adults who are potentially experiencing, but not reporting, suicide ideation [41]. The Interpersonal Needs Questionnaire [56] is the validated assessment for both perceived burdensomeness and thwarted belongingness. Perceived burdensomeness is assessed via 6 self-report items, and thwarted belongingness is assessed via 9 self-report items on this measure [56]. There are not specific cutoffs that determine high versus low perceived burdensomeness or thwarted belongingness, but older adults’ responses can provide information about their experiences of these constructs. Administration of the Interpersonal Needs Questionnaire can provide information about potential risk for suicide among older adults who may otherwise deny thoughts of suicide or death.

If the screening for suicide ideation or death ideation is positive (ie, the older adult endorses thoughts of suicide or death), the treating primary care practitioner must then follow up with additional questions to determine current level of suicide risk. To make this determination, at a minimum, follow-up questions should focus on whether the older adult has any intent to die by suicide (eg, “Do you have any intent to act on your thoughts of suicide?”), as well as whether he or she has a plan to die by suicide (eg, “Have you begun formulating a plan to die by suicide?”). When asking about a plan, it is important to determine how specific the plan is. For example, an older adult with a specific method identified and date selected to implement the plan is at much higher risk than an older adult with a relatively vague idea. It is also critical to assess for the older adult’s access to means for suicide. If an older adult has a specific plan and has the capability to carry out the plan (eg, plans to overdose on prescription medication and has large quantities of medication or high-lethality medication at home), he or she is more likely to die by suicide than an older adult who does not have access to means (eg, only has small quantities of low-lethality medication available). A general assessment of risk factors and previous suicidal behavior (ie, any previous suicide attempts) also informs decisions about level of risk and interventions.

After a screening or assessment is completed, a risk determination must be made and documented. Acute suicide risk can be categorized as low, moderate, or high. It is not appropriate to say that there is “no” suicide risk present. Low risk occurs when there is no current suicide ideation, no plan to die by suicide, and no intent to act on suicidal thoughts, especially when the patient has no history of suicidal behavior and few risk factors [57]. Moderate risk is evident when there is current suicide ideation, but no specific plan to die by suicide or intent to act on suicidal thoughts. There are likely warning signs or risk factors, which may include previous suicidal behaviors, present in moderate suicide risk [57]. High risk is indicated by current suicide ideation with plan to die by suicide and suicidal intent. There are significant warning signs and risk factors present; there may also be a recent suicide attempt, though this is not a requirement for a high risk determination [57]. Undetermined suicide risk occurs when a practitioner cannot accurately assess risk, but concern regarding suicide is present; this is primarily used when a patient refuses to answer questions about suicide. Undetermined risk should be treated as at least moderate risk. Because research shows that death ideation has similar outcomes to suicide ideation in older adults [14], death ideation should also be factored into determinations of suicide risk; reports of death ideation may indicate low or moderate risk in older adults, dependent upon other risk factors, suicidal intent, and plan.

After a risk determination is made, it must be documented in the medical record. The level of risk and rationale for that determination must be included [58]. Stating only the level of risk without a rationale (ie, the older adult’s responses to questions) is not adequate, and documenting only the older adult’s responses without a determination of risk is also not sufficient. Finally, it is critical to document the intervention that occurred or steps taken after the level of risk was determined.

Critically, stating only that there was no indication of suicide risk is inadequate. For example, documenting “No evidence of suicide risk” is not appropriate. This documentation does not indicate that the older adult was specifically asked about suicide ideation, death ideation, suicidal intent, or plan to die by suicide. It also does not indicate a level of suicide risk. Examples of appropriate documentation include:

 Patient was asked about suicide risk. She denied current suicide ideation but reported death ideation. She denied any current suicidal intent or plan. She also denied any previous suicide attempts. Therefore, acute suicide risk was deemed to be low. Provided patient with wallet card about the National Suicide Prevention Lifeline. Also called the Friendship Line while in the room with the patient to connect her with services. Finally, provided a brief list of local mental health professionals to patient; the patient reported she would like to see Dr. Smith. Called and left a message for Dr. Smith with referral information with patient during appointment.

Patient was asked about suicide risk. He reported both death ideation and suicide ideation. He also reported a nonspecific plan (ie, causing a single-vehicle motor vehicle accident, with no specific plan for the motor vehicle accident or timeframe) and denied any intent to act on his thoughts of suicide. He reported one previous suicide attempt, at age 22, by overdose on over-the-counter medication. He reported that this attempt did not require medical attention. Therefore, acute suicide risk was determined to be moderate. Patient was introduced to the behavioral health specialist, who met with the patient during the appointment to conduct further assessment and intervention.

Specific Intervention Strategies

Despite the fact that the pace of the primary care setting often does not allow for time-intensive intervention, there are ways to address suicide risk in this setting. Importantly, no-suicide contracts should not be used at any time [59,60]. No-suicide contracts are documents that patients who are experiencing suicide ideation are required to sign that state that they will not die by suicide while under the care of the practitioner. These contracts have no evidence of effectiveness, and some researchers argue that they may in fact damage the relationship with patients and serve the practitioner’s needs more than the patient’s needs [59].

One of the best options for older adults at low acute suicide risk is to provide resources and referrals. The National Suicide Prevention Lifeline can be reached at 1-800-273-TALK (8255); trained counselors are available to speak to patients at all times. Wallet cards with information about the National Suicide Prevention Lifeline are available at no charge from the US Substance Abuse and Mental Health Services Administration online store. The Friendship Line is another service available free to adults ages 60 and older, 24 hours per day, 7 days per week; this line can be reached at 1-800-971-0016. The Friendship Line, which is managed by the Institute on Aging, also provides outreach calls to older adults who may be isolated or lonely, increasing connectedness and potentially reducing suicide risk.

Having a ready list of local mental health professionals with expertise in geriatrics and suicide risk to provide to the patient is also beneficial. Recall, though, that older adults are less likely to seek out and receive mental health services [19]; therefore, connecting the patient with resources or referrals during the appointment is critical. If the practitioner does not have time to do this, having a medical assistant or other staff member that the patient knows engage in this step may be appropriate. For example, the patient can call the Friendship Line or National Suicide Prevention Lifeline while in the room with the practitioner, which may reduce anxiety or stigma about doing so and connect the patient with services. Similarly, calling a local mental health professional to make a referral during the appointment may increase the likelihood that the older adult will follow up on the referral.

The most ideal method of intervention for moderate or high acute suicide risk is a warm handoff to a behavioral or mental health specialist. As primary care and behavioral health become more integrated and financially viable as reimbursement through the Centers for Medicare and Medicaid Services improves [61], it is becoming increasingly likely that such a specialist will be on-site and available. Research has found that collaborative care in primary care reduces suicide risk in older adults [46–48,62]. Mental health specialists can conduct more comprehensive assessments and spend more time intervening to reduce suicide risk among older adults with death or suicide ideation. If an on-site behavioral health specialist is not available, older adults at high suicide risk may need to be referred to an emergency department for further evaluation and follow-up. Each state has its own laws and procedures regarding this process, which should be incorporated into a practice’s procedures for addressing high suicide risk. The procedure often involves ensuring that the older adult is accompanied at all times (ie, not left alone in a room), alerting emergency services (usually via phone call to an emergency line, such as 911), and completion of paperwork by a practitioner asserting that the patient is a danger to self. Police or other emergency personnel are then responsible for transporting the patient for further evaluation and determination of whether hospitalization is required.

If more time is available, either via the treating primary care practitioner or other patient care staff in the office, other brief interventions may be beneficial. First, means safety discussions are critical, particularly for older adults with plans for suicide or access to highly lethal means. In such discussions, patients are encouraged to restrict access to the methods that they may use to die by suicide. Plans for restricting access are developed, and when possible, a support person is enlisted to ensure that the plans are carried out. For example, if an older adult has access to firearms (eg, keeps a loaded weapon in his or her nightstand), he or she is encouraged to restrict his or her access to it. Ideally, this is through removing the weapon from the home, either permanently or until suicide risk reduces (eg, giving it to a friend, turning it over to police), but more safe storage may also be an option if the older adult is not willing to remove the weapon from the home. This may mean using a gun lock or storing the weapon in a gun safe, storing ammunition separately from an unloaded weapon, removing the firing pin, or otherwise disassembling the weapon. Means safety counseling has been shown to be effective in reducing suicide rates [63] and is acceptable to patients [64]. Studies indicate that over 90% of individuals who make a suicide attempt and survive do not go on to die by suicide [65]; therefore, reducing access to highly lethal means during a suicidal crisis may be key in reducing suicide rates. Though an in-depth review of means safety counseling is outside the scope of this article, readers are directed to Bryan, Stone, and Rudd’s article for a practical overview of means safety discussions [66].

Second, safety planning is a brief intervention that may be beneficial in the primary care setting [67,68]. The goal of a safety plan is to create an individualized plan to remain safe during a suicidal crisis. Means safety discussion is the last of 6 steps in the safety plan [68]. The first 5 steps include identifying warning signs, using internal coping strategies, social connectedness as distraction, social support for the crisis, and professionals that can be used as resources. When patients can identify specific, individualized warning signs that occur prior to a crisis, they can then use strategies to cope and prevent the crisis from worsening. Coping strategies that are encouraged are first internal (ie, those that can be done without relying on anyone else), such as exercise or journaling. If those do not improve the patient’s mood, then he or she is encouraged to use people or social settings as a distraction (eg, people watching at the mall, calling an acquaintance to chat), and if he or she is still feeling bad, encouraged to get social support for the crisis (eg, calling a family member to discuss the crisis and get support). Finally, if all of these steps are not effective, the older adult is encouraged to reach out to professional supports, such as a mental health provider, the National Suicide Prevention Lifeline, or 911 (or go to an emergency room). Readers are encouraged to review Stanley and Brown’s articles for comprehensive details about safety planning as an intervention [67,68]. Additionally, an article with specific adaptations for safety planning with older adults is forthcoming [69].

Conclusion

Older adults, particularly older men, are at high risk for suicide [1,2], and primary care practitioners are a critical component of older adult suicide prevention. Older adults frequently see primary care practitioners within a month prior to death by suicide [20,21]; primary care practitioners are uniquely qualified to address a broad range of potential risk factors, and may have more interactions and familiarity with older adults at risk for suicide than other medical professionals [20–22]. Primary care practitioners should be prepared to identify risk factors and warning signs for older adult suicide, ask appropriate questions to screen for suicide risk, and intervene to prevent suicide. Screening can consist of standardized written questionnaires or oral questioning, and interventions may include providing resources and referrals, discussions about means safety, safety planning, and handoff to a mental health specialist. Interventions for suicide risk are likely feasible and acceptable in primary care [46–48]. Primary care practitioners have an important role to play in older adult suicide prevention, and must be prepared to interact with older adults who may be at risk for suicide.

Corresponding author: Danielle R. Jahn, PhD, Primary Care Institute, 605 NE 1st St, Gainesville, FL 32605, [email protected].

Financial disclosures: None reported.

From the Primary Care Institute, Gainesville, FL.

Abstract

• Objective: To provide primary care practitioners with the knowledge required to identify and address older adult suicide risk in their practice.
• Methods: Review of the literature and good clinical practices.
• Results: Primary care practitioners play an important role in older adult suicide prevention and must have knowledge about older adult suicide risk, including risk factors and warning signs in this age-group. Practitioners also must appropriately screen for and manage suicide risk. Older adults, particularly older men, are at high risk for suicide, though they may be less likely to report suicide ideation. Additionally, older adults frequently see primary care practitioners within a month prior to death by suicide. A number of older adult–specific risk factors are reviewed, and appropriate screening and intervention for the primary care setting are discussed.
• Conclusion: Primary care practitioners are uniquely qualified to address a broad range of potential risk factors and should be prepared to identify risk factors and warning signs for older adult suicide, ask appropriate questions to screen for suicide risk, and intervene to prevent suicide.

Key words: suicide; older adults; risk factors; screening; safety planning.

Primary care practitioners play an important role in older adult suicide prevention and have a responsibility to identify and address suicide risk among older adults. To do so, practitioners must understand the problem of older adult suicide, recognize risk factors for suicide in older adults, screen for suicide risk, and appropriately assess and manage suicide risk. Primary care practitioners may face challenges in completing these tasks; the goal of this article is to assist practitioners in addressing these challenges.

Suicide in Older Adults

The United States has recently seen increases in suicide rates across the lifespan; from 1999 to 2014, the suicide rate rose by 24% across all ages [3]. Among both men and women aged 65 to 74, the suicide rate increased in this time period [3]. The high suicide rate among older adults is particularly important to address given the increasing numbers of older adults in the United States. By 2050, the older adult population in the United States is expected to reach 88.5 million, more than double the older adult population in 2010 [4]. Additionally, the generation that is currently aging into older adulthood has historically had higher rates of suicide across their lifespan [5]. Given that suicide rates also increase in older adulthood for men, the coming decades may evidence even higher rates of suicide among older adults than previously and it is critical that older adult suicide prevention becomes a public health priority.

It is also essential to discuss other suicide-related outcomes among older adults, including suicide attempts and suicide ideation. This is critical particularly because the ratio of suicide attempts to deaths by suicide in this age-group is 4 to 1 [1]. This is in contrast to the ratio of attempts to deaths across all ages, which is 25 suicide attempts per death by suicide [1]. This means that suicide prevention must occur before a first suicide attempt is made; suicide attempts cannot be used a marker of elevated suicide risk in older adults or an indication that intervention is needed. Intervention is required prior to suicide risk becoming elevated to the point of a suicide attempt.

It is also critical to recognize that despite the fact that suicide rates rise with age, reports of suicide ideation decrease with age [7,8]. Across all ages, 3.9% of Americans report past-year suicide ideation; however, only 2.7% of older adults report thoughts of suicide [9]. The discrepancy with the increasing rates of death by suicide with age suggest that suicide risk, and thereby opportunities for intervention, may be missed in this age-group [10].

However, older adults may be more willing to report death ideation, as research has found that over 15% of older adults endorse death ideation [11–13]. Death ideation is a desire for death without a specific desire to end one’s own life, and is an important suicide-related outcome, as older adults with death ideation appear the same as those with suicide ideation in terms of depression, hopelessness, and history of suicidal behavior [14]. Additionally, older adults with death ideation had more hospitalizations, more outpatient visits, and more medical issues than older adults with suicide ideation [15]. Therefore, death ideation should be taken as seriously as suicide ideation in older adults [14]. In sum, the high rates of death by suicide, the likelihood of death on a first or early suicide attempt, and the discrepancy between decreasing reports of suicide ideation and increasing rates of death by suicide among older adults indicate that older adult suicide is an important public health problem.

Suicide Prevention Strategies

Many suicide prevention strategies to date have focused on indicated prevention, which concentrates on individuals already identified at high risk (eg, those with suicide ideation or who have made a suicide attempt) [16]. However, because older adults may not report suicide ideation or survive a first suicide attempt, indicated prevention is likely not enough to be effective in older adult suicide prevention. A multilevel suicide prevention strategy [17] is required to prevent older adult suicide [18]. Older adult suicide prevention must include indicated prevention but must also include selective and universal prevention [16]. Selective prevention focuses on groups who may be at risk for suicide (eg, individuals with depression, older adults) and universal prevention focuses on the entire population (eg, interventions to reduce mental health stigma) [16]. To prevent older adult suicide, crisis intervention is critical, but suicide prevention efforts upstream of the development of a suicidal crisis are also essential.

The Importance of Primary Care

Research indicates that primary care is one of the best settings in which to engage in older adult suicide prevention [18]. Older adults are significantly less likely to receive specialty mental health care than younger adults, even when they have depressive symptoms [19]. Additionally, among older adults who died by suicide, 58% had contact with a primary care provider within a month of their deaths, compared to only 11% who had contact with a mental health specialist [20]. Among older adults who died by suicide, 67% saw any provider in the 4 weeks prior to their death [21]. Approximately 10% of older adults saw an outpatient mental health provider, 11% saw a primary care physician for a mental health issue, and 40% saw a primary care physician for a non-mental health issue [21]. Therefore, because older adults are less likely to receive specialty mental health treatment and so often seen a primary care practitioner prior to death by suicide, primary care may be the ideal place for older adult suicide risk to be detected and addressed, especially as many older adults visit primary care without a mental health presenting concern prior to their death by suicide.

Additionally, older adults may be more likely to disclose suicide ideation to primary care practitioners, with whom they are more familiar, than physicians in other settings (eg, emergency departments). Research has shown that familiarity with a primary care physician significantly increases the likelihood of patient disclosure of psychosocial issues to the physician [22]. Primary care providers also have a critical role as care coordinators; many older adults also see specialty physicians and use the emergency department. In fact, older adults are more likely to use the emergency department than younger adults, but emergency departments are not equipped to navigate the complex care needs of this population [23]. Primary care practitioners are important in ensuring that health issues of older adults are addressed by coordinating with specialists, hospitals (eg, inpatient stays, emergency department visits, surgery) and other health services (eg, home health care, physical therapy). Approximately 35% of older adults in the United States experience a lack of care coordination [24], which can negatively impact their health and leave issues such as suicide ideation unaddressed. Primary care practitioners may be critical in screening for mental health issues and suicide risk during even routine visits because of their familiarity with patients, and also play an important role in coordinating care for older adults to improve well-being and to ensure that critical issues, such as suicide ideation, are appropriately addressed.

Primary care practitioners can also be key in upstream prevention. Primary care practitioners are in a unique role to address risk factors for suicide prior to the development of a suicidal crisis. Because older adults frequently see primary care practitioners, such practitioners may have more opportunities to identify risk factors (eg, chronic pain, depression). Primary care practitioners are also trained to treat a broad range of conditions, providing the skills to address many different risk factors.

Finally, primary care is a setting in which screening for depression and suicide ideation among older adults is recommended. The US Preventive Services Task Force recommends screening for depression in all adults and older adults and provides recommended screening instruments, some of which include questions about self-harm or suicide risk [25]. However, this same group has concluded that there is insufficient evidence to support a recommendation for suicide risk screening [26]. Despite this, the Joint Commission recently released an alert that recommends screening for suicide risk in all settings, including primary care [27]. The Joint Commission requirement for ambulatory care that is relevant to suicide is PC.04.01.01: The organization has a process that addresses the patient’s need for continuing care, treatment, or services after discharge or transfer; behavioral health settings have additional suicide-specific requirements. The recommendations, though, go far beyond this requirement for primary care. The Joint Commission specifically notes that primary care clinicians play an important role in detecting suicide ideation and recommends that primary care practitioners review each patient’s history for suicide risk factors, screen all patients for suicide risk, review screenings before patients leave appointments, and take appropriate actions to address suicide risk when needed [27]. Further details are available in the Joint Commission’s Sentinel Event Alert titled, “Detecting and treating suicide ideation in all settings” [27]. Given these recommendations, primary care is an important setting in which to identify and address suicide risk.

Risk Factors for Older Adult Suicide

Numerous reviews exist that cover many risk factors for suicide in older adults [18,28]. This article will focus briefly on risk factors that are likely to be recognized and potentially addressed by primary care practitioners. Risk factors that apply across the lifespan can be recalled through a mnemonic: IS PATH WARM [29]. These risk factors include suicide Ideation, Substance abuse, Purposelessness, Anxiety (including agitation and poor sleep), feeling Trapped, Hopelessness, social Withdrawal, Anger or rage, Recklessness (ie, engaging in risky activities), and Mood changes. The National Suicide Prevention Lifeline also includes being in unbearable physical pain, perceiving one’s self as a burden to others, and seeking revenge on others as risk factors [30]. More specific to older adults, Conwell notes 5 categories or domains of risk factors with strong research support: psychiatric symptoms, somatic illness, functional impairment, social integration, and personality traits and coping [18,31].

Affective or mood disorders, particularly depression and depressive symptoms, are some of the most well-studied and strongest risk factors for older adult suicide [31]; 71% to 97% of all older adults who die by suicide have psychiatric illnesses [28]. Mood disorders, including major depressive episodes, are most consistently linked to older adult suicide risk; there is evidence as well for anxiety disorders and substance abuse disorders as risk factors, though it is somewhat mixed [28]. Therefore, screening for depression, anxiety, and substance abuse may be key to recognizing potential suicide risk. However, depression and anxiety do not present similarly in younger and older adults [32,33]. Depressive symptoms in older adults may be more somatic (eg, agitation, gastrointestinal symptoms) [32] and may reflect more anhedonia than mood changes [33]. Anxiety in older adults tends to be reported as stress or tension, whereas younger adults report feeling anxious or worried [33]. Additionally, substance abuse is often underrecognized, underdiagnosed, and undertreated in older adults [34]. Proactive screening for substance abuse is important as it may not interfere with work or other obligations in older adults, and therefore substance abuse may not be identified by older adults or others in their lives.

Physical illness may also be a risk factor for suicide [28,31]. Numerous diagnoses have been linked to suicide risk, including cancers, neurodegenerative diseases (eg, amyotrophic lateral sclerosis, Huntington disease), spinal cord injury, cardiovascular disease, and pulmonary disease [28,35]. However, overall illness burden (ie, number of chronic illnesses) [28] and self-perceived health [36] appear to be stronger risk factors than any specific illness. Additionally, authors have suggested that illness itself may not be a particularly strong risk factor, but the effect of illness on depressive symptoms [35], functioning, pain, or hopelessness due to the potential for decline over time [28] may increase suicide risk in older adults. Pain itself has been identified as a risk factor for suicide, as have perceptions of burden to others, hopelessness, and functional impairment [28].

In terms of functional impairment, research has shown that impairment in completing instrumental activities of daily living is associated with higher risk for death by suicide, and cognitive impairment may also be associated with elevated suicide risk [28]. However, there are some discrepant findings regarding the role of dementia in suicide risk, which may reflect medical and psychiatric comorbidities, as well as different stages of dementia or levels of cognitive impairment (eg, hopelessness about cognitive decline may increase suicide risk shortly after diagnosis, whereas lack of insight may decrease risk later in the course of the illness) [37]. Related to functional or cognitive impairment is perceived burdensomeness (ie, the perception that one is a liability or burden to others, to the point that others would be better off if one was gone) [38], which may also be associated with suicide risk in older adults [39,40]. Researchers have found that the interaction between perceived burdensomeness and thwarted belongingness (ie, a belief that one lacks reciprocal caring relationships and does not belong) identified older adults who were likely experiencing suicide ideation but did not report it [41]. These findings indicate that perceived burdensomeness and thwarted belongingness may be key in identifying older adults at risk for suicide.

Thwarted belongingness has also been linked to suicide ideation in older adults [41]. In fact, studies suggest that social integration is especially important for reducing suicide risk in this population [28,31,42]. A larger social network, living with others, and being active in the community are each protective against suicide [28]. Bereavement, which can reduce social connectedness and acts as a significant life stressor, is also an important risk factor [31]. Retirement may also reduce social connectedness, and employment changes have been identified as a suicide risk factor for older adults [28]. Retirement has been linked to risk for death by suicide in this population [43], and may not only serve to reduce social connectedness, but for some older adults may also be a significant role loss or loss of sense of purpose that can influence suicide risk.

Finally, rigid personality traits or coping styles are a risk factor for suicide among older adults [28,31]. As older adults face potential losses, health changes, and functional decline, effective positive coping strategies and flexibility are key to maintaining well-being. If older adults are unable to flexibly cope with these challenges, their risk for suicide increases [28].

In addition to risk factors, which confer suicide risk but do not necessarily suggest that an older adult is thinking about suicide, warning signs exist that indicate that suicide risk is imminent. These include suicidal communication (ie, talking or writing about suicide), seeking access to means, and making preparations for suicide (eg, ensuring a will is in place, giving away prized possessions). One important note is that discussing and preparing for death may be developmentally appropriate for older adults, particularly those with chronic illnesses; however, such appropriate preparation is critically different from talking about suicide or a desire for death.

Additionally, a lack of planning for the future may be a warning sign. For example, older adults who decline to schedule medical follow-up or do not wish to refill needed prescriptions may be exhibiting warning signs that should be addressed. Similarly, not following needed medical regimens (eg, an older adult with diabetes no longer taking insulin) is also a warning sign. Other, potentially more subtle warning signs may include significant changes in mood, sleep, or social interactions. Older adults may become agitated and sleep less when they are considering suicide, or may feel more at ease after they have made the decision to die by suicide and their sleep or mood may improve. Withdrawing from valued others may also be a warning sign. Finally, recent major changes (eg, loss of a spouse, moving to an assisted living facility) may be triggers for suicide risk and can serve as warning signs themselves.

Specific Screening Strategies

Given the numerous risk factors and warning signs for older adult suicide, as well as the time limitations that primary care practitioners face [44,45], it would be impractical to comprehensively assess each older adult who presents at a primary care practice. Therefore, more specific screening is necessary. Most importantly, every older adult should be screened for suicide ideation and death ideation at every visit. Screening at every visit is critical because suicide ideation may develop at any point. Previous research has included screening of over 29,000 older adults in 11 primary care settings for suicide ideation, risk of alcohol misuse, and mental health disorders [15], suggesting that suicide risk screening is feasible. Other studies have also successfully used widespread screening for depression and suicide ideation among older adults in primary care [46–48]. Additionally, in an emergency department setting, universal suicide risk screening has been associated with significantly improved risk detection [49], indicating that improved screening may be beneficial in identifying suicide risk. Importantly, asking about suicide does not cause thoughts of suicide [50]. Additionally, it is a myth that those who talk about suicide ideation will not act on these thoughts [51].

When primary care practitioners inquire about suicide ideation, they should also ask about death ideation; though some may believe that death ideation is not as significant in terms of suicide risk as suicide ideation, recall that research has not found differences in previous suicide attempts or current hopelessness among older adults with death ideation versus suicide ideation [14]. Therefore, screening for death ideation should be completed as part of every suicide risk screening.

Screening can take many forms. Screening may be oral; asking an older adult if he or she is having thoughts of suicide or is experiencing a desire to die is a brief, 2-question screening that may provide valuable information (eg, “Are you having thoughts about your own death or wanting to die?”, “Are you having thoughts of killing yourself or thinking about suicide?”). This screening may be conducted by medical assistants, nurses, care managers, or physicians, with the patient’s responses documented. Importantly, a standard procedure should be implemented to ensure older adults are consistently asked about suicide risk at each visit, but do not feel inundated by such questions from numerous staff.

If verbal questions are asked, they must be asked appropriately. Euphemisms or indirect language should not be used during a screening; older adults should be directly asked about thoughts of death and suicide, not simply asked questions such as, “Have you ever had thoughts of harming or hurting yourself?” A question like this does not adequately assess current suicide risk, as it does not assess current thoughts, nor does it specifically inquire about suicide ideation (ie, killing one’s self). It is also important to phrase questions in a manner that invites honest responses and conveys an openness to listening. For example, asking, “You’re not thinking about suicide, are you?” suggests that the practitioner wants the older adult to say no and is not comfortable with the older adult endorsing suicide ideation. Open questions that allow endorsement or denial (eg, “Are you having thoughts of killing yourself?”) imply that the practitioner is receptive to either an endorsement or denial of suicide ideation.

Alternatively, a written screening can be used; older adults may complete a questionnaire prior to their appointment or while waiting to see their practitioner. Such an assessment may be a brief screening (eg, using similar yes/no questions to an oral screening), or may be a standardized measure. For example, the Geriatric Suicide Ideation Scale [52] is a 31-item self-report measure that provides scores for suicide ideation, death ideation, loss of personal and social worth, and perceived meaning in life. Though there are not standard cutoffs that suggest high versus low suicide risk, responses can be reviewed to identify whether older adults are reporting suicide ideation or death ideation, and can also be compared to norms (ie, average scores) from other older adults [52]. This measure also has the benefit of 2 subscales that do not specifically require reporting thoughts of suicide or death (ie, loss of personal and social worth, perceived meaning in life), which may give practitioners an indication of an older adult’s suicide risk even if the older adult is not comfortable disclosing suicide ideation, as has been shown in previous research [7,8].

Similarly, the Geriatric Depression Scale, which has a validated 15-item version [53], does not directly ask about suicide ideation but has a 5-item subscale that has been found to be highly correlated with reported suicide ideation [54]. When administered to older adult primary care patients, this subscale was an effective measure of suicide ideation; a score of ≥ 1 was the best cutoff for determining whether an older adult reported suicide ideation [55].

Additionally, as noted previously, the interaction between perceived burdensomeness and thwarted belongingness may identify older adults who are potentially experiencing, but not reporting, suicide ideation [41]. The Interpersonal Needs Questionnaire [56] is the validated assessment for both perceived burdensomeness and thwarted belongingness. Perceived burdensomeness is assessed via 6 self-report items, and thwarted belongingness is assessed via 9 self-report items on this measure [56]. There are not specific cutoffs that determine high versus low perceived burdensomeness or thwarted belongingness, but older adults’ responses can provide information about their experiences of these constructs. Administration of the Interpersonal Needs Questionnaire can provide information about potential risk for suicide among older adults who may otherwise deny thoughts of suicide or death.

If the screening for suicide ideation or death ideation is positive (ie, the older adult endorses thoughts of suicide or death), the treating primary care practitioner must then follow up with additional questions to determine current level of suicide risk. To make this determination, at a minimum, follow-up questions should focus on whether the older adult has any intent to die by suicide (eg, “Do you have any intent to act on your thoughts of suicide?”), as well as whether he or she has a plan to die by suicide (eg, “Have you begun formulating a plan to die by suicide?”). When asking about a plan, it is important to determine how specific the plan is. For example, an older adult with a specific method identified and date selected to implement the plan is at much higher risk than an older adult with a relatively vague idea. It is also critical to assess for the older adult’s access to means for suicide. If an older adult has a specific plan and has the capability to carry out the plan (eg, plans to overdose on prescription medication and has large quantities of medication or high-lethality medication at home), he or she is more likely to die by suicide than an older adult who does not have access to means (eg, only has small quantities of low-lethality medication available). A general assessment of risk factors and previous suicidal behavior (ie, any previous suicide attempts) also informs decisions about level of risk and interventions.

After a screening or assessment is completed, a risk determination must be made and documented. Acute suicide risk can be categorized as low, moderate, or high. It is not appropriate to say that there is “no” suicide risk present. Low risk occurs when there is no current suicide ideation, no plan to die by suicide, and no intent to act on suicidal thoughts, especially when the patient has no history of suicidal behavior and few risk factors [57]. Moderate risk is evident when there is current suicide ideation, but no specific plan to die by suicide or intent to act on suicidal thoughts. There are likely warning signs or risk factors, which may include previous suicidal behaviors, present in moderate suicide risk [57]. High risk is indicated by current suicide ideation with plan to die by suicide and suicidal intent. There are significant warning signs and risk factors present; there may also be a recent suicide attempt, though this is not a requirement for a high risk determination [57]. Undetermined suicide risk occurs when a practitioner cannot accurately assess risk, but concern regarding suicide is present; this is primarily used when a patient refuses to answer questions about suicide. Undetermined risk should be treated as at least moderate risk. Because research shows that death ideation has similar outcomes to suicide ideation in older adults [14], death ideation should also be factored into determinations of suicide risk; reports of death ideation may indicate low or moderate risk in older adults, dependent upon other risk factors, suicidal intent, and plan.

After a risk determination is made, it must be documented in the medical record. The level of risk and rationale for that determination must be included [58]. Stating only the level of risk without a rationale (ie, the older adult’s responses to questions) is not adequate, and documenting only the older adult’s responses without a determination of risk is also not sufficient. Finally, it is critical to document the intervention that occurred or steps taken after the level of risk was determined.

Critically, stating only that there was no indication of suicide risk is inadequate. For example, documenting “No evidence of suicide risk” is not appropriate. This documentation does not indicate that the older adult was specifically asked about suicide ideation, death ideation, suicidal intent, or plan to die by suicide. It also does not indicate a level of suicide risk. Examples of appropriate documentation include:

 Patient was asked about suicide risk. She denied current suicide ideation but reported death ideation. She denied any current suicidal intent or plan. She also denied any previous suicide attempts. Therefore, acute suicide risk was deemed to be low. Provided patient with wallet card about the National Suicide Prevention Lifeline. Also called the Friendship Line while in the room with the patient to connect her with services. Finally, provided a brief list of local mental health professionals to patient; the patient reported she would like to see Dr. Smith. Called and left a message for Dr. Smith with referral information with patient during appointment.

Patient was asked about suicide risk. He reported both death ideation and suicide ideation. He also reported a nonspecific plan (ie, causing a single-vehicle motor vehicle accident, with no specific plan for the motor vehicle accident or timeframe) and denied any intent to act on his thoughts of suicide. He reported one previous suicide attempt, at age 22, by overdose on over-the-counter medication. He reported that this attempt did not require medical attention. Therefore, acute suicide risk was determined to be moderate. Patient was introduced to the behavioral health specialist, who met with the patient during the appointment to conduct further assessment and intervention.

Specific Intervention Strategies

Despite the fact that the pace of the primary care setting often does not allow for time-intensive intervention, there are ways to address suicide risk in this setting. Importantly, no-suicide contracts should not be used at any time [59,60]. No-suicide contracts are documents that patients who are experiencing suicide ideation are required to sign that state that they will not die by suicide while under the care of the practitioner. These contracts have no evidence of effectiveness, and some researchers argue that they may in fact damage the relationship with patients and serve the practitioner’s needs more than the patient’s needs [59].

One of the best options for older adults at low acute suicide risk is to provide resources and referrals. The National Suicide Prevention Lifeline can be reached at 1-800-273-TALK (8255); trained counselors are available to speak to patients at all times. Wallet cards with information about the National Suicide Prevention Lifeline are available at no charge from the US Substance Abuse and Mental Health Services Administration online store. The Friendship Line is another service available free to adults ages 60 and older, 24 hours per day, 7 days per week; this line can be reached at 1-800-971-0016. The Friendship Line, which is managed by the Institute on Aging, also provides outreach calls to older adults who may be isolated or lonely, increasing connectedness and potentially reducing suicide risk.

Having a ready list of local mental health professionals with expertise in geriatrics and suicide risk to provide to the patient is also beneficial. Recall, though, that older adults are less likely to seek out and receive mental health services [19]; therefore, connecting the patient with resources or referrals during the appointment is critical. If the practitioner does not have time to do this, having a medical assistant or other staff member that the patient knows engage in this step may be appropriate. For example, the patient can call the Friendship Line or National Suicide Prevention Lifeline while in the room with the practitioner, which may reduce anxiety or stigma about doing so and connect the patient with services. Similarly, calling a local mental health professional to make a referral during the appointment may increase the likelihood that the older adult will follow up on the referral.

The most ideal method of intervention for moderate or high acute suicide risk is a warm handoff to a behavioral or mental health specialist. As primary care and behavioral health become more integrated and financially viable as reimbursement through the Centers for Medicare and Medicaid Services improves [61], it is becoming increasingly likely that such a specialist will be on-site and available. Research has found that collaborative care in primary care reduces suicide risk in older adults [46–48,62]. Mental health specialists can conduct more comprehensive assessments and spend more time intervening to reduce suicide risk among older adults with death or suicide ideation. If an on-site behavioral health specialist is not available, older adults at high suicide risk may need to be referred to an emergency department for further evaluation and follow-up. Each state has its own laws and procedures regarding this process, which should be incorporated into a practice’s procedures for addressing high suicide risk. The procedure often involves ensuring that the older adult is accompanied at all times (ie, not left alone in a room), alerting emergency services (usually via phone call to an emergency line, such as 911), and completion of paperwork by a practitioner asserting that the patient is a danger to self. Police or other emergency personnel are then responsible for transporting the patient for further evaluation and determination of whether hospitalization is required.

If more time is available, either via the treating primary care practitioner or other patient care staff in the office, other brief interventions may be beneficial. First, means safety discussions are critical, particularly for older adults with plans for suicide or access to highly lethal means. In such discussions, patients are encouraged to restrict access to the methods that they may use to die by suicide. Plans for restricting access are developed, and when possible, a support person is enlisted to ensure that the plans are carried out. For example, if an older adult has access to firearms (eg, keeps a loaded weapon in his or her nightstand), he or she is encouraged to restrict his or her access to it. Ideally, this is through removing the weapon from the home, either permanently or until suicide risk reduces (eg, giving it to a friend, turning it over to police), but more safe storage may also be an option if the older adult is not willing to remove the weapon from the home. This may mean using a gun lock or storing the weapon in a gun safe, storing ammunition separately from an unloaded weapon, removing the firing pin, or otherwise disassembling the weapon. Means safety counseling has been shown to be effective in reducing suicide rates [63] and is acceptable to patients [64]. Studies indicate that over 90% of individuals who make a suicide attempt and survive do not go on to die by suicide [65]; therefore, reducing access to highly lethal means during a suicidal crisis may be key in reducing suicide rates. Though an in-depth review of means safety counseling is outside the scope of this article, readers are directed to Bryan, Stone, and Rudd’s article for a practical overview of means safety discussions [66].

Second, safety planning is a brief intervention that may be beneficial in the primary care setting [67,68]. The goal of a safety plan is to create an individualized plan to remain safe during a suicidal crisis. Means safety discussion is the last of 6 steps in the safety plan [68]. The first 5 steps include identifying warning signs, using internal coping strategies, social connectedness as distraction, social support for the crisis, and professionals that can be used as resources. When patients can identify specific, individualized warning signs that occur prior to a crisis, they can then use strategies to cope and prevent the crisis from worsening. Coping strategies that are encouraged are first internal (ie, those that can be done without relying on anyone else), such as exercise or journaling. If those do not improve the patient’s mood, then he or she is encouraged to use people or social settings as a distraction (eg, people watching at the mall, calling an acquaintance to chat), and if he or she is still feeling bad, encouraged to get social support for the crisis (eg, calling a family member to discuss the crisis and get support). Finally, if all of these steps are not effective, the older adult is encouraged to reach out to professional supports, such as a mental health provider, the National Suicide Prevention Lifeline, or 911 (or go to an emergency room). Readers are encouraged to review Stanley and Brown’s articles for comprehensive details about safety planning as an intervention [67,68]. Additionally, an article with specific adaptations for safety planning with older adults is forthcoming [69].

Conclusion

Older adults, particularly older men, are at high risk for suicide [1,2], and primary care practitioners are a critical component of older adult suicide prevention. Older adults frequently see primary care practitioners within a month prior to death by suicide [20,21]; primary care practitioners are uniquely qualified to address a broad range of potential risk factors, and may have more interactions and familiarity with older adults at risk for suicide than other medical professionals [20–22]. Primary care practitioners should be prepared to identify risk factors and warning signs for older adult suicide, ask appropriate questions to screen for suicide risk, and intervene to prevent suicide. Screening can consist of standardized written questionnaires or oral questioning, and interventions may include providing resources and referrals, discussions about means safety, safety planning, and handoff to a mental health specialist. Interventions for suicide risk are likely feasible and acceptable in primary care [46–48]. Primary care practitioners have an important role to play in older adult suicide prevention, and must be prepared to interact with older adults who may be at risk for suicide.

Corresponding author: Danielle R. Jahn, PhD, Primary Care Institute, 605 NE 1st St, Gainesville, FL 32605, [email protected].

Financial disclosures: None reported.

MITCHEL L. ZOLER

FRONTLINE MEDICAL NEWS

Mobile stroke units—specially equipped ambulances that bring a diagnostic computed tomography (CT) scanner and therapeutic thrombolysis directly to patients in the field—have begun to proliferate across the United States, although they remain investigational, with no clear proof of their incremental clinical value or cost-effectiveness.

The first US mobile stroke unit (MSU) launched in Houston, Texas in early 2014 (following the world’s first in Berlin, Germany, which began running in early 2011), and by early 2017, at least eight other US MSUs were in operation, most of them put into service during the prior 15 months. United States MSU locations now include Cleveland, Ohio; Denver, Colorado; Memphis, Tennessee; New York, New York; Toledo, Ohio; Trenton, New Jersey; and Northwestern Medicine and Rush University Medical Center in the western Chicago, Illinois region. A tenth MSU is slated to start operation at the University of California, Los Angeles later this year.

Early data collected at some of these sites show that initiating care of an acute ischemic stroke patient in an MSU shaves precious minutes off the time it takes to initiate thrombolytic therapy with tissue plasminogen activator (tPA), and findings from preliminary analyses suggest better functional outcomes for patients treated this way. However, leaders in the nascent field readily admit that the data needed to clearly prove the benefit patients receive from operating MSUs are still a few years off. This uncertainty about the added benefit to patients from MSUs couples with one clear fact: MSUs are expensive to start up, with a price tag of roughly $1 million to get an MSU on the road for the first time; they are also expensive to operate, with one estimate for the annual cost of keeping an MSU on the street at about $500,000 per year for staffing, supplies, and other expenses.

“Every US MSU I know of started with philanthropic gifts, but you need a business model” to keep the program running long-term, James C. Grotta, MD, said during a session focused on MSUs at the International Stroke Conference sponsored by the American Heart Association. “You can’t sustain an MSU with philanthropy,” said Dr Grotta, professor of neurology at the University of Texas Health Science Center in Houston, director and founder of the Houston MSU, and acknowledged “godfather” of all US MSUs.

“We believe that MSUs are very worthwhile and that the clinical and economic benefits of earlier stroke treatment [made possible with MSUs] could offset the costs, but we need to show this,” admitted May Nour, MD, a vascular and interventional neurologist at the University of California, Los Angeles (UCLA), and director of the soon-to-launch Los Angeles MSU.

The concept behind MSUs is simple: Each one carries a CT scanner on board so that once the vehicle’s staff identifies a patient with clinical signs of a significant-acute ischemic stroke in the field and confirms that the timing of the stroke onset suggests eligibility for tPA treatment, a CT scan can immediately be run on-site to finalize tPA eligibility. The MSU staff can then begin infusing the drug in the ambulance as it speeds the patient to an appropriate hospital.

In addition, many MSUs now carry a scanner that can perform a CT angiogram (CTA) to locate the occluding clot. If a large vessel occlusion is found, the crew can bring the patient directly to a comprehensive stroke center for a thrombectomy. If thrombectomy is not appropriate, the MSU crew may take the patient to a primary stroke center where thrombectomy is not available.

Another advantage to MSUs, in addition to quicker initiation of thrombolysis, is “getting patients to where they need to go faster and more directly,” said Dr Nour.

“Instead of bringing patients first to a hospital that’s unable to do thrombectomy and where treatment gets slowed down, with an MSU you can give tPA on the street and go straight to a thrombectomy center,” agreed Jeffrey L. Saver, MD, professor of neurology and director of the stroke unit at UCLA. “The MSU offers the tantalizing possibility that you can give tPA with no time hit because you can give it on the way directly to a comprehensive stroke center,” Dr Saver said during a session at the meeting.

Early Data on Effectiveness

Dr Nour reported some of the best evidence for the incremental clinical benefit of MSUs based on the reduced time for starting a tPA infusion. She used data the Berlin group published in September 2016 that compared the treatment courses and outcomes of patients managed with an MSU to similar patients managed by conventional ambulance transport for whom CT scan assessment and the start of tPA treatment did not begin until the patient reached a hospital. The German analysis showed that, in the observational Pre-hospital Acute Neurological Therapy and Optimization of Medical Care in Stroke Patients–Study (PHANTOM-S), among 353 patients treated by conventional transport, the median time from stroke onset to thrombolysis was 112 minutes, compared with a median of 73 minutes among 305 patients managed with an MSU, a statistically significant difference.¹ However, the study found no significant difference for its primary endpoint: the percentage of patients with a modified Rankin Scale score of 1 or lower when measured 90 days after their respective strokes. This outcome occurred in 47% of the control patients managed conventionally and in 53% of those managed by an MSU, a difference that fell short of statistical significance

Dr Nour attributed the lack of statistical significance for this primary endpoint to the relatively small number of patients enrolled in PHANTOM-S. “The study was underpowered,” she said.

Dr Nour presented an analysis at the meeting that extrapolated the results out to 1,000 hypothetical patients and tallied the benefits that a larger number of patients could expect to receive if their outcomes paralleled those seen in the published results. It showed that among 1,000 stroke patients treated with an MSU, 58 were expected to be free from disability 90 days later, and an additional 124 patients would have some improvement in their 90-day clinical outcome based on their modified Rankin Scale scores when compared with patients undergoing conventional hospitalization.

“If this finding was confirmed in a larger, controlled study, it would suggest that MSU-based thrombolysis has substantial clinical benefit,” she concluded.

Another recent report looked at the first 100 stroke patients treated by the Cleveland MSU during 2014. Researchers at the Cleveland Clinic and Case Western Reserve University said that 16 of those 100 patients received tPA, and the median time from their emergency call to thrombolytic treatment was 38.5 minutes faster than for 53 stroke patients treated during the same period at EDs operated by the Cleveland Clinic, a statistically significant difference.² However, this report included no data on clinical outcomes.

Running the Financial Numbers

Nailing down the incremental clinical benefit from MSUs is clearly a very important part of determining the value of this strategy, but another very practical concern is how much the service costs and whether it is financially sustainable.

“We did a cost-effectiveness analysis based on the PHANTOM-S data, and we were conservative by only looking at the benefit from early tPA treatment,” Heinrich J. Audebert, MD, professor of neurology at Charité Hospital in Berlin and head of the team running Berlin’s MSU, said during the MSU session at the meeting. “We did not take into account saving money by avoiding long-term stroke disability and just considered the cost of [immediate] care and the quality-adjusted life years. We calculated a cost of $35,000 per quality-adjusted life year, which is absolutely acceptable.”

He cautioned that this analysis was not based on actual outcomes but on the numbers needed to treat calculated from the PHANTOM-S results. “We need to now show this in controlled trials,” he admitted.

During his talk at the same session, Dr Grotta ran through the numbers for the Houston program. They spent $1.1 million to put their MSU into service in early 2014, and, based on the expenses accrued since then, he estimated an annual staffing cost of about $400,000 and an annual operating cost of about $100,000, for a total estimated 5-year cost of about $3.6 million. Staffing of the Houston MSU started with a registered nurse, CT technician, paramedic, and vascular neurologist, although, like most other US MSUs, the onboard neurologist has since been replaced by a second paramedic, and the neurological diagnostic consult is done via a telemedicine link.

Income from transport reimbursement, currently $500 per trip, and reimbursements of $17,000 above costs for administering tPA and of roughly $40,000 above costs for performing thrombectomy, are balancing these costs. Based on an estimated additional one thrombolysis case per month and one additional thrombectomy case per month, the MSU yields a potential incremental income to the hospital running the MSU of about $3.8 million over 5 years—enough to balance the operating cost, Dr Grotta said.

A key part of controlling costs is having the neurological consult done via a telemedicine link rather than by neurologist at the MSU. “Telemedicine reduces operational costs and improves efficiency,” noted M. Shazam Hussain, MD, interim director of the Cerebrovascular Center at the Cleveland Clinic. “Cost-effectiveness is a very important part of the concept” of MSUs, he said at the session.

The Houston group reported results from a study that directly compared the diagnostic performance of an onboard neurologist with that of a telemedicine neurologist linked-in remotely during MSU deployments for 174 patients. For these cases, the two neurologists each made an independent diagnosis that the researchers then compared. The two diagnoses concurred for 88% of the cases, Tzu-Ching Wu, MD, reported at the meeting. This rate of agreement matched the incidence of concordance between two neurologists who independently assessed the same patients at the hospital,³ said Dr Wu, a vascular neurologist and director of the telemedicine program at the University of Texas Health Science Center in Houston.

“The results support using telemedicine as the primary means of assessment on the MSU,” said Dr Wu. “This may enhance MSU efficiency and reduce costs.” His group’s next study of MSU telemedicine will compare the time needed to make a diagnostic decision using the two approaches, which Dr Wu reported was something not formally examined in the study.

However, telemedicine assessment of CT results gathered in an MSU has one major limitation: the time needed to transmit the huge amount of information from a CTA.

The MSU used by clinicians at the University of Tennessee, Memphis, incorporates an extremely powerful battery that enables “full CT scanner capability with a moving gantry,” said Andrei V. Alexandrov, MD, professor and chairman of neurology at the university. With this set up “we can do in-the-field multiphasic CT angiography from the aortic arch up within 4 minutes. The challenge of doing this is simple. It’s 1.7 gigabytes of data,” which would take a prohibitively long time to transmit from a remote site, he explained. As a result, the complete set of images from the field CTA is delivered on a memory stick to the attending hospital neurologist once the MSU returns.

Waiting for More Data

Despite these advances and the steady recent growth of MSUs, significant skepticism remains. “While mobile stroke units seem like a good idea and there is genuine hope that they will improve outcomes for selected stroke patients, there is not yet any evidence that this is the case,” wrote Bryan Bledsoe, DO, in a January 2017 editorial in the Journal of Emergency Medical Services. “They are expensive and financially nonsustainable. Without widespread deployment, they stand to benefit few, if any, patients. The money spent on these devices would be better spent on improving the current EMS system, including paramedic education, the availability of stroke centers, and on the early recognition of ELVO [emergent large vessel occlusion] strokes,” wrote Dr Bledsoe, professor of emergency medicine at the University of Nevada in Las Vegas.

Two other experts voiced concerns about MSUs in an editorial that accompanied a Cleveland Clinic report in March.⁴ “Even if MSUs meet an acceptable societal threshold for cost-effectiveness, cost-efficiency may prove a taller order to achieve return on investment for individual health systems and communities,” wrote Andrew M. Southerland, MD, and Ethan S. Brandler, MD. They cited the Cleveland report, which noted that the group’s first 100 MSU-treated patients came from a total of 317 MSU deployments and included 217 trips that were canceled prior to the MSU’s arrival at the patient’s location. In Berlin’s initial experience, more than 2,000 MSU deployments led to 200 tPA treatments and 349 cancellations before arrival, noted Dr Southerland, a neurologist at the University of Virginia in Charlottesville, and Dr Brandler, an emergency medicine physician at Stony Brook (NY) University.

“Hope remains that future trials may demonstrate the ultimate potential of mobile stroke units to improve long-term outcomes for more patients by treating them more quickly and effectively. In the meantime, ongoing efforts are needed to streamline MSU cost and efficiency,” they wrote.

Proponents of MSUs agree that what’s needed now are more data to prove efficacy and cost-effectiveness, as well as better integration into EMS programs. The first opportunity for documenting the clinical impact of MSUs on larger numbers of US patients may be from the BEnefits of Stroke Treatment Delivered using a Mobile Stroke Unit Compared to Standard Management by Emergency Medical Services (BEST-MSU) Study, funded by the Patient-Centered Outcomes Research Institute. This study is collecting data from the MSU programs in Denver, Houston, and Memphis. Although currently designed to enroll 697 patients, Dr Grotta said he hopes to bring the number up to 1,000 patients.

“We are following the health care use and its cost for every enrolled MSU and conventional patient for 1 year,” Dr Grotta explained in an interview. He hopes these results will provide the data needed to move MSUs from investigational status to routine and reimbursable care.

References

1. Kunz A, Ebinger M, Geisler F, et al. Functional outcomes of pre-hospital thrombolysis in a mobile stroke treatment unit compared with conventional care: an observational registry study. Lancet Neurol. 2016;15(10):1035-1043. doi:10.1016/S1474-4422(16)30129-6.

2. Taqui A, Cerejo R, Itrat A, et al; Cleveland Pre-Hospital Acute Stroke Treatment (PHAST) Group. Reduction in time to treatment in prehospital telemedicine evaluation and thrombolysis. Neurology. 2017 March 8. [Epub ahead of print]. doi:10.1212/WNL.0000000000003786.

3. Ramadan AR, Denny MC, Vahidy F, et al. Agreement among stroke faculty and fellows in treating ischemic stroke patients with tissue-type plasminogen activator and thrombectomy. Stroke. 2017;48(1):222-224. doi:10.1161/STROKEAHA.116.015214.

4. Southerland AM, Brandler ES. The cost-efficiency of mobile stroke units: Where the rubber meets the road. Neurology. 2017 Mar 8. [Epub ahead of print]. doi:10.1212/WNL.0000000000003833.

Pulmonary Embolism Common in Patients With Acute Exacerbations of COPD

JIM KLING

FRONTLINE MEDICAL NEWS

About 16% of patients with unexplained acute exacerbations of chronic obstructive pulmonary disease (AECOPD) had an accompanying pulmonary embolism (PE), usually in regions that could be targeted with anticoagulants, according to a new systematic review and meta-analysis.

Approximately 70% of AECOPD cases develop in response to an infection, but about 30% of the time, an AE has no clear cause, the authors said in a report on their research. There is a known biological link between inflammation and coagulation, which suggests that patients experiencing AECOPD may be at increased risk of PE.

The researchers reviewed and analyzed seven studies, comprising 880 patients. Among the authors’ reasons for conducting this research was to update the pooled prevalence of PE in AECOPD from a previous systematic review published in Chest in 2009.

The meta-analysis revealed that 16.1% of patients with AECOPD were also diagnosed with PE (95% confidence interval [CI], 8.3%-25.8%). There was a wide range of variation between individual studies (prevalence 3.3%-29.1%). In six studies that reported on deep vein thrombosis (DVT), the pooled prevalence of DVT was 10.5% (95% CI, 4.3%-19.0%).

Five of the studies identified the PE location. An analysis of those studies showed that 35% were in the main pulmonary artery, and 31.7% were in the lobar and interlobar arteries. Such findings “[suggest] that the majority of these embolisms have important clinical consequences,” the authors wrote.

The researchers also looked at clinical markers that accompanied AECOPD and found a potential signal with respect to pleuritic chest pain. One study found a strong association between pleuritic chest pain and AECOPD patients with PE (81% vs 40% in those without PE). A second study showed a similar association (24% in PE vs 11.5% in non-PE patients), and a third study found no significant difference.

The presence of PE was also linked to hypotension, syncope, and acute right failure on ultrasonography, suggesting that PE may be associated with heart failure.

Patients with PE were less likely to have symptoms consistent with a respiratory tract infection. They also tended to have higher mortality rates and longer hospitalization rates compared with those without PE.

The meta-analysis had some limitations, including the heterogeneity of findings in the included studies, as well as the potential for publication bias, since reports showing unusually low or high rates may be more likely to be published, the researchers noted. There was also a high proportion of male subjects in the included studies.

Overall, the researchers concluded that PE is more likely in patients with pleuritic chest pain and signs of heart failure, and less likely in patients with signs of a respiratory infection. That information “might add to the clinical decision-making in patients with an AECOPD, because it would be undesirable to perform [CT pulmonary angiography] in every patient with an AECOPD,” the researchers wrote.

Aleva FE, Voets LW, Simons SO, de Mast Q, van der Ven AJ, Heijdra YF. Prevalence and localization of pulmonary embolism in unexplained acute exacerbations of COPD: A systematic review and meta-analysis. Chest. 2017;151(3):544-554. doi:10.1016/j.chest.2016.07.034.

Norepinephrine Shortage Linked to Mortality in Patients With Septic Shock

AMY KARON

FRONTLINE MEDICAL NEWS

A national shortage of norepinephrine in the United States was associated with higher rates of mortality among patients hospitalized with septic shock, investigators reported.

Rates of in-hospital mortality in 2011 were 40% during quarters when hospitals were facing shortages and 36% when they were not, Emily Vail, MD, and her associates said at the International Symposium on Intensive Care and Emergency Medicine. The report was published simultaneously in JAMA.

The link between norepinephrine shortage and death from septic shock persisted even after the researchers accounted for numerous clinical and demographic factors (adjusted odds ratio, 1.2; 95% CI, 1.01 to 1.30; P = .03), wrote Dr Vail of Columbia University, New York.

Drug shortages are common in the United States, but few studies have explored their effects on patient outcomes. Investigators compared mortality rates among affected patients during 3-month intervals when hospitals were and were not using at least 20% less norepinephrine than baseline. The researchers used Premier Healthcare Database, which includes both standard claims and detailed, dated logs of all services billed to patients or insurance, with minimal missing data.

A total of 77% patients admitted with septic shock received norepinephrine before the shortage. During the lowest point of the shortage, 56% of patients received it, the researchers reported. Clinicians most often used phenylephrine instead, prescribing it to up to 54% of patients during the worst time of the shortage. The absolute increase in mortality during the quarters of shortage was 3.7% (95% CI, 1.5%-6.0%).

Several factors might explain the link between norepinephrine shortage and mortality, the investigators said. The vasopressors chosen to replace norepinephrine might result directly in worse outcomes, but a decrease in norepinephrine use also might be a proxy for relevant variables such as delayed use of vasopressors, lack of knowledge of how to optimally dose vasopressors besides norepinephrine, or the absence of a pharmacist dedicated to helping optimize the use of limited supplies.

The study did not uncover a dose-response association between greater decreases in norepinephrine use and increased mortality, the researchers noted. “This may be due to a threshold effect of vasopressor shortage on mortality, or lack of power due to relatively few hospital quarters at the extreme levels of vasopressor shortage,” they wrote.

Because the deaths captured included only those that occurred in-hospital, “the results may have underestimated mortality, particularly for hospitals that tend to transfer patients early to other skilled care facilities,” the researchers noted.

The cohort of patients was limited to those who received vasopressors for 2 or more days and excluded patients who died on the first day of vasopressor treatment, the researchers said.

Vail E, Gershengorn HB, Hua M, Walkey AJ, Rubenfeld G, Wunsch H. Association between US norepinephrine shortage and mortality among patients with septic shock. JAMA.  21 March 2017. [Epub ahead of print]. doi:10.1001/jama.2017.2841.

MITCHEL L. ZOLER

FRONTLINE MEDICAL NEWS

Mobile stroke units—specially equipped ambulances that bring a diagnostic computed tomography (CT) scanner and therapeutic thrombolysis directly to patients in the field—have begun to proliferate across the United States, although they remain investigational, with no clear proof of their incremental clinical value or cost-effectiveness.

The first US mobile stroke unit (MSU) launched in Houston, Texas in early 2014 (following the world’s first in Berlin, Germany, which began running in early 2011), and by early 2017, at least eight other US MSUs were in operation, most of them put into service during the prior 15 months. United States MSU locations now include Cleveland, Ohio; Denver, Colorado; Memphis, Tennessee; New York, New York; Toledo, Ohio; Trenton, New Jersey; and Northwestern Medicine and Rush University Medical Center in the western Chicago, Illinois region. A tenth MSU is slated to start operation at the University of California, Los Angeles later this year.

Early data collected at some of these sites show that initiating care of an acute ischemic stroke patient in an MSU shaves precious minutes off the time it takes to initiate thrombolytic therapy with tissue plasminogen activator (tPA), and findings from preliminary analyses suggest better functional outcomes for patients treated this way. However, leaders in the nascent field readily admit that the data needed to clearly prove the benefit patients receive from operating MSUs are still a few years off. This uncertainty about the added benefit to patients from MSUs couples with one clear fact: MSUs are expensive to start up, with a price tag of roughly $1 million to get an MSU on the road for the first time; they are also expensive to operate, with one estimate for the annual cost of keeping an MSU on the street at about $500,000 per year for staffing, supplies, and other expenses.

“Every US MSU I know of started with philanthropic gifts, but you need a business model” to keep the program running long-term, James C. Grotta, MD, said during a session focused on MSUs at the International Stroke Conference sponsored by the American Heart Association. “You can’t sustain an MSU with philanthropy,” said Dr Grotta, professor of neurology at the University of Texas Health Science Center in Houston, director and founder of the Houston MSU, and acknowledged “godfather” of all US MSUs.

“We believe that MSUs are very worthwhile and that the clinical and economic benefits of earlier stroke treatment [made possible with MSUs] could offset the costs, but we need to show this,” admitted May Nour, MD, a vascular and interventional neurologist at the University of California, Los Angeles (UCLA), and director of the soon-to-launch Los Angeles MSU.

The concept behind MSUs is simple: Each one carries a CT scanner on board so that once the vehicle’s staff identifies a patient with clinical signs of a significant-acute ischemic stroke in the field and confirms that the timing of the stroke onset suggests eligibility for tPA treatment, a CT scan can immediately be run on-site to finalize tPA eligibility. The MSU staff can then begin infusing the drug in the ambulance as it speeds the patient to an appropriate hospital.

In addition, many MSUs now carry a scanner that can perform a CT angiogram (CTA) to locate the occluding clot. If a large vessel occlusion is found, the crew can bring the patient directly to a comprehensive stroke center for a thrombectomy. If thrombectomy is not appropriate, the MSU crew may take the patient to a primary stroke center where thrombectomy is not available.

Another advantage to MSUs, in addition to quicker initiation of thrombolysis, is “getting patients to where they need to go faster and more directly,” said Dr Nour.

“Instead of bringing patients first to a hospital that’s unable to do thrombectomy and where treatment gets slowed down, with an MSU you can give tPA on the street and go straight to a thrombectomy center,” agreed Jeffrey L. Saver, MD, professor of neurology and director of the stroke unit at UCLA. “The MSU offers the tantalizing possibility that you can give tPA with no time hit because you can give it on the way directly to a comprehensive stroke center,” Dr Saver said during a session at the meeting.

Early Data on Effectiveness

Dr Nour reported some of the best evidence for the incremental clinical benefit of MSUs based on the reduced time for starting a tPA infusion. She used data the Berlin group published in September 2016 that compared the treatment courses and outcomes of patients managed with an MSU to similar patients managed by conventional ambulance transport for whom CT scan assessment and the start of tPA treatment did not begin until the patient reached a hospital. The German analysis showed that, in the observational Pre-hospital Acute Neurological Therapy and Optimization of Medical Care in Stroke Patients–Study (PHANTOM-S), among 353 patients treated by conventional transport, the median time from stroke onset to thrombolysis was 112 minutes, compared with a median of 73 minutes among 305 patients managed with an MSU, a statistically significant difference.¹ However, the study found no significant difference for its primary endpoint: the percentage of patients with a modified Rankin Scale score of 1 or lower when measured 90 days after their respective strokes. This outcome occurred in 47% of the control patients managed conventionally and in 53% of those managed by an MSU, a difference that fell short of statistical significance

Dr Nour attributed the lack of statistical significance for this primary endpoint to the relatively small number of patients enrolled in PHANTOM-S. “The study was underpowered,” she said.

Dr Nour presented an analysis at the meeting that extrapolated the results out to 1,000 hypothetical patients and tallied the benefits that a larger number of patients could expect to receive if their outcomes paralleled those seen in the published results. It showed that among 1,000 stroke patients treated with an MSU, 58 were expected to be free from disability 90 days later, and an additional 124 patients would have some improvement in their 90-day clinical outcome based on their modified Rankin Scale scores when compared with patients undergoing conventional hospitalization.

“If this finding was confirmed in a larger, controlled study, it would suggest that MSU-based thrombolysis has substantial clinical benefit,” she concluded.

Another recent report looked at the first 100 stroke patients treated by the Cleveland MSU during 2014. Researchers at the Cleveland Clinic and Case Western Reserve University said that 16 of those 100 patients received tPA, and the median time from their emergency call to thrombolytic treatment was 38.5 minutes faster than for 53 stroke patients treated during the same period at EDs operated by the Cleveland Clinic, a statistically significant difference.² However, this report included no data on clinical outcomes.

Running the Financial Numbers

Nailing down the incremental clinical benefit from MSUs is clearly a very important part of determining the value of this strategy, but another very practical concern is how much the service costs and whether it is financially sustainable.

“We did a cost-effectiveness analysis based on the PHANTOM-S data, and we were conservative by only looking at the benefit from early tPA treatment,” Heinrich J. Audebert, MD, professor of neurology at Charité Hospital in Berlin and head of the team running Berlin’s MSU, said during the MSU session at the meeting. “We did not take into account saving money by avoiding long-term stroke disability and just considered the cost of [immediate] care and the quality-adjusted life years. We calculated a cost of $35,000 per quality-adjusted life year, which is absolutely acceptable.”

He cautioned that this analysis was not based on actual outcomes but on the numbers needed to treat calculated from the PHANTOM-S results. “We need to now show this in controlled trials,” he admitted.

During his talk at the same session, Dr Grotta ran through the numbers for the Houston program. They spent $1.1 million to put their MSU into service in early 2014, and, based on the expenses accrued since then, he estimated an annual staffing cost of about $400,000 and an annual operating cost of about $100,000, for a total estimated 5-year cost of about $3.6 million. Staffing of the Houston MSU started with a registered nurse, CT technician, paramedic, and vascular neurologist, although, like most other US MSUs, the onboard neurologist has since been replaced by a second paramedic, and the neurological diagnostic consult is done via a telemedicine link.

Income from transport reimbursement, currently $500 per trip, and reimbursements of $17,000 above costs for administering tPA and of roughly $40,000 above costs for performing thrombectomy, are balancing these costs. Based on an estimated additional one thrombolysis case per month and one additional thrombectomy case per month, the MSU yields a potential incremental income to the hospital running the MSU of about $3.8 million over 5 years—enough to balance the operating cost, Dr Grotta said.

A key part of controlling costs is having the neurological consult done via a telemedicine link rather than by neurologist at the MSU. “Telemedicine reduces operational costs and improves efficiency,” noted M. Shazam Hussain, MD, interim director of the Cerebrovascular Center at the Cleveland Clinic. “Cost-effectiveness is a very important part of the concept” of MSUs, he said at the session.

The Houston group reported results from a study that directly compared the diagnostic performance of an onboard neurologist with that of a telemedicine neurologist linked-in remotely during MSU deployments for 174 patients. For these cases, the two neurologists each made an independent diagnosis that the researchers then compared. The two diagnoses concurred for 88% of the cases, Tzu-Ching Wu, MD, reported at the meeting. This rate of agreement matched the incidence of concordance between two neurologists who independently assessed the same patients at the hospital,³ said Dr Wu, a vascular neurologist and director of the telemedicine program at the University of Texas Health Science Center in Houston.

“The results support using telemedicine as the primary means of assessment on the MSU,” said Dr Wu. “This may enhance MSU efficiency and reduce costs.” His group’s next study of MSU telemedicine will compare the time needed to make a diagnostic decision using the two approaches, which Dr Wu reported was something not formally examined in the study.

However, telemedicine assessment of CT results gathered in an MSU has one major limitation: the time needed to transmit the huge amount of information from a CTA.

The MSU used by clinicians at the University of Tennessee, Memphis, incorporates an extremely powerful battery that enables “full CT scanner capability with a moving gantry,” said Andrei V. Alexandrov, MD, professor and chairman of neurology at the university. With this set up “we can do in-the-field multiphasic CT angiography from the aortic arch up within 4 minutes. The challenge of doing this is simple. It’s 1.7 gigabytes of data,” which would take a prohibitively long time to transmit from a remote site, he explained. As a result, the complete set of images from the field CTA is delivered on a memory stick to the attending hospital neurologist once the MSU returns.

Waiting for More Data

Despite these advances and the steady recent growth of MSUs, significant skepticism remains. “While mobile stroke units seem like a good idea and there is genuine hope that they will improve outcomes for selected stroke patients, there is not yet any evidence that this is the case,” wrote Bryan Bledsoe, DO, in a January 2017 editorial in the Journal of Emergency Medical Services. “They are expensive and financially nonsustainable. Without widespread deployment, they stand to benefit few, if any, patients. The money spent on these devices would be better spent on improving the current EMS system, including paramedic education, the availability of stroke centers, and on the early recognition of ELVO [emergent large vessel occlusion] strokes,” wrote Dr Bledsoe, professor of emergency medicine at the University of Nevada in Las Vegas.

Two other experts voiced concerns about MSUs in an editorial that accompanied a Cleveland Clinic report in March.⁴ “Even if MSUs meet an acceptable societal threshold for cost-effectiveness, cost-efficiency may prove a taller order to achieve return on investment for individual health systems and communities,” wrote Andrew M. Southerland, MD, and Ethan S. Brandler, MD. They cited the Cleveland report, which noted that the group’s first 100 MSU-treated patients came from a total of 317 MSU deployments and included 217 trips that were canceled prior to the MSU’s arrival at the patient’s location. In Berlin’s initial experience, more than 2,000 MSU deployments led to 200 tPA treatments and 349 cancellations before arrival, noted Dr Southerland, a neurologist at the University of Virginia in Charlottesville, and Dr Brandler, an emergency medicine physician at Stony Brook (NY) University.

“Hope remains that future trials may demonstrate the ultimate potential of mobile stroke units to improve long-term outcomes for more patients by treating them more quickly and effectively. In the meantime, ongoing efforts are needed to streamline MSU cost and efficiency,” they wrote.

Proponents of MSUs agree that what’s needed now are more data to prove efficacy and cost-effectiveness, as well as better integration into EMS programs. The first opportunity for documenting the clinical impact of MSUs on larger numbers of US patients may be from the BEnefits of Stroke Treatment Delivered using a Mobile Stroke Unit Compared to Standard Management by Emergency Medical Services (BEST-MSU) Study, funded by the Patient-Centered Outcomes Research Institute. This study is collecting data from the MSU programs in Denver, Houston, and Memphis. Although currently designed to enroll 697 patients, Dr Grotta said he hopes to bring the number up to 1,000 patients.

“We are following the health care use and its cost for every enrolled MSU and conventional patient for 1 year,” Dr Grotta explained in an interview. He hopes these results will provide the data needed to move MSUs from investigational status to routine and reimbursable care.

References

1. Kunz A, Ebinger M, Geisler F, et al. Functional outcomes of pre-hospital thrombolysis in a mobile stroke treatment unit compared with conventional care: an observational registry study. Lancet Neurol. 2016;15(10):1035-1043. doi:10.1016/S1474-4422(16)30129-6.

2. Taqui A, Cerejo R, Itrat A, et al; Cleveland Pre-Hospital Acute Stroke Treatment (PHAST) Group. Reduction in time to treatment in prehospital telemedicine evaluation and thrombolysis. Neurology. 2017 March 8. [Epub ahead of print]. doi:10.1212/WNL.0000000000003786.

3. Ramadan AR, Denny MC, Vahidy F, et al. Agreement among stroke faculty and fellows in treating ischemic stroke patients with tissue-type plasminogen activator and thrombectomy. Stroke. 2017;48(1):222-224. doi:10.1161/STROKEAHA.116.015214.

4. Southerland AM, Brandler ES. The cost-efficiency of mobile stroke units: Where the rubber meets the road. Neurology. 2017 Mar 8. [Epub ahead of print]. doi:10.1212/WNL.0000000000003833.

Pulmonary Embolism Common in Patients With Acute Exacerbations of COPD

JIM KLING

FRONTLINE MEDICAL NEWS

About 16% of patients with unexplained acute exacerbations of chronic obstructive pulmonary disease (AECOPD) had an accompanying pulmonary embolism (PE), usually in regions that could be targeted with anticoagulants, according to a new systematic review and meta-analysis.

Approximately 70% of AECOPD cases develop in response to an infection, but about 30% of the time, an AE has no clear cause, the authors said in a report on their research. There is a known biological link between inflammation and coagulation, which suggests that patients experiencing AECOPD may be at increased risk of PE.

The researchers reviewed and analyzed seven studies, comprising 880 patients. Among the authors’ reasons for conducting this research was to update the pooled prevalence of PE in AECOPD from a previous systematic review published in Chest in 2009.

The meta-analysis revealed that 16.1% of patients with AECOPD were also diagnosed with PE (95% confidence interval [CI], 8.3%-25.8%). There was a wide range of variation between individual studies (prevalence 3.3%-29.1%). In six studies that reported on deep vein thrombosis (DVT), the pooled prevalence of DVT was 10.5% (95% CI, 4.3%-19.0%).

Five of the studies identified the PE location. An analysis of those studies showed that 35% were in the main pulmonary artery, and 31.7% were in the lobar and interlobar arteries. Such findings “[suggest] that the majority of these embolisms have important clinical consequences,” the authors wrote.

The researchers also looked at clinical markers that accompanied AECOPD and found a potential signal with respect to pleuritic chest pain. One study found a strong association between pleuritic chest pain and AECOPD patients with PE (81% vs 40% in those without PE). A second study showed a similar association (24% in PE vs 11.5% in non-PE patients), and a third study found no significant difference.

The presence of PE was also linked to hypotension, syncope, and acute right failure on ultrasonography, suggesting that PE may be associated with heart failure.

Patients with PE were less likely to have symptoms consistent with a respiratory tract infection. They also tended to have higher mortality rates and longer hospitalization rates compared with those without PE.

The meta-analysis had some limitations, including the heterogeneity of findings in the included studies, as well as the potential for publication bias, since reports showing unusually low or high rates may be more likely to be published, the researchers noted. There was also a high proportion of male subjects in the included studies.

Overall, the researchers concluded that PE is more likely in patients with pleuritic chest pain and signs of heart failure, and less likely in patients with signs of a respiratory infection. That information “might add to the clinical decision-making in patients with an AECOPD, because it would be undesirable to perform [CT pulmonary angiography] in every patient with an AECOPD,” the researchers wrote.

Aleva FE, Voets LW, Simons SO, de Mast Q, van der Ven AJ, Heijdra YF. Prevalence and localization of pulmonary embolism in unexplained acute exacerbations of COPD: A systematic review and meta-analysis. Chest. 2017;151(3):544-554. doi:10.1016/j.chest.2016.07.034.

Norepinephrine Shortage Linked to Mortality in Patients With Septic Shock

AMY KARON

FRONTLINE MEDICAL NEWS

A national shortage of norepinephrine in the United States was associated with higher rates of mortality among patients hospitalized with septic shock, investigators reported.

Rates of in-hospital mortality in 2011 were 40% during quarters when hospitals were facing shortages and 36% when they were not, Emily Vail, MD, and her associates said at the International Symposium on Intensive Care and Emergency Medicine. The report was published simultaneously in JAMA.

The link between norepinephrine shortage and death from septic shock persisted even after the researchers accounted for numerous clinical and demographic factors (adjusted odds ratio, 1.2; 95% CI, 1.01 to 1.30; P = .03), wrote Dr Vail of Columbia University, New York.

Drug shortages are common in the United States, but few studies have explored their effects on patient outcomes. Investigators compared mortality rates among affected patients during 3-month intervals when hospitals were and were not using at least 20% less norepinephrine than baseline. The researchers used Premier Healthcare Database, which includes both standard claims and detailed, dated logs of all services billed to patients or insurance, with minimal missing data.

A total of 77% patients admitted with septic shock received norepinephrine before the shortage. During the lowest point of the shortage, 56% of patients received it, the researchers reported. Clinicians most often used phenylephrine instead, prescribing it to up to 54% of patients during the worst time of the shortage. The absolute increase in mortality during the quarters of shortage was 3.7% (95% CI, 1.5%-6.0%).

Several factors might explain the link between norepinephrine shortage and mortality, the investigators said. The vasopressors chosen to replace norepinephrine might result directly in worse outcomes, but a decrease in norepinephrine use also might be a proxy for relevant variables such as delayed use of vasopressors, lack of knowledge of how to optimally dose vasopressors besides norepinephrine, or the absence of a pharmacist dedicated to helping optimize the use of limited supplies.

The study did not uncover a dose-response association between greater decreases in norepinephrine use and increased mortality, the researchers noted. “This may be due to a threshold effect of vasopressor shortage on mortality, or lack of power due to relatively few hospital quarters at the extreme levels of vasopressor shortage,” they wrote.

Because the deaths captured included only those that occurred in-hospital, “the results may have underestimated mortality, particularly for hospitals that tend to transfer patients early to other skilled care facilities,” the researchers noted.

The cohort of patients was limited to those who received vasopressors for 2 or more days and excluded patients who died on the first day of vasopressor treatment, the researchers said.

Vail E, Gershengorn HB, Hua M, Walkey AJ, Rubenfeld G, Wunsch H. Association between US norepinephrine shortage and mortality among patients with septic shock. JAMA.  21 March 2017. [Epub ahead of print]. doi:10.1001/jama.2017.2841.

MITCHEL L. ZOLER

FRONTLINE MEDICAL NEWS

Mobile stroke units—specially equipped ambulances that bring a diagnostic computed tomography (CT) scanner and therapeutic thrombolysis directly to patients in the field—have begun to proliferate across the United States, although they remain investigational, with no clear proof of their incremental clinical value or cost-effectiveness.

The first US mobile stroke unit (MSU) launched in Houston, Texas in early 2014 (following the world’s first in Berlin, Germany, which began running in early 2011), and by early 2017, at least eight other US MSUs were in operation, most of them put into service during the prior 15 months. United States MSU locations now include Cleveland, Ohio; Denver, Colorado; Memphis, Tennessee; New York, New York; Toledo, Ohio; Trenton, New Jersey; and Northwestern Medicine and Rush University Medical Center in the western Chicago, Illinois region. A tenth MSU is slated to start operation at the University of California, Los Angeles later this year.

Early data collected at some of these sites show that initiating care of an acute ischemic stroke patient in an MSU shaves precious minutes off the time it takes to initiate thrombolytic therapy with tissue plasminogen activator (tPA), and findings from preliminary analyses suggest better functional outcomes for patients treated this way. However, leaders in the nascent field readily admit that the data needed to clearly prove the benefit patients receive from operating MSUs are still a few years off. This uncertainty about the added benefit to patients from MSUs couples with one clear fact: MSUs are expensive to start up, with a price tag of roughly $1 million to get an MSU on the road for the first time; they are also expensive to operate, with one estimate for the annual cost of keeping an MSU on the street at about $500,000 per year for staffing, supplies, and other expenses.

“Every US MSU I know of started with philanthropic gifts, but you need a business model” to keep the program running long-term, James C. Grotta, MD, said during a session focused on MSUs at the International Stroke Conference sponsored by the American Heart Association. “You can’t sustain an MSU with philanthropy,” said Dr Grotta, professor of neurology at the University of Texas Health Science Center in Houston, director and founder of the Houston MSU, and acknowledged “godfather” of all US MSUs.

“We believe that MSUs are very worthwhile and that the clinical and economic benefits of earlier stroke treatment [made possible with MSUs] could offset the costs, but we need to show this,” admitted May Nour, MD, a vascular and interventional neurologist at the University of California, Los Angeles (UCLA), and director of the soon-to-launch Los Angeles MSU.

The concept behind MSUs is simple: Each one carries a CT scanner on board so that once the vehicle’s staff identifies a patient with clinical signs of a significant-acute ischemic stroke in the field and confirms that the timing of the stroke onset suggests eligibility for tPA treatment, a CT scan can immediately be run on-site to finalize tPA eligibility. The MSU staff can then begin infusing the drug in the ambulance as it speeds the patient to an appropriate hospital.

In addition, many MSUs now carry a scanner that can perform a CT angiogram (CTA) to locate the occluding clot. If a large vessel occlusion is found, the crew can bring the patient directly to a comprehensive stroke center for a thrombectomy. If thrombectomy is not appropriate, the MSU crew may take the patient to a primary stroke center where thrombectomy is not available.

Another advantage to MSUs, in addition to quicker initiation of thrombolysis, is “getting patients to where they need to go faster and more directly,” said Dr Nour.

“Instead of bringing patients first to a hospital that’s unable to do thrombectomy and where treatment gets slowed down, with an MSU you can give tPA on the street and go straight to a thrombectomy center,” agreed Jeffrey L. Saver, MD, professor of neurology and director of the stroke unit at UCLA. “The MSU offers the tantalizing possibility that you can give tPA with no time hit because you can give it on the way directly to a comprehensive stroke center,” Dr Saver said during a session at the meeting.

Early Data on Effectiveness

Dr Nour reported some of the best evidence for the incremental clinical benefit of MSUs based on the reduced time for starting a tPA infusion. She used data the Berlin group published in September 2016 that compared the treatment courses and outcomes of patients managed with an MSU to similar patients managed by conventional ambulance transport for whom CT scan assessment and the start of tPA treatment did not begin until the patient reached a hospital. The German analysis showed that, in the observational Pre-hospital Acute Neurological Therapy and Optimization of Medical Care in Stroke Patients–Study (PHANTOM-S), among 353 patients treated by conventional transport, the median time from stroke onset to thrombolysis was 112 minutes, compared with a median of 73 minutes among 305 patients managed with an MSU, a statistically significant difference.¹ However, the study found no significant difference for its primary endpoint: the percentage of patients with a modified Rankin Scale score of 1 or lower when measured 90 days after their respective strokes. This outcome occurred in 47% of the control patients managed conventionally and in 53% of those managed by an MSU, a difference that fell short of statistical significance

Dr Nour attributed the lack of statistical significance for this primary endpoint to the relatively small number of patients enrolled in PHANTOM-S. “The study was underpowered,” she said.

Dr Nour presented an analysis at the meeting that extrapolated the results out to 1,000 hypothetical patients and tallied the benefits that a larger number of patients could expect to receive if their outcomes paralleled those seen in the published results. It showed that among 1,000 stroke patients treated with an MSU, 58 were expected to be free from disability 90 days later, and an additional 124 patients would have some improvement in their 90-day clinical outcome based on their modified Rankin Scale scores when compared with patients undergoing conventional hospitalization.

“If this finding was confirmed in a larger, controlled study, it would suggest that MSU-based thrombolysis has substantial clinical benefit,” she concluded.

Another recent report looked at the first 100 stroke patients treated by the Cleveland MSU during 2014. Researchers at the Cleveland Clinic and Case Western Reserve University said that 16 of those 100 patients received tPA, and the median time from their emergency call to thrombolytic treatment was 38.5 minutes faster than for 53 stroke patients treated during the same period at EDs operated by the Cleveland Clinic, a statistically significant difference.² However, this report included no data on clinical outcomes.

Running the Financial Numbers

Nailing down the incremental clinical benefit from MSUs is clearly a very important part of determining the value of this strategy, but another very practical concern is how much the service costs and whether it is financially sustainable.

“We did a cost-effectiveness analysis based on the PHANTOM-S data, and we were conservative by only looking at the benefit from early tPA treatment,” Heinrich J. Audebert, MD, professor of neurology at Charité Hospital in Berlin and head of the team running Berlin’s MSU, said during the MSU session at the meeting. “We did not take into account saving money by avoiding long-term stroke disability and just considered the cost of [immediate] care and the quality-adjusted life years. We calculated a cost of $35,000 per quality-adjusted life year, which is absolutely acceptable.”

He cautioned that this analysis was not based on actual outcomes but on the numbers needed to treat calculated from the PHANTOM-S results. “We need to now show this in controlled trials,” he admitted.

During his talk at the same session, Dr Grotta ran through the numbers for the Houston program. They spent $1.1 million to put their MSU into service in early 2014, and, based on the expenses accrued since then, he estimated an annual staffing cost of about $400,000 and an annual operating cost of about $100,000, for a total estimated 5-year cost of about $3.6 million. Staffing of the Houston MSU started with a registered nurse, CT technician, paramedic, and vascular neurologist, although, like most other US MSUs, the onboard neurologist has since been replaced by a second paramedic, and the neurological diagnostic consult is done via a telemedicine link.

Income from transport reimbursement, currently $500 per trip, and reimbursements of $17,000 above costs for administering tPA and of roughly $40,000 above costs for performing thrombectomy, are balancing these costs. Based on an estimated additional one thrombolysis case per month and one additional thrombectomy case per month, the MSU yields a potential incremental income to the hospital running the MSU of about $3.8 million over 5 years—enough to balance the operating cost, Dr Grotta said.

A key part of controlling costs is having the neurological consult done via a telemedicine link rather than by neurologist at the MSU. “Telemedicine reduces operational costs and improves efficiency,” noted M. Shazam Hussain, MD, interim director of the Cerebrovascular Center at the Cleveland Clinic. “Cost-effectiveness is a very important part of the concept” of MSUs, he said at the session.

The Houston group reported results from a study that directly compared the diagnostic performance of an onboard neurologist with that of a telemedicine neurologist linked-in remotely during MSU deployments for 174 patients. For these cases, the two neurologists each made an independent diagnosis that the researchers then compared. The two diagnoses concurred for 88% of the cases, Tzu-Ching Wu, MD, reported at the meeting. This rate of agreement matched the incidence of concordance between two neurologists who independently assessed the same patients at the hospital,³ said Dr Wu, a vascular neurologist and director of the telemedicine program at the University of Texas Health Science Center in Houston.

“The results support using telemedicine as the primary means of assessment on the MSU,” said Dr Wu. “This may enhance MSU efficiency and reduce costs.” His group’s next study of MSU telemedicine will compare the time needed to make a diagnostic decision using the two approaches, which Dr Wu reported was something not formally examined in the study.

However, telemedicine assessment of CT results gathered in an MSU has one major limitation: the time needed to transmit the huge amount of information from a CTA.

The MSU used by clinicians at the University of Tennessee, Memphis, incorporates an extremely powerful battery that enables “full CT scanner capability with a moving gantry,” said Andrei V. Alexandrov, MD, professor and chairman of neurology at the university. With this set up “we can do in-the-field multiphasic CT angiography from the aortic arch up within 4 minutes. The challenge of doing this is simple. It’s 1.7 gigabytes of data,” which would take a prohibitively long time to transmit from a remote site, he explained. As a result, the complete set of images from the field CTA is delivered on a memory stick to the attending hospital neurologist once the MSU returns.

Waiting for More Data

Despite these advances and the steady recent growth of MSUs, significant skepticism remains. “While mobile stroke units seem like a good idea and there is genuine hope that they will improve outcomes for selected stroke patients, there is not yet any evidence that this is the case,” wrote Bryan Bledsoe, DO, in a January 2017 editorial in the Journal of Emergency Medical Services. “They are expensive and financially nonsustainable. Without widespread deployment, they stand to benefit few, if any, patients. The money spent on these devices would be better spent on improving the current EMS system, including paramedic education, the availability of stroke centers, and on the early recognition of ELVO [emergent large vessel occlusion] strokes,” wrote Dr Bledsoe, professor of emergency medicine at the University of Nevada in Las Vegas.

Two other experts voiced concerns about MSUs in an editorial that accompanied a Cleveland Clinic report in March.⁴ “Even if MSUs meet an acceptable societal threshold for cost-effectiveness, cost-efficiency may prove a taller order to achieve return on investment for individual health systems and communities,” wrote Andrew M. Southerland, MD, and Ethan S. Brandler, MD. They cited the Cleveland report, which noted that the group’s first 100 MSU-treated patients came from a total of 317 MSU deployments and included 217 trips that were canceled prior to the MSU’s arrival at the patient’s location. In Berlin’s initial experience, more than 2,000 MSU deployments led to 200 tPA treatments and 349 cancellations before arrival, noted Dr Southerland, a neurologist at the University of Virginia in Charlottesville, and Dr Brandler, an emergency medicine physician at Stony Brook (NY) University.

“Hope remains that future trials may demonstrate the ultimate potential of mobile stroke units to improve long-term outcomes for more patients by treating them more quickly and effectively. In the meantime, ongoing efforts are needed to streamline MSU cost and efficiency,” they wrote.

Proponents of MSUs agree that what’s needed now are more data to prove efficacy and cost-effectiveness, as well as better integration into EMS programs. The first opportunity for documenting the clinical impact of MSUs on larger numbers of US patients may be from the BEnefits of Stroke Treatment Delivered using a Mobile Stroke Unit Compared to Standard Management by Emergency Medical Services (BEST-MSU) Study, funded by the Patient-Centered Outcomes Research Institute. This study is collecting data from the MSU programs in Denver, Houston, and Memphis. Although currently designed to enroll 697 patients, Dr Grotta said he hopes to bring the number up to 1,000 patients.

“We are following the health care use and its cost for every enrolled MSU and conventional patient for 1 year,” Dr Grotta explained in an interview. He hopes these results will provide the data needed to move MSUs from investigational status to routine and reimbursable care.

References

1. Kunz A, Ebinger M, Geisler F, et al. Functional outcomes of pre-hospital thrombolysis in a mobile stroke treatment unit compared with conventional care: an observational registry study. Lancet Neurol. 2016;15(10):1035-1043. doi:10.1016/S1474-4422(16)30129-6.

2. Taqui A, Cerejo R, Itrat A, et al; Cleveland Pre-Hospital Acute Stroke Treatment (PHAST) Group. Reduction in time to treatment in prehospital telemedicine evaluation and thrombolysis. Neurology. 2017 March 8. [Epub ahead of print]. doi:10.1212/WNL.0000000000003786.

3. Ramadan AR, Denny MC, Vahidy F, et al. Agreement among stroke faculty and fellows in treating ischemic stroke patients with tissue-type plasminogen activator and thrombectomy. Stroke. 2017;48(1):222-224. doi:10.1161/STROKEAHA.116.015214.

4. Southerland AM, Brandler ES. The cost-efficiency of mobile stroke units: Where the rubber meets the road. Neurology. 2017 Mar 8. [Epub ahead of print]. doi:10.1212/WNL.0000000000003833.

Pulmonary Embolism Common in Patients With Acute Exacerbations of COPD

JIM KLING

FRONTLINE MEDICAL NEWS

About 16% of patients with unexplained acute exacerbations of chronic obstructive pulmonary disease (AECOPD) had an accompanying pulmonary embolism (PE), usually in regions that could be targeted with anticoagulants, according to a new systematic review and meta-analysis.

Approximately 70% of AECOPD cases develop in response to an infection, but about 30% of the time, an AE has no clear cause, the authors said in a report on their research. There is a known biological link between inflammation and coagulation, which suggests that patients experiencing AECOPD may be at increased risk of PE.

The researchers reviewed and analyzed seven studies, comprising 880 patients. Among the authors’ reasons for conducting this research was to update the pooled prevalence of PE in AECOPD from a previous systematic review published in Chest in 2009.

The meta-analysis revealed that 16.1% of patients with AECOPD were also diagnosed with PE (95% confidence interval [CI], 8.3%-25.8%). There was a wide range of variation between individual studies (prevalence 3.3%-29.1%). In six studies that reported on deep vein thrombosis (DVT), the pooled prevalence of DVT was 10.5% (95% CI, 4.3%-19.0%).

Five of the studies identified the PE location. An analysis of those studies showed that 35% were in the main pulmonary artery, and 31.7% were in the lobar and interlobar arteries. Such findings “[suggest] that the majority of these embolisms have important clinical consequences,” the authors wrote.

The researchers also looked at clinical markers that accompanied AECOPD and found a potential signal with respect to pleuritic chest pain. One study found a strong association between pleuritic chest pain and AECOPD patients with PE (81% vs 40% in those without PE). A second study showed a similar association (24% in PE vs 11.5% in non-PE patients), and a third study found no significant difference.

The presence of PE was also linked to hypotension, syncope, and acute right failure on ultrasonography, suggesting that PE may be associated with heart failure.

Patients with PE were less likely to have symptoms consistent with a respiratory tract infection. They also tended to have higher mortality rates and longer hospitalization rates compared with those without PE.

The meta-analysis had some limitations, including the heterogeneity of findings in the included studies, as well as the potential for publication bias, since reports showing unusually low or high rates may be more likely to be published, the researchers noted. There was also a high proportion of male subjects in the included studies.

Overall, the researchers concluded that PE is more likely in patients with pleuritic chest pain and signs of heart failure, and less likely in patients with signs of a respiratory infection. That information “might add to the clinical decision-making in patients with an AECOPD, because it would be undesirable to perform [CT pulmonary angiography] in every patient with an AECOPD,” the researchers wrote.

Aleva FE, Voets LW, Simons SO, de Mast Q, van der Ven AJ, Heijdra YF. Prevalence and localization of pulmonary embolism in unexplained acute exacerbations of COPD: A systematic review and meta-analysis. Chest. 2017;151(3):544-554. doi:10.1016/j.chest.2016.07.034.

Norepinephrine Shortage Linked to Mortality in Patients With Septic Shock

AMY KARON

FRONTLINE MEDICAL NEWS

A national shortage of norepinephrine in the United States was associated with higher rates of mortality among patients hospitalized with septic shock, investigators reported.

Rates of in-hospital mortality in 2011 were 40% during quarters when hospitals were facing shortages and 36% when they were not, Emily Vail, MD, and her associates said at the International Symposium on Intensive Care and Emergency Medicine. The report was published simultaneously in JAMA.

The link between norepinephrine shortage and death from septic shock persisted even after the researchers accounted for numerous clinical and demographic factors (adjusted odds ratio, 1.2; 95% CI, 1.01 to 1.30; P = .03), wrote Dr Vail of Columbia University, New York.

Drug shortages are common in the United States, but few studies have explored their effects on patient outcomes. Investigators compared mortality rates among affected patients during 3-month intervals when hospitals were and were not using at least 20% less norepinephrine than baseline. The researchers used Premier Healthcare Database, which includes both standard claims and detailed, dated logs of all services billed to patients or insurance, with minimal missing data.

A total of 77% patients admitted with septic shock received norepinephrine before the shortage. During the lowest point of the shortage, 56% of patients received it, the researchers reported. Clinicians most often used phenylephrine instead, prescribing it to up to 54% of patients during the worst time of the shortage. The absolute increase in mortality during the quarters of shortage was 3.7% (95% CI, 1.5%-6.0%).

Several factors might explain the link between norepinephrine shortage and mortality, the investigators said. The vasopressors chosen to replace norepinephrine might result directly in worse outcomes, but a decrease in norepinephrine use also might be a proxy for relevant variables such as delayed use of vasopressors, lack of knowledge of how to optimally dose vasopressors besides norepinephrine, or the absence of a pharmacist dedicated to helping optimize the use of limited supplies.

The study did not uncover a dose-response association between greater decreases in norepinephrine use and increased mortality, the researchers noted. “This may be due to a threshold effect of vasopressor shortage on mortality, or lack of power due to relatively few hospital quarters at the extreme levels of vasopressor shortage,” they wrote.

Because the deaths captured included only those that occurred in-hospital, “the results may have underestimated mortality, particularly for hospitals that tend to transfer patients early to other skilled care facilities,” the researchers noted.

The cohort of patients was limited to those who received vasopressors for 2 or more days and excluded patients who died on the first day of vasopressor treatment, the researchers said.

Vail E, Gershengorn HB, Hua M, Walkey AJ, Rubenfeld G, Wunsch H. Association between US norepinephrine shortage and mortality among patients with septic shock. JAMA.  21 March 2017. [Epub ahead of print]. doi:10.1001/jama.2017.2841.

Take-Home Points

• According to the orthopedic literature, ST and LTO for a TSA produce excellent clinical outcomes, and technique selection should be based on surgeon discretion and expertise.
• Compared with the LTO approach, the ST approach produced significantly more forward elevation improvement and trended toward more external rotation and abduction and fewer revisions.
• ST and LTO approaches for a TSA result in similar Constant scores, pain scores, radiographic outcomes, and complication rates.

During total shoulder arthroplasty (TSA) exposure, the subscapularis muscle must be mobilized; its repair is crucial to the stability of the arthroplasty. The subscapularis is the largest rotator cuff muscle and has a contractile force equal to that of the other 3 muscles combined.^1,2 Traditionally it is mobilized with a tenotomy just medial to the tendon’s insertion onto the lesser tuberosity. Over the past 15 years, however, numerous authors have reported dysfunction after subscapularis tenotomy (ST). In 2003, Miller and colleagues³ reported that, at 2-year follow-up, almost 70% of patients had abnormal belly-press and liftoff tests, surrogate markers of subscapularis function. Other authors have found increased rates of anterior instability after subscapularis rupture.^4,5

In 2005, Gerber and colleagues⁶ introduced a technique for circumventing surgical division of the subscapularis. They described a lesser tuberosity osteotomy (LTO), in which the subscapularis tendon is detached with a bone fragment 5 mm to 10 mm in thickness and 3 cm to 4 cm in length. This approach was based on the premise that bone-to-bone healing is more reliable than tendon-to-tendon healing. Initial studies reported successful osteotomy healing, improved clinical outcome scores, and fewer abnormalities with belly-press and liftoff tests.^2,6 More recent literature, however, has questioned the necessity of LTO.^2,4,7-9We performed a systematic review to evaluate the literature, describe ST and LTO, and summarize the radiographic and clinical outcomes of both techniques. We hypothesized there would be no significant clinical differences between these approaches.

Methods

Search Strategy and Study Selection

Using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we systematically reviewed the literature.¹⁰ Searches were completed in September 2014 using the PubMed Medline database and the Cochrane Central Register of Clinical Trials. Two reviewers (Dr. Louie, Dr. Levy) independently performed the search and assessed eligibility of all relevant studies based on predetermined inclusion criteria. Disagreements between reviewers were resolved by discussion. Key word selection was designed to capture all English-language studies with clinical and/or radiographic outcomes and level I to IV evidence. We used an electronic search algorithm with key words and a series of NOT phrases to match certain exclusion criteria:

(((((((((((((((((((((((((((((((((((((total[Text Word]) AND shoulder[Title]) AND arthroplasty[Title] AND (English[lang]))) NOT reverse[Title/Abstract]) NOT hemiarthroplasty[Title]) NOT nonoperative[Title]) NOT nonsurgical[Title] AND (English[lang]))) NOT rheumatoid[Title/Abstract]) NOT inflammatory[Title/Abstract]) NOT elbow[Title/Abstract]) NOT wrist[Title/Abstract]) NOT hip[Title/Abstract]) NOT knee[Title/Abstract]) NOT ankle[Title/Abstract] AND (English[lang]))) NOT biomechanic[Title/Abstract]) NOT biomechanics[Title/Abstract]) NOT biomechanical [Title/Abstract]) NOT cadaveric[Title/Abstract]) NOT revision[Title]) NOT resurfacing[Title/Abstract]) NOT surface[Title/Abstract]) NOT interphalangeal[Title/Abstract] AND (English[lang]))) NOT radiostereometric[Title/Abstract] AND (English[lang]))) NOT cmc[Title/Abstract]) NOT carpometacarpal[Title/Abstract]) NOT cervical[Title/Abstract]) NOT histology[Title/Abstract]) NOT histological[Title/Abstract]) NOT collagen[Title/Abstract] AND (English[lang]))) NOT kinematic[Title/Abstract]) NOT kinematics[Title/Abstract] AND (English[lang]))) NOT vitro[Title/Abstract] AND (English[lang]))) NOT inverted[Title/Abstract]) NOT grammont[Title/Abstract]) NOT arthrodesis[Title/Abstract]) NOT fusion[Title/Abstract]) NOT reverse[Title/Abstract] AND (English[lang]))

Study exclusion criteria consisted of cadaveric, biomechanical, histologic, and kinematic results as well as analyses of nonoperative management, hemiarthroplasty, or reverse TSA. Studies were excluded if they did not report clinical and/or radiographic data. Minimum mean follow-up was 2 years. To discount the effect of other TSA technical innovations, we evaluated the same period for the 2 surgical approaches. The first study with clinical outcomes after LTO was published in early 2005,⁶ so all studies published before 2005 were excluded.

We reviewed all references within the studies included by the initial search algorithm: randomized control trials, retrospective and prospective cohort designs, case series, and treatment studies. Technical notes, review papers, letters to the editor, and level V evidence reviews were excluded. To avoid counting patients twice, we compared each study’s authors and data collection period with those of the other studies. If there was overlap in authorship, period, and place, only the study with the longer follow-up or more comprehensive data was included. All trials comparing ST and LTO were included. If the authors of a TSA study did not describe the approach used, that study was excluded from our review.

Data Extraction

We collected details of study design, sample size, and patient demographics (sex, age, hand dominance, primary diagnosis). We also abstracted surgical factors about the glenoid component (cemented vs uncemented; pegged vs keeled; all-polyethylene vs metal-backed) and the humeral component (cemented vs press-fit; stemmed vs stemless). Clinical outcomes included pain scores, functional scores, number of revisions, range of motion (ROM), and subscapularis-specific tests (eg, belly-press, liftoff). As pain scales varied between studies, all values were converted to a 10-point scoring scale (0 = no pain; 10 = maximum pain) for comparisons. Numerous functional outcome scores were reported, but the Constant score was the only one consistently used across studies, making it a good choice for comparisons. One study used Penn Shoulder Scores (PSSs) and directly compared ST and LTO groups, so its data were included. In addition, radiographic data were compiled: radiolucencies around the humeral stem and glenoid component, humeral head subluxation/migration, and osteotomy healing. The only consistent radiographic parameter available for comparisons between groups was the presence of radiolucencies.

The Modified Coleman Methodology Score (MCMS), described by Cowan and colleagues,¹¹ was used to evaluate the methodologic quality of each study. The MCMS is a 15-item instrument that has been used to assess both randomized and nonrandomized trials.^12,13 It has a scaled score ranging from 0 to 100 (85-100, excellent; 70-84, good; 55-69, fair; <55, poor). Study quality was not factored into the data synthesis analysis.

Statistical Analysis

Data are reported as weighted means and standard deviations. A mean was calculated for each study reporting on a respective data point and was then weighed according to the study sample size. The result was that the nonweighted means from studies with smaller samples did not carry as much weight as those from studies with larger samples. Student t tests and 2-way analysis of variance were used to compare the ST and LTO groups and assess differences over time (SPSS Version 18; IBM). An α of 0.05 was set as statistically significant.

Results

Twenty studies (1420 shoulders, 1392 patients) were included in the final dataset (Figure).^2,6,8,14-30 

The youngest patients in the ST and LTO groups were 22 years and 19 years of age, respectively.

Discussion

Our goal in this systematic review was to analyze outcomes associated with ST and LTO in a heterogenous TSA population. We hypothesized TSA with ST or LTO would produce similar clinical and radiographic outcomes. There were no significant differences in Constant scores, pain scores, radiolucencies, or complications between the 2 groups. The ST group showed trends toward wider ROM improvements and fewer revisions, but only the change in forward elevation was significant. The components used in the 2 groups were similar with the exception of a lack of keeled glenoids and cemented humeral stems in the LTO group; data stratification controlling for these differences revealed no change in outcomes.

The optimal method of subscapularis mobilization for TSA remains a source of debate. Jackson and colleagues²³ found significant improvements in Neer and DASH scores after ST. However, 7 of 15 patients ruptured the subscapularis after 6 months and had significantly lower DASH scores. In 2005, Gerber and colleagues⁶ first described the LTO technique as an alternative to ST. After a mean of 39 months, 89% of their patients had a negative belly-press test, and 75% had a normal liftoff test. Radiographic evaluation revealed that the osteotomized fragment had healed in an anatomical position in all shoulders. In a large case series, Small and colleagues²⁰ used radiographs and computed tomography to further investigate LTO healing rates and found that 89% of patients had bony union by 6 months and that smoking was a significant risk factor for nonunion.

Biomechanical studies comparing ST and LTO approaches have shown mixed results. Ponce and colleagues² found decreased cyclic displacement and increased maximum load to failure with LTO, but Giuseffi and colleagues³² showed less cyclic displacement with ST and no difference in load to failure. Others authors have found no significant differences in stiffness or maximum load to failure.³³ Van den Berghe and colleagues⁷ reported a higher failure rate in bone-to-bone repairs compared with tendon-to-tendon constructs. Moreover, they found that suture cut-out through bone tunnels is the primary mode of LTO failure, so many LTO surgeons now pass sutures around the humeral stem instead.

Three TSA studies directly compared ST and LTO approaches. Buckley and colleagues¹⁴ analyzed 60 TSAs and found no significant differences in WOOS, DASH, or Constant scores between groups. The authors described an ST subgroup with subscapularis attenuation on ultrasound but did not report the group as having any inferior functional outcome. Scalise and colleagues¹⁵ showed improved strength and PSSs in both groups after 2 years. However, the LTO group had a lower rate of subscapularis tears and significantly higher PSSs. Finally, Jandhyala and colleagues¹⁶ reported more favorable outcomes with LTO, which trended toward wider ROM and significantly higher belly-press test grades. Lapner and colleagues³⁴ conducted a randomized, controlled trial (often referenced) and found no significant differences between the 2 groups in terms of strength or functional outcome at 2-year follow-up. Their study, however, included hemiarthroplasties and did not substratify the TSA population, so we did not include it in our review.

Our systematic review found significantly more forward elevation improvement for the ST group than the LTO group, which may suggest improved ROM with a soft-tissue approach than a bony approach. At the same time, the ST group trended toward better passive external rotation relative to the LTO group. This trend indicates fewer constraints to external rotation in the ST group, possibly attributable to a more attenuated subscapularis after tenotomy. Subscapularis tear or attenuation was more commonly reported in the ST group than in the LTO group, though not significantly so. This may indicate that more ST studies than LTO studies specially emphasized postoperative subscapularis function, but these data also highlight some authors’ concerns regarding subscapularis dysfunction after tenotomy.^6,15,16The study populations’ complication rates were similar, just over 17%. The LTO group trended toward a higher revision rate, but it was not statistically significant. The LTO group also had significantly fewer patients with osteoarthritis and more patients with posttraumatic arthritis, so this group may have had more complex patients predisposed to a higher likelihood of revision surgery. Revisions were most commonly performed for aseptic loosening; theoretically, if osteotomies heal less effectively than tenotomies, the LTO approach could produce component instability and aseptic loosening. However, no prior studies or other clinical findings from this review suggest LTO predisposes to aseptic loosening. Overall, the uneven revision rates represent a clinical concern that should be monitored as larger samples of patients undergo ST and LTO procedures.

Glenoid radiolucencies were the only radiographic parameter consistently reported in the included studies. Twelve ST studies had radiolucency data—compared with only 2 LTO studies. Thus, our ability to compare radiographic outcomes was limited. Our data revealed similar rates of glenoid radiolucencies between the 2 approaches. The clinical relevance of radiolucencies is questioned by some authors, and, indeed, Razmjou and colleagues²⁵ found no correlation of radiolucencies with patient satisfaction. Nevertheless, early presence of radiolucencies may raise concerns about progressive loss of fixation,^35,36 so this should be monitored.

Limitations of this systematic review reflect the studies analyzed. We minimized selection bias by including level I to IV evidence, but most studies were level IV, and only 1 was level I. As such, there was a relative paucity of consistent clinical and radiographic data. For instance, although many ST studies reported patient satisfaction as an outcomes measure, only 1 LTO study commented on it. Perhaps the relative novelty of the LTO approach has prompted some authors to focus more on technical details and less on reporting a variety of outcome measures. As mentioned earlier, the significance of radiolucency data is controversial, and determination of their presence or absence depends on the observer. A radiolucency found in one study may not qualify as one in a study that uses different criteria. However, lucency data were the most frequently and reliably reported radiographic parameter, so we deemed it the most appropriate method for comparing radiographic outcomes. Finally, the baseline differences in diagnosis between the ST and LTO groups complicated comparisons. We stratified the groups by component design because use of keeled or pegged implants or humeral cemented or press-fit stems was usually a uniform feature of each study—enabling removal of certain studies for data stratification. However, we were unable to stratify by original diagnosis because these groups were not stratified within the individual studies.

Conclusion

Our systematic review found similar Constant scores, pain scores, radiographic outcomes, and complication rates for the ST and LTO approaches. Compared with the LTO approach, the ST approach produced significantly more forward elevation improvement and trended toward more external rotation and abduction and fewer revisions. Although not definitive, these data suggest the ST approach may provide more stability over the long term, but additional comprehensive studies are needed to increase the sample size and the power of the trends elucidated in this review. According to the orthopedic literature, both techniques produce excellent clinical outcomes, and technique selection should be based on surgeon discretion and expertise.

Am J Orthop. 2017;46(2):E131-E138. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Take-Home Points

• According to the orthopedic literature, ST and LTO for a TSA produce excellent clinical outcomes, and technique selection should be based on surgeon discretion and expertise.
• Compared with the LTO approach, the ST approach produced significantly more forward elevation improvement and trended toward more external rotation and abduction and fewer revisions.
• ST and LTO approaches for a TSA result in similar Constant scores, pain scores, radiographic outcomes, and complication rates.

During total shoulder arthroplasty (TSA) exposure, the subscapularis muscle must be mobilized; its repair is crucial to the stability of the arthroplasty. The subscapularis is the largest rotator cuff muscle and has a contractile force equal to that of the other 3 muscles combined.^1,2 Traditionally it is mobilized with a tenotomy just medial to the tendon’s insertion onto the lesser tuberosity. Over the past 15 years, however, numerous authors have reported dysfunction after subscapularis tenotomy (ST). In 2003, Miller and colleagues³ reported that, at 2-year follow-up, almost 70% of patients had abnormal belly-press and liftoff tests, surrogate markers of subscapularis function. Other authors have found increased rates of anterior instability after subscapularis rupture.^4,5

In 2005, Gerber and colleagues⁶ introduced a technique for circumventing surgical division of the subscapularis. They described a lesser tuberosity osteotomy (LTO), in which the subscapularis tendon is detached with a bone fragment 5 mm to 10 mm in thickness and 3 cm to 4 cm in length. This approach was based on the premise that bone-to-bone healing is more reliable than tendon-to-tendon healing. Initial studies reported successful osteotomy healing, improved clinical outcome scores, and fewer abnormalities with belly-press and liftoff tests.^2,6 More recent literature, however, has questioned the necessity of LTO.^2,4,7-9We performed a systematic review to evaluate the literature, describe ST and LTO, and summarize the radiographic and clinical outcomes of both techniques. We hypothesized there would be no significant clinical differences between these approaches.

Methods

Search Strategy and Study Selection

Using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we systematically reviewed the literature.¹⁰ Searches were completed in September 2014 using the PubMed Medline database and the Cochrane Central Register of Clinical Trials. Two reviewers (Dr. Louie, Dr. Levy) independently performed the search and assessed eligibility of all relevant studies based on predetermined inclusion criteria. Disagreements between reviewers were resolved by discussion. Key word selection was designed to capture all English-language studies with clinical and/or radiographic outcomes and level I to IV evidence. We used an electronic search algorithm with key words and a series of NOT phrases to match certain exclusion criteria:

(((((((((((((((((((((((((((((((((((((total[Text Word]) AND shoulder[Title]) AND arthroplasty[Title] AND (English[lang]))) NOT reverse[Title/Abstract]) NOT hemiarthroplasty[Title]) NOT nonoperative[Title]) NOT nonsurgical[Title] AND (English[lang]))) NOT rheumatoid[Title/Abstract]) NOT inflammatory[Title/Abstract]) NOT elbow[Title/Abstract]) NOT wrist[Title/Abstract]) NOT hip[Title/Abstract]) NOT knee[Title/Abstract]) NOT ankle[Title/Abstract] AND (English[lang]))) NOT biomechanic[Title/Abstract]) NOT biomechanics[Title/Abstract]) NOT biomechanical [Title/Abstract]) NOT cadaveric[Title/Abstract]) NOT revision[Title]) NOT resurfacing[Title/Abstract]) NOT surface[Title/Abstract]) NOT interphalangeal[Title/Abstract] AND (English[lang]))) NOT radiostereometric[Title/Abstract] AND (English[lang]))) NOT cmc[Title/Abstract]) NOT carpometacarpal[Title/Abstract]) NOT cervical[Title/Abstract]) NOT histology[Title/Abstract]) NOT histological[Title/Abstract]) NOT collagen[Title/Abstract] AND (English[lang]))) NOT kinematic[Title/Abstract]) NOT kinematics[Title/Abstract] AND (English[lang]))) NOT vitro[Title/Abstract] AND (English[lang]))) NOT inverted[Title/Abstract]) NOT grammont[Title/Abstract]) NOT arthrodesis[Title/Abstract]) NOT fusion[Title/Abstract]) NOT reverse[Title/Abstract] AND (English[lang]))

Study exclusion criteria consisted of cadaveric, biomechanical, histologic, and kinematic results as well as analyses of nonoperative management, hemiarthroplasty, or reverse TSA. Studies were excluded if they did not report clinical and/or radiographic data. Minimum mean follow-up was 2 years. To discount the effect of other TSA technical innovations, we evaluated the same period for the 2 surgical approaches. The first study with clinical outcomes after LTO was published in early 2005,⁶ so all studies published before 2005 were excluded.

We reviewed all references within the studies included by the initial search algorithm: randomized control trials, retrospective and prospective cohort designs, case series, and treatment studies. Technical notes, review papers, letters to the editor, and level V evidence reviews were excluded. To avoid counting patients twice, we compared each study’s authors and data collection period with those of the other studies. If there was overlap in authorship, period, and place, only the study with the longer follow-up or more comprehensive data was included. All trials comparing ST and LTO were included. If the authors of a TSA study did not describe the approach used, that study was excluded from our review.

Data Extraction

We collected details of study design, sample size, and patient demographics (sex, age, hand dominance, primary diagnosis). We also abstracted surgical factors about the glenoid component (cemented vs uncemented; pegged vs keeled; all-polyethylene vs metal-backed) and the humeral component (cemented vs press-fit; stemmed vs stemless). Clinical outcomes included pain scores, functional scores, number of revisions, range of motion (ROM), and subscapularis-specific tests (eg, belly-press, liftoff). As pain scales varied between studies, all values were converted to a 10-point scoring scale (0 = no pain; 10 = maximum pain) for comparisons. Numerous functional outcome scores were reported, but the Constant score was the only one consistently used across studies, making it a good choice for comparisons. One study used Penn Shoulder Scores (PSSs) and directly compared ST and LTO groups, so its data were included. In addition, radiographic data were compiled: radiolucencies around the humeral stem and glenoid component, humeral head subluxation/migration, and osteotomy healing. The only consistent radiographic parameter available for comparisons between groups was the presence of radiolucencies.

The Modified Coleman Methodology Score (MCMS), described by Cowan and colleagues,¹¹ was used to evaluate the methodologic quality of each study. The MCMS is a 15-item instrument that has been used to assess both randomized and nonrandomized trials.^12,13 It has a scaled score ranging from 0 to 100 (85-100, excellent; 70-84, good; 55-69, fair; <55, poor). Study quality was not factored into the data synthesis analysis.

Statistical Analysis

Data are reported as weighted means and standard deviations. A mean was calculated for each study reporting on a respective data point and was then weighed according to the study sample size. The result was that the nonweighted means from studies with smaller samples did not carry as much weight as those from studies with larger samples. Student t tests and 2-way analysis of variance were used to compare the ST and LTO groups and assess differences over time (SPSS Version 18; IBM). An α of 0.05 was set as statistically significant.

Results

Twenty studies (1420 shoulders, 1392 patients) were included in the final dataset (Figure).^2,6,8,14-30 

The youngest patients in the ST and LTO groups were 22 years and 19 years of age, respectively.

Discussion

Our goal in this systematic review was to analyze outcomes associated with ST and LTO in a heterogenous TSA population. We hypothesized TSA with ST or LTO would produce similar clinical and radiographic outcomes. There were no significant differences in Constant scores, pain scores, radiolucencies, or complications between the 2 groups. The ST group showed trends toward wider ROM improvements and fewer revisions, but only the change in forward elevation was significant. The components used in the 2 groups were similar with the exception of a lack of keeled glenoids and cemented humeral stems in the LTO group; data stratification controlling for these differences revealed no change in outcomes.

The optimal method of subscapularis mobilization for TSA remains a source of debate. Jackson and colleagues²³ found significant improvements in Neer and DASH scores after ST. However, 7 of 15 patients ruptured the subscapularis after 6 months and had significantly lower DASH scores. In 2005, Gerber and colleagues⁶ first described the LTO technique as an alternative to ST. After a mean of 39 months, 89% of their patients had a negative belly-press test, and 75% had a normal liftoff test. Radiographic evaluation revealed that the osteotomized fragment had healed in an anatomical position in all shoulders. In a large case series, Small and colleagues²⁰ used radiographs and computed tomography to further investigate LTO healing rates and found that 89% of patients had bony union by 6 months and that smoking was a significant risk factor for nonunion.

Biomechanical studies comparing ST and LTO approaches have shown mixed results. Ponce and colleagues² found decreased cyclic displacement and increased maximum load to failure with LTO, but Giuseffi and colleagues³² showed less cyclic displacement with ST and no difference in load to failure. Others authors have found no significant differences in stiffness or maximum load to failure.³³ Van den Berghe and colleagues⁷ reported a higher failure rate in bone-to-bone repairs compared with tendon-to-tendon constructs. Moreover, they found that suture cut-out through bone tunnels is the primary mode of LTO failure, so many LTO surgeons now pass sutures around the humeral stem instead.

Three TSA studies directly compared ST and LTO approaches. Buckley and colleagues¹⁴ analyzed 60 TSAs and found no significant differences in WOOS, DASH, or Constant scores between groups. The authors described an ST subgroup with subscapularis attenuation on ultrasound but did not report the group as having any inferior functional outcome. Scalise and colleagues¹⁵ showed improved strength and PSSs in both groups after 2 years. However, the LTO group had a lower rate of subscapularis tears and significantly higher PSSs. Finally, Jandhyala and colleagues¹⁶ reported more favorable outcomes with LTO, which trended toward wider ROM and significantly higher belly-press test grades. Lapner and colleagues³⁴ conducted a randomized, controlled trial (often referenced) and found no significant differences between the 2 groups in terms of strength or functional outcome at 2-year follow-up. Their study, however, included hemiarthroplasties and did not substratify the TSA population, so we did not include it in our review.

Our systematic review found significantly more forward elevation improvement for the ST group than the LTO group, which may suggest improved ROM with a soft-tissue approach than a bony approach. At the same time, the ST group trended toward better passive external rotation relative to the LTO group. This trend indicates fewer constraints to external rotation in the ST group, possibly attributable to a more attenuated subscapularis after tenotomy. Subscapularis tear or attenuation was more commonly reported in the ST group than in the LTO group, though not significantly so. This may indicate that more ST studies than LTO studies specially emphasized postoperative subscapularis function, but these data also highlight some authors’ concerns regarding subscapularis dysfunction after tenotomy.^6,15,16The study populations’ complication rates were similar, just over 17%. The LTO group trended toward a higher revision rate, but it was not statistically significant. The LTO group also had significantly fewer patients with osteoarthritis and more patients with posttraumatic arthritis, so this group may have had more complex patients predisposed to a higher likelihood of revision surgery. Revisions were most commonly performed for aseptic loosening; theoretically, if osteotomies heal less effectively than tenotomies, the LTO approach could produce component instability and aseptic loosening. However, no prior studies or other clinical findings from this review suggest LTO predisposes to aseptic loosening. Overall, the uneven revision rates represent a clinical concern that should be monitored as larger samples of patients undergo ST and LTO procedures.

Glenoid radiolucencies were the only radiographic parameter consistently reported in the included studies. Twelve ST studies had radiolucency data—compared with only 2 LTO studies. Thus, our ability to compare radiographic outcomes was limited. Our data revealed similar rates of glenoid radiolucencies between the 2 approaches. The clinical relevance of radiolucencies is questioned by some authors, and, indeed, Razmjou and colleagues²⁵ found no correlation of radiolucencies with patient satisfaction. Nevertheless, early presence of radiolucencies may raise concerns about progressive loss of fixation,^35,36 so this should be monitored.

Limitations of this systematic review reflect the studies analyzed. We minimized selection bias by including level I to IV evidence, but most studies were level IV, and only 1 was level I. As such, there was a relative paucity of consistent clinical and radiographic data. For instance, although many ST studies reported patient satisfaction as an outcomes measure, only 1 LTO study commented on it. Perhaps the relative novelty of the LTO approach has prompted some authors to focus more on technical details and less on reporting a variety of outcome measures. As mentioned earlier, the significance of radiolucency data is controversial, and determination of their presence or absence depends on the observer. A radiolucency found in one study may not qualify as one in a study that uses different criteria. However, lucency data were the most frequently and reliably reported radiographic parameter, so we deemed it the most appropriate method for comparing radiographic outcomes. Finally, the baseline differences in diagnosis between the ST and LTO groups complicated comparisons. We stratified the groups by component design because use of keeled or pegged implants or humeral cemented or press-fit stems was usually a uniform feature of each study—enabling removal of certain studies for data stratification. However, we were unable to stratify by original diagnosis because these groups were not stratified within the individual studies.

Conclusion

Our systematic review found similar Constant scores, pain scores, radiographic outcomes, and complication rates for the ST and LTO approaches. Compared with the LTO approach, the ST approach produced significantly more forward elevation improvement and trended toward more external rotation and abduction and fewer revisions. Although not definitive, these data suggest the ST approach may provide more stability over the long term, but additional comprehensive studies are needed to increase the sample size and the power of the trends elucidated in this review. According to the orthopedic literature, both techniques produce excellent clinical outcomes, and technique selection should be based on surgeon discretion and expertise.

Am J Orthop. 2017;46(2):E131-E138. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Take-Home Points

• According to the orthopedic literature, ST and LTO for a TSA produce excellent clinical outcomes, and technique selection should be based on surgeon discretion and expertise.
• Compared with the LTO approach, the ST approach produced significantly more forward elevation improvement and trended toward more external rotation and abduction and fewer revisions.
• ST and LTO approaches for a TSA result in similar Constant scores, pain scores, radiographic outcomes, and complication rates.

During total shoulder arthroplasty (TSA) exposure, the subscapularis muscle must be mobilized; its repair is crucial to the stability of the arthroplasty. The subscapularis is the largest rotator cuff muscle and has a contractile force equal to that of the other 3 muscles combined.^1,2 Traditionally it is mobilized with a tenotomy just medial to the tendon’s insertion onto the lesser tuberosity. Over the past 15 years, however, numerous authors have reported dysfunction after subscapularis tenotomy (ST). In 2003, Miller and colleagues³ reported that, at 2-year follow-up, almost 70% of patients had abnormal belly-press and liftoff tests, surrogate markers of subscapularis function. Other authors have found increased rates of anterior instability after subscapularis rupture.^4,5

In 2005, Gerber and colleagues⁶ introduced a technique for circumventing surgical division of the subscapularis. They described a lesser tuberosity osteotomy (LTO), in which the subscapularis tendon is detached with a bone fragment 5 mm to 10 mm in thickness and 3 cm to 4 cm in length. This approach was based on the premise that bone-to-bone healing is more reliable than tendon-to-tendon healing. Initial studies reported successful osteotomy healing, improved clinical outcome scores, and fewer abnormalities with belly-press and liftoff tests.^2,6 More recent literature, however, has questioned the necessity of LTO.^2,4,7-9We performed a systematic review to evaluate the literature, describe ST and LTO, and summarize the radiographic and clinical outcomes of both techniques. We hypothesized there would be no significant clinical differences between these approaches.

Methods

Search Strategy and Study Selection

Using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we systematically reviewed the literature.¹⁰ Searches were completed in September 2014 using the PubMed Medline database and the Cochrane Central Register of Clinical Trials. Two reviewers (Dr. Louie, Dr. Levy) independently performed the search and assessed eligibility of all relevant studies based on predetermined inclusion criteria. Disagreements between reviewers were resolved by discussion. Key word selection was designed to capture all English-language studies with clinical and/or radiographic outcomes and level I to IV evidence. We used an electronic search algorithm with key words and a series of NOT phrases to match certain exclusion criteria:

(((((((((((((((((((((((((((((((((((((total[Text Word]) AND shoulder[Title]) AND arthroplasty[Title] AND (English[lang]))) NOT reverse[Title/Abstract]) NOT hemiarthroplasty[Title]) NOT nonoperative[Title]) NOT nonsurgical[Title] AND (English[lang]))) NOT rheumatoid[Title/Abstract]) NOT inflammatory[Title/Abstract]) NOT elbow[Title/Abstract]) NOT wrist[Title/Abstract]) NOT hip[Title/Abstract]) NOT knee[Title/Abstract]) NOT ankle[Title/Abstract] AND (English[lang]))) NOT biomechanic[Title/Abstract]) NOT biomechanics[Title/Abstract]) NOT biomechanical [Title/Abstract]) NOT cadaveric[Title/Abstract]) NOT revision[Title]) NOT resurfacing[Title/Abstract]) NOT surface[Title/Abstract]) NOT interphalangeal[Title/Abstract] AND (English[lang]))) NOT radiostereometric[Title/Abstract] AND (English[lang]))) NOT cmc[Title/Abstract]) NOT carpometacarpal[Title/Abstract]) NOT cervical[Title/Abstract]) NOT histology[Title/Abstract]) NOT histological[Title/Abstract]) NOT collagen[Title/Abstract] AND (English[lang]))) NOT kinematic[Title/Abstract]) NOT kinematics[Title/Abstract] AND (English[lang]))) NOT vitro[Title/Abstract] AND (English[lang]))) NOT inverted[Title/Abstract]) NOT grammont[Title/Abstract]) NOT arthrodesis[Title/Abstract]) NOT fusion[Title/Abstract]) NOT reverse[Title/Abstract] AND (English[lang]))

Study exclusion criteria consisted of cadaveric, biomechanical, histologic, and kinematic results as well as analyses of nonoperative management, hemiarthroplasty, or reverse TSA. Studies were excluded if they did not report clinical and/or radiographic data. Minimum mean follow-up was 2 years. To discount the effect of other TSA technical innovations, we evaluated the same period for the 2 surgical approaches. The first study with clinical outcomes after LTO was published in early 2005,⁶ so all studies published before 2005 were excluded.

We reviewed all references within the studies included by the initial search algorithm: randomized control trials, retrospective and prospective cohort designs, case series, and treatment studies. Technical notes, review papers, letters to the editor, and level V evidence reviews were excluded. To avoid counting patients twice, we compared each study’s authors and data collection period with those of the other studies. If there was overlap in authorship, period, and place, only the study with the longer follow-up or more comprehensive data was included. All trials comparing ST and LTO were included. If the authors of a TSA study did not describe the approach used, that study was excluded from our review.

Data Extraction

We collected details of study design, sample size, and patient demographics (sex, age, hand dominance, primary diagnosis). We also abstracted surgical factors about the glenoid component (cemented vs uncemented; pegged vs keeled; all-polyethylene vs metal-backed) and the humeral component (cemented vs press-fit; stemmed vs stemless). Clinical outcomes included pain scores, functional scores, number of revisions, range of motion (ROM), and subscapularis-specific tests (eg, belly-press, liftoff). As pain scales varied between studies, all values were converted to a 10-point scoring scale (0 = no pain; 10 = maximum pain) for comparisons. Numerous functional outcome scores were reported, but the Constant score was the only one consistently used across studies, making it a good choice for comparisons. One study used Penn Shoulder Scores (PSSs) and directly compared ST and LTO groups, so its data were included. In addition, radiographic data were compiled: radiolucencies around the humeral stem and glenoid component, humeral head subluxation/migration, and osteotomy healing. The only consistent radiographic parameter available for comparisons between groups was the presence of radiolucencies.

The Modified Coleman Methodology Score (MCMS), described by Cowan and colleagues,¹¹ was used to evaluate the methodologic quality of each study. The MCMS is a 15-item instrument that has been used to assess both randomized and nonrandomized trials.^12,13 It has a scaled score ranging from 0 to 100 (85-100, excellent; 70-84, good; 55-69, fair; <55, poor). Study quality was not factored into the data synthesis analysis.

Statistical Analysis

Data are reported as weighted means and standard deviations. A mean was calculated for each study reporting on a respective data point and was then weighed according to the study sample size. The result was that the nonweighted means from studies with smaller samples did not carry as much weight as those from studies with larger samples. Student t tests and 2-way analysis of variance were used to compare the ST and LTO groups and assess differences over time (SPSS Version 18; IBM). An α of 0.05 was set as statistically significant.

Results

Twenty studies (1420 shoulders, 1392 patients) were included in the final dataset (Figure).^2,6,8,14-30 

The youngest patients in the ST and LTO groups were 22 years and 19 years of age, respectively.

Discussion

Our goal in this systematic review was to analyze outcomes associated with ST and LTO in a heterogenous TSA population. We hypothesized TSA with ST or LTO would produce similar clinical and radiographic outcomes. There were no significant differences in Constant scores, pain scores, radiolucencies, or complications between the 2 groups. The ST group showed trends toward wider ROM improvements and fewer revisions, but only the change in forward elevation was significant. The components used in the 2 groups were similar with the exception of a lack of keeled glenoids and cemented humeral stems in the LTO group; data stratification controlling for these differences revealed no change in outcomes.

The optimal method of subscapularis mobilization for TSA remains a source of debate. Jackson and colleagues²³ found significant improvements in Neer and DASH scores after ST. However, 7 of 15 patients ruptured the subscapularis after 6 months and had significantly lower DASH scores. In 2005, Gerber and colleagues⁶ first described the LTO technique as an alternative to ST. After a mean of 39 months, 89% of their patients had a negative belly-press test, and 75% had a normal liftoff test. Radiographic evaluation revealed that the osteotomized fragment had healed in an anatomical position in all shoulders. In a large case series, Small and colleagues²⁰ used radiographs and computed tomography to further investigate LTO healing rates and found that 89% of patients had bony union by 6 months and that smoking was a significant risk factor for nonunion.

Biomechanical studies comparing ST and LTO approaches have shown mixed results. Ponce and colleagues² found decreased cyclic displacement and increased maximum load to failure with LTO, but Giuseffi and colleagues³² showed less cyclic displacement with ST and no difference in load to failure. Others authors have found no significant differences in stiffness or maximum load to failure.³³ Van den Berghe and colleagues⁷ reported a higher failure rate in bone-to-bone repairs compared with tendon-to-tendon constructs. Moreover, they found that suture cut-out through bone tunnels is the primary mode of LTO failure, so many LTO surgeons now pass sutures around the humeral stem instead.

Three TSA studies directly compared ST and LTO approaches. Buckley and colleagues¹⁴ analyzed 60 TSAs and found no significant differences in WOOS, DASH, or Constant scores between groups. The authors described an ST subgroup with subscapularis attenuation on ultrasound but did not report the group as having any inferior functional outcome. Scalise and colleagues¹⁵ showed improved strength and PSSs in both groups after 2 years. However, the LTO group had a lower rate of subscapularis tears and significantly higher PSSs. Finally, Jandhyala and colleagues¹⁶ reported more favorable outcomes with LTO, which trended toward wider ROM and significantly higher belly-press test grades. Lapner and colleagues³⁴ conducted a randomized, controlled trial (often referenced) and found no significant differences between the 2 groups in terms of strength or functional outcome at 2-year follow-up. Their study, however, included hemiarthroplasties and did not substratify the TSA population, so we did not include it in our review.

Our systematic review found significantly more forward elevation improvement for the ST group than the LTO group, which may suggest improved ROM with a soft-tissue approach than a bony approach. At the same time, the ST group trended toward better passive external rotation relative to the LTO group. This trend indicates fewer constraints to external rotation in the ST group, possibly attributable to a more attenuated subscapularis after tenotomy. Subscapularis tear or attenuation was more commonly reported in the ST group than in the LTO group, though not significantly so. This may indicate that more ST studies than LTO studies specially emphasized postoperative subscapularis function, but these data also highlight some authors’ concerns regarding subscapularis dysfunction after tenotomy.^6,15,16The study populations’ complication rates were similar, just over 17%. The LTO group trended toward a higher revision rate, but it was not statistically significant. The LTO group also had significantly fewer patients with osteoarthritis and more patients with posttraumatic arthritis, so this group may have had more complex patients predisposed to a higher likelihood of revision surgery. Revisions were most commonly performed for aseptic loosening; theoretically, if osteotomies heal less effectively than tenotomies, the LTO approach could produce component instability and aseptic loosening. However, no prior studies or other clinical findings from this review suggest LTO predisposes to aseptic loosening. Overall, the uneven revision rates represent a clinical concern that should be monitored as larger samples of patients undergo ST and LTO procedures.

Glenoid radiolucencies were the only radiographic parameter consistently reported in the included studies. Twelve ST studies had radiolucency data—compared with only 2 LTO studies. Thus, our ability to compare radiographic outcomes was limited. Our data revealed similar rates of glenoid radiolucencies between the 2 approaches. The clinical relevance of radiolucencies is questioned by some authors, and, indeed, Razmjou and colleagues²⁵ found no correlation of radiolucencies with patient satisfaction. Nevertheless, early presence of radiolucencies may raise concerns about progressive loss of fixation,^35,36 so this should be monitored.

Limitations of this systematic review reflect the studies analyzed. We minimized selection bias by including level I to IV evidence, but most studies were level IV, and only 1 was level I. As such, there was a relative paucity of consistent clinical and radiographic data. For instance, although many ST studies reported patient satisfaction as an outcomes measure, only 1 LTO study commented on it. Perhaps the relative novelty of the LTO approach has prompted some authors to focus more on technical details and less on reporting a variety of outcome measures. As mentioned earlier, the significance of radiolucency data is controversial, and determination of their presence or absence depends on the observer. A radiolucency found in one study may not qualify as one in a study that uses different criteria. However, lucency data were the most frequently and reliably reported radiographic parameter, so we deemed it the most appropriate method for comparing radiographic outcomes. Finally, the baseline differences in diagnosis between the ST and LTO groups complicated comparisons. We stratified the groups by component design because use of keeled or pegged implants or humeral cemented or press-fit stems was usually a uniform feature of each study—enabling removal of certain studies for data stratification. However, we were unable to stratify by original diagnosis because these groups were not stratified within the individual studies.

Conclusion

Our systematic review found similar Constant scores, pain scores, radiographic outcomes, and complication rates for the ST and LTO approaches. Compared with the LTO approach, the ST approach produced significantly more forward elevation improvement and trended toward more external rotation and abduction and fewer revisions. Although not definitive, these data suggest the ST approach may provide more stability over the long term, but additional comprehensive studies are needed to increase the sample size and the power of the trends elucidated in this review. According to the orthopedic literature, both techniques produce excellent clinical outcomes, and technique selection should be based on surgeon discretion and expertise.

Am J Orthop. 2017;46(2):E131-E138. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Two issues of emerging importance are being addressed in the literature: caring for patients with obesity and the concept of delivering value-based care. Value-based care does not mean providing the cheapest care; “value” places importance on quality as well as cost. In this Update, we present 3 practices that the evidence says will deliver value:

• endometrial biopsy in all obese women. Although performing more endometrial biopsies in younger women with a body mass index (BMI) in the obese range will not be less expensive initially, the procedure’s value likely will be in early diagnosis, which hopefully will translate to eventual health care system savings.
• use of the levonorgestrel-releasing intrauterine device (LNG-IUD) in obese patients experiencing abnormal uterine bleeding (AUB). This practice appears to add value in the context of AUB.
• performance of routine diagnostic hysteroscopy in the office setting. We should reconsider our current habits and traditions of performing routine diagnostic hysteroscopy in the operating room (OR) as we move toward providing value-based care.

Read about obesity as a risk factor for endometrial hyperplasia

Endometrial sampling and obesity: Forget the "age 45" rule 

Wise MR, Gill P, Lensen S, Thompson JM, Farquhar CM. Body mass index trumps age in decision for endometrial biopsy: cohort study of symptomatic premenopausal women. Am J Obstet Gynecol. 2016;215(5):598.e1-e8.

How do we bring more value to our patients with AUB? We are well aware that heavy menstrual bleeding places a burden on many women; AUB affects 30% of those of reproductive age. The condition often results in lost workdays and diminished quality of life. It also is associated with significant cost expenditures for hygiene products. It is important not only to bring value to women with heavy menstrual bleeding but also to consider our increasingly expensive health care system.

Obesity is a significant problem that likely will increase the number of women presenting with AUB to ObGyns. Recent studies from New Zealand--which has 33% of its population classified as obese--have provided valuable information.¹

Photo: Shutterstock

Obesity is a risk factor for endometrial hyperplasia

In a large retrospective cohort study, Wise and colleagues analyzed data from 916 premenopausal women referred for AUB who had an endometrial biopsy from 2008 to 2014. The setting was a single large urban secondary women's health service in New Zealand. This study challenges the concept of age-related biopsy guidelines.

Of the 916 women, half were obese. Almost 5% of the women had complex endometrial hyperplasia with atypia or cancer. This incidence had risen from 3% in the years 1995 to 1997, likely due to the rising incidence of obesity. Women with a BMI ≥30 kg/m2 were 4 times more likely to develop complex hyperplasia or cancer than normal-weight women.

Other factors associated with an increased risk for complex hyperplasia or cancer were nulliparity (odds ratio [OR], 2.51; 95% confidence interval [CI], 1.25-5.05), anemia (OR, 2.38; 95% CI, 1.25-4.56), and a thickened endometrium on ultrasonography (defined as >12 mm; OR, 4.04; 95% CI, 1.69-9.65). Age was not a significant risk factor in this group.  

Read about using LNG-IUD to treat AUB in obese women

Small study shows LNG-IUD is effective for treating heavy menstrual bleeding in obese patients

Shaw V, Vandal AC, Coomarasamy C, Ekeroma AJ. The effectiveness of the levonorgestrel intrauterine system in obese women with heavy menstrual bleeding. Aust N Z J Obstet Gynaecol. 2016;56(6):619-623.

In another recent study from New Zealand, researchers set out to assess the efficacy of the LNG-IUD for the treatment of heavy menstrual bleeding in obese women. This study is important because there are very few studies of the LNG-IUD in the obese population, and none that have studied quality-of-life measures. 

Shaw and colleagues conducted the prospective observational study at a tertiary teaching hospital. Twenty obese (BMI >30 kg/m2) women with heavy menstrual bleeding agreed to treatment with an LNG-IUD, and 14 completed the study (2 had a device expulsion, 1 had a device removed for pain, and 1 had a device removed for infection; 2 were lost to follow-up). The women were aged 27 to 52 years (median, 40.5 years), and their BMI ranged from 30 to 68 kg/m2 (median, 40.6 kg/m2). At recruitment, 6 months, and 12 months, participants completed the Menstrual Impact Questionnaire and the Pictorial Bleeding Assessment Chart--2 validated tools.

Photo: Shutterstock

Compared with baseline Pictorial Bleeding Assessment scores, the authors found the LNG-IUD to be effective in 73.2% (95% CI, 55.3%-83.9%) of women at 6 months and in 92.8% (95% CI, 80.0%-97.4%) of women at 12 months. Taking into consideration device failures, including removed and expelled LNG-IUDs (which occurred in 4 women, or 20%, in the intent-to-treat analysis), the actual efficacy rate was 67%. Similarly, there was significant improvement at 6 and 12 months in Menstrual Impact Questionnaire scores for social activities, work performance, tiredness, productivity, hygiene,  and depression.

Read about doing more diagnostic hysteroscopy in the office

Is it time to abandon diagnostic hysteroscopy in the OR?

Leung S, Leyland N, Murji A. Decreasing diagnostic hysteroscopy performed in the operating room: a quality improvement initiative. J Obstet Gynaecol Can. 2016;38(4):351-356.

Diagnostic hysteroscopy: Are we stuck in the 1990s? Why are we still performing so many diagnostic hysteroscopies in the OR, thus subjecting our patients to general anesthesia and using our precious OR time? That is the question asked by a group of researchers in Canada. 

According to data from the Ontario Ministry of Health and Long Term Care, diagnostic hysteroscopy was performed 10,027 times in the 2013-2014 fiscal year. Ontario researchers designed and implemented a quality improvement initiative at their institution and successfully decreased the number of diagnostic hysteroscopies performed in their hospital by 70% from their baseline 12-month period. The improvements resulted in a savings of 78 hours of case costing, or $126,984. When these data are extrapolated to the Ontario population (in which more than  10,000 diagnostic hysteroscopies were performed), potentially 7,000 women could avoid the risk of general anesthesia and the health care system could save $11 million. 

Re-education protocol was key to reducing OR procedures

How did the researchers accomplish their results? The multifaceted intervention had  3 key components:

Staff education and review. Many surgeons were performing diagnostic hysteroscopy in the OR because that is how they were trained, and they were unaware of less invasive options. An awareness campaign was conducted by e-mail, during staff meetings, and at rounds. 

Accessible sonohysterography. This diagnostic modality was made more accessible to referring physicians in a timely manner.

Initiation of an operative hysteroscopy education program. To allow more surgeons greater comfort with office hysteroscopy, the authors instituted didactic sessions, dry and wet lab simulations, and mentorship.  

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.

Two issues of emerging importance are being addressed in the literature: caring for patients with obesity and the concept of delivering value-based care. Value-based care does not mean providing the cheapest care; “value” places importance on quality as well as cost. In this Update, we present 3 practices that the evidence says will deliver value:

• endometrial biopsy in all obese women. Although performing more endometrial biopsies in younger women with a body mass index (BMI) in the obese range will not be less expensive initially, the procedure’s value likely will be in early diagnosis, which hopefully will translate to eventual health care system savings.
• use of the levonorgestrel-releasing intrauterine device (LNG-IUD) in obese patients experiencing abnormal uterine bleeding (AUB). This practice appears to add value in the context of AUB.
• performance of routine diagnostic hysteroscopy in the office setting. We should reconsider our current habits and traditions of performing routine diagnostic hysteroscopy in the operating room (OR) as we move toward providing value-based care.

Read about obesity as a risk factor for endometrial hyperplasia

Endometrial sampling and obesity: Forget the "age 45" rule 

Wise MR, Gill P, Lensen S, Thompson JM, Farquhar CM. Body mass index trumps age in decision for endometrial biopsy: cohort study of symptomatic premenopausal women. Am J Obstet Gynecol. 2016;215(5):598.e1-e8.

How do we bring more value to our patients with AUB? We are well aware that heavy menstrual bleeding places a burden on many women; AUB affects 30% of those of reproductive age. The condition often results in lost workdays and diminished quality of life. It also is associated with significant cost expenditures for hygiene products. It is important not only to bring value to women with heavy menstrual bleeding but also to consider our increasingly expensive health care system.

Obesity is a significant problem that likely will increase the number of women presenting with AUB to ObGyns. Recent studies from New Zealand--which has 33% of its population classified as obese--have provided valuable information.¹

Photo: Shutterstock

Obesity is a risk factor for endometrial hyperplasia

In a large retrospective cohort study, Wise and colleagues analyzed data from 916 premenopausal women referred for AUB who had an endometrial biopsy from 2008 to 2014. The setting was a single large urban secondary women's health service in New Zealand. This study challenges the concept of age-related biopsy guidelines.

Of the 916 women, half were obese. Almost 5% of the women had complex endometrial hyperplasia with atypia or cancer. This incidence had risen from 3% in the years 1995 to 1997, likely due to the rising incidence of obesity. Women with a BMI ≥30 kg/m2 were 4 times more likely to develop complex hyperplasia or cancer than normal-weight women.

Other factors associated with an increased risk for complex hyperplasia or cancer were nulliparity (odds ratio [OR], 2.51; 95% confidence interval [CI], 1.25-5.05), anemia (OR, 2.38; 95% CI, 1.25-4.56), and a thickened endometrium on ultrasonography (defined as >12 mm; OR, 4.04; 95% CI, 1.69-9.65). Age was not a significant risk factor in this group.  

Read about using LNG-IUD to treat AUB in obese women

Small study shows LNG-IUD is effective for treating heavy menstrual bleeding in obese patients

Shaw V, Vandal AC, Coomarasamy C, Ekeroma AJ. The effectiveness of the levonorgestrel intrauterine system in obese women with heavy menstrual bleeding. Aust N Z J Obstet Gynaecol. 2016;56(6):619-623.

In another recent study from New Zealand, researchers set out to assess the efficacy of the LNG-IUD for the treatment of heavy menstrual bleeding in obese women. This study is important because there are very few studies of the LNG-IUD in the obese population, and none that have studied quality-of-life measures. 

Shaw and colleagues conducted the prospective observational study at a tertiary teaching hospital. Twenty obese (BMI >30 kg/m2) women with heavy menstrual bleeding agreed to treatment with an LNG-IUD, and 14 completed the study (2 had a device expulsion, 1 had a device removed for pain, and 1 had a device removed for infection; 2 were lost to follow-up). The women were aged 27 to 52 years (median, 40.5 years), and their BMI ranged from 30 to 68 kg/m2 (median, 40.6 kg/m2). At recruitment, 6 months, and 12 months, participants completed the Menstrual Impact Questionnaire and the Pictorial Bleeding Assessment Chart--2 validated tools.

Photo: Shutterstock

Compared with baseline Pictorial Bleeding Assessment scores, the authors found the LNG-IUD to be effective in 73.2% (95% CI, 55.3%-83.9%) of women at 6 months and in 92.8% (95% CI, 80.0%-97.4%) of women at 12 months. Taking into consideration device failures, including removed and expelled LNG-IUDs (which occurred in 4 women, or 20%, in the intent-to-treat analysis), the actual efficacy rate was 67%. Similarly, there was significant improvement at 6 and 12 months in Menstrual Impact Questionnaire scores for social activities, work performance, tiredness, productivity, hygiene,  and depression.

Read about doing more diagnostic hysteroscopy in the office

Is it time to abandon diagnostic hysteroscopy in the OR?

Leung S, Leyland N, Murji A. Decreasing diagnostic hysteroscopy performed in the operating room: a quality improvement initiative. J Obstet Gynaecol Can. 2016;38(4):351-356.

Diagnostic hysteroscopy: Are we stuck in the 1990s? Why are we still performing so many diagnostic hysteroscopies in the OR, thus subjecting our patients to general anesthesia and using our precious OR time? That is the question asked by a group of researchers in Canada. 

According to data from the Ontario Ministry of Health and Long Term Care, diagnostic hysteroscopy was performed 10,027 times in the 2013-2014 fiscal year. Ontario researchers designed and implemented a quality improvement initiative at their institution and successfully decreased the number of diagnostic hysteroscopies performed in their hospital by 70% from their baseline 12-month period. The improvements resulted in a savings of 78 hours of case costing, or $126,984. When these data are extrapolated to the Ontario population (in which more than  10,000 diagnostic hysteroscopies were performed), potentially 7,000 women could avoid the risk of general anesthesia and the health care system could save $11 million. 

Re-education protocol was key to reducing OR procedures

How did the researchers accomplish their results? The multifaceted intervention had  3 key components:

Staff education and review. Many surgeons were performing diagnostic hysteroscopy in the OR because that is how they were trained, and they were unaware of less invasive options. An awareness campaign was conducted by e-mail, during staff meetings, and at rounds. 

Accessible sonohysterography. This diagnostic modality was made more accessible to referring physicians in a timely manner.

Initiation of an operative hysteroscopy education program. To allow more surgeons greater comfort with office hysteroscopy, the authors instituted didactic sessions, dry and wet lab simulations, and mentorship.  

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.

Two issues of emerging importance are being addressed in the literature: caring for patients with obesity and the concept of delivering value-based care. Value-based care does not mean providing the cheapest care; “value” places importance on quality as well as cost. In this Update, we present 3 practices that the evidence says will deliver value:

• endometrial biopsy in all obese women. Although performing more endometrial biopsies in younger women with a body mass index (BMI) in the obese range will not be less expensive initially, the procedure’s value likely will be in early diagnosis, which hopefully will translate to eventual health care system savings.
• use of the levonorgestrel-releasing intrauterine device (LNG-IUD) in obese patients experiencing abnormal uterine bleeding (AUB). This practice appears to add value in the context of AUB.
• performance of routine diagnostic hysteroscopy in the office setting. We should reconsider our current habits and traditions of performing routine diagnostic hysteroscopy in the operating room (OR) as we move toward providing value-based care.

Read about obesity as a risk factor for endometrial hyperplasia

Endometrial sampling and obesity: Forget the "age 45" rule 

Wise MR, Gill P, Lensen S, Thompson JM, Farquhar CM. Body mass index trumps age in decision for endometrial biopsy: cohort study of symptomatic premenopausal women. Am J Obstet Gynecol. 2016;215(5):598.e1-e8.

How do we bring more value to our patients with AUB? We are well aware that heavy menstrual bleeding places a burden on many women; AUB affects 30% of those of reproductive age. The condition often results in lost workdays and diminished quality of life. It also is associated with significant cost expenditures for hygiene products. It is important not only to bring value to women with heavy menstrual bleeding but also to consider our increasingly expensive health care system.

Obesity is a significant problem that likely will increase the number of women presenting with AUB to ObGyns. Recent studies from New Zealand--which has 33% of its population classified as obese--have provided valuable information.¹

Photo: Shutterstock

Obesity is a risk factor for endometrial hyperplasia

In a large retrospective cohort study, Wise and colleagues analyzed data from 916 premenopausal women referred for AUB who had an endometrial biopsy from 2008 to 2014. The setting was a single large urban secondary women's health service in New Zealand. This study challenges the concept of age-related biopsy guidelines.

Of the 916 women, half were obese. Almost 5% of the women had complex endometrial hyperplasia with atypia or cancer. This incidence had risen from 3% in the years 1995 to 1997, likely due to the rising incidence of obesity. Women with a BMI ≥30 kg/m2 were 4 times more likely to develop complex hyperplasia or cancer than normal-weight women.

Other factors associated with an increased risk for complex hyperplasia or cancer were nulliparity (odds ratio [OR], 2.51; 95% confidence interval [CI], 1.25-5.05), anemia (OR, 2.38; 95% CI, 1.25-4.56), and a thickened endometrium on ultrasonography (defined as >12 mm; OR, 4.04; 95% CI, 1.69-9.65). Age was not a significant risk factor in this group.  

Read about using LNG-IUD to treat AUB in obese women

Small study shows LNG-IUD is effective for treating heavy menstrual bleeding in obese patients

Shaw V, Vandal AC, Coomarasamy C, Ekeroma AJ. The effectiveness of the levonorgestrel intrauterine system in obese women with heavy menstrual bleeding. Aust N Z J Obstet Gynaecol. 2016;56(6):619-623.

In another recent study from New Zealand, researchers set out to assess the efficacy of the LNG-IUD for the treatment of heavy menstrual bleeding in obese women. This study is important because there are very few studies of the LNG-IUD in the obese population, and none that have studied quality-of-life measures. 

Shaw and colleagues conducted the prospective observational study at a tertiary teaching hospital. Twenty obese (BMI >30 kg/m2) women with heavy menstrual bleeding agreed to treatment with an LNG-IUD, and 14 completed the study (2 had a device expulsion, 1 had a device removed for pain, and 1 had a device removed for infection; 2 were lost to follow-up). The women were aged 27 to 52 years (median, 40.5 years), and their BMI ranged from 30 to 68 kg/m2 (median, 40.6 kg/m2). At recruitment, 6 months, and 12 months, participants completed the Menstrual Impact Questionnaire and the Pictorial Bleeding Assessment Chart--2 validated tools.

Photo: Shutterstock

Compared with baseline Pictorial Bleeding Assessment scores, the authors found the LNG-IUD to be effective in 73.2% (95% CI, 55.3%-83.9%) of women at 6 months and in 92.8% (95% CI, 80.0%-97.4%) of women at 12 months. Taking into consideration device failures, including removed and expelled LNG-IUDs (which occurred in 4 women, or 20%, in the intent-to-treat analysis), the actual efficacy rate was 67%. Similarly, there was significant improvement at 6 and 12 months in Menstrual Impact Questionnaire scores for social activities, work performance, tiredness, productivity, hygiene,  and depression.

Read about doing more diagnostic hysteroscopy in the office

Is it time to abandon diagnostic hysteroscopy in the OR?

Leung S, Leyland N, Murji A. Decreasing diagnostic hysteroscopy performed in the operating room: a quality improvement initiative. J Obstet Gynaecol Can. 2016;38(4):351-356.

Diagnostic hysteroscopy: Are we stuck in the 1990s? Why are we still performing so many diagnostic hysteroscopies in the OR, thus subjecting our patients to general anesthesia and using our precious OR time? That is the question asked by a group of researchers in Canada. 

According to data from the Ontario Ministry of Health and Long Term Care, diagnostic hysteroscopy was performed 10,027 times in the 2013-2014 fiscal year. Ontario researchers designed and implemented a quality improvement initiative at their institution and successfully decreased the number of diagnostic hysteroscopies performed in their hospital by 70% from their baseline 12-month period. The improvements resulted in a savings of 78 hours of case costing, or $126,984. When these data are extrapolated to the Ontario population (in which more than  10,000 diagnostic hysteroscopies were performed), potentially 7,000 women could avoid the risk of general anesthesia and the health care system could save $11 million. 

Re-education protocol was key to reducing OR procedures

How did the researchers accomplish their results? The multifaceted intervention had  3 key components:

Staff education and review. Many surgeons were performing diagnostic hysteroscopy in the OR because that is how they were trained, and they were unaware of less invasive options. An awareness campaign was conducted by e-mail, during staff meetings, and at rounds. 

Accessible sonohysterography. This diagnostic modality was made more accessible to referring physicians in a timely manner.

Initiation of an operative hysteroscopy education program. To allow more surgeons greater comfort with office hysteroscopy, the authors instituted didactic sessions, dry and wet lab simulations, and mentorship.  

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.

More than one-third of Americans and > 20% of veterans have obesity with a body mass index (BMI) ≥ 30 kg/m².^1,2 It is well documented that patients with obesity have altered lipid metabolism, drug distribution, and drug clearance.^3-5 As many as 8.2 million Americans may receive statin (3-hydroxymethylglutaryl coenzyme A reductase inhibitors) prescriptions if the American College of Cardiology/American Heart Association 2013 Cholesterol Guidelines are followed; therefore, it is important to examine how the efficacy of these drugs is altered in patients with obesity.⁶

Multiple studies have examined the benefits of statin therapy through lowering low-density lipoprotein cholesterol (LDL-C); however, few have examined the impact of obesity on statin efficacy. For example, only 18% of subjects in the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) trial were classified as having obesity, and subjects in the Scandinavian Simvastatin Survival Study (4S) trial had a mean BMI of only 26 kg/m².^7,8 Though statins decreased mortality in both of these studies, it is unknown whether the lipid-lowering effects were the same for participants with and without obesity. The Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS) demonstrated a decrease in major cardiovascular events and all-cause mortality with atorvastatin 10 mg daily therapy in a sample where more than one-third of subjects had obesity.⁹ However, the mean baseline BMI of subjects in both study groups was only 28 kg/m², and outcomes for those with and without obesity were not compared.⁹

Studies that have examined statin efficacy in those with and without obesity include the Heart Protection Study (HPS), a post hoc analysis of the West of Scotland Coronary Prevention Study (WOSCOPS), and a meta-analysis by Blassetto and colleagues. The HPS examined the event rate of vascular events with simvastatin 40 mg daily in patients with diabetes mellitus (DM).¹⁰ Though these subgroups were compared in HPS, no statistical difference was demonstrated between these groups for the rate of vascular events among those with and without DM.¹⁰ However, the obesity subgroup’s event rate ratios were consistently higher than were those for the nonobese group.¹⁰

A post hoc analysis of WOSCOPS examined obesity as a factor for change in LDL-C with pravastatin 40 mg therapy.¹¹ Though the authors found that no significant difference was present between those with and those without obesity, the data supporting this claim were not disclosed, which makes drawing clinical conclusions from this analysis difficult.¹¹ A meta-analysis by Blassetto and colleagues examined the association between rosuvastatin’s efficacy in lowering LDL-C among the subgroups of hypertension, atherosclerosis, type 2 DM, and obesity.¹² Though these subgroups were not compared statistically, the obesity subgroup had the lowest mean percent change in lowering LDL-C. Moreover, patients without obesity were not examined as a subgroup.¹²

With the expected increase in statin therapy and a significant portion of the U.S. population having obesity, it is necessary to determine if obesity alters the efficacy of statins. This study was conducted to determine the effect of obesity on the percent change in LDL-C with statin therapy within a veteran population.

Methods

This study was a retrospective review examining follow-up data from January 1, 2009 to July 1, 2014 from the VA Midsouth Healthcare Network. This network services more than 350,000 patients each year in Tennessee, Kentucky, and West Virginia. Data were gathered and analyzed on the VA Informatics and Computing Infrastructure (VINCI) servers. Patients were included in this study if they were aged ≥ 18 years with a new filled prescription for simvastatin 20 mg or simvastatin 40 mg daily. Simvastatin was chosen because it was the formulary statin during the study period. This study was approved by the James H. Quillen VAMC/East Tennessee State University Institutional Review Board.

Patients were excluded if they had received treatment for hyperlipidemia (niacin, colestyramine, colestipol, colesevelam, other statins, gemfibrozil, fenofibrate, omega-3 ethyl esters, ezetimibe) during the 6 weeks prior to the initial fill date of the statin prescription. Patients whose simvastatin therapy did not span the follow-up period from the time of filling to the follow-up lipid panel were excluded, as were those who had not filled a simvastatin prescription within 30 days of their baseline lipid panel. Also excluded were patients who were newly established at the VA, pregnant, or receiving concomitant antihyperlipidemia agents, dialysis, or interacting medications (tacrolimus, cyclosporine, atazanavir, darunavir, nelfinavir, saquinavir, ritonavir, indinavir, lopinavir, tipranavir, fosamprenavir, fluconazole, voriconazole, itraconazole, voriconazole, posaconazole, amiodarone, or colchicine). Patients with a BMI < 18 kg/m², hepatic failure as measured by an aspartate transaminase/alanine transaminase (AST/ALT) ratio > 3 times the upper limit of normal, hepatitis, a history of alcoholism, any change in statin dose prior to follow-up cholesterol values, or no follow-up LDL-C values also were excluded.

The baseline data collected included age, sex, weight, height, BMI, hemoglobin A_1c, LDL-C, ALT/AST, and serum creatinine (SCr). All other laboratory results were required to be within 270 days of the time the lipid panel was obtained. The index date was set as the date the initial prescription was filled between February 1, 2009 and April 1, 2014. Follow-up levels for LDL-C were obtained 40 to 95 days after the index date. Direct LDL-C values were preferred unless only calculated values were available. Calculated LDL-C values were determined by using the Friedewald equation. An audit of 150 patient charts was conducted to ensure the integrity of data pulled from the database.

The percent changes in LDL-C were calculated for those with and without obesity for both simvastatin 20 mg daily and simvastatin 40 mg daily. The primary outcome was the percent change in LDL-C from baseline. All laboratory values were compared using independent 2-tailed t tests with α set to .05. To have an 80% chance of detecting a 5% difference in percent change in LDL-C between the experimental and control groups, 129 patients were required. To determine whether an association was present, a correlation between BMI and percent change in LDL-C was conducted. All statistics were conducted using SAS software (Cary, North Carolina).

Results

From January 2009 through July 2014, 35,216 patients were initially screened. The majority of patients did not have a baseline LDL-C value and were excluded. A total of 1,183 patients with simvastatin 20 mg daily (BMI < 30 = 661; BMI ≥ 30 = 1,122) and 478 patients with simvastatin 40 mg daily (BMI < 30 = 259; BMI ≥ 30 = 219) met the inclusion criteria.

Baseline characteristics were similar between groups except for a slightly higher age in both groups without obesity (Table). Hepatic and renal serum markers indicated a baseline of adequate organ function for drug clearance for all groups. The mean baseline BMI of those without obesity was about 26 kg/m², which is considered overweight. Baseline LDL-C values were clinically similar for those with and without obesity, though statistically different (145 mg/dL for the nonobese group and 141 mg/dL for the obese group, P < .05). The percent change in LDL-C was not statistically significant for those with and without obesity for simvastatin 20 mg daily (P = .293) or simvastatin 40 mg daily (P = .2773) (Figure). No correlation was found between the continuous percent change in LDL-C and continuous BMI for either simvastatin dosage (r² = 0.0016 and 0.0028, respectively).

Discussion

In this retrospective chart review, it was determined that obesity did not affect the percent change in LDL-C from baseline with statin therapy. The HPS found similar results as a secondary endpoint, although that study was underpowered.¹⁰ In this study, all groups met power, and there was still no difference between those with and without obesity.

Nicholls and colleagues examined REVERSAL study data to determine whether BMI greater than the median BMI impacted inflammatory markers or lipid levels with atorvastatin 80 mg daily or pravastatin 40 mg daily. The REVERSAL study authors found no difference in percent change LDL-C between those above the median BMI compared with those below the median BMI for patients on pravastatin therapy. However, the authors did find a difference in percent change LDL-C with atorvastatin therapy.¹³ No difference in percent change LDL-C was present with simvastatin therapy in this study. As simvastatin is more lipophilic than is atorvastatin, lipophilicity remains an area for further study for statin therapy in patients with obesity.

The surrogate marker of percent change in LDL-C was used for the primary outcome in this study. The ACC/AHA 2013 guidelines and the National Lipid Association 2014 guidelines recommend an alternative goal of 30% to 50% change in LDL-C from baseline.^14,15 Using this clinically relevant marker compensated for differences in baseline LDL-C and limited the effect of these differences on the primary outcome of this study.

Limitations

This study did not include patients who were underweight (BMI < 18 kg/m²), as these patients have previously demonstrated decreased outcomes with statin therapy.¹⁶ However, this limits these data to only those patients that have a BMI of at least 18 kg/m². Limitations of this study also included the inability to consider adherence and lifestyle changes. These limitations were unavoidable due to the nature of a retrospective chart review.

Conclusion

The prevalence of obesity is increasing, and it is a disease that alters pharmacokinetics and lipid metabolism. Though this study did not find a difference between the LDL-C-lowering efficacy of simvastatin in those with and without obesity, continued study of the effect of obesity on the efficacy of medications is vital.

Acknowledgments
This material is the result of work supported with resources and the use of facilities at the James H. Qullen VAMC in Mountain Home, Tennessee.

More than one-third of Americans and > 20% of veterans have obesity with a body mass index (BMI) ≥ 30 kg/m².^1,2 It is well documented that patients with obesity have altered lipid metabolism, drug distribution, and drug clearance.^3-5 As many as 8.2 million Americans may receive statin (3-hydroxymethylglutaryl coenzyme A reductase inhibitors) prescriptions if the American College of Cardiology/American Heart Association 2013 Cholesterol Guidelines are followed; therefore, it is important to examine how the efficacy of these drugs is altered in patients with obesity.⁶

Multiple studies have examined the benefits of statin therapy through lowering low-density lipoprotein cholesterol (LDL-C); however, few have examined the impact of obesity on statin efficacy. For example, only 18% of subjects in the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) trial were classified as having obesity, and subjects in the Scandinavian Simvastatin Survival Study (4S) trial had a mean BMI of only 26 kg/m².^7,8 Though statins decreased mortality in both of these studies, it is unknown whether the lipid-lowering effects were the same for participants with and without obesity. The Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS) demonstrated a decrease in major cardiovascular events and all-cause mortality with atorvastatin 10 mg daily therapy in a sample where more than one-third of subjects had obesity.⁹ However, the mean baseline BMI of subjects in both study groups was only 28 kg/m², and outcomes for those with and without obesity were not compared.⁹

Studies that have examined statin efficacy in those with and without obesity include the Heart Protection Study (HPS), a post hoc analysis of the West of Scotland Coronary Prevention Study (WOSCOPS), and a meta-analysis by Blassetto and colleagues. The HPS examined the event rate of vascular events with simvastatin 40 mg daily in patients with diabetes mellitus (DM).¹⁰ Though these subgroups were compared in HPS, no statistical difference was demonstrated between these groups for the rate of vascular events among those with and without DM.¹⁰ However, the obesity subgroup’s event rate ratios were consistently higher than were those for the nonobese group.¹⁰

A post hoc analysis of WOSCOPS examined obesity as a factor for change in LDL-C with pravastatin 40 mg therapy.¹¹ Though the authors found that no significant difference was present between those with and those without obesity, the data supporting this claim were not disclosed, which makes drawing clinical conclusions from this analysis difficult.¹¹ A meta-analysis by Blassetto and colleagues examined the association between rosuvastatin’s efficacy in lowering LDL-C among the subgroups of hypertension, atherosclerosis, type 2 DM, and obesity.¹² Though these subgroups were not compared statistically, the obesity subgroup had the lowest mean percent change in lowering LDL-C. Moreover, patients without obesity were not examined as a subgroup.¹²

With the expected increase in statin therapy and a significant portion of the U.S. population having obesity, it is necessary to determine if obesity alters the efficacy of statins. This study was conducted to determine the effect of obesity on the percent change in LDL-C with statin therapy within a veteran population.

Methods

This study was a retrospective review examining follow-up data from January 1, 2009 to July 1, 2014 from the VA Midsouth Healthcare Network. This network services more than 350,000 patients each year in Tennessee, Kentucky, and West Virginia. Data were gathered and analyzed on the VA Informatics and Computing Infrastructure (VINCI) servers. Patients were included in this study if they were aged ≥ 18 years with a new filled prescription for simvastatin 20 mg or simvastatin 40 mg daily. Simvastatin was chosen because it was the formulary statin during the study period. This study was approved by the James H. Quillen VAMC/East Tennessee State University Institutional Review Board.

Patients were excluded if they had received treatment for hyperlipidemia (niacin, colestyramine, colestipol, colesevelam, other statins, gemfibrozil, fenofibrate, omega-3 ethyl esters, ezetimibe) during the 6 weeks prior to the initial fill date of the statin prescription. Patients whose simvastatin therapy did not span the follow-up period from the time of filling to the follow-up lipid panel were excluded, as were those who had not filled a simvastatin prescription within 30 days of their baseline lipid panel. Also excluded were patients who were newly established at the VA, pregnant, or receiving concomitant antihyperlipidemia agents, dialysis, or interacting medications (tacrolimus, cyclosporine, atazanavir, darunavir, nelfinavir, saquinavir, ritonavir, indinavir, lopinavir, tipranavir, fosamprenavir, fluconazole, voriconazole, itraconazole, voriconazole, posaconazole, amiodarone, or colchicine). Patients with a BMI < 18 kg/m², hepatic failure as measured by an aspartate transaminase/alanine transaminase (AST/ALT) ratio > 3 times the upper limit of normal, hepatitis, a history of alcoholism, any change in statin dose prior to follow-up cholesterol values, or no follow-up LDL-C values also were excluded.

The baseline data collected included age, sex, weight, height, BMI, hemoglobin A_1c, LDL-C, ALT/AST, and serum creatinine (SCr). All other laboratory results were required to be within 270 days of the time the lipid panel was obtained. The index date was set as the date the initial prescription was filled between February 1, 2009 and April 1, 2014. Follow-up levels for LDL-C were obtained 40 to 95 days after the index date. Direct LDL-C values were preferred unless only calculated values were available. Calculated LDL-C values were determined by using the Friedewald equation. An audit of 150 patient charts was conducted to ensure the integrity of data pulled from the database.

The percent changes in LDL-C were calculated for those with and without obesity for both simvastatin 20 mg daily and simvastatin 40 mg daily. The primary outcome was the percent change in LDL-C from baseline. All laboratory values were compared using independent 2-tailed t tests with α set to .05. To have an 80% chance of detecting a 5% difference in percent change in LDL-C between the experimental and control groups, 129 patients were required. To determine whether an association was present, a correlation between BMI and percent change in LDL-C was conducted. All statistics were conducted using SAS software (Cary, North Carolina).

Results

From January 2009 through July 2014, 35,216 patients were initially screened. The majority of patients did not have a baseline LDL-C value and were excluded. A total of 1,183 patients with simvastatin 20 mg daily (BMI < 30 = 661; BMI ≥ 30 = 1,122) and 478 patients with simvastatin 40 mg daily (BMI < 30 = 259; BMI ≥ 30 = 219) met the inclusion criteria.

Baseline characteristics were similar between groups except for a slightly higher age in both groups without obesity (Table). Hepatic and renal serum markers indicated a baseline of adequate organ function for drug clearance for all groups. The mean baseline BMI of those without obesity was about 26 kg/m², which is considered overweight. Baseline LDL-C values were clinically similar for those with and without obesity, though statistically different (145 mg/dL for the nonobese group and 141 mg/dL for the obese group, P < .05). The percent change in LDL-C was not statistically significant for those with and without obesity for simvastatin 20 mg daily (P = .293) or simvastatin 40 mg daily (P = .2773) (Figure). No correlation was found between the continuous percent change in LDL-C and continuous BMI for either simvastatin dosage (r² = 0.0016 and 0.0028, respectively).

Discussion

In this retrospective chart review, it was determined that obesity did not affect the percent change in LDL-C from baseline with statin therapy. The HPS found similar results as a secondary endpoint, although that study was underpowered.¹⁰ In this study, all groups met power, and there was still no difference between those with and without obesity.

Nicholls and colleagues examined REVERSAL study data to determine whether BMI greater than the median BMI impacted inflammatory markers or lipid levels with atorvastatin 80 mg daily or pravastatin 40 mg daily. The REVERSAL study authors found no difference in percent change LDL-C between those above the median BMI compared with those below the median BMI for patients on pravastatin therapy. However, the authors did find a difference in percent change LDL-C with atorvastatin therapy.¹³ No difference in percent change LDL-C was present with simvastatin therapy in this study. As simvastatin is more lipophilic than is atorvastatin, lipophilicity remains an area for further study for statin therapy in patients with obesity.

The surrogate marker of percent change in LDL-C was used for the primary outcome in this study. The ACC/AHA 2013 guidelines and the National Lipid Association 2014 guidelines recommend an alternative goal of 30% to 50% change in LDL-C from baseline.^14,15 Using this clinically relevant marker compensated for differences in baseline LDL-C and limited the effect of these differences on the primary outcome of this study.

Limitations

This study did not include patients who were underweight (BMI < 18 kg/m²), as these patients have previously demonstrated decreased outcomes with statin therapy.¹⁶ However, this limits these data to only those patients that have a BMI of at least 18 kg/m². Limitations of this study also included the inability to consider adherence and lifestyle changes. These limitations were unavoidable due to the nature of a retrospective chart review.

Conclusion

The prevalence of obesity is increasing, and it is a disease that alters pharmacokinetics and lipid metabolism. Though this study did not find a difference between the LDL-C-lowering efficacy of simvastatin in those with and without obesity, continued study of the effect of obesity on the efficacy of medications is vital.

Acknowledgments
This material is the result of work supported with resources and the use of facilities at the James H. Qullen VAMC in Mountain Home, Tennessee.

More than one-third of Americans and > 20% of veterans have obesity with a body mass index (BMI) ≥ 30 kg/m².^1,2 It is well documented that patients with obesity have altered lipid metabolism, drug distribution, and drug clearance.^3-5 As many as 8.2 million Americans may receive statin (3-hydroxymethylglutaryl coenzyme A reductase inhibitors) prescriptions if the American College of Cardiology/American Heart Association 2013 Cholesterol Guidelines are followed; therefore, it is important to examine how the efficacy of these drugs is altered in patients with obesity.⁶

Multiple studies have examined the benefits of statin therapy through lowering low-density lipoprotein cholesterol (LDL-C); however, few have examined the impact of obesity on statin efficacy. For example, only 18% of subjects in the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) trial were classified as having obesity, and subjects in the Scandinavian Simvastatin Survival Study (4S) trial had a mean BMI of only 26 kg/m².^7,8 Though statins decreased mortality in both of these studies, it is unknown whether the lipid-lowering effects were the same for participants with and without obesity. The Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS) demonstrated a decrease in major cardiovascular events and all-cause mortality with atorvastatin 10 mg daily therapy in a sample where more than one-third of subjects had obesity.⁹ However, the mean baseline BMI of subjects in both study groups was only 28 kg/m², and outcomes for those with and without obesity were not compared.⁹

Studies that have examined statin efficacy in those with and without obesity include the Heart Protection Study (HPS), a post hoc analysis of the West of Scotland Coronary Prevention Study (WOSCOPS), and a meta-analysis by Blassetto and colleagues. The HPS examined the event rate of vascular events with simvastatin 40 mg daily in patients with diabetes mellitus (DM).¹⁰ Though these subgroups were compared in HPS, no statistical difference was demonstrated between these groups for the rate of vascular events among those with and without DM.¹⁰ However, the obesity subgroup’s event rate ratios were consistently higher than were those for the nonobese group.¹⁰

A post hoc analysis of WOSCOPS examined obesity as a factor for change in LDL-C with pravastatin 40 mg therapy.¹¹ Though the authors found that no significant difference was present between those with and those without obesity, the data supporting this claim were not disclosed, which makes drawing clinical conclusions from this analysis difficult.¹¹ A meta-analysis by Blassetto and colleagues examined the association between rosuvastatin’s efficacy in lowering LDL-C among the subgroups of hypertension, atherosclerosis, type 2 DM, and obesity.¹² Though these subgroups were not compared statistically, the obesity subgroup had the lowest mean percent change in lowering LDL-C. Moreover, patients without obesity were not examined as a subgroup.¹²

With the expected increase in statin therapy and a significant portion of the U.S. population having obesity, it is necessary to determine if obesity alters the efficacy of statins. This study was conducted to determine the effect of obesity on the percent change in LDL-C with statin therapy within a veteran population.

Methods

This study was a retrospective review examining follow-up data from January 1, 2009 to July 1, 2014 from the VA Midsouth Healthcare Network. This network services more than 350,000 patients each year in Tennessee, Kentucky, and West Virginia. Data were gathered and analyzed on the VA Informatics and Computing Infrastructure (VINCI) servers. Patients were included in this study if they were aged ≥ 18 years with a new filled prescription for simvastatin 20 mg or simvastatin 40 mg daily. Simvastatin was chosen because it was the formulary statin during the study period. This study was approved by the James H. Quillen VAMC/East Tennessee State University Institutional Review Board.

Patients were excluded if they had received treatment for hyperlipidemia (niacin, colestyramine, colestipol, colesevelam, other statins, gemfibrozil, fenofibrate, omega-3 ethyl esters, ezetimibe) during the 6 weeks prior to the initial fill date of the statin prescription. Patients whose simvastatin therapy did not span the follow-up period from the time of filling to the follow-up lipid panel were excluded, as were those who had not filled a simvastatin prescription within 30 days of their baseline lipid panel. Also excluded were patients who were newly established at the VA, pregnant, or receiving concomitant antihyperlipidemia agents, dialysis, or interacting medications (tacrolimus, cyclosporine, atazanavir, darunavir, nelfinavir, saquinavir, ritonavir, indinavir, lopinavir, tipranavir, fosamprenavir, fluconazole, voriconazole, itraconazole, voriconazole, posaconazole, amiodarone, or colchicine). Patients with a BMI < 18 kg/m², hepatic failure as measured by an aspartate transaminase/alanine transaminase (AST/ALT) ratio > 3 times the upper limit of normal, hepatitis, a history of alcoholism, any change in statin dose prior to follow-up cholesterol values, or no follow-up LDL-C values also were excluded.

The baseline data collected included age, sex, weight, height, BMI, hemoglobin A_1c, LDL-C, ALT/AST, and serum creatinine (SCr). All other laboratory results were required to be within 270 days of the time the lipid panel was obtained. The index date was set as the date the initial prescription was filled between February 1, 2009 and April 1, 2014. Follow-up levels for LDL-C were obtained 40 to 95 days after the index date. Direct LDL-C values were preferred unless only calculated values were available. Calculated LDL-C values were determined by using the Friedewald equation. An audit of 150 patient charts was conducted to ensure the integrity of data pulled from the database.

The percent changes in LDL-C were calculated for those with and without obesity for both simvastatin 20 mg daily and simvastatin 40 mg daily. The primary outcome was the percent change in LDL-C from baseline. All laboratory values were compared using independent 2-tailed t tests with α set to .05. To have an 80% chance of detecting a 5% difference in percent change in LDL-C between the experimental and control groups, 129 patients were required. To determine whether an association was present, a correlation between BMI and percent change in LDL-C was conducted. All statistics were conducted using SAS software (Cary, North Carolina).

Results

From January 2009 through July 2014, 35,216 patients were initially screened. The majority of patients did not have a baseline LDL-C value and were excluded. A total of 1,183 patients with simvastatin 20 mg daily (BMI < 30 = 661; BMI ≥ 30 = 1,122) and 478 patients with simvastatin 40 mg daily (BMI < 30 = 259; BMI ≥ 30 = 219) met the inclusion criteria.

Baseline characteristics were similar between groups except for a slightly higher age in both groups without obesity (Table). Hepatic and renal serum markers indicated a baseline of adequate organ function for drug clearance for all groups. The mean baseline BMI of those without obesity was about 26 kg/m², which is considered overweight. Baseline LDL-C values were clinically similar for those with and without obesity, though statistically different (145 mg/dL for the nonobese group and 141 mg/dL for the obese group, P < .05). The percent change in LDL-C was not statistically significant for those with and without obesity for simvastatin 20 mg daily (P = .293) or simvastatin 40 mg daily (P = .2773) (Figure). No correlation was found between the continuous percent change in LDL-C and continuous BMI for either simvastatin dosage (r² = 0.0016 and 0.0028, respectively).

Discussion

In this retrospective chart review, it was determined that obesity did not affect the percent change in LDL-C from baseline with statin therapy. The HPS found similar results as a secondary endpoint, although that study was underpowered.¹⁰ In this study, all groups met power, and there was still no difference between those with and without obesity.

Nicholls and colleagues examined REVERSAL study data to determine whether BMI greater than the median BMI impacted inflammatory markers or lipid levels with atorvastatin 80 mg daily or pravastatin 40 mg daily. The REVERSAL study authors found no difference in percent change LDL-C between those above the median BMI compared with those below the median BMI for patients on pravastatin therapy. However, the authors did find a difference in percent change LDL-C with atorvastatin therapy.¹³ No difference in percent change LDL-C was present with simvastatin therapy in this study. As simvastatin is more lipophilic than is atorvastatin, lipophilicity remains an area for further study for statin therapy in patients with obesity.

The surrogate marker of percent change in LDL-C was used for the primary outcome in this study. The ACC/AHA 2013 guidelines and the National Lipid Association 2014 guidelines recommend an alternative goal of 30% to 50% change in LDL-C from baseline.^14,15 Using this clinically relevant marker compensated for differences in baseline LDL-C and limited the effect of these differences on the primary outcome of this study.

Limitations

This study did not include patients who were underweight (BMI < 18 kg/m²), as these patients have previously demonstrated decreased outcomes with statin therapy.¹⁶ However, this limits these data to only those patients that have a BMI of at least 18 kg/m². Limitations of this study also included the inability to consider adherence and lifestyle changes. These limitations were unavoidable due to the nature of a retrospective chart review.

Conclusion

The prevalence of obesity is increasing, and it is a disease that alters pharmacokinetics and lipid metabolism. Though this study did not find a difference between the LDL-C-lowering efficacy of simvastatin in those with and without obesity, continued study of the effect of obesity on the efficacy of medications is vital.

Acknowledgments
This material is the result of work supported with resources and the use of facilities at the James H. Qullen VAMC in Mountain Home, Tennessee.

Take-Home Points

• Lateral patella dislocation is sufficiently treated with modern versions of patellofemoral surgery.
• Comprehensive assessment for underlying osseous pathology is paramount (torsional abnormalities of the femur or tibia, trochlea dysplasia, patella alta, etc).
• In such cases, isolated medial patellofemoral ligament reconstructions will fail. Instead, the underlying osseous abnormalities must be addressed during concomitant procedures (derotational osteotomy, tibial tubercle transfer, trochleoplasty, etc).

The incidence of patellar instability is high, particularly in young females. In principle, cases of patellar instability can be classified as traumatic (dislocation is caused by external, often direct forces) or nontraumatic (anatomy predisposes to instability).^1-4

Anatomy Predisposing to Patella Dislocation

Most patients present with specific anatomical factors that predispose to patellar instability (isolated or combined).

Of the osteochondral factors, dysplasia of the femoral trochlea (trochlea groove [TG]) is most important. In healthy patients, the concave trochlea stabilizes the patella in knee flexion angles above 20°. In particular, the lateral facet of the trochlea plays a key role in withstanding the lateralizing quadriceps vector. The dysplastic trochlea, which has a flat or even a convex surface, destabilizes the patella (Figure 1). Moreover, patella alta is a pivotal factor in the development of LPD.

Diagnostics

Physical Examination

It is recommended that the physician starts the examination by assessing the walking and standing patient while focusing on torsional malalignment of the lower extremities (increased antetorsion of the femur, increased external torsion of the tibia), which is often indicated by squinting patellae.^8,27,28

Imaging

Radiographs are the basis for each patient’s imaging analysis. For a patient with valgus or varus clinical appearance, a weight-bearing whole-leg radiograph is used to precisely assess the degree of deformity in the frontal plane. A true lateral radiograph (congruent posterior condyles) provides information about patellar height (patella alta/infera). Most indices that quantify patellar height use the tibia as reference (eg, tuberosity, anterior aspect of articulation surface).

MRI is the gold standard for LPD diagnosis—it can be used to easily identify soft-tissue lesions and establish their patellar or femoral location (eg, MPFL rupture). MRI also provides information on potential pathologies of quadriceps tendon, patella tendon, and infrapatellar fat pad. Compared with radiographs, MRI is more sensitive in detecting osteochondral lesions in LPD.

Treatment

MPFL Reconstruction

Isolated MPFL reconstruction is commonly regarded as a standard, straightforward procedure.

Trochleoplasty

In cases of recurrent LPD or a flat or convex trochlea (Dejour type B, C, or D dysplasia), deepening trochleoplasty should be considered.

Osteotomy

The most popular type of osteotomy in the setting of LPD is the transfer of the TT (TTT).

Derotational osteotomies of the femur (externally rotating) provide good outcomes in patients with LPD and associated torsional deformities,^61-63 though the literature is incongruent with respect to whether rotational osteotomies of the femur should be performed at the proximal or distal aspect.^64-67 In the majority of our LPD cases, we combine femoral derotation with MPFL reconstruction.

Treatment Algorithms

We suggest using different algorithms for primary LPD (Figure 22, Tables 1-2) and recurrent LPD (Figure 23).

Conclusion

In skeletally mature patients, LPD is sufficiently treated with modern versions of patellofemoral surgery. Comprehensive assessment for underlying pathology is paramount as preparation for developing an appropriate surgical plan for the patient.

Am J Orthop. 2017;46(2):E86-E96. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Take-Home Points

• Lateral patella dislocation is sufficiently treated with modern versions of patellofemoral surgery.
• Comprehensive assessment for underlying osseous pathology is paramount (torsional abnormalities of the femur or tibia, trochlea dysplasia, patella alta, etc).
• In such cases, isolated medial patellofemoral ligament reconstructions will fail. Instead, the underlying osseous abnormalities must be addressed during concomitant procedures (derotational osteotomy, tibial tubercle transfer, trochleoplasty, etc).

The incidence of patellar instability is high, particularly in young females. In principle, cases of patellar instability can be classified as traumatic (dislocation is caused by external, often direct forces) or nontraumatic (anatomy predisposes to instability).^1-4

Anatomy Predisposing to Patella Dislocation

Most patients present with specific anatomical factors that predispose to patellar instability (isolated or combined).

Of the osteochondral factors, dysplasia of the femoral trochlea (trochlea groove [TG]) is most important. In healthy patients, the concave trochlea stabilizes the patella in knee flexion angles above 20°. In particular, the lateral facet of the trochlea plays a key role in withstanding the lateralizing quadriceps vector. The dysplastic trochlea, which has a flat or even a convex surface, destabilizes the patella (Figure 1). Moreover, patella alta is a pivotal factor in the development of LPD.

Diagnostics

Physical Examination

It is recommended that the physician starts the examination by assessing the walking and standing patient while focusing on torsional malalignment of the lower extremities (increased antetorsion of the femur, increased external torsion of the tibia), which is often indicated by squinting patellae.^8,27,28

Imaging

Radiographs are the basis for each patient’s imaging analysis. For a patient with valgus or varus clinical appearance, a weight-bearing whole-leg radiograph is used to precisely assess the degree of deformity in the frontal plane. A true lateral radiograph (congruent posterior condyles) provides information about patellar height (patella alta/infera). Most indices that quantify patellar height use the tibia as reference (eg, tuberosity, anterior aspect of articulation surface).

MRI is the gold standard for LPD diagnosis—it can be used to easily identify soft-tissue lesions and establish their patellar or femoral location (eg, MPFL rupture). MRI also provides information on potential pathologies of quadriceps tendon, patella tendon, and infrapatellar fat pad. Compared with radiographs, MRI is more sensitive in detecting osteochondral lesions in LPD.

Treatment

MPFL Reconstruction

Isolated MPFL reconstruction is commonly regarded as a standard, straightforward procedure.

Trochleoplasty

In cases of recurrent LPD or a flat or convex trochlea (Dejour type B, C, or D dysplasia), deepening trochleoplasty should be considered.

Osteotomy

The most popular type of osteotomy in the setting of LPD is the transfer of the TT (TTT).

Derotational osteotomies of the femur (externally rotating) provide good outcomes in patients with LPD and associated torsional deformities,^61-63 though the literature is incongruent with respect to whether rotational osteotomies of the femur should be performed at the proximal or distal aspect.^64-67 In the majority of our LPD cases, we combine femoral derotation with MPFL reconstruction.

Treatment Algorithms

We suggest using different algorithms for primary LPD (Figure 22, Tables 1-2) and recurrent LPD (Figure 23).

Conclusion

In skeletally mature patients, LPD is sufficiently treated with modern versions of patellofemoral surgery. Comprehensive assessment for underlying pathology is paramount as preparation for developing an appropriate surgical plan for the patient.

Am J Orthop. 2017;46(2):E86-E96. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Take-Home Points

• Lateral patella dislocation is sufficiently treated with modern versions of patellofemoral surgery.
• Comprehensive assessment for underlying osseous pathology is paramount (torsional abnormalities of the femur or tibia, trochlea dysplasia, patella alta, etc).
• In such cases, isolated medial patellofemoral ligament reconstructions will fail. Instead, the underlying osseous abnormalities must be addressed during concomitant procedures (derotational osteotomy, tibial tubercle transfer, trochleoplasty, etc).

The incidence of patellar instability is high, particularly in young females. In principle, cases of patellar instability can be classified as traumatic (dislocation is caused by external, often direct forces) or nontraumatic (anatomy predisposes to instability).^1-4

Anatomy Predisposing to Patella Dislocation

Most patients present with specific anatomical factors that predispose to patellar instability (isolated or combined).

Of the osteochondral factors, dysplasia of the femoral trochlea (trochlea groove [TG]) is most important. In healthy patients, the concave trochlea stabilizes the patella in knee flexion angles above 20°. In particular, the lateral facet of the trochlea plays a key role in withstanding the lateralizing quadriceps vector. The dysplastic trochlea, which has a flat or even a convex surface, destabilizes the patella (Figure 1). Moreover, patella alta is a pivotal factor in the development of LPD.

Diagnostics

Physical Examination

It is recommended that the physician starts the examination by assessing the walking and standing patient while focusing on torsional malalignment of the lower extremities (increased antetorsion of the femur, increased external torsion of the tibia), which is often indicated by squinting patellae.^8,27,28

Imaging

Radiographs are the basis for each patient’s imaging analysis. For a patient with valgus or varus clinical appearance, a weight-bearing whole-leg radiograph is used to precisely assess the degree of deformity in the frontal plane. A true lateral radiograph (congruent posterior condyles) provides information about patellar height (patella alta/infera). Most indices that quantify patellar height use the tibia as reference (eg, tuberosity, anterior aspect of articulation surface).

MRI is the gold standard for LPD diagnosis—it can be used to easily identify soft-tissue lesions and establish their patellar or femoral location (eg, MPFL rupture). MRI also provides information on potential pathologies of quadriceps tendon, patella tendon, and infrapatellar fat pad. Compared with radiographs, MRI is more sensitive in detecting osteochondral lesions in LPD.

Treatment

MPFL Reconstruction

Isolated MPFL reconstruction is commonly regarded as a standard, straightforward procedure.

Trochleoplasty

In cases of recurrent LPD or a flat or convex trochlea (Dejour type B, C, or D dysplasia), deepening trochleoplasty should be considered.

Osteotomy

The most popular type of osteotomy in the setting of LPD is the transfer of the TT (TTT).

Derotational osteotomies of the femur (externally rotating) provide good outcomes in patients with LPD and associated torsional deformities,^61-63 though the literature is incongruent with respect to whether rotational osteotomies of the femur should be performed at the proximal or distal aspect.^64-67 In the majority of our LPD cases, we combine femoral derotation with MPFL reconstruction.

Treatment Algorithms

We suggest using different algorithms for primary LPD (Figure 22, Tables 1-2) and recurrent LPD (Figure 23).

Conclusion

In skeletally mature patients, LPD is sufficiently treated with modern versions of patellofemoral surgery. Comprehensive assessment for underlying pathology is paramount as preparation for developing an appropriate surgical plan for the patient.

Am J Orthop. 2017;46(2):E86-E96. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Acute extremity pain is a common presentation seen daily in EDs. While most etiologies of extremity pain are benign, the complications of acute compartment syndrome are associated with significant morbidity. Moreover, acute compartment syndrome remains a difficult diagnosis that is often missed on initial presentation. Morbidity results from an increased pressure in an anatomically closed space, progressing to decreased perfusion and rapid tissue destruction.

Case

An obese 55-year-old man with a medical history of coronary artery disease, for which he was on aspirin therapy, presented for evaluation of right shin pain. The patient stated that he completed a 5-km race earlier that morning with his son. Immediately following the race, he experienced increasing right shin pain, which he attempted to initially manage with ice compresses and over-the-counter ibuprofen. He noted that neither the ice compresses nor the ibuprofen relieved his pain and that by 5:00 pm, the pain had worsened to the point where he had difficulty walking, prompting his visit to the ED.

Upon arrival at the ED, the patient was ambulatory but had significant pain at both rest and movement. His vital signs and his oxygen saturation on room air were normal. On physical examination, he had normal sensation to the entire right lower extremity and had equal pulses in both feet. The anterolateral aspect of the shin was exquisitely tender to light touch, and the patient was unable to dorsiflex or plantar flex without extreme pain. On passive dorsiflexion and plantar flexion of his right foot, he had exquisite pain. On palpation, the anterior shin was firm compared to the other muscle beds.

Epidemiology

Acute compartment syndrome—elevation of interstitial pressure in closed fascial compartment—affects 10 times as many men as women, at an average age of 32 years old and with an annual incidence of 7.3 per 100,000 men and 0.7 per 100,000 for women.¹ McQueen et al¹ found that the most common cause of acute compartment syndrome was fracture (69%), followed by soft tissue injury (23%). Younger patients are more likely to develop acute compartment syndrome from trauma because they typically have larger muscle beds with more tissue to become edematous compared to the older, hypotrophic muscles of elderly patients.

Pathophysiology

The fascia surrounds the major muscle groups and neurovascular bundles in the extremities to create distinct compartments. Since the fascia is not a compliant structure, it is typically not able to tolerate increases in volume or pressure in a given compartment. Compartment perfusion pressure is the mean arterial pressure minus the compartment pressure. Normal compartment pressure in adults is between 0 to 8 mm Hg.² When compartment perfusion pressures are below 70 to 80 mm Hg, there is an increased risk of compartment syndrome.

Although the exact pathophysiology of acute compartment syndrome is still debated,³ the most commonly accepted theory is the arteriovenous pressure gradient theory.⁴ In this theory, the rise in intracompartment pressure increases venous pressure, which in turn reduces the arteriovenous pressure gradient, reducing local tissue perfusion. The reduction in tissue perfusion, coupled with a reduction in venous drainage, causes significant tissue edema. This change in vascular pressure also causes a reduction in lymphatic drainage, further increasing pressure in the compartment. Finally, the edematous tissue compresses the arterioles leading to end-organ ischemia.⁵

Initially an absolute threshold compartment pressure was thought to cause irreversible tissue ischemia,⁶ but this theory has slowly lost favor after it was found that hypertension was actually protective in compartment syndrome.⁷ Current thinking is that the difference between the diastolic pressure and the compartment pressure leads to tissue ischemia (ie, acute compartment syndrome delta pressure = diastolic blood pressure [BP] – measured compartment pressure).^6,8

In 1996, McQueen and Court-Brown⁶ prospectively admitted all tibial diaphyseal fractures and continuously monitored their anterior compartment pressure. Using a delta pressure value of less than 30 mm Hg, only three patients were diagnosed with acute compartment syndrome and required fasciotomy. The patients’ absolute compartment pressures were 45 mm Hg, 65 mm Hg, and 75 mm Hg, while the delta pressures were 15 mm Hg, 10 mm Hg, and 15 mm Hg, respectively. Conversely, 53 patients had absolute compartment pressures over 30 mm Hg; 30 patients had pressure over 40 mm Hg; four patients had pressure over 50 mm Hg; and none required fasciotomy. This study highlights that the absolute compartment pressure is not helpful in making the diagnosis, and it is the elevated delta pressure that secures the diagnosis.

Etiology

Compartment syndrome is the end result of many different injury patterns. While fracture is the number one cause of compartment syndrome, many types of soft tissue injuries can also lead to compartment syndrome. Nonfracture etiologies of compartment syndrome are relatively uncommon, and as such can lead to a delay in diagnosis.

Fracture

Almost 70% of all cases of compartment syndrome are due to fracture.¹ Fractures of the tibia, distal radius, and ulna are the most common injuries that lead to acute compartment syndrome. Interestingly, acute compartment syndrome is caused by an equal distribution of high-energy and low-energy mechanisms of injuries.¹ Because the increase in compartment pressure is highest at the fracture site,⁹ it is imperative to measure pressures at the site of the fracture. Contrary to traditional teaching, an open fracture does not reduce the risk of compartment syndrome. McQueen and Court-Brown⁶ found there was no difference in the intracompartment pressure between open and closed fractures.

Fracture reduction and manipulation can actually increase the risk of compartment syndrome. In one case series, fracture manipulation increased compartment pressure by reducing the total volume in a stretched compartment.¹⁰ Dresing et al¹⁰ found the average pressure increased by 21 mm Hg during wrist reduction, warranting close observation after fracture reduction and close observation of the patient’s pain and neurovascular status.

McQueen et al¹¹ evaluated the risk factors for the development of acute compartment syndrome from tibial diaphyseal fractures and found that younger patients were at the highest risk. Patients between ages 10 to 19 years old had an odds ratio (OR) of 12.09; 20 to 29 years old had an OR of 9.84; and patients older than age 40 years had an OR of 1.¹¹ As previously stated, younger patients have larger muscle volumes compared to their older counterparts and therefore have less space for edema after the primary muscle injury.

Soft Tissue Injury

Direct soft tissue injury can lead to a rise in compartment pressures due to trauma, infections, and burns even in the absence of fractures. Unfortunately, under these circumstances, patients with direct soft tissue injury are at high risk for a delay in diagnosis.¹² The primary injury can be worsened by underlying coagulopathies.¹ A circumferential constrictive eschar from burns can also cause external compression to a compartment¹³ as well as edema, which decreases the compliance of the fascia, leading to a rise in compartment pressure.

Vascular Injuries and Unusual Causes

Arterial Vessel Damage. Injuries to single arterial vessels can also lend to the development of acute compartment syndrome. Arterial damage from high-energy trauma causes acute compartment syndromes due to the rapid development of a hematoma and pressure in affected compartments. Loss of the arterial blood flow from the traumatized artery also causes cell necrosis and edema to the muscle bed, further increasing the compartment pressure. The result of these injuries is the development of acute compartment syndrome in uncommon locations such as the thigh^{14 and foot.15}

Arterial damage from relatively low-energy ankle-inversion injuries have also been implicated in development of acute compartment syndrome of the foot.¹⁵ Conversely, damage to branches of an artery may cause symptoms in the compartments of the proximal extremity, but spare the blood flow and pulsations to the distal portion.¹³ This atypical mechanism of injury requires the physician to maintain a high index of suspicion and consider arteriography and direct pressure management in diagnosis and treatment of this condition.

Deep Vein Thrombosis. Deep vein thrombosis (DVT) can also be associated with acute compartment syndrome. A large clot burden, such as that observed in phlegmasia cerulea dolens, can lead to reduced venous flow and increased pressure, resulting in decreased arteriovenous gradient and tissue perfusion. Acute compartment syndrome caused by extensive DVT is often treated with anticoagulation therapy, thrombolysis or thrombectomy, but fasciotomy also has a role as an adjunct treatment to reduce compartment pressure sufficiently to return blood flow.¹⁶

Medication-Induced Compartment Syndrome

Injections of medications or illicit drugs can lead to increased compartment pressure through several independent mechanisms (Table).¹⁷ Local tissue vasotoxicity from direct injection of a caustic agent can cause direct muscle necrosis and edema. In addition, prolonged external compression while lying in a coma-like state induced by alcohol intoxication or central nervous system suppressant drugs, or a state of unconsciousness from any cause, can produce direct injury to the compartment (Table).

Diagnosis

Signs and Symptoms

Diagnosis of acute compartment syndrome is primarily clinical, using compartment pressure measurement as an adjunct in evaluation. Because the features of early acute compartment syndrome are nonspecific, a high clinical suspicion must be maintained for all at-risk populations.

The classic features such as pain, pallor, paresthesias, paralysis, and pulselessness are all late findings of acute compartment syndrome and are associated with irreversible damage. However, pain out of proportion to injury and pain with passive stretch of muscles are early symptoms that require further attention and monitoring.⁸

The earliest objective finding on physical examination is compartment firmness.⁸ Unfortunately, the sensitivity of physical examination by orthopedic physicians is low (22%-26%) on cadaver models with elevated compartment pressures.¹⁸ Peripheral nerve tissue is very sensitive to ischemia and will stop functioning after 75 minutes.⁹ A review of clinical findings in acute compartment syndrome showed that the positive predictive values of these individual symptoms are low, but there is a high likelihood of compartment syndrome when at least three clinical findings are present simultaneously.¹⁹ In patients who are at high risk for developing acute compartment syndrome, but who may not be able to describe or who do not show clear symptoms (eg, patients who are obtunded, intubated, or very young/old), compartment pressure measurement can be a valuable aid in the diagnosis.

Compartment Pressure Measurement

There are several readily available methods to directly measure the compartment pressure. It is imperative to measure the compartment pressure closest to the fracture location (within 5 cm) because the pressure dissipates as distance increases from the fracture site.²⁰

Solid-State Transducer Intracompartmental Catheter. The Stryker Intra-Compartmental Pressure Monitor System (Stryker Surgical) is a commonly used solid-state transducer intracompartmental catheter (STIC) that allows measurement of compartment pressure.

The STIC system consists of a side-port needle, syringe of saline flush, and a digital read-out manometer. It has been validated against commonly used alternatives and found to be accurate^21,22 with a confidence interval between ± 5 to 6.23. This device uses a side port needle to allow for testing multiple compartments with the same needle as it is less likely to be occluded by tissue when compared to a standard needle.

The following technique should be employed to properly measure compartment pressure using the Stryker STIC device²³:

1. Place the side port needle on the tapered end of the diaphragm chamber.
2. Connect the prefilled syringe of normal saline to the diaphragm chamber.
3. Place the diaphragm chamber in the pressure monitor with the black side down and push until it is seated in the device.
4. Close the cover until it snaps.
5. Place the needle up and fill the system with normal saline from the syringe until there are no air bubbles in the system.
6. Turn the pressure monitor on.
7. Select an intended angle and press the “Zero” button and wait until it reads “00.”
8. Under sterile technique and appropriately anesthetized skin, insert the device into the compartment. Once in the compartment, slowly inject a small amount of saline into the compartment and record the provided number.

For details on needle-placement techniques, including depths, see Figures 1 to 4 for lower extremity compartments and Figures 5 to 7 for upper extremity compartments.²⁴

Laboratory Evaluation

Although the diagnosis of compartment syndrome is made by clinical findings and direct pressure measurement, laboratory tests can support the diagnosis.

Serum creatinine phosphokinase (CPK) is elevated with muscle necrosis. Both CPK and myoglobin proteins are glomerulotoxic, and acute kidney injury is a common complication of acute compartment syndrome. A CPK of greater than 1,000 IU/L has a sensitivity of 0.91 for acute compartment syndrome, but a specificity of only 0.52.2

In a multivariate model for predicting acute compartment syndrome, CPK greater than 4,000 IU/L, chloride greater than 104 mEq/L, and a blood urea nitrogen less than 10 mmol/L were found to be predictive of compartment syndrome during a patient’s hospital admission. No patient had compartment syndrome when all three variables were negative, and all patients with all three positive variables had acute compartment syndrome.²² This model was conducted on admitted patients during their inpatient hospital stay; therefore its application in the ED may not be valid, and the model has yet to be validated prospectively.

Treatment

Prompt surgical consultation for decompressive fasciotomy is paramount to the management of acute compartment syndrome in the ED. When acute compartment syndrome is suspected, elevation of the affected extremity is suggested in an attempt to decrease swelling.²⁷ The optimum height of elevation remains controversial; to prevent a decrease in arterial blood flow, it has been suggested not to raise the affected extremity above the level of the heart.⁸

A low systemic BP should be corrected to hopefully increase the compartment perfusion, and any applied external compressive forces (eg, casts, splints, dressings, eschars) should be removed.⁸ Removal of a cast can reduce the intracompartment pressure by 85%.⁵ Finally, applying cool compresses to the affected region can help reduce edema as a temporizing measure. Direct application of ice to the skin should be avoided to prevent cold-induced injury to the skin.

Appropriate medical resuscitation is imperative to good outcomes. Identifying and intervening when hypotension is present is necessary to improve tissue perfusion. Cellular derangement and death that can lead to hypocalcaemia, hyperkalemia, metabolic acidosis, and renal failure, require prompt recognition and correction.

At-Risk Populations

Pediatric Patients

Diagnosis of acute compartment syndrome in the general pediatric population is very difficult and therefore unfortunately associated with delays in diagnosis. The average time from injury to diagnosis can vary from 18.2to 31.1 hours.^28,29 In children younger than age 3 years, 60% of acute compartment syndrome cases are due to trauma; 27% are due to invasive infections; and 13% develop from intravenous (IV) infiltration.³⁰ Supracondylar humerus fractures are associated with increased risk of compartment syndrome. The volar compartment of the forearm is at risk after reduction of the fracture and when the elbow is flexed beyond 90°.³¹

Intubated and Obtunded Patients

Intubated and obtunded patients require special attention to prevent and/or identify the presence of acute compartment syndrome. Since clinical examination for compartment syndrome in these patients is unreliable, serial or continuous compartment pressure measurements are required to monitor for acute compartment syndrome.

Laboratory analysis, including monitoring of CPK levels, can also help identify developing compartment syndrome in intubated, sedated, or neurologically compromised patients.³² Onset of unexplained myoglobinuria or acute renal failure in an intubated patient should lead to consideration of compartment syndrome. In addition to laboratory studies, examination of atypical locations, such as the back or gluteal compartments, can also assist in identifying compartment syndrome in impaired patients.

Complications

The complications of compartment syndrome can be severe, and are typically organized as early and late stages of the disease.

Early Clinical Complications

Even with prompt diagnosis, acute compartment syndrome can lead to significant metabolic derangements. Patients with compartment syndrome are at significant risk for rhabdomyolysis and resultant renal failure from acute tubal necrosis. Likewise, both myocyte damage and death can cause extracellular electrolyte shifts, and hyperkalemia, metabolic acidosis, and hypocalcemia are frequently encountered under these circumstances.

Late Clinical Complications

Necrotic muscle is a significant risk factor for bacterial superinfection.³³ Necrotic muscle may quickly be seeded by bacteria, and lead to sepsis. Necrotic muscle may therefore require repeated debridement and even possible extremity amputation for infection control. Likewise, muscle necrosis can lead to muscle contractures and loss of function of the affected extremity.³

Medicolegal Complications

Delay in the diagnosis of acute compartment syndrome has become an increasing source of medicolegal liability. In a 2004 review by Bhattacharyya and Vrahas³⁴ of 23 years of claims from a medical malpractice insurer, only 19 claims were made for compartment syndrome. In this series, the following four risk factors were associated with an unsuccessful defense: (1) a linear association between the number of documented cardinal signs of compartment syndrome and an indemnity payment; (2) delays in fasciotomy; (3) poor communication with the patient and nursing staff; (4) and failure to intervene after documentation of an abnormal physical finding. All of the above were associated with a negative legal outcome.

Case Conclusion

The patient had a firm anterior compartment, CPK of 9,100 IU/L, normal renal function, compartment pressure of 60 mm Hg, and diastolic pressure of 80 mm Hg at the time of the procedure. Because the patient had a delta pressure of 20 mm Hg, orthopedic services were consulted, and the patient was taken to the operating room, where he underwent a bicompartment fasciotomy of the right lateral calf. The compartments were tense when opened and there was no evidence of myonecrosis. The patient was given continuous IV fluids and observed in the hospital for 2 days as his CPKs trended downward without subsequent renal injury.

Conclusion

Compartment syndrome requires high clinical suspicion for early diagnosis and treatment to prevent major disability. Early recognition of this condition is paramount, as the classical presentation of the five “Ps”—pain, pallor, pulselessness, paresthesias, and paralysis—are all late findings associated with irreversible consequences.

Given the difficulty in establishing the diagnosis by physical examination findings, the emergency physician (EP) should check and monitor compartment pressures when considering the diagnosis of acute compartment syndrome. In patients with acute compartment syndrome, delayed fasciotomies lead to poor outcomes and a 10-fold increase in surgical complications, such as infection and renal failure.³⁵

Although traumatic fractures are the most common cause of acute compartment syndrome, EPs must also recognize that obtundation, intubation, coagulopathies, and seemingly minor traumas all can potentially cause or lead to acute compartment syndrome.

Acute extremity pain is a common presentation seen daily in EDs. While most etiologies of extremity pain are benign, the complications of acute compartment syndrome are associated with significant morbidity. Moreover, acute compartment syndrome remains a difficult diagnosis that is often missed on initial presentation. Morbidity results from an increased pressure in an anatomically closed space, progressing to decreased perfusion and rapid tissue destruction.

Case

An obese 55-year-old man with a medical history of coronary artery disease, for which he was on aspirin therapy, presented for evaluation of right shin pain. The patient stated that he completed a 5-km race earlier that morning with his son. Immediately following the race, he experienced increasing right shin pain, which he attempted to initially manage with ice compresses and over-the-counter ibuprofen. He noted that neither the ice compresses nor the ibuprofen relieved his pain and that by 5:00 pm, the pain had worsened to the point where he had difficulty walking, prompting his visit to the ED.

Upon arrival at the ED, the patient was ambulatory but had significant pain at both rest and movement. His vital signs and his oxygen saturation on room air were normal. On physical examination, he had normal sensation to the entire right lower extremity and had equal pulses in both feet. The anterolateral aspect of the shin was exquisitely tender to light touch, and the patient was unable to dorsiflex or plantar flex without extreme pain. On passive dorsiflexion and plantar flexion of his right foot, he had exquisite pain. On palpation, the anterior shin was firm compared to the other muscle beds.

Epidemiology

Acute compartment syndrome—elevation of interstitial pressure in closed fascial compartment—affects 10 times as many men as women, at an average age of 32 years old and with an annual incidence of 7.3 per 100,000 men and 0.7 per 100,000 for women.¹ McQueen et al¹ found that the most common cause of acute compartment syndrome was fracture (69%), followed by soft tissue injury (23%). Younger patients are more likely to develop acute compartment syndrome from trauma because they typically have larger muscle beds with more tissue to become edematous compared to the older, hypotrophic muscles of elderly patients.

Pathophysiology

The fascia surrounds the major muscle groups and neurovascular bundles in the extremities to create distinct compartments. Since the fascia is not a compliant structure, it is typically not able to tolerate increases in volume or pressure in a given compartment. Compartment perfusion pressure is the mean arterial pressure minus the compartment pressure. Normal compartment pressure in adults is between 0 to 8 mm Hg.² When compartment perfusion pressures are below 70 to 80 mm Hg, there is an increased risk of compartment syndrome.

Although the exact pathophysiology of acute compartment syndrome is still debated,³ the most commonly accepted theory is the arteriovenous pressure gradient theory.⁴ In this theory, the rise in intracompartment pressure increases venous pressure, which in turn reduces the arteriovenous pressure gradient, reducing local tissue perfusion. The reduction in tissue perfusion, coupled with a reduction in venous drainage, causes significant tissue edema. This change in vascular pressure also causes a reduction in lymphatic drainage, further increasing pressure in the compartment. Finally, the edematous tissue compresses the arterioles leading to end-organ ischemia.⁵

Initially an absolute threshold compartment pressure was thought to cause irreversible tissue ischemia,⁶ but this theory has slowly lost favor after it was found that hypertension was actually protective in compartment syndrome.⁷ Current thinking is that the difference between the diastolic pressure and the compartment pressure leads to tissue ischemia (ie, acute compartment syndrome delta pressure = diastolic blood pressure [BP] – measured compartment pressure).^6,8

In 1996, McQueen and Court-Brown⁶ prospectively admitted all tibial diaphyseal fractures and continuously monitored their anterior compartment pressure. Using a delta pressure value of less than 30 mm Hg, only three patients were diagnosed with acute compartment syndrome and required fasciotomy. The patients’ absolute compartment pressures were 45 mm Hg, 65 mm Hg, and 75 mm Hg, while the delta pressures were 15 mm Hg, 10 mm Hg, and 15 mm Hg, respectively. Conversely, 53 patients had absolute compartment pressures over 30 mm Hg; 30 patients had pressure over 40 mm Hg; four patients had pressure over 50 mm Hg; and none required fasciotomy. This study highlights that the absolute compartment pressure is not helpful in making the diagnosis, and it is the elevated delta pressure that secures the diagnosis.

Etiology

Compartment syndrome is the end result of many different injury patterns. While fracture is the number one cause of compartment syndrome, many types of soft tissue injuries can also lead to compartment syndrome. Nonfracture etiologies of compartment syndrome are relatively uncommon, and as such can lead to a delay in diagnosis.

Fracture

Almost 70% of all cases of compartment syndrome are due to fracture.¹ Fractures of the tibia, distal radius, and ulna are the most common injuries that lead to acute compartment syndrome. Interestingly, acute compartment syndrome is caused by an equal distribution of high-energy and low-energy mechanisms of injuries.¹ Because the increase in compartment pressure is highest at the fracture site,⁹ it is imperative to measure pressures at the site of the fracture. Contrary to traditional teaching, an open fracture does not reduce the risk of compartment syndrome. McQueen and Court-Brown⁶ found there was no difference in the intracompartment pressure between open and closed fractures.

Fracture reduction and manipulation can actually increase the risk of compartment syndrome. In one case series, fracture manipulation increased compartment pressure by reducing the total volume in a stretched compartment.¹⁰ Dresing et al¹⁰ found the average pressure increased by 21 mm Hg during wrist reduction, warranting close observation after fracture reduction and close observation of the patient’s pain and neurovascular status.

McQueen et al¹¹ evaluated the risk factors for the development of acute compartment syndrome from tibial diaphyseal fractures and found that younger patients were at the highest risk. Patients between ages 10 to 19 years old had an odds ratio (OR) of 12.09; 20 to 29 years old had an OR of 9.84; and patients older than age 40 years had an OR of 1.¹¹ As previously stated, younger patients have larger muscle volumes compared to their older counterparts and therefore have less space for edema after the primary muscle injury.

Soft Tissue Injury

Direct soft tissue injury can lead to a rise in compartment pressures due to trauma, infections, and burns even in the absence of fractures. Unfortunately, under these circumstances, patients with direct soft tissue injury are at high risk for a delay in diagnosis.¹² The primary injury can be worsened by underlying coagulopathies.¹ A circumferential constrictive eschar from burns can also cause external compression to a compartment¹³ as well as edema, which decreases the compliance of the fascia, leading to a rise in compartment pressure.

Vascular Injuries and Unusual Causes

Arterial Vessel Damage. Injuries to single arterial vessels can also lend to the development of acute compartment syndrome. Arterial damage from high-energy trauma causes acute compartment syndromes due to the rapid development of a hematoma and pressure in affected compartments. Loss of the arterial blood flow from the traumatized artery also causes cell necrosis and edema to the muscle bed, further increasing the compartment pressure. The result of these injuries is the development of acute compartment syndrome in uncommon locations such as the thigh^{14 and foot.15}

Arterial damage from relatively low-energy ankle-inversion injuries have also been implicated in development of acute compartment syndrome of the foot.¹⁵ Conversely, damage to branches of an artery may cause symptoms in the compartments of the proximal extremity, but spare the blood flow and pulsations to the distal portion.¹³ This atypical mechanism of injury requires the physician to maintain a high index of suspicion and consider arteriography and direct pressure management in diagnosis and treatment of this condition.

Deep Vein Thrombosis. Deep vein thrombosis (DVT) can also be associated with acute compartment syndrome. A large clot burden, such as that observed in phlegmasia cerulea dolens, can lead to reduced venous flow and increased pressure, resulting in decreased arteriovenous gradient and tissue perfusion. Acute compartment syndrome caused by extensive DVT is often treated with anticoagulation therapy, thrombolysis or thrombectomy, but fasciotomy also has a role as an adjunct treatment to reduce compartment pressure sufficiently to return blood flow.¹⁶

Medication-Induced Compartment Syndrome

Injections of medications or illicit drugs can lead to increased compartment pressure through several independent mechanisms (Table).¹⁷ Local tissue vasotoxicity from direct injection of a caustic agent can cause direct muscle necrosis and edema. In addition, prolonged external compression while lying in a coma-like state induced by alcohol intoxication or central nervous system suppressant drugs, or a state of unconsciousness from any cause, can produce direct injury to the compartment (Table).

Diagnosis

Signs and Symptoms

Diagnosis of acute compartment syndrome is primarily clinical, using compartment pressure measurement as an adjunct in evaluation. Because the features of early acute compartment syndrome are nonspecific, a high clinical suspicion must be maintained for all at-risk populations.

The classic features such as pain, pallor, paresthesias, paralysis, and pulselessness are all late findings of acute compartment syndrome and are associated with irreversible damage. However, pain out of proportion to injury and pain with passive stretch of muscles are early symptoms that require further attention and monitoring.⁸

The earliest objective finding on physical examination is compartment firmness.⁸ Unfortunately, the sensitivity of physical examination by orthopedic physicians is low (22%-26%) on cadaver models with elevated compartment pressures.¹⁸ Peripheral nerve tissue is very sensitive to ischemia and will stop functioning after 75 minutes.⁹ A review of clinical findings in acute compartment syndrome showed that the positive predictive values of these individual symptoms are low, but there is a high likelihood of compartment syndrome when at least three clinical findings are present simultaneously.¹⁹ In patients who are at high risk for developing acute compartment syndrome, but who may not be able to describe or who do not show clear symptoms (eg, patients who are obtunded, intubated, or very young/old), compartment pressure measurement can be a valuable aid in the diagnosis.

Compartment Pressure Measurement

There are several readily available methods to directly measure the compartment pressure. It is imperative to measure the compartment pressure closest to the fracture location (within 5 cm) because the pressure dissipates as distance increases from the fracture site.²⁰

Solid-State Transducer Intracompartmental Catheter. The Stryker Intra-Compartmental Pressure Monitor System (Stryker Surgical) is a commonly used solid-state transducer intracompartmental catheter (STIC) that allows measurement of compartment pressure.

The STIC system consists of a side-port needle, syringe of saline flush, and a digital read-out manometer. It has been validated against commonly used alternatives and found to be accurate^21,22 with a confidence interval between ± 5 to 6.23. This device uses a side port needle to allow for testing multiple compartments with the same needle as it is less likely to be occluded by tissue when compared to a standard needle.

The following technique should be employed to properly measure compartment pressure using the Stryker STIC device²³:

1. Place the side port needle on the tapered end of the diaphragm chamber.
2. Connect the prefilled syringe of normal saline to the diaphragm chamber.
3. Place the diaphragm chamber in the pressure monitor with the black side down and push until it is seated in the device.
4. Close the cover until it snaps.
5. Place the needle up and fill the system with normal saline from the syringe until there are no air bubbles in the system.
6. Turn the pressure monitor on.
7. Select an intended angle and press the “Zero” button and wait until it reads “00.”
8. Under sterile technique and appropriately anesthetized skin, insert the device into the compartment. Once in the compartment, slowly inject a small amount of saline into the compartment and record the provided number.

For details on needle-placement techniques, including depths, see Figures 1 to 4 for lower extremity compartments and Figures 5 to 7 for upper extremity compartments.²⁴

Laboratory Evaluation

Although the diagnosis of compartment syndrome is made by clinical findings and direct pressure measurement, laboratory tests can support the diagnosis.

Serum creatinine phosphokinase (CPK) is elevated with muscle necrosis. Both CPK and myoglobin proteins are glomerulotoxic, and acute kidney injury is a common complication of acute compartment syndrome. A CPK of greater than 1,000 IU/L has a sensitivity of 0.91 for acute compartment syndrome, but a specificity of only 0.52.2

In a multivariate model for predicting acute compartment syndrome, CPK greater than 4,000 IU/L, chloride greater than 104 mEq/L, and a blood urea nitrogen less than 10 mmol/L were found to be predictive of compartment syndrome during a patient’s hospital admission. No patient had compartment syndrome when all three variables were negative, and all patients with all three positive variables had acute compartment syndrome.²² This model was conducted on admitted patients during their inpatient hospital stay; therefore its application in the ED may not be valid, and the model has yet to be validated prospectively.

Treatment

Prompt surgical consultation for decompressive fasciotomy is paramount to the management of acute compartment syndrome in the ED. When acute compartment syndrome is suspected, elevation of the affected extremity is suggested in an attempt to decrease swelling.²⁷ The optimum height of elevation remains controversial; to prevent a decrease in arterial blood flow, it has been suggested not to raise the affected extremity above the level of the heart.⁸

A low systemic BP should be corrected to hopefully increase the compartment perfusion, and any applied external compressive forces (eg, casts, splints, dressings, eschars) should be removed.⁸ Removal of a cast can reduce the intracompartment pressure by 85%.⁵ Finally, applying cool compresses to the affected region can help reduce edema as a temporizing measure. Direct application of ice to the skin should be avoided to prevent cold-induced injury to the skin.

Appropriate medical resuscitation is imperative to good outcomes. Identifying and intervening when hypotension is present is necessary to improve tissue perfusion. Cellular derangement and death that can lead to hypocalcaemia, hyperkalemia, metabolic acidosis, and renal failure, require prompt recognition and correction.

At-Risk Populations

Pediatric Patients

Diagnosis of acute compartment syndrome in the general pediatric population is very difficult and therefore unfortunately associated with delays in diagnosis. The average time from injury to diagnosis can vary from 18.2to 31.1 hours.^28,29 In children younger than age 3 years, 60% of acute compartment syndrome cases are due to trauma; 27% are due to invasive infections; and 13% develop from intravenous (IV) infiltration.³⁰ Supracondylar humerus fractures are associated with increased risk of compartment syndrome. The volar compartment of the forearm is at risk after reduction of the fracture and when the elbow is flexed beyond 90°.³¹

Intubated and Obtunded Patients

Intubated and obtunded patients require special attention to prevent and/or identify the presence of acute compartment syndrome. Since clinical examination for compartment syndrome in these patients is unreliable, serial or continuous compartment pressure measurements are required to monitor for acute compartment syndrome.

Laboratory analysis, including monitoring of CPK levels, can also help identify developing compartment syndrome in intubated, sedated, or neurologically compromised patients.³² Onset of unexplained myoglobinuria or acute renal failure in an intubated patient should lead to consideration of compartment syndrome. In addition to laboratory studies, examination of atypical locations, such as the back or gluteal compartments, can also assist in identifying compartment syndrome in impaired patients.

Complications

The complications of compartment syndrome can be severe, and are typically organized as early and late stages of the disease.

Early Clinical Complications

Even with prompt diagnosis, acute compartment syndrome can lead to significant metabolic derangements. Patients with compartment syndrome are at significant risk for rhabdomyolysis and resultant renal failure from acute tubal necrosis. Likewise, both myocyte damage and death can cause extracellular electrolyte shifts, and hyperkalemia, metabolic acidosis, and hypocalcemia are frequently encountered under these circumstances.

Late Clinical Complications

Necrotic muscle is a significant risk factor for bacterial superinfection.³³ Necrotic muscle may quickly be seeded by bacteria, and lead to sepsis. Necrotic muscle may therefore require repeated debridement and even possible extremity amputation for infection control. Likewise, muscle necrosis can lead to muscle contractures and loss of function of the affected extremity.³

Medicolegal Complications

Delay in the diagnosis of acute compartment syndrome has become an increasing source of medicolegal liability. In a 2004 review by Bhattacharyya and Vrahas³⁴ of 23 years of claims from a medical malpractice insurer, only 19 claims were made for compartment syndrome. In this series, the following four risk factors were associated with an unsuccessful defense: (1) a linear association between the number of documented cardinal signs of compartment syndrome and an indemnity payment; (2) delays in fasciotomy; (3) poor communication with the patient and nursing staff; (4) and failure to intervene after documentation of an abnormal physical finding. All of the above were associated with a negative legal outcome.

Case Conclusion

The patient had a firm anterior compartment, CPK of 9,100 IU/L, normal renal function, compartment pressure of 60 mm Hg, and diastolic pressure of 80 mm Hg at the time of the procedure. Because the patient had a delta pressure of 20 mm Hg, orthopedic services were consulted, and the patient was taken to the operating room, where he underwent a bicompartment fasciotomy of the right lateral calf. The compartments were tense when opened and there was no evidence of myonecrosis. The patient was given continuous IV fluids and observed in the hospital for 2 days as his CPKs trended downward without subsequent renal injury.

Conclusion

Compartment syndrome requires high clinical suspicion for early diagnosis and treatment to prevent major disability. Early recognition of this condition is paramount, as the classical presentation of the five “Ps”—pain, pallor, pulselessness, paresthesias, and paralysis—are all late findings associated with irreversible consequences.

Given the difficulty in establishing the diagnosis by physical examination findings, the emergency physician (EP) should check and monitor compartment pressures when considering the diagnosis of acute compartment syndrome. In patients with acute compartment syndrome, delayed fasciotomies lead to poor outcomes and a 10-fold increase in surgical complications, such as infection and renal failure.³⁵

Although traumatic fractures are the most common cause of acute compartment syndrome, EPs must also recognize that obtundation, intubation, coagulopathies, and seemingly minor traumas all can potentially cause or lead to acute compartment syndrome.

Acute extremity pain is a common presentation seen daily in EDs. While most etiologies of extremity pain are benign, the complications of acute compartment syndrome are associated with significant morbidity. Moreover, acute compartment syndrome remains a difficult diagnosis that is often missed on initial presentation. Morbidity results from an increased pressure in an anatomically closed space, progressing to decreased perfusion and rapid tissue destruction.

Case

An obese 55-year-old man with a medical history of coronary artery disease, for which he was on aspirin therapy, presented for evaluation of right shin pain. The patient stated that he completed a 5-km race earlier that morning with his son. Immediately following the race, he experienced increasing right shin pain, which he attempted to initially manage with ice compresses and over-the-counter ibuprofen. He noted that neither the ice compresses nor the ibuprofen relieved his pain and that by 5:00 pm, the pain had worsened to the point where he had difficulty walking, prompting his visit to the ED.

Upon arrival at the ED, the patient was ambulatory but had significant pain at both rest and movement. His vital signs and his oxygen saturation on room air were normal. On physical examination, he had normal sensation to the entire right lower extremity and had equal pulses in both feet. The anterolateral aspect of the shin was exquisitely tender to light touch, and the patient was unable to dorsiflex or plantar flex without extreme pain. On passive dorsiflexion and plantar flexion of his right foot, he had exquisite pain. On palpation, the anterior shin was firm compared to the other muscle beds.

Epidemiology

Acute compartment syndrome—elevation of interstitial pressure in closed fascial compartment—affects 10 times as many men as women, at an average age of 32 years old and with an annual incidence of 7.3 per 100,000 men and 0.7 per 100,000 for women.¹ McQueen et al¹ found that the most common cause of acute compartment syndrome was fracture (69%), followed by soft tissue injury (23%). Younger patients are more likely to develop acute compartment syndrome from trauma because they typically have larger muscle beds with more tissue to become edematous compared to the older, hypotrophic muscles of elderly patients.

Pathophysiology

The fascia surrounds the major muscle groups and neurovascular bundles in the extremities to create distinct compartments. Since the fascia is not a compliant structure, it is typically not able to tolerate increases in volume or pressure in a given compartment. Compartment perfusion pressure is the mean arterial pressure minus the compartment pressure. Normal compartment pressure in adults is between 0 to 8 mm Hg.² When compartment perfusion pressures are below 70 to 80 mm Hg, there is an increased risk of compartment syndrome.

Although the exact pathophysiology of acute compartment syndrome is still debated,³ the most commonly accepted theory is the arteriovenous pressure gradient theory.⁴ In this theory, the rise in intracompartment pressure increases venous pressure, which in turn reduces the arteriovenous pressure gradient, reducing local tissue perfusion. The reduction in tissue perfusion, coupled with a reduction in venous drainage, causes significant tissue edema. This change in vascular pressure also causes a reduction in lymphatic drainage, further increasing pressure in the compartment. Finally, the edematous tissue compresses the arterioles leading to end-organ ischemia.⁵

Initially an absolute threshold compartment pressure was thought to cause irreversible tissue ischemia,⁶ but this theory has slowly lost favor after it was found that hypertension was actually protective in compartment syndrome.⁷ Current thinking is that the difference between the diastolic pressure and the compartment pressure leads to tissue ischemia (ie, acute compartment syndrome delta pressure = diastolic blood pressure [BP] – measured compartment pressure).^6,8

In 1996, McQueen and Court-Brown⁶ prospectively admitted all tibial diaphyseal fractures and continuously monitored their anterior compartment pressure. Using a delta pressure value of less than 30 mm Hg, only three patients were diagnosed with acute compartment syndrome and required fasciotomy. The patients’ absolute compartment pressures were 45 mm Hg, 65 mm Hg, and 75 mm Hg, while the delta pressures were 15 mm Hg, 10 mm Hg, and 15 mm Hg, respectively. Conversely, 53 patients had absolute compartment pressures over 30 mm Hg; 30 patients had pressure over 40 mm Hg; four patients had pressure over 50 mm Hg; and none required fasciotomy. This study highlights that the absolute compartment pressure is not helpful in making the diagnosis, and it is the elevated delta pressure that secures the diagnosis.

Etiology

Compartment syndrome is the end result of many different injury patterns. While fracture is the number one cause of compartment syndrome, many types of soft tissue injuries can also lead to compartment syndrome. Nonfracture etiologies of compartment syndrome are relatively uncommon, and as such can lead to a delay in diagnosis.

Fracture

Almost 70% of all cases of compartment syndrome are due to fracture.¹ Fractures of the tibia, distal radius, and ulna are the most common injuries that lead to acute compartment syndrome. Interestingly, acute compartment syndrome is caused by an equal distribution of high-energy and low-energy mechanisms of injuries.¹ Because the increase in compartment pressure is highest at the fracture site,⁹ it is imperative to measure pressures at the site of the fracture. Contrary to traditional teaching, an open fracture does not reduce the risk of compartment syndrome. McQueen and Court-Brown⁶ found there was no difference in the intracompartment pressure between open and closed fractures.

Fracture reduction and manipulation can actually increase the risk of compartment syndrome. In one case series, fracture manipulation increased compartment pressure by reducing the total volume in a stretched compartment.¹⁰ Dresing et al¹⁰ found the average pressure increased by 21 mm Hg during wrist reduction, warranting close observation after fracture reduction and close observation of the patient’s pain and neurovascular status.

McQueen et al¹¹ evaluated the risk factors for the development of acute compartment syndrome from tibial diaphyseal fractures and found that younger patients were at the highest risk. Patients between ages 10 to 19 years old had an odds ratio (OR) of 12.09; 20 to 29 years old had an OR of 9.84; and patients older than age 40 years had an OR of 1.¹¹ As previously stated, younger patients have larger muscle volumes compared to their older counterparts and therefore have less space for edema after the primary muscle injury.

Soft Tissue Injury

Direct soft tissue injury can lead to a rise in compartment pressures due to trauma, infections, and burns even in the absence of fractures. Unfortunately, under these circumstances, patients with direct soft tissue injury are at high risk for a delay in diagnosis.¹² The primary injury can be worsened by underlying coagulopathies.¹ A circumferential constrictive eschar from burns can also cause external compression to a compartment¹³ as well as edema, which decreases the compliance of the fascia, leading to a rise in compartment pressure.

Vascular Injuries and Unusual Causes

Arterial Vessel Damage. Injuries to single arterial vessels can also lend to the development of acute compartment syndrome. Arterial damage from high-energy trauma causes acute compartment syndromes due to the rapid development of a hematoma and pressure in affected compartments. Loss of the arterial blood flow from the traumatized artery also causes cell necrosis and edema to the muscle bed, further increasing the compartment pressure. The result of these injuries is the development of acute compartment syndrome in uncommon locations such as the thigh^{14 and foot.15}

Arterial damage from relatively low-energy ankle-inversion injuries have also been implicated in development of acute compartment syndrome of the foot.¹⁵ Conversely, damage to branches of an artery may cause symptoms in the compartments of the proximal extremity, but spare the blood flow and pulsations to the distal portion.¹³ This atypical mechanism of injury requires the physician to maintain a high index of suspicion and consider arteriography and direct pressure management in diagnosis and treatment of this condition.

Deep Vein Thrombosis. Deep vein thrombosis (DVT) can also be associated with acute compartment syndrome. A large clot burden, such as that observed in phlegmasia cerulea dolens, can lead to reduced venous flow and increased pressure, resulting in decreased arteriovenous gradient and tissue perfusion. Acute compartment syndrome caused by extensive DVT is often treated with anticoagulation therapy, thrombolysis or thrombectomy, but fasciotomy also has a role as an adjunct treatment to reduce compartment pressure sufficiently to return blood flow.¹⁶

Medication-Induced Compartment Syndrome

Injections of medications or illicit drugs can lead to increased compartment pressure through several independent mechanisms (Table).¹⁷ Local tissue vasotoxicity from direct injection of a caustic agent can cause direct muscle necrosis and edema. In addition, prolonged external compression while lying in a coma-like state induced by alcohol intoxication or central nervous system suppressant drugs, or a state of unconsciousness from any cause, can produce direct injury to the compartment (Table).

Diagnosis

Signs and Symptoms

Diagnosis of acute compartment syndrome is primarily clinical, using compartment pressure measurement as an adjunct in evaluation. Because the features of early acute compartment syndrome are nonspecific, a high clinical suspicion must be maintained for all at-risk populations.

The classic features such as pain, pallor, paresthesias, paralysis, and pulselessness are all late findings of acute compartment syndrome and are associated with irreversible damage. However, pain out of proportion to injury and pain with passive stretch of muscles are early symptoms that require further attention and monitoring.⁸

The earliest objective finding on physical examination is compartment firmness.⁸ Unfortunately, the sensitivity of physical examination by orthopedic physicians is low (22%-26%) on cadaver models with elevated compartment pressures.¹⁸ Peripheral nerve tissue is very sensitive to ischemia and will stop functioning after 75 minutes.⁹ A review of clinical findings in acute compartment syndrome showed that the positive predictive values of these individual symptoms are low, but there is a high likelihood of compartment syndrome when at least three clinical findings are present simultaneously.¹⁹ In patients who are at high risk for developing acute compartment syndrome, but who may not be able to describe or who do not show clear symptoms (eg, patients who are obtunded, intubated, or very young/old), compartment pressure measurement can be a valuable aid in the diagnosis.

Compartment Pressure Measurement

There are several readily available methods to directly measure the compartment pressure. It is imperative to measure the compartment pressure closest to the fracture location (within 5 cm) because the pressure dissipates as distance increases from the fracture site.²⁰

Solid-State Transducer Intracompartmental Catheter. The Stryker Intra-Compartmental Pressure Monitor System (Stryker Surgical) is a commonly used solid-state transducer intracompartmental catheter (STIC) that allows measurement of compartment pressure.

The STIC system consists of a side-port needle, syringe of saline flush, and a digital read-out manometer. It has been validated against commonly used alternatives and found to be accurate^21,22 with a confidence interval between ± 5 to 6.23. This device uses a side port needle to allow for testing multiple compartments with the same needle as it is less likely to be occluded by tissue when compared to a standard needle.

The following technique should be employed to properly measure compartment pressure using the Stryker STIC device²³:

1. Place the side port needle on the tapered end of the diaphragm chamber.
2. Connect the prefilled syringe of normal saline to the diaphragm chamber.
3. Place the diaphragm chamber in the pressure monitor with the black side down and push until it is seated in the device.
4. Close the cover until it snaps.
5. Place the needle up and fill the system with normal saline from the syringe until there are no air bubbles in the system.
6. Turn the pressure monitor on.
7. Select an intended angle and press the “Zero” button and wait until it reads “00.”
8. Under sterile technique and appropriately anesthetized skin, insert the device into the compartment. Once in the compartment, slowly inject a small amount of saline into the compartment and record the provided number.

For details on needle-placement techniques, including depths, see Figures 1 to 4 for lower extremity compartments and Figures 5 to 7 for upper extremity compartments.²⁴

Laboratory Evaluation

Although the diagnosis of compartment syndrome is made by clinical findings and direct pressure measurement, laboratory tests can support the diagnosis.

Serum creatinine phosphokinase (CPK) is elevated with muscle necrosis. Both CPK and myoglobin proteins are glomerulotoxic, and acute kidney injury is a common complication of acute compartment syndrome. A CPK of greater than 1,000 IU/L has a sensitivity of 0.91 for acute compartment syndrome, but a specificity of only 0.52.2

In a multivariate model for predicting acute compartment syndrome, CPK greater than 4,000 IU/L, chloride greater than 104 mEq/L, and a blood urea nitrogen less than 10 mmol/L were found to be predictive of compartment syndrome during a patient’s hospital admission. No patient had compartment syndrome when all three variables were negative, and all patients with all three positive variables had acute compartment syndrome.²² This model was conducted on admitted patients during their inpatient hospital stay; therefore its application in the ED may not be valid, and the model has yet to be validated prospectively.

Treatment

Prompt surgical consultation for decompressive fasciotomy is paramount to the management of acute compartment syndrome in the ED. When acute compartment syndrome is suspected, elevation of the affected extremity is suggested in an attempt to decrease swelling.²⁷ The optimum height of elevation remains controversial; to prevent a decrease in arterial blood flow, it has been suggested not to raise the affected extremity above the level of the heart.⁸

A low systemic BP should be corrected to hopefully increase the compartment perfusion, and any applied external compressive forces (eg, casts, splints, dressings, eschars) should be removed.⁸ Removal of a cast can reduce the intracompartment pressure by 85%.⁵ Finally, applying cool compresses to the affected region can help reduce edema as a temporizing measure. Direct application of ice to the skin should be avoided to prevent cold-induced injury to the skin.

Appropriate medical resuscitation is imperative to good outcomes. Identifying and intervening when hypotension is present is necessary to improve tissue perfusion. Cellular derangement and death that can lead to hypocalcaemia, hyperkalemia, metabolic acidosis, and renal failure, require prompt recognition and correction.

At-Risk Populations

Pediatric Patients

Diagnosis of acute compartment syndrome in the general pediatric population is very difficult and therefore unfortunately associated with delays in diagnosis. The average time from injury to diagnosis can vary from 18.2to 31.1 hours.^28,29 In children younger than age 3 years, 60% of acute compartment syndrome cases are due to trauma; 27% are due to invasive infections; and 13% develop from intravenous (IV) infiltration.³⁰ Supracondylar humerus fractures are associated with increased risk of compartment syndrome. The volar compartment of the forearm is at risk after reduction of the fracture and when the elbow is flexed beyond 90°.³¹

Intubated and Obtunded Patients

Intubated and obtunded patients require special attention to prevent and/or identify the presence of acute compartment syndrome. Since clinical examination for compartment syndrome in these patients is unreliable, serial or continuous compartment pressure measurements are required to monitor for acute compartment syndrome.

Laboratory analysis, including monitoring of CPK levels, can also help identify developing compartment syndrome in intubated, sedated, or neurologically compromised patients.³² Onset of unexplained myoglobinuria or acute renal failure in an intubated patient should lead to consideration of compartment syndrome. In addition to laboratory studies, examination of atypical locations, such as the back or gluteal compartments, can also assist in identifying compartment syndrome in impaired patients.

Complications

The complications of compartment syndrome can be severe, and are typically organized as early and late stages of the disease.

Early Clinical Complications

Even with prompt diagnosis, acute compartment syndrome can lead to significant metabolic derangements. Patients with compartment syndrome are at significant risk for rhabdomyolysis and resultant renal failure from acute tubal necrosis. Likewise, both myocyte damage and death can cause extracellular electrolyte shifts, and hyperkalemia, metabolic acidosis, and hypocalcemia are frequently encountered under these circumstances.

Late Clinical Complications

Necrotic muscle is a significant risk factor for bacterial superinfection.³³ Necrotic muscle may quickly be seeded by bacteria, and lead to sepsis. Necrotic muscle may therefore require repeated debridement and even possible extremity amputation for infection control. Likewise, muscle necrosis can lead to muscle contractures and loss of function of the affected extremity.³

Medicolegal Complications

Delay in the diagnosis of acute compartment syndrome has become an increasing source of medicolegal liability. In a 2004 review by Bhattacharyya and Vrahas³⁴ of 23 years of claims from a medical malpractice insurer, only 19 claims were made for compartment syndrome. In this series, the following four risk factors were associated with an unsuccessful defense: (1) a linear association between the number of documented cardinal signs of compartment syndrome and an indemnity payment; (2) delays in fasciotomy; (3) poor communication with the patient and nursing staff; (4) and failure to intervene after documentation of an abnormal physical finding. All of the above were associated with a negative legal outcome.

Case Conclusion

The patient had a firm anterior compartment, CPK of 9,100 IU/L, normal renal function, compartment pressure of 60 mm Hg, and diastolic pressure of 80 mm Hg at the time of the procedure. Because the patient had a delta pressure of 20 mm Hg, orthopedic services were consulted, and the patient was taken to the operating room, where he underwent a bicompartment fasciotomy of the right lateral calf. The compartments were tense when opened and there was no evidence of myonecrosis. The patient was given continuous IV fluids and observed in the hospital for 2 days as his CPKs trended downward without subsequent renal injury.

Conclusion

Compartment syndrome requires high clinical suspicion for early diagnosis and treatment to prevent major disability. Early recognition of this condition is paramount, as the classical presentation of the five “Ps”—pain, pallor, pulselessness, paresthesias, and paralysis—are all late findings associated with irreversible consequences.

Given the difficulty in establishing the diagnosis by physical examination findings, the emergency physician (EP) should check and monitor compartment pressures when considering the diagnosis of acute compartment syndrome. In patients with acute compartment syndrome, delayed fasciotomies lead to poor outcomes and a 10-fold increase in surgical complications, such as infection and renal failure.³⁵

Although traumatic fractures are the most common cause of acute compartment syndrome, EPs must also recognize that obtundation, intubation, coagulopathies, and seemingly minor traumas all can potentially cause or lead to acute compartment syndrome.

Editor’s Note: This article has been adapted from an article originally published in Federal Practitioner (Clement C, Stock C. Who overdoses at a VA emergency department? Fed Prac. 2016;33[11]:14-19. http://www.fedprac.com).

Overdose deaths remain epidemic throughout the United States. The rates of unintentional overdose deaths, increasing by 137% between 2000 and 2014, have been driven by a 4-fold increase in prescription opioid overdoses during that period.^1-3

Veterans died of accidental overdose at a rate of 19.85 deaths/100,000 people compared with a rate of 10.49 deaths in the general population, based on 2005 data.⁴ There is wide state-by-state variation, with the lowest age-adjusted opioid overdose death rate of 1.9 deaths/100,000 person-years among veterans in Mississippi and the highest rate in Utah of 33.9 deaths/100,000 person-years, using 2001 to 2009 data.⁵ These data can be compared with a crude general population overdose death rate of 10.6 deaths per 100,000 person-years in Mississippi and 18.4 deaths per 100,000 person-years in the general Utah population during that same period.⁶

Overdose deaths in the United States occur most often in persons aged 25 to 54 years.⁷ Older age has been associated with iatrogenic opioid overdose in hospitalized patients.⁸ Pulmonary disease, cardiovascular disease (CVD), and psychiatric disorders, including past or present substance use, have been associated with an increased risk of opioid overdose.⁹ However, veterans with substance use disorders are less likely to be prescribed opioids than are nonveterans with substance use disorders.¹⁰ Also, concomitant use of sedating medications, such as benzodiazepines (BZDs), can increase mortality from opioid overdose.¹¹ Patients prescribed opioids for chronic pain conditions often take BZDs for various reasons.¹² Veterans seem more likely to receive opioids to treat chronic pain but at lower average daily doses than doses prescribed to nonveterans.¹⁰

Emergency management of life-threatening opioid overdose includes prompt administration of naloxone.¹³ Naloxone is approved by the US Food and Drug Administration for complete or partial reversal of opioid-induced clinical effects, most critically respiratory depression.^14,15 Naloxone administration in the ED may serve as a surrogate for an overdose event. During the study period, naloxone take-home kits were not available in the Veterans Affairs (VA) setting.

A 2010 ED study described demographic information and comorbidities in opioid overdose, but the study did not include veterans.¹⁶ The clinical characteristics of veterans treated for opioid overdose have not been published. Because identifying characteristics of veterans who overdose may help tailor overdose-prevention efforts, the objective of this study is to describe clinical characteristics of veterans treated for opioid overdose.

Methods

A retrospective chart review and archived data study was approved by the University of Utah and VA Institutional Review Boards, and conducted at the George E. Wahlen Veterans Affairs Medical Center (VAMC) in Salt Lake City, Utah. This chart review included veterans who were admitted to the ED and treated with naloxone between January 1, 2009 and January 1, 2013. 

The authors used the Pharmacy Benefits Management Data Manager to extract data from the VA Data Warehouse and verified the data by open chart review (Table). The following data were collected: ED visit date (overdose date); demographic information, including age, gender, and race; evidence of next of kin or other contact at the same address as the veteran; diagnoses based on International Classification of Diseases, 9th Revision (ICD-9) codes, including sleep apnea, obesity, cardiac disease, pulmonary disease, mental health diagnoses (ICD-9 codes 290-302 [wild card characters (*) included many subdiagnoses]), cancer, and substance use disorders and/or dependencies (SUDD); tobacco use; VA-issued prescription opioid and BZD availability, including dose, fill dates, quantities dispensed, and day supplies; specialty of opioid prescriber; urine-drug screening (UDS) results; and outcome of the overdose. 

No standardized research criteria identify overdose in medical chart review.¹⁷ For each identified patient, the authors reviewed provider and nursing notes charted during an ED visit that included naloxone administration. The event was included as an opioid overdose when notes indicated that the veteran was unresponsive and given naloxone, which resulted in increased respirations or increased responsiveness. Cases were excluded if the reason for naloxone administration was anything other than opioid overdose.

Medical, mental health, and SUDD diagnoses were included only if the veteran had more than three patient-care encounters (PCE) with ICD-9 codes for a specific diagnosis entered by providers. A PCE used in the electronic medical record (EMR) helps collect, manage, and display outpatient encounter data, including providers, procedure codes, and diagnostic codes. Tobacco use was extracted from health factors documented during primary care visit screenings. (Health factors help capture data entered in note templates in the EMR and can be used to query trends.) A diagnosis of obesity was based on a calculated body mass index of at or greater than 30 kg/m² on the day of the ED visit date or the most recently charted height and weight. The type of SUDD was stratified into opioids (ICD-9 codes 304.0*), sedatives (ICD-9 codes 304.1*), alcohol (ICD-9 codes 303.*), and other (ICD-9 codes 304.2-305.9).

The dosage of opioids and BZDs available to a veteran was determined by using methods similar to those described by Gomes et al¹⁸: the dose of opioids and BZDs available based on prescriptions dispensed during the 120 days prior to the ED visit date and the dose available on the day of the ED visit date if prescription instructions were being followed. Prescription opioids and BZDs were converted to daily morphineequivalent dose (MED) and daily lorazepam equivalent dose (LED), using established methods.^19,20

Veterans were stratified into four groups based on prescribed medication availability: opioids only, BZDs only, opioids and BZDs, and neither opioids nor BZDs. The specialty of the opioid prescribers was categorized as primary care, pain specialist, surgeon, emergency specialist, or hospitalist (discharge prescription). Veteran EMRs contain a list of medications obtained outside the VA facility, referred to as non-VA prescriptions. These medications were not included in the analysis because accuracy could not be verified.

A study author reviewed the results of any UDS performed up to 120 days before the ED visit date to determine whether the result reflected the currently prescribed prescription medications. If the UDS was positive for the prescribed opioids and/or BZDs and for any nonprescribed drug, including alcohol, the UDS was classified as not reflective. If the prescribed BZD was alprazolam, clonazepam, or lorazepam, a BZD-positive UDS was not required for the UDS to be considered reflective because of the sensitivity of the UDS BZD immunoassay used at the George E. Wahlen VAMC clinical laboratory.²¹

Outcomes of the overdose were categorized as discharged, hospitalized, or deceased. Descriptive statistical analyses were performed using Microsoft Excel. Group comparisons were performed using Pearson chi-square or Student t test.

Results

The ED at the George E. Wahlen VAMC averages 64 visits per day, almost 94,000 visits within the study period. One hundred seventy ED visits between January 1, 2009 and January 1, 2013, involved naloxone administration. Ninety-two visits met the inclusion criteria of opioid overdose, representing about 0.002% of all ED visits at this facility (Figure 1). Six veterans had multiple ED visits within the study period, including four veterans who were in the opioid-only group.

The majority of veterans in this study were non-Hispanic white (n = 83, 90%), male (n = 88, 96%), with a mean age of 63 years. Less than 40% listed a next of kin or contact person living at their address.

Based on prescriptions available within 120 days before the overdose, 67 veterans (73%) possessed opioid and/or BZD prescriptions. In this group, the MED available on the day of the ED visit ranged from 7.5 mg to 830 mg. The MED was less than or equal to 200 mg in 71.6% and less than or equal to 50 mg in 34.3% of these cases. Veterans prescribed both opioids and BZDs had higher MED (average, 259 mg) available within 120 days of the ED visit than did those prescribed opioids only (average, 118 mg) (P = .015; standard deviation [SD], 132.9). The LED ranged from 1 mg to 12 mg for veterans with available BZDs.

Based on prescriptions available on the day of opioid overdose, 53 veterans (58%) had opioid prescriptions. The ranges of MED and LED available on the day of overdose were the same as the 120-day availability period. The average MED was 183 mg in veterans prescribed both opioids and BZDs and 126 mg in those prescribed opioids only (P = .283; SD, 168.65; Figure 2). The time between the last opioid fill date and the overdose visit date averaged 20 days (range, 0 to 28 days) in veterans prescribed opioids.

Discussion

This retrospective review identified 92 veterans who were treated with naloxone in the ED for opioid overdose during a 4-year period at the George E. Wahlen VAMC. Seventy-eight cases were excluded because the reason entered in charts for naloxone administration was itching, constipation, altered mental status, or unclear documentation.

Veterans in this study were, on average, older than the overdose fatalities in the United States. Opioid-overdose deaths in all US states and in Utah alone occur most frequently in non-Hispanic white men aged between 35 and 54 years.^7,22,23 In the 2010 Nationwide Emergency Department Sample of 136,000 opioid overdoses, of which 98% survived, most were aged 18 to 54 years.¹⁶ The older age in this study most likely reflects the age range of veterans served in the Veterans Health Administration (VHA); however, as more young veterans enter the VHA, the age range of overdose victims may more closely resemble the age ranges found in previous studies. Post hoc analysis showed eight veterans (9%) with probable intentional opioid overdose based on chart review, whereas the incidence of intentional prescription drug overdose in the United States is 17.1%.²⁴

In Utah, almost 93% of fatal overdoses occur at a residential location.²² Less than half of the veterans in this study had a contact or next of kin listed as living at the same address. Although veterans may not have identified someone living with them, in many cases, it is likely another person witnessed the overdose. Relying on EMRs to identify who should receive prevention education in addition to the veteran, may result in missed opportunities to include another person likely to witness an overdose.²⁵ Prescribers should make a conscious effort to ask veterans to identify someone who may be able to assist with rescue efforts in the event of an overdose.

Diagnoses associated with increased risk of opioid-overdose death include sleep apnea, morbid obesity, pulmonary disease or CVD, and/or a history of psychiatric disorders and SUDD.^8,9,16 In a large sample of older veterans, only 64% had at least one medical or psychiatric diagnosis.²⁶ Less than half of the 18,000 VA primary care patients in five VA centers had any psychiatric condition, and less than 65% had CVD, pulmonary disease, or cancer.²⁷ All veterans in this study had medical and psychiatric comorbidity.

In contrast, a large ED sample described by Yokell et al¹⁶ found chronic mental conditions in 33.9%, circulatory disorders in 29.1%, and respiratory conditions in 25.6% of their sample. Bohnert et al⁹ found a significantly elevated hazard ratio (HR) for any psychiatric disorder in a sample of nearly 4,500 veterans. There was variation in the HR when individual psychiatric diagnoses were broken out, with bipolar disorder having the largest HR and schizophrenia having the lowest but still elevated HR.⁹ In this study, individual diagnoses were not broken out because the smaller sample size could diminish the clinical significance of any apparent differences.

Edlund et al¹⁰ found that less than 8% of veterans treated with opioids for chronic noncancer pain had nonopioid SUDD. Bohnert et al⁹ found an HR of 21.95 for overdose death among those with opioid-use disorders. The sample in this study had a much higher incidence of nonopioid SUDD compared with that of the study by Edlund et al,¹⁰ but none of the veterans in this study had a documented history of opioid-use disorder. The absence of opioid-use disorders in this sample is unexpected and points to a need for providers to screen for opioid-use disorder whenever opioids are prescribed or renewed. If prevention practices were directed only to those with opioid SUDDs, none of the veterans in this study would have been included in those efforts. Non-SUDD providers should address the risks of opioid overdose in veterans with sleep apnea, morbid obesity, pulmonary disease or CVD, and/or a history of psychiatric disorders.

Gomes et al¹⁸ found that greater than 100 mg MED available on the day of overdose doubled the risk of opioid-related mortality. The VA/Department of Defense Clinical Practice Guideline for Management of Opioid Therapy for Chronic Pain identifies 200 mg MED as a threshold to define high-dose opioid therapy.²⁸ Fulton-Kehoe et al²⁹ found that 28% of overdose victims were prescribed less than 50 mg MED. In this study, the average dose available to veterans was greater than 100 mg MED; however, one-third of all study veterans had less than 50 mg MED available. Using a threshold dose of 50 mg MED to target prevention efforts would capture only two-thirds of those who experienced overdose; a 200-mg MED threshold would exclude the majority, based on the average MED in each group in this study. Overdose education should be provided to veterans with access to opioids, regardless of dose.

Use of BZDs with opioids may result in greater central nervous system (CNS) depression, pharmacokinetic interactions, or pharmacodynamic interactions at the µ- opioid receptor.^30-32 About one-third of veterans in this study were prescribed opioids and BZDs concurrently, a combination noted in about 33% of opioid overdose deaths reported by the Centers for Disease Control and Prevention.²⁴ Individuals taking methadone combined with BZDs have been found to have severe medical outcomes.³³ If preventive efforts are targeted to those receiving opioids and other CNS depressants, such as BZDs, about half (42%) of the veterans in this study would not receive a potentially life-saving message about preventing overdoses. All veterans with opioids should be educated about the additional risk of overdose posed by drug interactions with other CNS depressants.

The time since the last fill of an opioid prescription ranged from 0 to 28 days. This time frame indicates that some overdoses may have occurred on the day an opioid was filled but most occurred near the end of the expected days’ supply. Because information about adherence or use of the opioid was not studied, it cannot be assumed that medication misuse is the primary reason for the overdose. Providing prevention efforts only at the time of medication dispensing would be insufficient. Clinicians should review local and remote prescription data, including via their states’ prescription drug monitoring program, when discussing the risk of overdose with veterans.

Most veterans had at least one UDS result in the chart. Although half the UDSs obtained reflected prescribed medications, the possibility of aberrant behaviors, which increases the risk of overdose, cannot be ruled out with the methods used in this study.³⁴ Medication management agreements that require UDSs for veterans with chronic pain were not mandatory at the George E. Wahlen VAMC during the study period, and those used did not mandate discontinuation of opioid therapy if suspected aberrant behaviors were present.

A Utah study based on interviews of overdose victims’ next of kin found that 76% were concerned about victims’ aberrant behaviors, such as medication misuse, prior to the death.²² In contrast, a study of commercial and Medicaid recipients estimated medication misuse rates in at or less than 30% of the sample.³⁵ Urine-drug screening results not reflective of the prescribed regimens have been found in up to 50% of patients receiving chronic opioid therapy.

The UDS findings in this study were determined by the authors and did not capture clinical decisions or interpretations made after results were available or whether these decisions resulted in overdose-prevention strategies, such as targeted education or changes in prescription availability. Targeting preventive efforts toward veterans only with UDS results suggesting medication misuse would have missed more than half the veterans in this study. Urine-drug screening should be used as a clinical monitoring tool whenever opioids, BZDs, or other substances are used or prescribed.

The VA now has a nationwide program, Opioid Overdose Education and Naloxone Distribution (OEND), promoting overdose education and take-home naloxone distribution for providers and patients to prevent opioid-related overdose deaths. A national SharePoint site has been created within the VA that lists resources to support this effort.

Almost all veterans in this review survived the overdose and were hospitalized following the ED visit. Other investigators also have found that the majority (51% to 98%) of overdose victims reaching the ED survived, but fewer patients (3% to 51%) in those studies were hospitalized.^16,36 It is unknown whether there are differences in risk factors associated with survived or fatal overdoses.

Limitations

Although Utah ranked third for drug-overdose death rates in 2008 and had the highest death rate among veterans from 2001 to 2009, this review captured only overdoses among veterans treated during the study period at the George E. Wahlen VAMC ED.^5,6 The number and characteristics of veterans during this same period who were treated for overdose in other community EDs or urgent care centers throughout Utah is unknown.

The definition of opioid and BZD dose available in this study may not represent actual use of opioids or BZDs because it was based on chart review of prescription dispensing information and UDS procedures at the George E. Wahlen VAMC, and medication misuse cannot be ruled out. This study did not evaluate specific aberrant behaviors.

Conclusion

Current overdose-prevention screening efforts primarily identify patients on high-dose opioids and those with SUDD. Many veterans in this study were older than the average US victims’ age, did not have SUDD, were prescribed opioid doses not considered high risk by current guidelines, were nearer the end of their medication supply, and had UDS reflective of prescribed medications. This study suggests that any veteran with access to opioids, whether prescribed or not, is at risk for an opioid overdose. Established risk factors may aid in developing overdose-prevention programs, but prevention should not be limited to veterans with prescribed opioids and known risk factors. Clinicians should screen patients for opioid-use disorder whenever opioids are prescribed and continue to screen them throughout therapy. Broader screening for overdose risk is needed to avoid missing important opportunities for overdose prevention.

Acknowledgments

Gale Anderson, VISN 19 PBM Data Manager, performed initial data query for the study.

Editor’s Note: This article has been adapted from an article originally published in Federal Practitioner (Clement C, Stock C. Who overdoses at a VA emergency department? Fed Prac. 2016;33[11]:14-19. http://www.fedprac.com).

Overdose deaths remain epidemic throughout the United States. The rates of unintentional overdose deaths, increasing by 137% between 2000 and 2014, have been driven by a 4-fold increase in prescription opioid overdoses during that period.^1-3

Veterans died of accidental overdose at a rate of 19.85 deaths/100,000 people compared with a rate of 10.49 deaths in the general population, based on 2005 data.⁴ There is wide state-by-state variation, with the lowest age-adjusted opioid overdose death rate of 1.9 deaths/100,000 person-years among veterans in Mississippi and the highest rate in Utah of 33.9 deaths/100,000 person-years, using 2001 to 2009 data.⁵ These data can be compared with a crude general population overdose death rate of 10.6 deaths per 100,000 person-years in Mississippi and 18.4 deaths per 100,000 person-years in the general Utah population during that same period.⁶

Overdose deaths in the United States occur most often in persons aged 25 to 54 years.⁷ Older age has been associated with iatrogenic opioid overdose in hospitalized patients.⁸ Pulmonary disease, cardiovascular disease (CVD), and psychiatric disorders, including past or present substance use, have been associated with an increased risk of opioid overdose.⁹ However, veterans with substance use disorders are less likely to be prescribed opioids than are nonveterans with substance use disorders.¹⁰ Also, concomitant use of sedating medications, such as benzodiazepines (BZDs), can increase mortality from opioid overdose.¹¹ Patients prescribed opioids for chronic pain conditions often take BZDs for various reasons.¹² Veterans seem more likely to receive opioids to treat chronic pain but at lower average daily doses than doses prescribed to nonveterans.¹⁰

Emergency management of life-threatening opioid overdose includes prompt administration of naloxone.¹³ Naloxone is approved by the US Food and Drug Administration for complete or partial reversal of opioid-induced clinical effects, most critically respiratory depression.^14,15 Naloxone administration in the ED may serve as a surrogate for an overdose event. During the study period, naloxone take-home kits were not available in the Veterans Affairs (VA) setting.

A 2010 ED study described demographic information and comorbidities in opioid overdose, but the study did not include veterans.¹⁶ The clinical characteristics of veterans treated for opioid overdose have not been published. Because identifying characteristics of veterans who overdose may help tailor overdose-prevention efforts, the objective of this study is to describe clinical characteristics of veterans treated for opioid overdose.

Methods

A retrospective chart review and archived data study was approved by the University of Utah and VA Institutional Review Boards, and conducted at the George E. Wahlen Veterans Affairs Medical Center (VAMC) in Salt Lake City, Utah. This chart review included veterans who were admitted to the ED and treated with naloxone between January 1, 2009 and January 1, 2013. 

The authors used the Pharmacy Benefits Management Data Manager to extract data from the VA Data Warehouse and verified the data by open chart review (Table). The following data were collected: ED visit date (overdose date); demographic information, including age, gender, and race; evidence of next of kin or other contact at the same address as the veteran; diagnoses based on International Classification of Diseases, 9th Revision (ICD-9) codes, including sleep apnea, obesity, cardiac disease, pulmonary disease, mental health diagnoses (ICD-9 codes 290-302 [wild card characters (*) included many subdiagnoses]), cancer, and substance use disorders and/or dependencies (SUDD); tobacco use; VA-issued prescription opioid and BZD availability, including dose, fill dates, quantities dispensed, and day supplies; specialty of opioid prescriber; urine-drug screening (UDS) results; and outcome of the overdose. 

No standardized research criteria identify overdose in medical chart review.¹⁷ For each identified patient, the authors reviewed provider and nursing notes charted during an ED visit that included naloxone administration. The event was included as an opioid overdose when notes indicated that the veteran was unresponsive and given naloxone, which resulted in increased respirations or increased responsiveness. Cases were excluded if the reason for naloxone administration was anything other than opioid overdose.

Medical, mental health, and SUDD diagnoses were included only if the veteran had more than three patient-care encounters (PCE) with ICD-9 codes for a specific diagnosis entered by providers. A PCE used in the electronic medical record (EMR) helps collect, manage, and display outpatient encounter data, including providers, procedure codes, and diagnostic codes. Tobacco use was extracted from health factors documented during primary care visit screenings. (Health factors help capture data entered in note templates in the EMR and can be used to query trends.) A diagnosis of obesity was based on a calculated body mass index of at or greater than 30 kg/m² on the day of the ED visit date or the most recently charted height and weight. The type of SUDD was stratified into opioids (ICD-9 codes 304.0*), sedatives (ICD-9 codes 304.1*), alcohol (ICD-9 codes 303.*), and other (ICD-9 codes 304.2-305.9).

The dosage of opioids and BZDs available to a veteran was determined by using methods similar to those described by Gomes et al¹⁸: the dose of opioids and BZDs available based on prescriptions dispensed during the 120 days prior to the ED visit date and the dose available on the day of the ED visit date if prescription instructions were being followed. Prescription opioids and BZDs were converted to daily morphineequivalent dose (MED) and daily lorazepam equivalent dose (LED), using established methods.^19,20

Veterans were stratified into four groups based on prescribed medication availability: opioids only, BZDs only, opioids and BZDs, and neither opioids nor BZDs. The specialty of the opioid prescribers was categorized as primary care, pain specialist, surgeon, emergency specialist, or hospitalist (discharge prescription). Veteran EMRs contain a list of medications obtained outside the VA facility, referred to as non-VA prescriptions. These medications were not included in the analysis because accuracy could not be verified.

A study author reviewed the results of any UDS performed up to 120 days before the ED visit date to determine whether the result reflected the currently prescribed prescription medications. If the UDS was positive for the prescribed opioids and/or BZDs and for any nonprescribed drug, including alcohol, the UDS was classified as not reflective. If the prescribed BZD was alprazolam, clonazepam, or lorazepam, a BZD-positive UDS was not required for the UDS to be considered reflective because of the sensitivity of the UDS BZD immunoassay used at the George E. Wahlen VAMC clinical laboratory.²¹

Outcomes of the overdose were categorized as discharged, hospitalized, or deceased. Descriptive statistical analyses were performed using Microsoft Excel. Group comparisons were performed using Pearson chi-square or Student t test.

Results

The ED at the George E. Wahlen VAMC averages 64 visits per day, almost 94,000 visits within the study period. One hundred seventy ED visits between January 1, 2009 and January 1, 2013, involved naloxone administration. Ninety-two visits met the inclusion criteria of opioid overdose, representing about 0.002% of all ED visits at this facility (Figure 1). Six veterans had multiple ED visits within the study period, including four veterans who were in the opioid-only group.

The majority of veterans in this study were non-Hispanic white (n = 83, 90%), male (n = 88, 96%), with a mean age of 63 years. Less than 40% listed a next of kin or contact person living at their address.

Based on prescriptions available within 120 days before the overdose, 67 veterans (73%) possessed opioid and/or BZD prescriptions. In this group, the MED available on the day of the ED visit ranged from 7.5 mg to 830 mg. The MED was less than or equal to 200 mg in 71.6% and less than or equal to 50 mg in 34.3% of these cases. Veterans prescribed both opioids and BZDs had higher MED (average, 259 mg) available within 120 days of the ED visit than did those prescribed opioids only (average, 118 mg) (P = .015; standard deviation [SD], 132.9). The LED ranged from 1 mg to 12 mg for veterans with available BZDs.

Based on prescriptions available on the day of opioid overdose, 53 veterans (58%) had opioid prescriptions. The ranges of MED and LED available on the day of overdose were the same as the 120-day availability period. The average MED was 183 mg in veterans prescribed both opioids and BZDs and 126 mg in those prescribed opioids only (P = .283; SD, 168.65; Figure 2). The time between the last opioid fill date and the overdose visit date averaged 20 days (range, 0 to 28 days) in veterans prescribed opioids.

Discussion

This retrospective review identified 92 veterans who were treated with naloxone in the ED for opioid overdose during a 4-year period at the George E. Wahlen VAMC. Seventy-eight cases were excluded because the reason entered in charts for naloxone administration was itching, constipation, altered mental status, or unclear documentation.

Veterans in this study were, on average, older than the overdose fatalities in the United States. Opioid-overdose deaths in all US states and in Utah alone occur most frequently in non-Hispanic white men aged between 35 and 54 years.^7,22,23 In the 2010 Nationwide Emergency Department Sample of 136,000 opioid overdoses, of which 98% survived, most were aged 18 to 54 years.¹⁶ The older age in this study most likely reflects the age range of veterans served in the Veterans Health Administration (VHA); however, as more young veterans enter the VHA, the age range of overdose victims may more closely resemble the age ranges found in previous studies. Post hoc analysis showed eight veterans (9%) with probable intentional opioid overdose based on chart review, whereas the incidence of intentional prescription drug overdose in the United States is 17.1%.²⁴

In Utah, almost 93% of fatal overdoses occur at a residential location.²² Less than half of the veterans in this study had a contact or next of kin listed as living at the same address. Although veterans may not have identified someone living with them, in many cases, it is likely another person witnessed the overdose. Relying on EMRs to identify who should receive prevention education in addition to the veteran, may result in missed opportunities to include another person likely to witness an overdose.²⁵ Prescribers should make a conscious effort to ask veterans to identify someone who may be able to assist with rescue efforts in the event of an overdose.

Diagnoses associated with increased risk of opioid-overdose death include sleep apnea, morbid obesity, pulmonary disease or CVD, and/or a history of psychiatric disorders and SUDD.^8,9,16 In a large sample of older veterans, only 64% had at least one medical or psychiatric diagnosis.²⁶ Less than half of the 18,000 VA primary care patients in five VA centers had any psychiatric condition, and less than 65% had CVD, pulmonary disease, or cancer.²⁷ All veterans in this study had medical and psychiatric comorbidity.

In contrast, a large ED sample described by Yokell et al¹⁶ found chronic mental conditions in 33.9%, circulatory disorders in 29.1%, and respiratory conditions in 25.6% of their sample. Bohnert et al⁹ found a significantly elevated hazard ratio (HR) for any psychiatric disorder in a sample of nearly 4,500 veterans. There was variation in the HR when individual psychiatric diagnoses were broken out, with bipolar disorder having the largest HR and schizophrenia having the lowest but still elevated HR.⁹ In this study, individual diagnoses were not broken out because the smaller sample size could diminish the clinical significance of any apparent differences.

Edlund et al¹⁰ found that less than 8% of veterans treated with opioids for chronic noncancer pain had nonopioid SUDD. Bohnert et al⁹ found an HR of 21.95 for overdose death among those with opioid-use disorders. The sample in this study had a much higher incidence of nonopioid SUDD compared with that of the study by Edlund et al,¹⁰ but none of the veterans in this study had a documented history of opioid-use disorder. The absence of opioid-use disorders in this sample is unexpected and points to a need for providers to screen for opioid-use disorder whenever opioids are prescribed or renewed. If prevention practices were directed only to those with opioid SUDDs, none of the veterans in this study would have been included in those efforts. Non-SUDD providers should address the risks of opioid overdose in veterans with sleep apnea, morbid obesity, pulmonary disease or CVD, and/or a history of psychiatric disorders.

Gomes et al¹⁸ found that greater than 100 mg MED available on the day of overdose doubled the risk of opioid-related mortality. The VA/Department of Defense Clinical Practice Guideline for Management of Opioid Therapy for Chronic Pain identifies 200 mg MED as a threshold to define high-dose opioid therapy.²⁸ Fulton-Kehoe et al²⁹ found that 28% of overdose victims were prescribed less than 50 mg MED. In this study, the average dose available to veterans was greater than 100 mg MED; however, one-third of all study veterans had less than 50 mg MED available. Using a threshold dose of 50 mg MED to target prevention efforts would capture only two-thirds of those who experienced overdose; a 200-mg MED threshold would exclude the majority, based on the average MED in each group in this study. Overdose education should be provided to veterans with access to opioids, regardless of dose.

Use of BZDs with opioids may result in greater central nervous system (CNS) depression, pharmacokinetic interactions, or pharmacodynamic interactions at the µ- opioid receptor.^30-32 About one-third of veterans in this study were prescribed opioids and BZDs concurrently, a combination noted in about 33% of opioid overdose deaths reported by the Centers for Disease Control and Prevention.²⁴ Individuals taking methadone combined with BZDs have been found to have severe medical outcomes.³³ If preventive efforts are targeted to those receiving opioids and other CNS depressants, such as BZDs, about half (42%) of the veterans in this study would not receive a potentially life-saving message about preventing overdoses. All veterans with opioids should be educated about the additional risk of overdose posed by drug interactions with other CNS depressants.

The time since the last fill of an opioid prescription ranged from 0 to 28 days. This time frame indicates that some overdoses may have occurred on the day an opioid was filled but most occurred near the end of the expected days’ supply. Because information about adherence or use of the opioid was not studied, it cannot be assumed that medication misuse is the primary reason for the overdose. Providing prevention efforts only at the time of medication dispensing would be insufficient. Clinicians should review local and remote prescription data, including via their states’ prescription drug monitoring program, when discussing the risk of overdose with veterans.

Most veterans had at least one UDS result in the chart. Although half the UDSs obtained reflected prescribed medications, the possibility of aberrant behaviors, which increases the risk of overdose, cannot be ruled out with the methods used in this study.³⁴ Medication management agreements that require UDSs for veterans with chronic pain were not mandatory at the George E. Wahlen VAMC during the study period, and those used did not mandate discontinuation of opioid therapy if suspected aberrant behaviors were present.

A Utah study based on interviews of overdose victims’ next of kin found that 76% were concerned about victims’ aberrant behaviors, such as medication misuse, prior to the death.²² In contrast, a study of commercial and Medicaid recipients estimated medication misuse rates in at or less than 30% of the sample.³⁵ Urine-drug screening results not reflective of the prescribed regimens have been found in up to 50% of patients receiving chronic opioid therapy.

The UDS findings in this study were determined by the authors and did not capture clinical decisions or interpretations made after results were available or whether these decisions resulted in overdose-prevention strategies, such as targeted education or changes in prescription availability. Targeting preventive efforts toward veterans only with UDS results suggesting medication misuse would have missed more than half the veterans in this study. Urine-drug screening should be used as a clinical monitoring tool whenever opioids, BZDs, or other substances are used or prescribed.

The VA now has a nationwide program, Opioid Overdose Education and Naloxone Distribution (OEND), promoting overdose education and take-home naloxone distribution for providers and patients to prevent opioid-related overdose deaths. A national SharePoint site has been created within the VA that lists resources to support this effort.

Almost all veterans in this review survived the overdose and were hospitalized following the ED visit. Other investigators also have found that the majority (51% to 98%) of overdose victims reaching the ED survived, but fewer patients (3% to 51%) in those studies were hospitalized.^16,36 It is unknown whether there are differences in risk factors associated with survived or fatal overdoses.

Limitations

Although Utah ranked third for drug-overdose death rates in 2008 and had the highest death rate among veterans from 2001 to 2009, this review captured only overdoses among veterans treated during the study period at the George E. Wahlen VAMC ED.^5,6 The number and characteristics of veterans during this same period who were treated for overdose in other community EDs or urgent care centers throughout Utah is unknown.

The definition of opioid and BZD dose available in this study may not represent actual use of opioids or BZDs because it was based on chart review of prescription dispensing information and UDS procedures at the George E. Wahlen VAMC, and medication misuse cannot be ruled out. This study did not evaluate specific aberrant behaviors.

Conclusion

Current overdose-prevention screening efforts primarily identify patients on high-dose opioids and those with SUDD. Many veterans in this study were older than the average US victims’ age, did not have SUDD, were prescribed opioid doses not considered high risk by current guidelines, were nearer the end of their medication supply, and had UDS reflective of prescribed medications. This study suggests that any veteran with access to opioids, whether prescribed or not, is at risk for an opioid overdose. Established risk factors may aid in developing overdose-prevention programs, but prevention should not be limited to veterans with prescribed opioids and known risk factors. Clinicians should screen patients for opioid-use disorder whenever opioids are prescribed and continue to screen them throughout therapy. Broader screening for overdose risk is needed to avoid missing important opportunities for overdose prevention.

Acknowledgments

Gale Anderson, VISN 19 PBM Data Manager, performed initial data query for the study.

Editor’s Note: This article has been adapted from an article originally published in Federal Practitioner (Clement C, Stock C. Who overdoses at a VA emergency department? Fed Prac. 2016;33[11]:14-19. http://www.fedprac.com).

Overdose deaths remain epidemic throughout the United States. The rates of unintentional overdose deaths, increasing by 137% between 2000 and 2014, have been driven by a 4-fold increase in prescription opioid overdoses during that period.^1-3

Veterans died of accidental overdose at a rate of 19.85 deaths/100,000 people compared with a rate of 10.49 deaths in the general population, based on 2005 data.⁴ There is wide state-by-state variation, with the lowest age-adjusted opioid overdose death rate of 1.9 deaths/100,000 person-years among veterans in Mississippi and the highest rate in Utah of 33.9 deaths/100,000 person-years, using 2001 to 2009 data.⁵ These data can be compared with a crude general population overdose death rate of 10.6 deaths per 100,000 person-years in Mississippi and 18.4 deaths per 100,000 person-years in the general Utah population during that same period.⁶

Overdose deaths in the United States occur most often in persons aged 25 to 54 years.⁷ Older age has been associated with iatrogenic opioid overdose in hospitalized patients.⁸ Pulmonary disease, cardiovascular disease (CVD), and psychiatric disorders, including past or present substance use, have been associated with an increased risk of opioid overdose.⁹ However, veterans with substance use disorders are less likely to be prescribed opioids than are nonveterans with substance use disorders.¹⁰ Also, concomitant use of sedating medications, such as benzodiazepines (BZDs), can increase mortality from opioid overdose.¹¹ Patients prescribed opioids for chronic pain conditions often take BZDs for various reasons.¹² Veterans seem more likely to receive opioids to treat chronic pain but at lower average daily doses than doses prescribed to nonveterans.¹⁰

Emergency management of life-threatening opioid overdose includes prompt administration of naloxone.¹³ Naloxone is approved by the US Food and Drug Administration for complete or partial reversal of opioid-induced clinical effects, most critically respiratory depression.^14,15 Naloxone administration in the ED may serve as a surrogate for an overdose event. During the study period, naloxone take-home kits were not available in the Veterans Affairs (VA) setting.

A 2010 ED study described demographic information and comorbidities in opioid overdose, but the study did not include veterans.¹⁶ The clinical characteristics of veterans treated for opioid overdose have not been published. Because identifying characteristics of veterans who overdose may help tailor overdose-prevention efforts, the objective of this study is to describe clinical characteristics of veterans treated for opioid overdose.

Methods

A retrospective chart review and archived data study was approved by the University of Utah and VA Institutional Review Boards, and conducted at the George E. Wahlen Veterans Affairs Medical Center (VAMC) in Salt Lake City, Utah. This chart review included veterans who were admitted to the ED and treated with naloxone between January 1, 2009 and January 1, 2013. 

The authors used the Pharmacy Benefits Management Data Manager to extract data from the VA Data Warehouse and verified the data by open chart review (Table). The following data were collected: ED visit date (overdose date); demographic information, including age, gender, and race; evidence of next of kin or other contact at the same address as the veteran; diagnoses based on International Classification of Diseases, 9th Revision (ICD-9) codes, including sleep apnea, obesity, cardiac disease, pulmonary disease, mental health diagnoses (ICD-9 codes 290-302 [wild card characters (*) included many subdiagnoses]), cancer, and substance use disorders and/or dependencies (SUDD); tobacco use; VA-issued prescription opioid and BZD availability, including dose, fill dates, quantities dispensed, and day supplies; specialty of opioid prescriber; urine-drug screening (UDS) results; and outcome of the overdose. 

No standardized research criteria identify overdose in medical chart review.¹⁷ For each identified patient, the authors reviewed provider and nursing notes charted during an ED visit that included naloxone administration. The event was included as an opioid overdose when notes indicated that the veteran was unresponsive and given naloxone, which resulted in increased respirations or increased responsiveness. Cases were excluded if the reason for naloxone administration was anything other than opioid overdose.

Medical, mental health, and SUDD diagnoses were included only if the veteran had more than three patient-care encounters (PCE) with ICD-9 codes for a specific diagnosis entered by providers. A PCE used in the electronic medical record (EMR) helps collect, manage, and display outpatient encounter data, including providers, procedure codes, and diagnostic codes. Tobacco use was extracted from health factors documented during primary care visit screenings. (Health factors help capture data entered in note templates in the EMR and can be used to query trends.) A diagnosis of obesity was based on a calculated body mass index of at or greater than 30 kg/m² on the day of the ED visit date or the most recently charted height and weight. The type of SUDD was stratified into opioids (ICD-9 codes 304.0*), sedatives (ICD-9 codes 304.1*), alcohol (ICD-9 codes 303.*), and other (ICD-9 codes 304.2-305.9).

The dosage of opioids and BZDs available to a veteran was determined by using methods similar to those described by Gomes et al¹⁸: the dose of opioids and BZDs available based on prescriptions dispensed during the 120 days prior to the ED visit date and the dose available on the day of the ED visit date if prescription instructions were being followed. Prescription opioids and BZDs were converted to daily morphineequivalent dose (MED) and daily lorazepam equivalent dose (LED), using established methods.^19,20

Veterans were stratified into four groups based on prescribed medication availability: opioids only, BZDs only, opioids and BZDs, and neither opioids nor BZDs. The specialty of the opioid prescribers was categorized as primary care, pain specialist, surgeon, emergency specialist, or hospitalist (discharge prescription). Veteran EMRs contain a list of medications obtained outside the VA facility, referred to as non-VA prescriptions. These medications were not included in the analysis because accuracy could not be verified.

A study author reviewed the results of any UDS performed up to 120 days before the ED visit date to determine whether the result reflected the currently prescribed prescription medications. If the UDS was positive for the prescribed opioids and/or BZDs and for any nonprescribed drug, including alcohol, the UDS was classified as not reflective. If the prescribed BZD was alprazolam, clonazepam, or lorazepam, a BZD-positive UDS was not required for the UDS to be considered reflective because of the sensitivity of the UDS BZD immunoassay used at the George E. Wahlen VAMC clinical laboratory.²¹

Outcomes of the overdose were categorized as discharged, hospitalized, or deceased. Descriptive statistical analyses were performed using Microsoft Excel. Group comparisons were performed using Pearson chi-square or Student t test.

Results

The ED at the George E. Wahlen VAMC averages 64 visits per day, almost 94,000 visits within the study period. One hundred seventy ED visits between January 1, 2009 and January 1, 2013, involved naloxone administration. Ninety-two visits met the inclusion criteria of opioid overdose, representing about 0.002% of all ED visits at this facility (Figure 1). Six veterans had multiple ED visits within the study period, including four veterans who were in the opioid-only group.

The majority of veterans in this study were non-Hispanic white (n = 83, 90%), male (n = 88, 96%), with a mean age of 63 years. Less than 40% listed a next of kin or contact person living at their address.

Based on prescriptions available within 120 days before the overdose, 67 veterans (73%) possessed opioid and/or BZD prescriptions. In this group, the MED available on the day of the ED visit ranged from 7.5 mg to 830 mg. The MED was less than or equal to 200 mg in 71.6% and less than or equal to 50 mg in 34.3% of these cases. Veterans prescribed both opioids and BZDs had higher MED (average, 259 mg) available within 120 days of the ED visit than did those prescribed opioids only (average, 118 mg) (P = .015; standard deviation [SD], 132.9). The LED ranged from 1 mg to 12 mg for veterans with available BZDs.

Based on prescriptions available on the day of opioid overdose, 53 veterans (58%) had opioid prescriptions. The ranges of MED and LED available on the day of overdose were the same as the 120-day availability period. The average MED was 183 mg in veterans prescribed both opioids and BZDs and 126 mg in those prescribed opioids only (P = .283; SD, 168.65; Figure 2). The time between the last opioid fill date and the overdose visit date averaged 20 days (range, 0 to 28 days) in veterans prescribed opioids.

Discussion

This retrospective review identified 92 veterans who were treated with naloxone in the ED for opioid overdose during a 4-year period at the George E. Wahlen VAMC. Seventy-eight cases were excluded because the reason entered in charts for naloxone administration was itching, constipation, altered mental status, or unclear documentation.

Veterans in this study were, on average, older than the overdose fatalities in the United States. Opioid-overdose deaths in all US states and in Utah alone occur most frequently in non-Hispanic white men aged between 35 and 54 years.^7,22,23 In the 2010 Nationwide Emergency Department Sample of 136,000 opioid overdoses, of which 98% survived, most were aged 18 to 54 years.¹⁶ The older age in this study most likely reflects the age range of veterans served in the Veterans Health Administration (VHA); however, as more young veterans enter the VHA, the age range of overdose victims may more closely resemble the age ranges found in previous studies. Post hoc analysis showed eight veterans (9%) with probable intentional opioid overdose based on chart review, whereas the incidence of intentional prescription drug overdose in the United States is 17.1%.²⁴

In Utah, almost 93% of fatal overdoses occur at a residential location.²² Less than half of the veterans in this study had a contact or next of kin listed as living at the same address. Although veterans may not have identified someone living with them, in many cases, it is likely another person witnessed the overdose. Relying on EMRs to identify who should receive prevention education in addition to the veteran, may result in missed opportunities to include another person likely to witness an overdose.²⁵ Prescribers should make a conscious effort to ask veterans to identify someone who may be able to assist with rescue efforts in the event of an overdose.

Diagnoses associated with increased risk of opioid-overdose death include sleep apnea, morbid obesity, pulmonary disease or CVD, and/or a history of psychiatric disorders and SUDD.^8,9,16 In a large sample of older veterans, only 64% had at least one medical or psychiatric diagnosis.²⁶ Less than half of the 18,000 VA primary care patients in five VA centers had any psychiatric condition, and less than 65% had CVD, pulmonary disease, or cancer.²⁷ All veterans in this study had medical and psychiatric comorbidity.

In contrast, a large ED sample described by Yokell et al¹⁶ found chronic mental conditions in 33.9%, circulatory disorders in 29.1%, and respiratory conditions in 25.6% of their sample. Bohnert et al⁹ found a significantly elevated hazard ratio (HR) for any psychiatric disorder in a sample of nearly 4,500 veterans. There was variation in the HR when individual psychiatric diagnoses were broken out, with bipolar disorder having the largest HR and schizophrenia having the lowest but still elevated HR.⁹ In this study, individual diagnoses were not broken out because the smaller sample size could diminish the clinical significance of any apparent differences.

Edlund et al¹⁰ found that less than 8% of veterans treated with opioids for chronic noncancer pain had nonopioid SUDD. Bohnert et al⁹ found an HR of 21.95 for overdose death among those with opioid-use disorders. The sample in this study had a much higher incidence of nonopioid SUDD compared with that of the study by Edlund et al,¹⁰ but none of the veterans in this study had a documented history of opioid-use disorder. The absence of opioid-use disorders in this sample is unexpected and points to a need for providers to screen for opioid-use disorder whenever opioids are prescribed or renewed. If prevention practices were directed only to those with opioid SUDDs, none of the veterans in this study would have been included in those efforts. Non-SUDD providers should address the risks of opioid overdose in veterans with sleep apnea, morbid obesity, pulmonary disease or CVD, and/or a history of psychiatric disorders.

Gomes et al¹⁸ found that greater than 100 mg MED available on the day of overdose doubled the risk of opioid-related mortality. The VA/Department of Defense Clinical Practice Guideline for Management of Opioid Therapy for Chronic Pain identifies 200 mg MED as a threshold to define high-dose opioid therapy.²⁸ Fulton-Kehoe et al²⁹ found that 28% of overdose victims were prescribed less than 50 mg MED. In this study, the average dose available to veterans was greater than 100 mg MED; however, one-third of all study veterans had less than 50 mg MED available. Using a threshold dose of 50 mg MED to target prevention efforts would capture only two-thirds of those who experienced overdose; a 200-mg MED threshold would exclude the majority, based on the average MED in each group in this study. Overdose education should be provided to veterans with access to opioids, regardless of dose.

Use of BZDs with opioids may result in greater central nervous system (CNS) depression, pharmacokinetic interactions, or pharmacodynamic interactions at the µ- opioid receptor.^30-32 About one-third of veterans in this study were prescribed opioids and BZDs concurrently, a combination noted in about 33% of opioid overdose deaths reported by the Centers for Disease Control and Prevention.²⁴ Individuals taking methadone combined with BZDs have been found to have severe medical outcomes.³³ If preventive efforts are targeted to those receiving opioids and other CNS depressants, such as BZDs, about half (42%) of the veterans in this study would not receive a potentially life-saving message about preventing overdoses. All veterans with opioids should be educated about the additional risk of overdose posed by drug interactions with other CNS depressants.

The time since the last fill of an opioid prescription ranged from 0 to 28 days. This time frame indicates that some overdoses may have occurred on the day an opioid was filled but most occurred near the end of the expected days’ supply. Because information about adherence or use of the opioid was not studied, it cannot be assumed that medication misuse is the primary reason for the overdose. Providing prevention efforts only at the time of medication dispensing would be insufficient. Clinicians should review local and remote prescription data, including via their states’ prescription drug monitoring program, when discussing the risk of overdose with veterans.

Most veterans had at least one UDS result in the chart. Although half the UDSs obtained reflected prescribed medications, the possibility of aberrant behaviors, which increases the risk of overdose, cannot be ruled out with the methods used in this study.³⁴ Medication management agreements that require UDSs for veterans with chronic pain were not mandatory at the George E. Wahlen VAMC during the study period, and those used did not mandate discontinuation of opioid therapy if suspected aberrant behaviors were present.

A Utah study based on interviews of overdose victims’ next of kin found that 76% were concerned about victims’ aberrant behaviors, such as medication misuse, prior to the death.²² In contrast, a study of commercial and Medicaid recipients estimated medication misuse rates in at or less than 30% of the sample.³⁵ Urine-drug screening results not reflective of the prescribed regimens have been found in up to 50% of patients receiving chronic opioid therapy.

The UDS findings in this study were determined by the authors and did not capture clinical decisions or interpretations made after results were available or whether these decisions resulted in overdose-prevention strategies, such as targeted education or changes in prescription availability. Targeting preventive efforts toward veterans only with UDS results suggesting medication misuse would have missed more than half the veterans in this study. Urine-drug screening should be used as a clinical monitoring tool whenever opioids, BZDs, or other substances are used or prescribed.

The VA now has a nationwide program, Opioid Overdose Education and Naloxone Distribution (OEND), promoting overdose education and take-home naloxone distribution for providers and patients to prevent opioid-related overdose deaths. A national SharePoint site has been created within the VA that lists resources to support this effort.

Almost all veterans in this review survived the overdose and were hospitalized following the ED visit. Other investigators also have found that the majority (51% to 98%) of overdose victims reaching the ED survived, but fewer patients (3% to 51%) in those studies were hospitalized.^16,36 It is unknown whether there are differences in risk factors associated with survived or fatal overdoses.

Limitations

Although Utah ranked third for drug-overdose death rates in 2008 and had the highest death rate among veterans from 2001 to 2009, this review captured only overdoses among veterans treated during the study period at the George E. Wahlen VAMC ED.^5,6 The number and characteristics of veterans during this same period who were treated for overdose in other community EDs or urgent care centers throughout Utah is unknown.

The definition of opioid and BZD dose available in this study may not represent actual use of opioids or BZDs because it was based on chart review of prescription dispensing information and UDS procedures at the George E. Wahlen VAMC, and medication misuse cannot be ruled out. This study did not evaluate specific aberrant behaviors.

Conclusion

Current overdose-prevention screening efforts primarily identify patients on high-dose opioids and those with SUDD. Many veterans in this study were older than the average US victims’ age, did not have SUDD, were prescribed opioid doses not considered high risk by current guidelines, were nearer the end of their medication supply, and had UDS reflective of prescribed medications. This study suggests that any veteran with access to opioids, whether prescribed or not, is at risk for an opioid overdose. Established risk factors may aid in developing overdose-prevention programs, but prevention should not be limited to veterans with prescribed opioids and known risk factors. Clinicians should screen patients for opioid-use disorder whenever opioids are prescribed and continue to screen them throughout therapy. Broader screening for overdose risk is needed to avoid missing important opportunities for overdose prevention.

Acknowledgments

Gale Anderson, VISN 19 PBM Data Manager, performed initial data query for the study.