Clinical Review

From the Harrison School of Pharmacy, Auburn University, Mobile, AL.

Abstract

• Objective: To summarize the literature relevant to managing dyslipidemia in the elderly and review recommendations for initiating lipid-lowering therapy.
• Methods: Review of the literature.
• Results: Statins are the most commonly utilized medication class for lipid-lowering in the general population, and they are recommended for primary prevention in patients between the ages of 40 to 75 with at least 1 risk factor for cardiovascular disease as well as for any patient needing secondary prevention. In the elderly, statins may be appropriate for both primary and secondary prevention if the benefits outweigh the risks. Based on the available evidence, it is safe to recommend statin therapy to elderly patients who require secondary prevention given the known benefits in reducing cardiovascular morbidity and mortality for patients up to the age of 80. For primary prevention, statin therapy may be beneficial, but one must carefully evaluate for comorbid conditions, life expectancy, concomitant medications, overall health status, frailty, and patient or family preference. Several other classes of lipid-lowering agents exist; however, there is not enough evidence for us to recommend use in the elderly population for cardiovascular risk reduction in either primary or secondary scenarios.
• Conclusion: Although clinical research in the elderly population is limited, evidence supports the use of statins in elderly patients for secondary prevention and in patients up to age 75 for primary prevention; however clinicians must use clinical judgement and take into consideration the patient’s situation regarding comorbidities, polypharmacy, and possible adverse effects. More high-quality evidence is necessary.

Key words: hyperlipidemia; geriatrics; elderly; patient-centered care; statin; cardiovascular disease.

The number of Americans age 65 years and older is projected to more than double, from 46 million today to over 98 million by 2060, and the 65-and-older age group’s share of the total population will rise to nearly 24% [1]. Life expectancy is now predicted to be > 20 years for women at age 65 and > 17 years for men at age 65 in many high-income countries, including the United States [2]. This demographic shift toward an older population will result in a higher burden of coronary heart disease and stroke, with atherosclerotic cardiovascular disease (ASCVD) prevalence and costs projected to increase substantially [3].

Among adults seeking medical care in the United States, roughly 95 million have a total cholesterol (TC) level of ≥ 200 mg/dL or more, and approximately 29 million have a TC > 240 mg/dL [4]. Cholesterol screening is important since most patients suffering from dyslipidemia are asymptomatic. Dyslipidemia is a major risk factor for the development of atherosclerotic disease. Because of the complications associated with dyslipidemia, it is vital that patients are provided with primary and/or secondary prevention strategies to reduce the risk of cardiovascular disease (CVD) and protect high-risk patients from recurring events. A clinical controversy exists surrounding the elderly population, concerning whether or not clinicians should be providing lipid-lowering treatment to this group of individuals for dyslipidemia. The evidence is limited for patients over age 65, and even more so for the very elderly (> 80 years); therefore, it is necessary to review the available evidence to make an appropriate decision when it comes to managing dyslipidemia in the elderly population

Currently, HMG-CoA reductase inhibitors (statins) are the only known class of medications for the treatment of dyslipidemia that will prevent both primary and secondary cardiovascular (CV) events, including death. Statin intensity (Table 1) 

Guideline Recommendations

Current guidelines differ in their recommendations for treating dyslipidemia in the elderly population. In 2016, the Task Force for the Management of Dyslipidemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) released updated guidelines for managing dyslipidemia. These guidelines recommend that older patients with established CVD be treated in the same way as younger patients because of the many benefits statin therapy demonstrated in clinical trials. They also suggest that statin therapy be started at a lower doses to achieve goals for primary prevention in the older population. In addition, CVD risk factors (hypertension, diabetes, dyslipidemia, smoking) should be addressed in this population to reduce CVD risk. They also acknowledged that primary prevention may not prolong life in the older adult, but treatment does reduce cardiovascular mortality and statin therapy is recommended to reduce the overall risk of CV morbidity in this population [11]. In contrast, The 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines changed the management and treatment of dyslipidemia by highlighting “statin benefit groups” rather than recommending a treat-to-target goal as guidelines had done for many years. ACC/AHA recommends a moderate-intensity statin for patients > 75 years of age for secondary prevention versus the use of a high-intensity statin for patients who are between the ages of 40 and 75 based on the pooled cohort risk equation. In patients over age 75 with no history of CVD, no specific recommendation is available for the use of lipid-lowering therapy at this time [12]. ACC/AHA is expected to publish a new set of guidelines sometime in 2018 and they are projected to utilize lipid-lowering goals in combination with the pooled cohort equation to assess overall risk in patients with dyslipidemia.

The 2015 National Lipid Association (NLA) released “Part 1” guidelines for the management of dyslipidemia and then provided “Part 2” about a year later, which focuses on management for special populations. To summarize, the NLA guidelines recommend that elderly patients between the ages of 65 and 80 receive a high-intensity statin for secondary prevention after special consideration of the potential risks and benefits. In patients over the age of 80, NLA recommends a moderate-intensity statin for secondary prevention. For primary prevention, NLA recommends utilizing the pooled cohort risk equation to analyze patient characteristics, keeping in mind that age is a driving factor for increased risk of CVD and that the actual risk for developing a CV event may be “overestimated” if the patient has no other risk factors other than their age. When evaluating patients between the ages of 65 and 79 for primary prevention, NLA suggests following Part 1 of the guidelines. In Part 1, NLA recommends evaluating the patient’s characteristics and suggests a moderate- or high-intensity statin if the patient is considered “very high risk” or “high risk” and a moderate-intensity statin for patients who are considered “moderate risk”. For patients over the age of 80, they recommend utilizing a moderate- or a low-intensity statin depending on frailty status or if significant comorbidities or polypharmacy exist [13,14].

In 2017, the American Association of Clinical Endocrinologist (AACE) released guidelines for the management of dyslipidemia and CVD prevention. AACE recommends that patients over age 65 be screened for dyslipidemia, and those who have multiple risk factors, other than age, should be considered for treatment with lipid-lowering therapy. AACE focuses on specific target LDL-C levels as treatment goals [15].

In addition to statins, other lipid-lowering therapies are used to treat dyslipidemia. The 2016 American College of Cardiology (ACC) Task Force reported on the use of non-statin therapies for the management of dyslipidemia and prevention of clinical ASCVD [16]. The committee concluded that ezetimibe added to statin therapy, bile acid sequestrants as monotherapy, and niacin as monotherapy all have some benefit for the prevention of clinical ASCVD. These guidelines also discuss the use of PCSK-9 inhibitors and their potential to decrease the risk of clinical ASCVD, but trials are currently ongoing to determine actual benefit. These guidelines address special populations but they do not consider the elderly in their recommendations. Currently, the only special populations included are patients with heart failure, those on hemodialysis, women who are of childbearing age or pregnant, and those with autoimmune diseases [16]. The literature available for each individual medication is discussed in further detail below.

Evidence for Secondary Prevention

The benefits of statin therapy for secondary prevention in the elderly is more established than it is for primary prevention (Table 2). 

The ASCOT–LLA (Anglo-Scandinavian Cardiac Outcomes Trial–Lipid Lowering Arm), published in 2003, evaluated the effect of atorvastatin 10 mg on reducing ASCVD events in moderate-risk patients between 40–79 years of age who had hypertension and normal or slightly elevated LDL-C levels, with at least 2 other risk factors for CVD (age > 55 years was considered a risk factor). The primary outcome was non-fatal MI including silent MI and fatal CHD. A significant reduction was seen in the primary endpoint. Over half of the study population was > 60 years of age, with a mean age of 63 years. In a post-hoc analysis, stroke prevention was found to be similar in patients who were > 70 years of age and those < 70 years of age [19].

One of the first trials to specifically analyze the impact of age on lipid-lowering therapy in secondary ASCVD prevention was the Scandinavian Simvastatin Survival Study (4S), published in 1994. They evaluated the effect of simvastatin 20 mg on CV-related mortality and morbidity in patients 35–70 years of age with hyperlipidemia and a history of angina or acute MI occurring > 6 months of the study starting. The primary outcome was all-cause mortality. The secondary endpoint was time to first major CV event, which included coronary death, non-fatal acute MI, resuscitated cardiac arrest, and silent MI. Simvastatin significantly reduced the primary outcome and CHD-related deaths. A subgroup analysis of the study population > 60 years of age showed that age made no significant impact on primary or secondary outcomes; however, investigators noted that these subgroup analyses had less statistical power than the population as a whole [20].

Published in 1998, the LIPID (Long-Term Intervention with Pravastatin in Ischemic Disease) study evaluated the effects of pravastatin 40 mg daily on CHD-related mortality and overall mortality in patients with hyperlipidemia and clinical ASCVD (previous MI or unstable angina). The primary outcome observed was fatal CHD. Pravastatin significantly reduced the primary outcome, overall mortality, and pre-specified CV events. In a subgroup analysis, age group ( 65, and > 70 years) had no significant impact on the combined outcome of death from CHD and nonfatal MI; however, patients 65 to 70 years of age made up less than half of the study population [21].

The Cholesterol and Recurrent Events (CARE) trial, published in 1996, looked at the effect of pravastatin 40mg therapy for secondary ASCVD prevention following an MI in patients who had average cholesterol levels (defined as TC < 240 mg/dL and LDL-C 115–174 mg/dL). The primary endpoint assessed was time to fatal CHD or nonfatal MI. To meet statistical power they looked at subgroups for a broader outcome of a major coronary event (including fatal CHD, nonfatal MI, bypass surgery, and angioplasty). Pravastatin significantly reduced the primary outcome. The significant reduction in coronary events produced by pravastatin was noted to be significantly greater in women and in patients with higher pretreatment levels of LDL-C, but was not significantly impacted by age group (24–59 vs. 60–75 years) [22].

The Heart Protection Study (HPS), published in 2002, looked at the long-term effects of lowering LDL-C with simvastatin 40 mg in patients 40 to 80 years of age at high risk for mortality due to either vascular or nonvascular causes. The primary outcome assessed was all-cause mortality, with fatal or nonfatal vascular events as co-primary outcomes for subcategory analyses. Simvastatin significantly reduced both primary and co-primary outcomes, but there was no significant difference when they looked at nonvascular mortality between groups. Neither age nor baseline LDL levels were reported to have had a significant impact on outcomes. Over half the population was > 65 years of age, and about one-third of the population was > 70 years of age [23].

The PROVE-IT/TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis in Myocardial Infarction 22) trial, published in 2004, compared pravastatin 40 mg (moderate-intensity) to atorvastatin 80 mg (high-intensity) for secondary ASCVD prevention in patients with recent acute coronary syndrome (ACS) 65 years of age and the mean age was 58 years [24].

The TNT (Treating to New Targets) trial, published in 2005, looked at secondary ASCVD prevention in regards to targeting LDL-C levels to < 100 mg/dL or < 70 mg/dL with atorvastatin 10 mg and atorvastatin 80 mg. Patients had stable coronary artery disease (CAD) and baseline LDL-C levels < 130 mg/dL. The primary endpoint was the occurrence of a CV event (CAD mortality, nonfatal MI not related to procedure, resuscitation after cardiac arrest, or fatal or nonfatal stroke). High-intensity atorvastatin (80 mg) significantly reduced the primary outcome. The mean age of the study population was approximately 61 years. The study reported no statistical interaction for age or sex in the primary outcome measure [25].

The Study Assessing Goals in the Elderly (SAGE), published in 2007, evaluated the effects of pravastatin 40 mg (moderate-intensity) vs atorvastatin 80 mg (high-intensity) on secondary ASCVD prevention in patients 65 to 85 years (mean age 72) with stable CHD, LDL-C 100–250 mg/dL, with at least 1 episode of myocardial ischemia with total ischemia duration > 3 minutes. The primary efficacy outcome observed was absolute change in total duration of myocardial ischemia on 48-hour ambulatory electrocardiographic monitoring from baseline to month 12. No significant difference was observed in efficacy between the two groups for the primary endpoint, but the intensive statin therapy group showed greater benefit respective to several secondary outcomes, including major acute CV events and death [26].

In summary, while these trials provide evidence that statin therapy is beneficial in a wide range of patients with clinical ASCVD and dyslipidemia, the trial data does not provide definitive guidance for treating elderly patients at this time. Given the small percentage of elderly patients that were included, some of the trial results reporting statistical significance in this age group hold less clinical significance. It appears that high-intensity statin therapy was more likely to effectively prevent clinical ASCVD and death than moderate-intensity statin therapy, but more evidence is needed regarding secondary prevention in patients over age 75.

Evidence for Primary Prevention

The PROSPER (PROspective Study of Pravastatin in the Elderly at Risk) was published in 2002 to assess the efficacy of pravastatin in patients between the ages of 70 and 82 (mean age 75 years) with pre-existing vascular disease (coronary, cerebral, or peripheral) or at an elevated risk (smoking, hypertension, or diabetes). Patients were randomized to receive either placebo or pravastatin 40 mg (a moderate-intensity statin). They found that pravastatin therapy reduced the risk of the composite outcome of CHD-related death, nonfatal MI, and fatal or nonfatal stroke in this elderly population. A post-hoc analysis comparing primary versus secondary prevention groups found no significant differences between these subgroups [7].

Han et al recently conducted a post hoc secondary analysis of older participants (65 years and older) in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial–Lipid-Lowering Trial (ALLHAT-LLT). The intervention for ALLHAT-LLT was 40 mg pravastatin. They found no significant differences in all-cause mortality or cardiovascular outcomes between the pravastatin and usual care groups [27]

JUPITER (Justification for Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin), published in 2008, examined the efficacy of rosuvastatin vs. placebo in low- to moderate-risk men 50 years and older and women 60 years and older using a composite outcome of MI, unstable angina, stroke, arterial revascularization, or CVD death. Rosuvastatin did significantly decrease the primary endpoint, however it did not reduce the risk of overall death [28]. A subgroup analysis was performed on the elderly (65–75 years) study participants in JUPITER demonstrating a significant risk reduction for the combined CV endpoint and a nonsignificant reduction of all-cause mortality [29].

CARDS (Collaborative Atorvastatin Diabetes Study), published in 2004, looked at statin use for primary prevention in high-risk patients with type 2 diabetes without high LDL-C, but they had to have at least 1 additional risk factor for CVD. The primary outcome was first acute CHD event (myocardial infarction including silent infarction, unstable angina, acute coronary heart disease death, resuscitated cardiac arrest), coronary revascularization procedures, or stroke. Atorvastatin 10 mg, a moderate-intensity statin, significantly decreased occurrence of the primary outcome [30]. A subgroup analysis was performed to evaluate patients specifically between the ages of 65 and 75 and found a similar outcome in the elderly with a significant reduction in first major CV event and stroke [31].

A recent study evaluating primary prevention in patients with an intermediate risk for CVD was the HOPE-3 (Heart Outcomes Prevention Evaluation), published in 2016. Two co-primary outcomes were evaluated: the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, while the second primary outcome also included revascularization, heart failure, and resuscitated cardiac arrest. Rosuvastatin significantly decreased occurrence of both co-primary endpoints. About half of the study populations was over the age of 65 with a median age of 71 [32].

In addition to these trials of primary prevention, summarized in Table 3, a meta-analysis was published in 2013 to assess whether statins reduce all-cause mortality and CV events in elderly people without established CV disease. 

As demonstrated by the above studies, it is evident that statins do help reduce the risk of CV events, regardless of statin intensity, but they do not consistently prevent death. However, the trials that did not demonstrate a significant outcome related to death utilized a moderate-intensity statin; if a high-intensity statin was used in those trials, there may have been a benefit [7,27]. More study is needed to evaluate the use of high-intensity statins in the elderly for the prevention of all-cause mortality and CV-related death.

Fortunately, the ongoing STAREE (STAtin Therapy for Reducing Events in the Elderly) study is looking specifically at the impact of statin therapy in adults 70 and older. Patients with a history of CVD or dementia are excluded. Results are set to be released in 2020 [34].

Risks of Using Statins in Older Adults

Statin use has been linked to a number of unwanted adverse effects.

Myalgia

Myalgia is variable but may occur in up to 25% of patients using statin therapy, and elderly patients typically experience more statin-associated myalgia than younger patients [35,36]. Elderly patients are more prone to decreased muscle mass and therefore may be at a higher risk of developing myalgia pain. Elderly patients are also utilizing more medications, leading to the potential for increased drug-drug interactions that could lead to myalgia. Elderly patients may also lose the function of drug metabolizing enzymes responsible for breaking down statin therapy, which may also increase the risk for statin-associated myalgia. One study demonstrated that elderly patients were more likely to discontinue statin therapy due to muscle pain and elderly patients reported more muscle side effects than their younger cohorts [37]. It is important to monitor for muscle pain and weakness in every patient. If they experience any myalgia, it is recommended to either lower the dose or discontinue the statin once it is determined to be statin-related. After myalgia resolves, therapy can be reinitiated at a lower dose or with a different statin if the patient is deemed high-risk. If creatine phosphokinase levels are greater than 10 times above the upper limit of normal, then discontinue the statin and wait for levels to return to normal. Re-initiation may be appropriate, but the the risks and benefits must be weighed. Simvastatin and atorvastatin are associated with higher rates of myalgia while pravastatin and rosuvastatin have the least myalgia pain associated with use [38,39].

Statin Intolerance

Statin intolerance, while not very common, is typically seen more often in special populations such as women, Asian patients, and the elderly. For a patient to be considered intolerant to statins, they need to have documented muscle symptoms or an elevated creatine phosphokinase level. Although not well defined, many clinicians consider improvement of symptoms with statin withdrawal as a diagnosis for statin intolerance. Typically patients are then rechallenged with 1 to 2 other statins and if still unable to tolerate, then different lipid-lowering therapies may be utilized [40]. In the elderly, it is important to rule out other causes for myalgia and monitor for significant drug interactions that may lead to muscle pain, particularly if the patient is requiring secondary prevention with statin therapy, before discontinuation.

Dementia

In 2012, the FDA issued a warning about the potential risk of cognitive impairment with the use of statins, which was based on case reports, not clinical trial data [41]. The NLA guidelines do not recommend baseline cognitive assessments prior to starting therapy and recommend that if patients do report cognitive impairment, other contributing factors and the risk associated with stopping statin therapy must be considered. Statin therapy may be discontinued to assess reversibility of symptoms, and if symptoms resolve, then it may be more beneficial to keep the patient off statin therapy. Clinicians may also consider lowering the dose or switching to another statin if they feel it is necessary for the patient to continue with a statin, particularly if the patient requires secondary prevention. Evidence suggests that statins are not associated with adverse effects on cognition and should not be withheld due to the potential for causing cognitive impairment alone [42]. The prevalence of cognitive impairment increases with age, so it is important for a clinician to rule out age-related processes or other disease states, such as Alzheimer’s, before discontinuation of previously tolerated statin therapy.

Renal Impairment

Kidney function must be evaluated prior to initiation of a statin in an elderly person as well as during the time the patient is taking a statin. Because statins are eliminated via the kidney, and because most elderly patients have decreased kidney function, the potential for drug build-up in the body is higher than in a younger patient and may lead to more adverse effects. Atorvastatin is the only option that does not require dose adjustment. All other statins should be adjusted based upon the level of renal impairment. The results from the SHARP study, published in 2011, showed that the combination of ezetimibe and simvastatin versus placebo significantly reduced ASCVD events in patients with moderate to severe chronic kidney disease, including those receiving dialysis. Specifically, this trial showed a significant reduction of ischemic events and occurrence of arterial revascularization procedures. Although the trial did not show a significant difference in incidence of MI or CHD-related mortality, the trial was not adequately powered to show differences in results among the individual ASCVD events and it is not clear whether the results can guide the use of statin therapy in all patients with chronic kidney disease [43]. Statins may be beneficial in renal insufficiency to lower LDL-C, but more studies are needed to assess CVD outcomes related to statin use in patients with a history of kidney disease [44].

Hepatic Function

Statins have been known to increase liver enzymes and in rare cases lead to liver injury, which typically has led to underutilization of therapy in clinical practice. Risk factors associated with this include preexisting hepatitis, advanced age, chronic alcohol use, and use of concomitant medications that may also cause hepatotoxicity, such as acetaminophen. When a statin-induced hepatic effect is suspected, it is important to first rule out other causes or disease states that may be undiagnosed. If no other cause can be found, clinicians may choose to reduce the statin dose, switch the statin, or discontinue the statin altogether if the risk outweighs the benefit. Additionally, statins do not have to be held in patients who have preexisting hepatic dysfunction if use is clearly indicated because the cardiovascular benefits typically outweigh the risks of causing liver injury. Clinical judgement is still warranted and patients with preexisting liver conditions should be monitored regularly [45].

Cost Considerations

Several studies have demonstrated that statin therapy, in the general population, is economical for both primary and secondary prevention of CVD [46,47]. The 4S study found simvastatin therapy to be cost-effective; for example, the cost per life year gained for a 70-year-old man with high chlesterol was $3800 [48]. In contrast, primary prevention in middle-aged men, based on the West of Scotland trial, averages about $35,000 per year of life gained [46]. In a 2015 study that utilized an established Markov simulation model, researchers studied adults 75 to 94 years and examined the cost-effectiveness of generic statins for primary prevention in this population. The authors estimated treating this population with statins over the next decade would be cost-effective. However, the researchers cautioned that the CV benefits and cost-effectiveness would be offset with even a modest increased risk of cognitive impairments or functional limitations. Statin use was not cost-effective in diabetes patients who did not have elevated LDL-C levels [49].

Non-Statin Therapies

Several other classes of medications are available for the management of hyperlipidemia; however, none of these lipid-lowering therapies have been found to reduce CVD events or mortality in the elderly population.

Ezetimibe

Ezetimibe blocks the absorption of intestinal cholesterol and is typically combined with statin therapy to lower LDL-C. Up until the IMPROVE-IT trial was published in 2015, ezetimibe did not have much use in clinical practice. This landmark trial was a large double-blind study that looked at secondary prevention in patients with ACS, comparing ezetimibe 10 mg and simvastatin 40 mg versus simvastatin 40 mg alone. The authors included patients over the age of 50 (mean age 64) with clinical ASCVD. They found that the addition of ezetimibe to simvastatin did reduce the primary composite outcome (CV mortality, major CV events, or nonfatal stroke) when compared to simvastatin alone [50]. This trial demonstrates clinical benefit with the addition of ezetimibe to statin therapy and adds additional evidence to support a target LDL-C of less than 70 mg/dL; however, the elderly population was not adequately represented in the study to allow extrapolation of these results to older patients.

PCSK-9 Inhibitors

The proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors are a newer class of monoclonal antibodies that were first approved by the US Food and Drug Administration in 2015. Alirocumab and evolocumab, both approved PCSK-9 inhibitors, bind to LDL receptors on the surface of hepatocytes and assist in the internalization of LDL receptors for lysosomal degradation. By inhibiting the binding of PCSK-9 to the LDL receptors, there is an overall increase in LDL receptors available on the cell surface to bind to LDL particles, thereby lowering LDL-C levels. Treatment with these agents are currently considered (in addition to diet and maximally tolerated statin therapy) in adult patients with heterozygous familial hypercholesterolemia or clinical ASCVD requiring further reduction in LDL-C. Two studies were published focusing on the use of PCSK-9 inhibitors: Open-label Study of Long-term Evaluation against LDL Cholesterol (OSLER) and the Tolerability of Alirocumab in High Cardiovascular Risk Patients with Hypercholesterolemia Not Adequately Controlled with Their Lipid Modifying Therapy (ODYSSEY LONG TERM). Overall, these studies demonstrated a 60% reduction of LDL-C among patients with high CVD risk on maximum-tolerated statin therapy. Furthermore, the ODYSSEY LONG TERM trial did find that the rate of major CVD adverse events was significantly lower with alirocumab added to maximum-tolerated statin therapy, with a hazard ratio of 0.52 [51].

One recent study of evolocumab, named the Further Cardiovascular OUtcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER), enrolled patients between the ages of 40 and 85 with 1 major CV risk factor or 2 minor CV risk factors. The primary endpoint was a composite of cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization. Evolocumab lowered major CV events by roughly 15% when added to statin therapy in patients who were at high risk for clinical ASCVD. The mean age of the patients in the trial was 63; however, it is unclear how many of the study participants were elderly [52].

Unfortunately, the studies discussed above do not represent the elderly population well and the agents have not been studied long-term to determine the effects of continued use beyond 2 years. Long-term outcome studies are currently underway; however, it is unknown at this time whether elderly patients are being considered in these studies. It is known that genetic variation of the PCSK-9 locus does lower LDL-C in the elderly but does not significantly lower their risk of vascular disease [51]. At this time, until further evidence is available, we do not recommend the use of PCSK-9 inhibitors in elderly patients.

Nicotinic Acid

Nicotinic acid (Niacin, Niacin ER), also known as vitamin B3, has been utilized for decades as a vitamin supplement, an anti-wrinkle agent, and is known to have neuroprotective effects. It has also been utilized for dyslipidemia and has had some benefits when used alone to decrease cardiovascular disease [53]. Unfortunately the Coronary Drug Project was completed in the 1980s and did not incorporate patients over the age of 64, therefore making the results difficult to apply to elderly patients today [54]. Other literature has been published in recent years to refute that study, claiming there is no additional benefit to using niacin for cardiovascular protection and these studies have included elderly patients. In the AIM-HIGH trial, published in 2011, approximately 46% of the patients were 65 or older. Patients who were previously taking statin therapy that had known cardiovascular disease were enrolled. Niacin added to simvastatin 40–80 mg lowered LDL-C, triglycerides, and increased HDL-C, but the addition of niacin was not proven to help lower the risk of cardiovascular events [55]. The HPS2-THRIVE study enrolled patients with known cardiovascular disease between the ages of 50 and 80 years and found no benefit in preventing CVD when adding niacin to statin therapy [56]. With its side effect profile, risk for increased glucose intolerance, and lack of evidence to demonstrate benefit for prevention of CV events, we do not recommend niacin for use in the elderly at this time.

Bile Acid Sequestrants

The ATP III guidelines [57] noted that when statins are not sufficient to lower high cholesterol, bile acid sequestrants also known as resins could be added. More recently, the 2016 ACC expert consensus on non-statin therapies for LDL-C lowering [16] stated resins may be considered in select circumstances as a second-line agent for adults with ezetimibe intolerance and with triglycerides

Fibrates

While fibrates (gemfibrozil, fenofibrate, clofibrate) have not been studied to demonstrate a reduction in CVD or CVD mortality in the elderly population, this medication class is beneficial in patients with hypertriglyceridemia to lower triglyceride levels and prevent pancreatitis. Fibrates are recommended for patients with triglyceride levels approaching 500 mg/dL. Fibrates can also increase high-density lipoproteins, which tend to be lower in the elderly population and considered a risk factor for CVD. Gemfibrozil is not recommended in combination with statin therapy due to an increased risk of myalgia. Fenofibrate is the drug of choice, particularly for diabetic patients with very uncontrolled triglyceride levels because it will not affect glucose levels [57]. At this time, we do not recommend the use of fibrates in the elderly population unless they are at risk for developing pancreatitis and have elevated triglyceride levels.

Patient-Centered Care

Evidence-based medicine can aid in making sound clinical decisions for proper patient care; however, treatment plans should consider the individual patient’s perspectives and needs, beliefs, expectations, and goals. In the elderly population, we must also consider factors such as finances, pill-burden, drug-drug interactions, physiological needs, comorbid disease states, and overall life expectancy. In addition, the elderly population is physiologically heterogeneous group and recommendations for therapy need to be individualized. Chronological age does not necessarily correspond to vascular age and risk factors for cardiovascular disease do not predict outcomes as well in the elderly as they do in younger patients. While older patients may view having to take 1 less medication as more important than preventing a heart attack or stroke at the age of 80, it is advisable to discuss all potential outcomes related to morbidity associated with the occurrence of an MI or stroke due to the lack of statin therapy. Additionally, pharmacists can play a vital role in evaluating elderly patients and their medication regimens. Elderly patients should undergo a medication reconciliation at each visit to evaluate drug-drug interactions, side effects, and potentially harmful medication combinations that may lead to increased adverse drug outcomes.

Conclusion

CHD increases with age, and most patients who have a CV event are more likely to die with advancing age. Based on the the limited available evidence, statin therapy is beneficial in the elderly population in reducing overall CV morbidity. We recommend beginning with with a moderate-intensity statin and adjusting accordingly. High-intensity statin therapy appears to be effective for elderly patients for secondary prevention, but clinicians should use clinical judgment and monitor for adverse events, particularly myalgia pain. At this time, we are unable to determine if non-statin therapies for the elderly would be beneficial and do not recommend their use unless the patient is at risk for pancreatitis, in which case a fenofibrate is recommended.

Corresponding author: Nicole A. Slater, PharmD, BCACP, Auburn University, Harrison School of Pharmacy, 650 Clinic Dr., Mobile, AL 36688.

Financial disclosures: None.

From the Harrison School of Pharmacy, Auburn University, Mobile, AL.

Abstract

• Objective: To summarize the literature relevant to managing dyslipidemia in the elderly and review recommendations for initiating lipid-lowering therapy.
• Methods: Review of the literature.
• Results: Statins are the most commonly utilized medication class for lipid-lowering in the general population, and they are recommended for primary prevention in patients between the ages of 40 to 75 with at least 1 risk factor for cardiovascular disease as well as for any patient needing secondary prevention. In the elderly, statins may be appropriate for both primary and secondary prevention if the benefits outweigh the risks. Based on the available evidence, it is safe to recommend statin therapy to elderly patients who require secondary prevention given the known benefits in reducing cardiovascular morbidity and mortality for patients up to the age of 80. For primary prevention, statin therapy may be beneficial, but one must carefully evaluate for comorbid conditions, life expectancy, concomitant medications, overall health status, frailty, and patient or family preference. Several other classes of lipid-lowering agents exist; however, there is not enough evidence for us to recommend use in the elderly population for cardiovascular risk reduction in either primary or secondary scenarios.
• Conclusion: Although clinical research in the elderly population is limited, evidence supports the use of statins in elderly patients for secondary prevention and in patients up to age 75 for primary prevention; however clinicians must use clinical judgement and take into consideration the patient’s situation regarding comorbidities, polypharmacy, and possible adverse effects. More high-quality evidence is necessary.

Key words: hyperlipidemia; geriatrics; elderly; patient-centered care; statin; cardiovascular disease.

The number of Americans age 65 years and older is projected to more than double, from 46 million today to over 98 million by 2060, and the 65-and-older age group’s share of the total population will rise to nearly 24% [1]. Life expectancy is now predicted to be > 20 years for women at age 65 and > 17 years for men at age 65 in many high-income countries, including the United States [2]. This demographic shift toward an older population will result in a higher burden of coronary heart disease and stroke, with atherosclerotic cardiovascular disease (ASCVD) prevalence and costs projected to increase substantially [3].

Among adults seeking medical care in the United States, roughly 95 million have a total cholesterol (TC) level of ≥ 200 mg/dL or more, and approximately 29 million have a TC > 240 mg/dL [4]. Cholesterol screening is important since most patients suffering from dyslipidemia are asymptomatic. Dyslipidemia is a major risk factor for the development of atherosclerotic disease. Because of the complications associated with dyslipidemia, it is vital that patients are provided with primary and/or secondary prevention strategies to reduce the risk of cardiovascular disease (CVD) and protect high-risk patients from recurring events. A clinical controversy exists surrounding the elderly population, concerning whether or not clinicians should be providing lipid-lowering treatment to this group of individuals for dyslipidemia. The evidence is limited for patients over age 65, and even more so for the very elderly (> 80 years); therefore, it is necessary to review the available evidence to make an appropriate decision when it comes to managing dyslipidemia in the elderly population

Currently, HMG-CoA reductase inhibitors (statins) are the only known class of medications for the treatment of dyslipidemia that will prevent both primary and secondary cardiovascular (CV) events, including death. Statin intensity (Table 1) 

Guideline Recommendations

Current guidelines differ in their recommendations for treating dyslipidemia in the elderly population. In 2016, the Task Force for the Management of Dyslipidemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) released updated guidelines for managing dyslipidemia. These guidelines recommend that older patients with established CVD be treated in the same way as younger patients because of the many benefits statin therapy demonstrated in clinical trials. They also suggest that statin therapy be started at a lower doses to achieve goals for primary prevention in the older population. In addition, CVD risk factors (hypertension, diabetes, dyslipidemia, smoking) should be addressed in this population to reduce CVD risk. They also acknowledged that primary prevention may not prolong life in the older adult, but treatment does reduce cardiovascular mortality and statin therapy is recommended to reduce the overall risk of CV morbidity in this population [11]. In contrast, The 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines changed the management and treatment of dyslipidemia by highlighting “statin benefit groups” rather than recommending a treat-to-target goal as guidelines had done for many years. ACC/AHA recommends a moderate-intensity statin for patients > 75 years of age for secondary prevention versus the use of a high-intensity statin for patients who are between the ages of 40 and 75 based on the pooled cohort risk equation. In patients over age 75 with no history of CVD, no specific recommendation is available for the use of lipid-lowering therapy at this time [12]. ACC/AHA is expected to publish a new set of guidelines sometime in 2018 and they are projected to utilize lipid-lowering goals in combination with the pooled cohort equation to assess overall risk in patients with dyslipidemia.

The 2015 National Lipid Association (NLA) released “Part 1” guidelines for the management of dyslipidemia and then provided “Part 2” about a year later, which focuses on management for special populations. To summarize, the NLA guidelines recommend that elderly patients between the ages of 65 and 80 receive a high-intensity statin for secondary prevention after special consideration of the potential risks and benefits. In patients over the age of 80, NLA recommends a moderate-intensity statin for secondary prevention. For primary prevention, NLA recommends utilizing the pooled cohort risk equation to analyze patient characteristics, keeping in mind that age is a driving factor for increased risk of CVD and that the actual risk for developing a CV event may be “overestimated” if the patient has no other risk factors other than their age. When evaluating patients between the ages of 65 and 79 for primary prevention, NLA suggests following Part 1 of the guidelines. In Part 1, NLA recommends evaluating the patient’s characteristics and suggests a moderate- or high-intensity statin if the patient is considered “very high risk” or “high risk” and a moderate-intensity statin for patients who are considered “moderate risk”. For patients over the age of 80, they recommend utilizing a moderate- or a low-intensity statin depending on frailty status or if significant comorbidities or polypharmacy exist [13,14].

In 2017, the American Association of Clinical Endocrinologist (AACE) released guidelines for the management of dyslipidemia and CVD prevention. AACE recommends that patients over age 65 be screened for dyslipidemia, and those who have multiple risk factors, other than age, should be considered for treatment with lipid-lowering therapy. AACE focuses on specific target LDL-C levels as treatment goals [15].

In addition to statins, other lipid-lowering therapies are used to treat dyslipidemia. The 2016 American College of Cardiology (ACC) Task Force reported on the use of non-statin therapies for the management of dyslipidemia and prevention of clinical ASCVD [16]. The committee concluded that ezetimibe added to statin therapy, bile acid sequestrants as monotherapy, and niacin as monotherapy all have some benefit for the prevention of clinical ASCVD. These guidelines also discuss the use of PCSK-9 inhibitors and their potential to decrease the risk of clinical ASCVD, but trials are currently ongoing to determine actual benefit. These guidelines address special populations but they do not consider the elderly in their recommendations. Currently, the only special populations included are patients with heart failure, those on hemodialysis, women who are of childbearing age or pregnant, and those with autoimmune diseases [16]. The literature available for each individual medication is discussed in further detail below.

Evidence for Secondary Prevention

The benefits of statin therapy for secondary prevention in the elderly is more established than it is for primary prevention (Table 2). 

The ASCOT–LLA (Anglo-Scandinavian Cardiac Outcomes Trial–Lipid Lowering Arm), published in 2003, evaluated the effect of atorvastatin 10 mg on reducing ASCVD events in moderate-risk patients between 40–79 years of age who had hypertension and normal or slightly elevated LDL-C levels, with at least 2 other risk factors for CVD (age > 55 years was considered a risk factor). The primary outcome was non-fatal MI including silent MI and fatal CHD. A significant reduction was seen in the primary endpoint. Over half of the study population was > 60 years of age, with a mean age of 63 years. In a post-hoc analysis, stroke prevention was found to be similar in patients who were > 70 years of age and those < 70 years of age [19].

One of the first trials to specifically analyze the impact of age on lipid-lowering therapy in secondary ASCVD prevention was the Scandinavian Simvastatin Survival Study (4S), published in 1994. They evaluated the effect of simvastatin 20 mg on CV-related mortality and morbidity in patients 35–70 years of age with hyperlipidemia and a history of angina or acute MI occurring > 6 months of the study starting. The primary outcome was all-cause mortality. The secondary endpoint was time to first major CV event, which included coronary death, non-fatal acute MI, resuscitated cardiac arrest, and silent MI. Simvastatin significantly reduced the primary outcome and CHD-related deaths. A subgroup analysis of the study population > 60 years of age showed that age made no significant impact on primary or secondary outcomes; however, investigators noted that these subgroup analyses had less statistical power than the population as a whole [20].

Published in 1998, the LIPID (Long-Term Intervention with Pravastatin in Ischemic Disease) study evaluated the effects of pravastatin 40 mg daily on CHD-related mortality and overall mortality in patients with hyperlipidemia and clinical ASCVD (previous MI or unstable angina). The primary outcome observed was fatal CHD. Pravastatin significantly reduced the primary outcome, overall mortality, and pre-specified CV events. In a subgroup analysis, age group ( 65, and > 70 years) had no significant impact on the combined outcome of death from CHD and nonfatal MI; however, patients 65 to 70 years of age made up less than half of the study population [21].

The Cholesterol and Recurrent Events (CARE) trial, published in 1996, looked at the effect of pravastatin 40mg therapy for secondary ASCVD prevention following an MI in patients who had average cholesterol levels (defined as TC < 240 mg/dL and LDL-C 115–174 mg/dL). The primary endpoint assessed was time to fatal CHD or nonfatal MI. To meet statistical power they looked at subgroups for a broader outcome of a major coronary event (including fatal CHD, nonfatal MI, bypass surgery, and angioplasty). Pravastatin significantly reduced the primary outcome. The significant reduction in coronary events produced by pravastatin was noted to be significantly greater in women and in patients with higher pretreatment levels of LDL-C, but was not significantly impacted by age group (24–59 vs. 60–75 years) [22].

The Heart Protection Study (HPS), published in 2002, looked at the long-term effects of lowering LDL-C with simvastatin 40 mg in patients 40 to 80 years of age at high risk for mortality due to either vascular or nonvascular causes. The primary outcome assessed was all-cause mortality, with fatal or nonfatal vascular events as co-primary outcomes for subcategory analyses. Simvastatin significantly reduced both primary and co-primary outcomes, but there was no significant difference when they looked at nonvascular mortality between groups. Neither age nor baseline LDL levels were reported to have had a significant impact on outcomes. Over half the population was > 65 years of age, and about one-third of the population was > 70 years of age [23].

The PROVE-IT/TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis in Myocardial Infarction 22) trial, published in 2004, compared pravastatin 40 mg (moderate-intensity) to atorvastatin 80 mg (high-intensity) for secondary ASCVD prevention in patients with recent acute coronary syndrome (ACS) 65 years of age and the mean age was 58 years [24].

The TNT (Treating to New Targets) trial, published in 2005, looked at secondary ASCVD prevention in regards to targeting LDL-C levels to < 100 mg/dL or < 70 mg/dL with atorvastatin 10 mg and atorvastatin 80 mg. Patients had stable coronary artery disease (CAD) and baseline LDL-C levels < 130 mg/dL. The primary endpoint was the occurrence of a CV event (CAD mortality, nonfatal MI not related to procedure, resuscitation after cardiac arrest, or fatal or nonfatal stroke). High-intensity atorvastatin (80 mg) significantly reduced the primary outcome. The mean age of the study population was approximately 61 years. The study reported no statistical interaction for age or sex in the primary outcome measure [25].

The Study Assessing Goals in the Elderly (SAGE), published in 2007, evaluated the effects of pravastatin 40 mg (moderate-intensity) vs atorvastatin 80 mg (high-intensity) on secondary ASCVD prevention in patients 65 to 85 years (mean age 72) with stable CHD, LDL-C 100–250 mg/dL, with at least 1 episode of myocardial ischemia with total ischemia duration > 3 minutes. The primary efficacy outcome observed was absolute change in total duration of myocardial ischemia on 48-hour ambulatory electrocardiographic monitoring from baseline to month 12. No significant difference was observed in efficacy between the two groups for the primary endpoint, but the intensive statin therapy group showed greater benefit respective to several secondary outcomes, including major acute CV events and death [26].

In summary, while these trials provide evidence that statin therapy is beneficial in a wide range of patients with clinical ASCVD and dyslipidemia, the trial data does not provide definitive guidance for treating elderly patients at this time. Given the small percentage of elderly patients that were included, some of the trial results reporting statistical significance in this age group hold less clinical significance. It appears that high-intensity statin therapy was more likely to effectively prevent clinical ASCVD and death than moderate-intensity statin therapy, but more evidence is needed regarding secondary prevention in patients over age 75.

Evidence for Primary Prevention

The PROSPER (PROspective Study of Pravastatin in the Elderly at Risk) was published in 2002 to assess the efficacy of pravastatin in patients between the ages of 70 and 82 (mean age 75 years) with pre-existing vascular disease (coronary, cerebral, or peripheral) or at an elevated risk (smoking, hypertension, or diabetes). Patients were randomized to receive either placebo or pravastatin 40 mg (a moderate-intensity statin). They found that pravastatin therapy reduced the risk of the composite outcome of CHD-related death, nonfatal MI, and fatal or nonfatal stroke in this elderly population. A post-hoc analysis comparing primary versus secondary prevention groups found no significant differences between these subgroups [7].

Han et al recently conducted a post hoc secondary analysis of older participants (65 years and older) in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial–Lipid-Lowering Trial (ALLHAT-LLT). The intervention for ALLHAT-LLT was 40 mg pravastatin. They found no significant differences in all-cause mortality or cardiovascular outcomes between the pravastatin and usual care groups [27]

JUPITER (Justification for Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin), published in 2008, examined the efficacy of rosuvastatin vs. placebo in low- to moderate-risk men 50 years and older and women 60 years and older using a composite outcome of MI, unstable angina, stroke, arterial revascularization, or CVD death. Rosuvastatin did significantly decrease the primary endpoint, however it did not reduce the risk of overall death [28]. A subgroup analysis was performed on the elderly (65–75 years) study participants in JUPITER demonstrating a significant risk reduction for the combined CV endpoint and a nonsignificant reduction of all-cause mortality [29].

CARDS (Collaborative Atorvastatin Diabetes Study), published in 2004, looked at statin use for primary prevention in high-risk patients with type 2 diabetes without high LDL-C, but they had to have at least 1 additional risk factor for CVD. The primary outcome was first acute CHD event (myocardial infarction including silent infarction, unstable angina, acute coronary heart disease death, resuscitated cardiac arrest), coronary revascularization procedures, or stroke. Atorvastatin 10 mg, a moderate-intensity statin, significantly decreased occurrence of the primary outcome [30]. A subgroup analysis was performed to evaluate patients specifically between the ages of 65 and 75 and found a similar outcome in the elderly with a significant reduction in first major CV event and stroke [31].

A recent study evaluating primary prevention in patients with an intermediate risk for CVD was the HOPE-3 (Heart Outcomes Prevention Evaluation), published in 2016. Two co-primary outcomes were evaluated: the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, while the second primary outcome also included revascularization, heart failure, and resuscitated cardiac arrest. Rosuvastatin significantly decreased occurrence of both co-primary endpoints. About half of the study populations was over the age of 65 with a median age of 71 [32].

In addition to these trials of primary prevention, summarized in Table 3, a meta-analysis was published in 2013 to assess whether statins reduce all-cause mortality and CV events in elderly people without established CV disease. 

As demonstrated by the above studies, it is evident that statins do help reduce the risk of CV events, regardless of statin intensity, but they do not consistently prevent death. However, the trials that did not demonstrate a significant outcome related to death utilized a moderate-intensity statin; if a high-intensity statin was used in those trials, there may have been a benefit [7,27]. More study is needed to evaluate the use of high-intensity statins in the elderly for the prevention of all-cause mortality and CV-related death.

Fortunately, the ongoing STAREE (STAtin Therapy for Reducing Events in the Elderly) study is looking specifically at the impact of statin therapy in adults 70 and older. Patients with a history of CVD or dementia are excluded. Results are set to be released in 2020 [34].

Risks of Using Statins in Older Adults

Statin use has been linked to a number of unwanted adverse effects.

Myalgia

Myalgia is variable but may occur in up to 25% of patients using statin therapy, and elderly patients typically experience more statin-associated myalgia than younger patients [35,36]. Elderly patients are more prone to decreased muscle mass and therefore may be at a higher risk of developing myalgia pain. Elderly patients are also utilizing more medications, leading to the potential for increased drug-drug interactions that could lead to myalgia. Elderly patients may also lose the function of drug metabolizing enzymes responsible for breaking down statin therapy, which may also increase the risk for statin-associated myalgia. One study demonstrated that elderly patients were more likely to discontinue statin therapy due to muscle pain and elderly patients reported more muscle side effects than their younger cohorts [37]. It is important to monitor for muscle pain and weakness in every patient. If they experience any myalgia, it is recommended to either lower the dose or discontinue the statin once it is determined to be statin-related. After myalgia resolves, therapy can be reinitiated at a lower dose or with a different statin if the patient is deemed high-risk. If creatine phosphokinase levels are greater than 10 times above the upper limit of normal, then discontinue the statin and wait for levels to return to normal. Re-initiation may be appropriate, but the the risks and benefits must be weighed. Simvastatin and atorvastatin are associated with higher rates of myalgia while pravastatin and rosuvastatin have the least myalgia pain associated with use [38,39].

Statin Intolerance

Statin intolerance, while not very common, is typically seen more often in special populations such as women, Asian patients, and the elderly. For a patient to be considered intolerant to statins, they need to have documented muscle symptoms or an elevated creatine phosphokinase level. Although not well defined, many clinicians consider improvement of symptoms with statin withdrawal as a diagnosis for statin intolerance. Typically patients are then rechallenged with 1 to 2 other statins and if still unable to tolerate, then different lipid-lowering therapies may be utilized [40]. In the elderly, it is important to rule out other causes for myalgia and monitor for significant drug interactions that may lead to muscle pain, particularly if the patient is requiring secondary prevention with statin therapy, before discontinuation.

Dementia

In 2012, the FDA issued a warning about the potential risk of cognitive impairment with the use of statins, which was based on case reports, not clinical trial data [41]. The NLA guidelines do not recommend baseline cognitive assessments prior to starting therapy and recommend that if patients do report cognitive impairment, other contributing factors and the risk associated with stopping statin therapy must be considered. Statin therapy may be discontinued to assess reversibility of symptoms, and if symptoms resolve, then it may be more beneficial to keep the patient off statin therapy. Clinicians may also consider lowering the dose or switching to another statin if they feel it is necessary for the patient to continue with a statin, particularly if the patient requires secondary prevention. Evidence suggests that statins are not associated with adverse effects on cognition and should not be withheld due to the potential for causing cognitive impairment alone [42]. The prevalence of cognitive impairment increases with age, so it is important for a clinician to rule out age-related processes or other disease states, such as Alzheimer’s, before discontinuation of previously tolerated statin therapy.

Renal Impairment

Kidney function must be evaluated prior to initiation of a statin in an elderly person as well as during the time the patient is taking a statin. Because statins are eliminated via the kidney, and because most elderly patients have decreased kidney function, the potential for drug build-up in the body is higher than in a younger patient and may lead to more adverse effects. Atorvastatin is the only option that does not require dose adjustment. All other statins should be adjusted based upon the level of renal impairment. The results from the SHARP study, published in 2011, showed that the combination of ezetimibe and simvastatin versus placebo significantly reduced ASCVD events in patients with moderate to severe chronic kidney disease, including those receiving dialysis. Specifically, this trial showed a significant reduction of ischemic events and occurrence of arterial revascularization procedures. Although the trial did not show a significant difference in incidence of MI or CHD-related mortality, the trial was not adequately powered to show differences in results among the individual ASCVD events and it is not clear whether the results can guide the use of statin therapy in all patients with chronic kidney disease [43]. Statins may be beneficial in renal insufficiency to lower LDL-C, but more studies are needed to assess CVD outcomes related to statin use in patients with a history of kidney disease [44].

Hepatic Function

Statins have been known to increase liver enzymes and in rare cases lead to liver injury, which typically has led to underutilization of therapy in clinical practice. Risk factors associated with this include preexisting hepatitis, advanced age, chronic alcohol use, and use of concomitant medications that may also cause hepatotoxicity, such as acetaminophen. When a statin-induced hepatic effect is suspected, it is important to first rule out other causes or disease states that may be undiagnosed. If no other cause can be found, clinicians may choose to reduce the statin dose, switch the statin, or discontinue the statin altogether if the risk outweighs the benefit. Additionally, statins do not have to be held in patients who have preexisting hepatic dysfunction if use is clearly indicated because the cardiovascular benefits typically outweigh the risks of causing liver injury. Clinical judgement is still warranted and patients with preexisting liver conditions should be monitored regularly [45].

Cost Considerations

Several studies have demonstrated that statin therapy, in the general population, is economical for both primary and secondary prevention of CVD [46,47]. The 4S study found simvastatin therapy to be cost-effective; for example, the cost per life year gained for a 70-year-old man with high chlesterol was $3800 [48]. In contrast, primary prevention in middle-aged men, based on the West of Scotland trial, averages about $35,000 per year of life gained [46]. In a 2015 study that utilized an established Markov simulation model, researchers studied adults 75 to 94 years and examined the cost-effectiveness of generic statins for primary prevention in this population. The authors estimated treating this population with statins over the next decade would be cost-effective. However, the researchers cautioned that the CV benefits and cost-effectiveness would be offset with even a modest increased risk of cognitive impairments or functional limitations. Statin use was not cost-effective in diabetes patients who did not have elevated LDL-C levels [49].

Non-Statin Therapies

Several other classes of medications are available for the management of hyperlipidemia; however, none of these lipid-lowering therapies have been found to reduce CVD events or mortality in the elderly population.

Ezetimibe

Ezetimibe blocks the absorption of intestinal cholesterol and is typically combined with statin therapy to lower LDL-C. Up until the IMPROVE-IT trial was published in 2015, ezetimibe did not have much use in clinical practice. This landmark trial was a large double-blind study that looked at secondary prevention in patients with ACS, comparing ezetimibe 10 mg and simvastatin 40 mg versus simvastatin 40 mg alone. The authors included patients over the age of 50 (mean age 64) with clinical ASCVD. They found that the addition of ezetimibe to simvastatin did reduce the primary composite outcome (CV mortality, major CV events, or nonfatal stroke) when compared to simvastatin alone [50]. This trial demonstrates clinical benefit with the addition of ezetimibe to statin therapy and adds additional evidence to support a target LDL-C of less than 70 mg/dL; however, the elderly population was not adequately represented in the study to allow extrapolation of these results to older patients.

PCSK-9 Inhibitors

The proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors are a newer class of monoclonal antibodies that were first approved by the US Food and Drug Administration in 2015. Alirocumab and evolocumab, both approved PCSK-9 inhibitors, bind to LDL receptors on the surface of hepatocytes and assist in the internalization of LDL receptors for lysosomal degradation. By inhibiting the binding of PCSK-9 to the LDL receptors, there is an overall increase in LDL receptors available on the cell surface to bind to LDL particles, thereby lowering LDL-C levels. Treatment with these agents are currently considered (in addition to diet and maximally tolerated statin therapy) in adult patients with heterozygous familial hypercholesterolemia or clinical ASCVD requiring further reduction in LDL-C. Two studies were published focusing on the use of PCSK-9 inhibitors: Open-label Study of Long-term Evaluation against LDL Cholesterol (OSLER) and the Tolerability of Alirocumab in High Cardiovascular Risk Patients with Hypercholesterolemia Not Adequately Controlled with Their Lipid Modifying Therapy (ODYSSEY LONG TERM). Overall, these studies demonstrated a 60% reduction of LDL-C among patients with high CVD risk on maximum-tolerated statin therapy. Furthermore, the ODYSSEY LONG TERM trial did find that the rate of major CVD adverse events was significantly lower with alirocumab added to maximum-tolerated statin therapy, with a hazard ratio of 0.52 [51].

One recent study of evolocumab, named the Further Cardiovascular OUtcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER), enrolled patients between the ages of 40 and 85 with 1 major CV risk factor or 2 minor CV risk factors. The primary endpoint was a composite of cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization. Evolocumab lowered major CV events by roughly 15% when added to statin therapy in patients who were at high risk for clinical ASCVD. The mean age of the patients in the trial was 63; however, it is unclear how many of the study participants were elderly [52].

Unfortunately, the studies discussed above do not represent the elderly population well and the agents have not been studied long-term to determine the effects of continued use beyond 2 years. Long-term outcome studies are currently underway; however, it is unknown at this time whether elderly patients are being considered in these studies. It is known that genetic variation of the PCSK-9 locus does lower LDL-C in the elderly but does not significantly lower their risk of vascular disease [51]. At this time, until further evidence is available, we do not recommend the use of PCSK-9 inhibitors in elderly patients.

Nicotinic Acid

Nicotinic acid (Niacin, Niacin ER), also known as vitamin B3, has been utilized for decades as a vitamin supplement, an anti-wrinkle agent, and is known to have neuroprotective effects. It has also been utilized for dyslipidemia and has had some benefits when used alone to decrease cardiovascular disease [53]. Unfortunately the Coronary Drug Project was completed in the 1980s and did not incorporate patients over the age of 64, therefore making the results difficult to apply to elderly patients today [54]. Other literature has been published in recent years to refute that study, claiming there is no additional benefit to using niacin for cardiovascular protection and these studies have included elderly patients. In the AIM-HIGH trial, published in 2011, approximately 46% of the patients were 65 or older. Patients who were previously taking statin therapy that had known cardiovascular disease were enrolled. Niacin added to simvastatin 40–80 mg lowered LDL-C, triglycerides, and increased HDL-C, but the addition of niacin was not proven to help lower the risk of cardiovascular events [55]. The HPS2-THRIVE study enrolled patients with known cardiovascular disease between the ages of 50 and 80 years and found no benefit in preventing CVD when adding niacin to statin therapy [56]. With its side effect profile, risk for increased glucose intolerance, and lack of evidence to demonstrate benefit for prevention of CV events, we do not recommend niacin for use in the elderly at this time.

Bile Acid Sequestrants

The ATP III guidelines [57] noted that when statins are not sufficient to lower high cholesterol, bile acid sequestrants also known as resins could be added. More recently, the 2016 ACC expert consensus on non-statin therapies for LDL-C lowering [16] stated resins may be considered in select circumstances as a second-line agent for adults with ezetimibe intolerance and with triglycerides

Fibrates

While fibrates (gemfibrozil, fenofibrate, clofibrate) have not been studied to demonstrate a reduction in CVD or CVD mortality in the elderly population, this medication class is beneficial in patients with hypertriglyceridemia to lower triglyceride levels and prevent pancreatitis. Fibrates are recommended for patients with triglyceride levels approaching 500 mg/dL. Fibrates can also increase high-density lipoproteins, which tend to be lower in the elderly population and considered a risk factor for CVD. Gemfibrozil is not recommended in combination with statin therapy due to an increased risk of myalgia. Fenofibrate is the drug of choice, particularly for diabetic patients with very uncontrolled triglyceride levels because it will not affect glucose levels [57]. At this time, we do not recommend the use of fibrates in the elderly population unless they are at risk for developing pancreatitis and have elevated triglyceride levels.

Patient-Centered Care

Evidence-based medicine can aid in making sound clinical decisions for proper patient care; however, treatment plans should consider the individual patient’s perspectives and needs, beliefs, expectations, and goals. In the elderly population, we must also consider factors such as finances, pill-burden, drug-drug interactions, physiological needs, comorbid disease states, and overall life expectancy. In addition, the elderly population is physiologically heterogeneous group and recommendations for therapy need to be individualized. Chronological age does not necessarily correspond to vascular age and risk factors for cardiovascular disease do not predict outcomes as well in the elderly as they do in younger patients. While older patients may view having to take 1 less medication as more important than preventing a heart attack or stroke at the age of 80, it is advisable to discuss all potential outcomes related to morbidity associated with the occurrence of an MI or stroke due to the lack of statin therapy. Additionally, pharmacists can play a vital role in evaluating elderly patients and their medication regimens. Elderly patients should undergo a medication reconciliation at each visit to evaluate drug-drug interactions, side effects, and potentially harmful medication combinations that may lead to increased adverse drug outcomes.

Conclusion

CHD increases with age, and most patients who have a CV event are more likely to die with advancing age. Based on the the limited available evidence, statin therapy is beneficial in the elderly population in reducing overall CV morbidity. We recommend beginning with with a moderate-intensity statin and adjusting accordingly. High-intensity statin therapy appears to be effective for elderly patients for secondary prevention, but clinicians should use clinical judgment and monitor for adverse events, particularly myalgia pain. At this time, we are unable to determine if non-statin therapies for the elderly would be beneficial and do not recommend their use unless the patient is at risk for pancreatitis, in which case a fenofibrate is recommended.

Corresponding author: Nicole A. Slater, PharmD, BCACP, Auburn University, Harrison School of Pharmacy, 650 Clinic Dr., Mobile, AL 36688.

Financial disclosures: None.

From the Harrison School of Pharmacy, Auburn University, Mobile, AL.

Abstract

• Objective: To summarize the literature relevant to managing dyslipidemia in the elderly and review recommendations for initiating lipid-lowering therapy.
• Methods: Review of the literature.
• Results: Statins are the most commonly utilized medication class for lipid-lowering in the general population, and they are recommended for primary prevention in patients between the ages of 40 to 75 with at least 1 risk factor for cardiovascular disease as well as for any patient needing secondary prevention. In the elderly, statins may be appropriate for both primary and secondary prevention if the benefits outweigh the risks. Based on the available evidence, it is safe to recommend statin therapy to elderly patients who require secondary prevention given the known benefits in reducing cardiovascular morbidity and mortality for patients up to the age of 80. For primary prevention, statin therapy may be beneficial, but one must carefully evaluate for comorbid conditions, life expectancy, concomitant medications, overall health status, frailty, and patient or family preference. Several other classes of lipid-lowering agents exist; however, there is not enough evidence for us to recommend use in the elderly population for cardiovascular risk reduction in either primary or secondary scenarios.
• Conclusion: Although clinical research in the elderly population is limited, evidence supports the use of statins in elderly patients for secondary prevention and in patients up to age 75 for primary prevention; however clinicians must use clinical judgement and take into consideration the patient’s situation regarding comorbidities, polypharmacy, and possible adverse effects. More high-quality evidence is necessary.

Key words: hyperlipidemia; geriatrics; elderly; patient-centered care; statin; cardiovascular disease.

The number of Americans age 65 years and older is projected to more than double, from 46 million today to over 98 million by 2060, and the 65-and-older age group’s share of the total population will rise to nearly 24% [1]. Life expectancy is now predicted to be > 20 years for women at age 65 and > 17 years for men at age 65 in many high-income countries, including the United States [2]. This demographic shift toward an older population will result in a higher burden of coronary heart disease and stroke, with atherosclerotic cardiovascular disease (ASCVD) prevalence and costs projected to increase substantially [3].

Among adults seeking medical care in the United States, roughly 95 million have a total cholesterol (TC) level of ≥ 200 mg/dL or more, and approximately 29 million have a TC > 240 mg/dL [4]. Cholesterol screening is important since most patients suffering from dyslipidemia are asymptomatic. Dyslipidemia is a major risk factor for the development of atherosclerotic disease. Because of the complications associated with dyslipidemia, it is vital that patients are provided with primary and/or secondary prevention strategies to reduce the risk of cardiovascular disease (CVD) and protect high-risk patients from recurring events. A clinical controversy exists surrounding the elderly population, concerning whether or not clinicians should be providing lipid-lowering treatment to this group of individuals for dyslipidemia. The evidence is limited for patients over age 65, and even more so for the very elderly (> 80 years); therefore, it is necessary to review the available evidence to make an appropriate decision when it comes to managing dyslipidemia in the elderly population

Currently, HMG-CoA reductase inhibitors (statins) are the only known class of medications for the treatment of dyslipidemia that will prevent both primary and secondary cardiovascular (CV) events, including death. Statin intensity (Table 1) 

Guideline Recommendations

Current guidelines differ in their recommendations for treating dyslipidemia in the elderly population. In 2016, the Task Force for the Management of Dyslipidemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) released updated guidelines for managing dyslipidemia. These guidelines recommend that older patients with established CVD be treated in the same way as younger patients because of the many benefits statin therapy demonstrated in clinical trials. They also suggest that statin therapy be started at a lower doses to achieve goals for primary prevention in the older population. In addition, CVD risk factors (hypertension, diabetes, dyslipidemia, smoking) should be addressed in this population to reduce CVD risk. They also acknowledged that primary prevention may not prolong life in the older adult, but treatment does reduce cardiovascular mortality and statin therapy is recommended to reduce the overall risk of CV morbidity in this population [11]. In contrast, The 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines changed the management and treatment of dyslipidemia by highlighting “statin benefit groups” rather than recommending a treat-to-target goal as guidelines had done for many years. ACC/AHA recommends a moderate-intensity statin for patients > 75 years of age for secondary prevention versus the use of a high-intensity statin for patients who are between the ages of 40 and 75 based on the pooled cohort risk equation. In patients over age 75 with no history of CVD, no specific recommendation is available for the use of lipid-lowering therapy at this time [12]. ACC/AHA is expected to publish a new set of guidelines sometime in 2018 and they are projected to utilize lipid-lowering goals in combination with the pooled cohort equation to assess overall risk in patients with dyslipidemia.

The 2015 National Lipid Association (NLA) released “Part 1” guidelines for the management of dyslipidemia and then provided “Part 2” about a year later, which focuses on management for special populations. To summarize, the NLA guidelines recommend that elderly patients between the ages of 65 and 80 receive a high-intensity statin for secondary prevention after special consideration of the potential risks and benefits. In patients over the age of 80, NLA recommends a moderate-intensity statin for secondary prevention. For primary prevention, NLA recommends utilizing the pooled cohort risk equation to analyze patient characteristics, keeping in mind that age is a driving factor for increased risk of CVD and that the actual risk for developing a CV event may be “overestimated” if the patient has no other risk factors other than their age. When evaluating patients between the ages of 65 and 79 for primary prevention, NLA suggests following Part 1 of the guidelines. In Part 1, NLA recommends evaluating the patient’s characteristics and suggests a moderate- or high-intensity statin if the patient is considered “very high risk” or “high risk” and a moderate-intensity statin for patients who are considered “moderate risk”. For patients over the age of 80, they recommend utilizing a moderate- or a low-intensity statin depending on frailty status or if significant comorbidities or polypharmacy exist [13,14].

In 2017, the American Association of Clinical Endocrinologist (AACE) released guidelines for the management of dyslipidemia and CVD prevention. AACE recommends that patients over age 65 be screened for dyslipidemia, and those who have multiple risk factors, other than age, should be considered for treatment with lipid-lowering therapy. AACE focuses on specific target LDL-C levels as treatment goals [15].

In addition to statins, other lipid-lowering therapies are used to treat dyslipidemia. The 2016 American College of Cardiology (ACC) Task Force reported on the use of non-statin therapies for the management of dyslipidemia and prevention of clinical ASCVD [16]. The committee concluded that ezetimibe added to statin therapy, bile acid sequestrants as monotherapy, and niacin as monotherapy all have some benefit for the prevention of clinical ASCVD. These guidelines also discuss the use of PCSK-9 inhibitors and their potential to decrease the risk of clinical ASCVD, but trials are currently ongoing to determine actual benefit. These guidelines address special populations but they do not consider the elderly in their recommendations. Currently, the only special populations included are patients with heart failure, those on hemodialysis, women who are of childbearing age or pregnant, and those with autoimmune diseases [16]. The literature available for each individual medication is discussed in further detail below.

Evidence for Secondary Prevention

The benefits of statin therapy for secondary prevention in the elderly is more established than it is for primary prevention (Table 2). 

The ASCOT–LLA (Anglo-Scandinavian Cardiac Outcomes Trial–Lipid Lowering Arm), published in 2003, evaluated the effect of atorvastatin 10 mg on reducing ASCVD events in moderate-risk patients between 40–79 years of age who had hypertension and normal or slightly elevated LDL-C levels, with at least 2 other risk factors for CVD (age > 55 years was considered a risk factor). The primary outcome was non-fatal MI including silent MI and fatal CHD. A significant reduction was seen in the primary endpoint. Over half of the study population was > 60 years of age, with a mean age of 63 years. In a post-hoc analysis, stroke prevention was found to be similar in patients who were > 70 years of age and those < 70 years of age [19].

One of the first trials to specifically analyze the impact of age on lipid-lowering therapy in secondary ASCVD prevention was the Scandinavian Simvastatin Survival Study (4S), published in 1994. They evaluated the effect of simvastatin 20 mg on CV-related mortality and morbidity in patients 35–70 years of age with hyperlipidemia and a history of angina or acute MI occurring > 6 months of the study starting. The primary outcome was all-cause mortality. The secondary endpoint was time to first major CV event, which included coronary death, non-fatal acute MI, resuscitated cardiac arrest, and silent MI. Simvastatin significantly reduced the primary outcome and CHD-related deaths. A subgroup analysis of the study population > 60 years of age showed that age made no significant impact on primary or secondary outcomes; however, investigators noted that these subgroup analyses had less statistical power than the population as a whole [20].

Published in 1998, the LIPID (Long-Term Intervention with Pravastatin in Ischemic Disease) study evaluated the effects of pravastatin 40 mg daily on CHD-related mortality and overall mortality in patients with hyperlipidemia and clinical ASCVD (previous MI or unstable angina). The primary outcome observed was fatal CHD. Pravastatin significantly reduced the primary outcome, overall mortality, and pre-specified CV events. In a subgroup analysis, age group ( 65, and > 70 years) had no significant impact on the combined outcome of death from CHD and nonfatal MI; however, patients 65 to 70 years of age made up less than half of the study population [21].

The Cholesterol and Recurrent Events (CARE) trial, published in 1996, looked at the effect of pravastatin 40mg therapy for secondary ASCVD prevention following an MI in patients who had average cholesterol levels (defined as TC < 240 mg/dL and LDL-C 115–174 mg/dL). The primary endpoint assessed was time to fatal CHD or nonfatal MI. To meet statistical power they looked at subgroups for a broader outcome of a major coronary event (including fatal CHD, nonfatal MI, bypass surgery, and angioplasty). Pravastatin significantly reduced the primary outcome. The significant reduction in coronary events produced by pravastatin was noted to be significantly greater in women and in patients with higher pretreatment levels of LDL-C, but was not significantly impacted by age group (24–59 vs. 60–75 years) [22].

The Heart Protection Study (HPS), published in 2002, looked at the long-term effects of lowering LDL-C with simvastatin 40 mg in patients 40 to 80 years of age at high risk for mortality due to either vascular or nonvascular causes. The primary outcome assessed was all-cause mortality, with fatal or nonfatal vascular events as co-primary outcomes for subcategory analyses. Simvastatin significantly reduced both primary and co-primary outcomes, but there was no significant difference when they looked at nonvascular mortality between groups. Neither age nor baseline LDL levels were reported to have had a significant impact on outcomes. Over half the population was > 65 years of age, and about one-third of the population was > 70 years of age [23].

The PROVE-IT/TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis in Myocardial Infarction 22) trial, published in 2004, compared pravastatin 40 mg (moderate-intensity) to atorvastatin 80 mg (high-intensity) for secondary ASCVD prevention in patients with recent acute coronary syndrome (ACS) 65 years of age and the mean age was 58 years [24].

The TNT (Treating to New Targets) trial, published in 2005, looked at secondary ASCVD prevention in regards to targeting LDL-C levels to < 100 mg/dL or < 70 mg/dL with atorvastatin 10 mg and atorvastatin 80 mg. Patients had stable coronary artery disease (CAD) and baseline LDL-C levels < 130 mg/dL. The primary endpoint was the occurrence of a CV event (CAD mortality, nonfatal MI not related to procedure, resuscitation after cardiac arrest, or fatal or nonfatal stroke). High-intensity atorvastatin (80 mg) significantly reduced the primary outcome. The mean age of the study population was approximately 61 years. The study reported no statistical interaction for age or sex in the primary outcome measure [25].

The Study Assessing Goals in the Elderly (SAGE), published in 2007, evaluated the effects of pravastatin 40 mg (moderate-intensity) vs atorvastatin 80 mg (high-intensity) on secondary ASCVD prevention in patients 65 to 85 years (mean age 72) with stable CHD, LDL-C 100–250 mg/dL, with at least 1 episode of myocardial ischemia with total ischemia duration > 3 minutes. The primary efficacy outcome observed was absolute change in total duration of myocardial ischemia on 48-hour ambulatory electrocardiographic monitoring from baseline to month 12. No significant difference was observed in efficacy between the two groups for the primary endpoint, but the intensive statin therapy group showed greater benefit respective to several secondary outcomes, including major acute CV events and death [26].

In summary, while these trials provide evidence that statin therapy is beneficial in a wide range of patients with clinical ASCVD and dyslipidemia, the trial data does not provide definitive guidance for treating elderly patients at this time. Given the small percentage of elderly patients that were included, some of the trial results reporting statistical significance in this age group hold less clinical significance. It appears that high-intensity statin therapy was more likely to effectively prevent clinical ASCVD and death than moderate-intensity statin therapy, but more evidence is needed regarding secondary prevention in patients over age 75.

Evidence for Primary Prevention

The PROSPER (PROspective Study of Pravastatin in the Elderly at Risk) was published in 2002 to assess the efficacy of pravastatin in patients between the ages of 70 and 82 (mean age 75 years) with pre-existing vascular disease (coronary, cerebral, or peripheral) or at an elevated risk (smoking, hypertension, or diabetes). Patients were randomized to receive either placebo or pravastatin 40 mg (a moderate-intensity statin). They found that pravastatin therapy reduced the risk of the composite outcome of CHD-related death, nonfatal MI, and fatal or nonfatal stroke in this elderly population. A post-hoc analysis comparing primary versus secondary prevention groups found no significant differences between these subgroups [7].

Han et al recently conducted a post hoc secondary analysis of older participants (65 years and older) in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial–Lipid-Lowering Trial (ALLHAT-LLT). The intervention for ALLHAT-LLT was 40 mg pravastatin. They found no significant differences in all-cause mortality or cardiovascular outcomes between the pravastatin and usual care groups [27]

JUPITER (Justification for Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin), published in 2008, examined the efficacy of rosuvastatin vs. placebo in low- to moderate-risk men 50 years and older and women 60 years and older using a composite outcome of MI, unstable angina, stroke, arterial revascularization, or CVD death. Rosuvastatin did significantly decrease the primary endpoint, however it did not reduce the risk of overall death [28]. A subgroup analysis was performed on the elderly (65–75 years) study participants in JUPITER demonstrating a significant risk reduction for the combined CV endpoint and a nonsignificant reduction of all-cause mortality [29].

CARDS (Collaborative Atorvastatin Diabetes Study), published in 2004, looked at statin use for primary prevention in high-risk patients with type 2 diabetes without high LDL-C, but they had to have at least 1 additional risk factor for CVD. The primary outcome was first acute CHD event (myocardial infarction including silent infarction, unstable angina, acute coronary heart disease death, resuscitated cardiac arrest), coronary revascularization procedures, or stroke. Atorvastatin 10 mg, a moderate-intensity statin, significantly decreased occurrence of the primary outcome [30]. A subgroup analysis was performed to evaluate patients specifically between the ages of 65 and 75 and found a similar outcome in the elderly with a significant reduction in first major CV event and stroke [31].

A recent study evaluating primary prevention in patients with an intermediate risk for CVD was the HOPE-3 (Heart Outcomes Prevention Evaluation), published in 2016. Two co-primary outcomes were evaluated: the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, while the second primary outcome also included revascularization, heart failure, and resuscitated cardiac arrest. Rosuvastatin significantly decreased occurrence of both co-primary endpoints. About half of the study populations was over the age of 65 with a median age of 71 [32].

In addition to these trials of primary prevention, summarized in Table 3, a meta-analysis was published in 2013 to assess whether statins reduce all-cause mortality and CV events in elderly people without established CV disease. 

As demonstrated by the above studies, it is evident that statins do help reduce the risk of CV events, regardless of statin intensity, but they do not consistently prevent death. However, the trials that did not demonstrate a significant outcome related to death utilized a moderate-intensity statin; if a high-intensity statin was used in those trials, there may have been a benefit [7,27]. More study is needed to evaluate the use of high-intensity statins in the elderly for the prevention of all-cause mortality and CV-related death.

Fortunately, the ongoing STAREE (STAtin Therapy for Reducing Events in the Elderly) study is looking specifically at the impact of statin therapy in adults 70 and older. Patients with a history of CVD or dementia are excluded. Results are set to be released in 2020 [34].

Risks of Using Statins in Older Adults

Statin use has been linked to a number of unwanted adverse effects.

Myalgia

Myalgia is variable but may occur in up to 25% of patients using statin therapy, and elderly patients typically experience more statin-associated myalgia than younger patients [35,36]. Elderly patients are more prone to decreased muscle mass and therefore may be at a higher risk of developing myalgia pain. Elderly patients are also utilizing more medications, leading to the potential for increased drug-drug interactions that could lead to myalgia. Elderly patients may also lose the function of drug metabolizing enzymes responsible for breaking down statin therapy, which may also increase the risk for statin-associated myalgia. One study demonstrated that elderly patients were more likely to discontinue statin therapy due to muscle pain and elderly patients reported more muscle side effects than their younger cohorts [37]. It is important to monitor for muscle pain and weakness in every patient. If they experience any myalgia, it is recommended to either lower the dose or discontinue the statin once it is determined to be statin-related. After myalgia resolves, therapy can be reinitiated at a lower dose or with a different statin if the patient is deemed high-risk. If creatine phosphokinase levels are greater than 10 times above the upper limit of normal, then discontinue the statin and wait for levels to return to normal. Re-initiation may be appropriate, but the the risks and benefits must be weighed. Simvastatin and atorvastatin are associated with higher rates of myalgia while pravastatin and rosuvastatin have the least myalgia pain associated with use [38,39].

Statin Intolerance

Statin intolerance, while not very common, is typically seen more often in special populations such as women, Asian patients, and the elderly. For a patient to be considered intolerant to statins, they need to have documented muscle symptoms or an elevated creatine phosphokinase level. Although not well defined, many clinicians consider improvement of symptoms with statin withdrawal as a diagnosis for statin intolerance. Typically patients are then rechallenged with 1 to 2 other statins and if still unable to tolerate, then different lipid-lowering therapies may be utilized [40]. In the elderly, it is important to rule out other causes for myalgia and monitor for significant drug interactions that may lead to muscle pain, particularly if the patient is requiring secondary prevention with statin therapy, before discontinuation.

Dementia

In 2012, the FDA issued a warning about the potential risk of cognitive impairment with the use of statins, which was based on case reports, not clinical trial data [41]. The NLA guidelines do not recommend baseline cognitive assessments prior to starting therapy and recommend that if patients do report cognitive impairment, other contributing factors and the risk associated with stopping statin therapy must be considered. Statin therapy may be discontinued to assess reversibility of symptoms, and if symptoms resolve, then it may be more beneficial to keep the patient off statin therapy. Clinicians may also consider lowering the dose or switching to another statin if they feel it is necessary for the patient to continue with a statin, particularly if the patient requires secondary prevention. Evidence suggests that statins are not associated with adverse effects on cognition and should not be withheld due to the potential for causing cognitive impairment alone [42]. The prevalence of cognitive impairment increases with age, so it is important for a clinician to rule out age-related processes or other disease states, such as Alzheimer’s, before discontinuation of previously tolerated statin therapy.

Renal Impairment

Kidney function must be evaluated prior to initiation of a statin in an elderly person as well as during the time the patient is taking a statin. Because statins are eliminated via the kidney, and because most elderly patients have decreased kidney function, the potential for drug build-up in the body is higher than in a younger patient and may lead to more adverse effects. Atorvastatin is the only option that does not require dose adjustment. All other statins should be adjusted based upon the level of renal impairment. The results from the SHARP study, published in 2011, showed that the combination of ezetimibe and simvastatin versus placebo significantly reduced ASCVD events in patients with moderate to severe chronic kidney disease, including those receiving dialysis. Specifically, this trial showed a significant reduction of ischemic events and occurrence of arterial revascularization procedures. Although the trial did not show a significant difference in incidence of MI or CHD-related mortality, the trial was not adequately powered to show differences in results among the individual ASCVD events and it is not clear whether the results can guide the use of statin therapy in all patients with chronic kidney disease [43]. Statins may be beneficial in renal insufficiency to lower LDL-C, but more studies are needed to assess CVD outcomes related to statin use in patients with a history of kidney disease [44].

Hepatic Function

Statins have been known to increase liver enzymes and in rare cases lead to liver injury, which typically has led to underutilization of therapy in clinical practice. Risk factors associated with this include preexisting hepatitis, advanced age, chronic alcohol use, and use of concomitant medications that may also cause hepatotoxicity, such as acetaminophen. When a statin-induced hepatic effect is suspected, it is important to first rule out other causes or disease states that may be undiagnosed. If no other cause can be found, clinicians may choose to reduce the statin dose, switch the statin, or discontinue the statin altogether if the risk outweighs the benefit. Additionally, statins do not have to be held in patients who have preexisting hepatic dysfunction if use is clearly indicated because the cardiovascular benefits typically outweigh the risks of causing liver injury. Clinical judgement is still warranted and patients with preexisting liver conditions should be monitored regularly [45].

Cost Considerations

Several studies have demonstrated that statin therapy, in the general population, is economical for both primary and secondary prevention of CVD [46,47]. The 4S study found simvastatin therapy to be cost-effective; for example, the cost per life year gained for a 70-year-old man with high chlesterol was $3800 [48]. In contrast, primary prevention in middle-aged men, based on the West of Scotland trial, averages about $35,000 per year of life gained [46]. In a 2015 study that utilized an established Markov simulation model, researchers studied adults 75 to 94 years and examined the cost-effectiveness of generic statins for primary prevention in this population. The authors estimated treating this population with statins over the next decade would be cost-effective. However, the researchers cautioned that the CV benefits and cost-effectiveness would be offset with even a modest increased risk of cognitive impairments or functional limitations. Statin use was not cost-effective in diabetes patients who did not have elevated LDL-C levels [49].

Non-Statin Therapies

Several other classes of medications are available for the management of hyperlipidemia; however, none of these lipid-lowering therapies have been found to reduce CVD events or mortality in the elderly population.

Ezetimibe

Ezetimibe blocks the absorption of intestinal cholesterol and is typically combined with statin therapy to lower LDL-C. Up until the IMPROVE-IT trial was published in 2015, ezetimibe did not have much use in clinical practice. This landmark trial was a large double-blind study that looked at secondary prevention in patients with ACS, comparing ezetimibe 10 mg and simvastatin 40 mg versus simvastatin 40 mg alone. The authors included patients over the age of 50 (mean age 64) with clinical ASCVD. They found that the addition of ezetimibe to simvastatin did reduce the primary composite outcome (CV mortality, major CV events, or nonfatal stroke) when compared to simvastatin alone [50]. This trial demonstrates clinical benefit with the addition of ezetimibe to statin therapy and adds additional evidence to support a target LDL-C of less than 70 mg/dL; however, the elderly population was not adequately represented in the study to allow extrapolation of these results to older patients.

PCSK-9 Inhibitors

The proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors are a newer class of monoclonal antibodies that were first approved by the US Food and Drug Administration in 2015. Alirocumab and evolocumab, both approved PCSK-9 inhibitors, bind to LDL receptors on the surface of hepatocytes and assist in the internalization of LDL receptors for lysosomal degradation. By inhibiting the binding of PCSK-9 to the LDL receptors, there is an overall increase in LDL receptors available on the cell surface to bind to LDL particles, thereby lowering LDL-C levels. Treatment with these agents are currently considered (in addition to diet and maximally tolerated statin therapy) in adult patients with heterozygous familial hypercholesterolemia or clinical ASCVD requiring further reduction in LDL-C. Two studies were published focusing on the use of PCSK-9 inhibitors: Open-label Study of Long-term Evaluation against LDL Cholesterol (OSLER) and the Tolerability of Alirocumab in High Cardiovascular Risk Patients with Hypercholesterolemia Not Adequately Controlled with Their Lipid Modifying Therapy (ODYSSEY LONG TERM). Overall, these studies demonstrated a 60% reduction of LDL-C among patients with high CVD risk on maximum-tolerated statin therapy. Furthermore, the ODYSSEY LONG TERM trial did find that the rate of major CVD adverse events was significantly lower with alirocumab added to maximum-tolerated statin therapy, with a hazard ratio of 0.52 [51].

One recent study of evolocumab, named the Further Cardiovascular OUtcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER), enrolled patients between the ages of 40 and 85 with 1 major CV risk factor or 2 minor CV risk factors. The primary endpoint was a composite of cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization. Evolocumab lowered major CV events by roughly 15% when added to statin therapy in patients who were at high risk for clinical ASCVD. The mean age of the patients in the trial was 63; however, it is unclear how many of the study participants were elderly [52].

Unfortunately, the studies discussed above do not represent the elderly population well and the agents have not been studied long-term to determine the effects of continued use beyond 2 years. Long-term outcome studies are currently underway; however, it is unknown at this time whether elderly patients are being considered in these studies. It is known that genetic variation of the PCSK-9 locus does lower LDL-C in the elderly but does not significantly lower their risk of vascular disease [51]. At this time, until further evidence is available, we do not recommend the use of PCSK-9 inhibitors in elderly patients.

Nicotinic Acid

Nicotinic acid (Niacin, Niacin ER), also known as vitamin B3, has been utilized for decades as a vitamin supplement, an anti-wrinkle agent, and is known to have neuroprotective effects. It has also been utilized for dyslipidemia and has had some benefits when used alone to decrease cardiovascular disease [53]. Unfortunately the Coronary Drug Project was completed in the 1980s and did not incorporate patients over the age of 64, therefore making the results difficult to apply to elderly patients today [54]. Other literature has been published in recent years to refute that study, claiming there is no additional benefit to using niacin for cardiovascular protection and these studies have included elderly patients. In the AIM-HIGH trial, published in 2011, approximately 46% of the patients were 65 or older. Patients who were previously taking statin therapy that had known cardiovascular disease were enrolled. Niacin added to simvastatin 40–80 mg lowered LDL-C, triglycerides, and increased HDL-C, but the addition of niacin was not proven to help lower the risk of cardiovascular events [55]. The HPS2-THRIVE study enrolled patients with known cardiovascular disease between the ages of 50 and 80 years and found no benefit in preventing CVD when adding niacin to statin therapy [56]. With its side effect profile, risk for increased glucose intolerance, and lack of evidence to demonstrate benefit for prevention of CV events, we do not recommend niacin for use in the elderly at this time.

Bile Acid Sequestrants

The ATP III guidelines [57] noted that when statins are not sufficient to lower high cholesterol, bile acid sequestrants also known as resins could be added. More recently, the 2016 ACC expert consensus on non-statin therapies for LDL-C lowering [16] stated resins may be considered in select circumstances as a second-line agent for adults with ezetimibe intolerance and with triglycerides

Fibrates

While fibrates (gemfibrozil, fenofibrate, clofibrate) have not been studied to demonstrate a reduction in CVD or CVD mortality in the elderly population, this medication class is beneficial in patients with hypertriglyceridemia to lower triglyceride levels and prevent pancreatitis. Fibrates are recommended for patients with triglyceride levels approaching 500 mg/dL. Fibrates can also increase high-density lipoproteins, which tend to be lower in the elderly population and considered a risk factor for CVD. Gemfibrozil is not recommended in combination with statin therapy due to an increased risk of myalgia. Fenofibrate is the drug of choice, particularly for diabetic patients with very uncontrolled triglyceride levels because it will not affect glucose levels [57]. At this time, we do not recommend the use of fibrates in the elderly population unless they are at risk for developing pancreatitis and have elevated triglyceride levels.

Patient-Centered Care

Evidence-based medicine can aid in making sound clinical decisions for proper patient care; however, treatment plans should consider the individual patient’s perspectives and needs, beliefs, expectations, and goals. In the elderly population, we must also consider factors such as finances, pill-burden, drug-drug interactions, physiological needs, comorbid disease states, and overall life expectancy. In addition, the elderly population is physiologically heterogeneous group and recommendations for therapy need to be individualized. Chronological age does not necessarily correspond to vascular age and risk factors for cardiovascular disease do not predict outcomes as well in the elderly as they do in younger patients. While older patients may view having to take 1 less medication as more important than preventing a heart attack or stroke at the age of 80, it is advisable to discuss all potential outcomes related to morbidity associated with the occurrence of an MI or stroke due to the lack of statin therapy. Additionally, pharmacists can play a vital role in evaluating elderly patients and their medication regimens. Elderly patients should undergo a medication reconciliation at each visit to evaluate drug-drug interactions, side effects, and potentially harmful medication combinations that may lead to increased adverse drug outcomes.

Conclusion

CHD increases with age, and most patients who have a CV event are more likely to die with advancing age. Based on the the limited available evidence, statin therapy is beneficial in the elderly population in reducing overall CV morbidity. We recommend beginning with with a moderate-intensity statin and adjusting accordingly. High-intensity statin therapy appears to be effective for elderly patients for secondary prevention, but clinicians should use clinical judgment and monitor for adverse events, particularly myalgia pain. At this time, we are unable to determine if non-statin therapies for the elderly would be beneficial and do not recommend their use unless the patient is at risk for pancreatitis, in which case a fenofibrate is recommended.

Corresponding author: Nicole A. Slater, PharmD, BCACP, Auburn University, Harrison School of Pharmacy, 650 Clinic Dr., Mobile, AL 36688.

Financial disclosures: None.

From the Department of Psychiatry, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA.

Abstract

• Objective: To provide a review of emergency department (ED)-based psychosocial interventions that support adult patients with an identified suicide risk towards a goal of reducing subsequent suicidal behavior through the period after discharge, which is known to be a time of high risk for suicidal behavior.
• Methods: Non-systematic review of the literature.
• Results: Multiple methods of engaging patients after discharge from the ED have been shown to reduce subsequent suicidal behaviors. These methods include sending caring letters in the mail, facilitating supportive phone conversations, case management, and protocols that combine different services. Overall, the existing literature is insufficient to recommend widespread adoption of any individual strategy or protocol. However, providing psychosocial and emotional support to patients with an identified suicide risk after they are discharged from the ED is feasible and may reduce subsequent suicidal behaviors. Templates for providing supportive outreach using different modalities now exist, and these may help guide the ongoing development and widespread adoption of more effective and cost-effective solutions.
• Conclusion: Many ED–based interventions that provide enhanced support to patients with suicide risk after they are discharged have demonstrated a potential to reduce the risk of future suicidal behavior.

Key words: suicide; emergency department.

Despite the fact that emergency department (ED) providers often feel unprepared to manage suicide risk, patients with significant suicide risk frequently receive care in EDs, whether or not they have sustained physical injuries resulting from suicidal behavior [1,2]. Patients make greater than 400,000 visits to EDs in the United States each year for suicidal and self-injurious behaviors (suicide attempts and self-injurious behaviors are typically coded in ways that make them indistinguishable from each other in retrospective analyses) [3], and it is estimated that 6% to 10% of all patients in EDs endorse suicidal ideation when asked, regardless of their original chief complaints [4]. Meanwhile, suicide has become the 10th leading cause of death in the United States [5], and the Joint Commission has charged all accredited health care organizations with providing comprehensive treatment to suicidal patients, which may range from immediately containing an acute risk to ensuring continuity of care in follow-up [5].

When an acute suicide risk is identified in the ED, the provider’s immediate next steps should be to place the patient in a safe area under constant observation and to provide an emergency assessment [5,6]. Although psychiatric consultation and/or psychiatric admission may follow this assessment, suicide risk does not require admission in all cases; and some patients with suicide risk may be discharged to an outpatient setting even without receiving a psychiatric consultation [1]. Regardless of whether an outpatient disposition from the ED is appropriate, however, the period that immediately follows discharge is a time of high risk for repeated suicidal behavior and suicide death [7–9], and only 30% to 50% of patients who are discharged from EDs after a self-harm incident actually keep a follow-up mental health appointment [9,10]. Therefore, any support given to patients through this transition out of the emergency care setting could be especially high-yield.

The Joint Commission recommends that all patients with suicidal ideation receive, at minimum, a referral to treatment, telephone numbers for local and national crisis support resources (including the National Suicide Prevention Lifeline 1-800-273-TALK), collaborative safety planning, and counseling to restrict access to lethal means upon discharge [5]. However, some programs have demonstrated the capacity to provide enhanced support to patients beyond discharge from the ED, with some success in reducing the rates of subsequent suicidal behaviors. This non-systematic review describes interventions that can be initiated in the context of an ED encounter with the purpose of reducing future suicidal behavior among adult patients. They are primarily psychosocial rather than clinical. Clinical interventions that apply psychotherapy [11–13] psychopharmacology [14], and specialized inpatient treatments [15] have been studied as well but are beyond the scope of this review.

[polldaddy:10107269]

Interventions to Support Patients At Risk of Suicide After Discharge from the ED

Brief Contact Interventions

The idea that maintaining written correspondence with patients who have a known suicide risk after discharge can reduce subsequent suicide rates originated with a study of psychiatric inpatients conducted by Motto and Bostrom, in which patients who had been admitted for depression but had declined outpatient treatment were randomly assigned to periodically receive letters containing supportive messages from staff members over a period of 5 years [16]. This study remarkably found that these so-called brief contact interventions (BCIs), which were personalized to each recipient but did not contain psychotherapy per se, were associated with a reduced rate of suicide throughout the duration of the program compared with no written contacts [16].

BCIs have since been adapted to other communication formats and have been studied in patients who were discharged directly from the ED after an evaluation of suicide risk or suicidal behavior. Typically, BCIs consist of short, supportive messages that are delivered at regular intervals (often once every 1–2 months) over a period of 1 to 5 years [17,18]. They notably do not contain psychotherapy content, although they may reinforce coping strategies or remind recipients of how to access help if needed [17,19]. They may arrive as postcards [20,21], letters [22], telephone outreach [23–25], or a combination of modalities [26].

Protocols that rely on BCIs alone vary in their structure and have yielded mixed results [18]. A meta-analysis of 12 BCI protocols conducted by Milner et al found that, overall, BCIs administered after a presentation to the ED for self-harm have been associated with a significant reduction in repeat suicide attempts per recipient but not in total suicide deaths [27]. Milner’s group did not recommend large-scale promotion of BCIs based on the inadequacy of data so far, but suggested that this strategy may yet show promise upon further study [27]. A key advantage of BCIs is that they are inexpensive to implement, particularly if they do not include a telephone outreach component [28]. Thus, even if the potential benefit to patients is small, administering BCIs can be cost-effective [28].

It should not come as a surprise, therefore, that the potential for incorporation of BCIs into mobile smartphone technology is currently under investigation. Individuals who own mobile phones typically keep them on their persons and turned on continuously, and thus this is a reliable platform for maintaining contact with a wide range of patients in real-time [17,29]. Developers of at least 2 BCI smartphone programs that rely on mobile text messaging have published their protocols [17,30]. However, whether these programs will succeed in meaningfully reducing suicide rates remains to be determined by future research.

Green Cards

Morgan et al conducted a study in the United Kingdom in which individuals who presented to EDs after a self-harm event received a “green card,” which contained encouraging messages about seeking help and provided contact information for emergency services with 24-hour availability [31]. The green card also facilitated access to a crisis admission if necessary. The green card was distributed first in the ED and a second time by mail 3 weeks later. No suicides occurred in either the intervention or control group, which received usual care, and no statistically significant differences in suicide reattempt rate were found between groups after 1 year [31].

Evans et al studied an updated version of the green card intervention in which the green card facilitated access to an on-call psychiatrist with 24-hour availability by telephone [32]. The updated card included encouraging messages about seeking help similar to the original green card described by Morgan; however, the psychiatry consultation via telephone replaced the offer of hospital admission [32]. This second trial of green cards also failed to show a reduction in the rate of suicide reattempts among green card recipients at 6 months and 1 year [32,33].

Brief Intervention and Contact

The World Health Organization’s Brief Intervention and Contact (BIC) protocol is a standardized, multi-step suicide prevention program that has been studied primarily in patients who present to EDs after a suicide attempt in middle-income countries [34]. BIC includes a 1-hour information session that is administered shortly prior to discharge, and subsequently provides 9 follow-up contact interventions at specified intervals over an 18-month period. Unlike in a typical BCI, the contacts in BIC are conducted by a clinician either face-to-face or over the phone and include standardized assessments of the patient’s condition, although they still do not include psychotherapy. BIC has been shown to reduce suicide attempts, suicide deaths, or both in India [34–36], Iran [34,36,37], China [34,36], Brazil [34,36], and Sri Lanka [34,36] but was not found to directly improve clinical outcomes in a study conducted in French Polynesia [38]. A meta-analysis conducted by Riblet et al concluded that BIC is effective in reducing suicide risk overall [39].

ED-SAFE

The Emergency Department Safety Assessment and Follow-up Evaluation (ED-SAFE) protocol was validated in 8 EDs in 7 states in the US that did not already provide psychiatric services internally [40]. Under this model, all patients in the ED receive a screening for suicide risk, and those with an initial positive screen receive a secondary screen administered by the ED physician, a self-administered safety plan, and a series of up to 11 phone contacts over the following year that are administered by trained mental health clinicians in a central location. The ED-SAFE phone contacts follow the Coping Long Term with Active Suicide Program (CLASP) protocol [41] and provide support around safety planning and treatment engagement. They have the capacity to engage the patients’ significant others directly if a significant other is available and the patient chooses to involve that person.

In a single multicenter study, ED-SAFE reduced the absolute risk of suicide attempt by 5%, and the relative risk by 20% compared to usual treatment [40]. An intermediate phase of the study compared the universal suicide screening alone (ie, without the safety plan or follow-up contacts) with usual care and did not find this to improve outcomes [40].

Case Management

Kawanishi et al conducted a randomized controlled trial of assertive case management, the ACTION-J study, for patients with psychiatric diagnoses who presented with self-harm to 17 participating EDs in Japan [42]. In the ACTION-J study, case managers were mental health clinicians who provided clinical evaluations, treatment planning, encouragement, and care coordination over the course of 7 scheduled face-to-face or phone contacts in the first 18 months, and additional contacts at 6-month intervals until the completion of the trial (up to a total of 5 years) [43]. The comparison intervention, enhanced usual care, consisted of psychoeducation provided at the time of the encounter in the ED without case management services. The assertive case management intervention was associated with a decrease in suicidal behavior in the first 6 months but not for the duration of the study, except in women, for whom the benefit lasted the full 18 months [42]. A subsequent analysis also found a decrease in the total number of self-harm episodes per person-year compared to enhanced usual care, although there was not a difference in the number of participants who experienced a repeat self-harm episode [43]. The benefit was most strongly pronounced among patients who had presented with an index suicide attempt [43].

Morthorst et al applied an alternative case management model for the assertive intervention for deliberate self harm (AID) trial, which took place in Denmark [44]. Participants were aged 12 and older and could have been recruited from medical or pediatric inpatient units as well as the ED after a self-harm event. AID employed psychiatric nurses to provide crisis intervention, crisis planning, problem solving, motivational support, family mediation, and assistance with keeping appointments over a period of 6 months following discharge. Outreach took place over the phone, by text message, in participants’ homes, in cafes, and at health and social services appointments. The intervention required at least 4 contacts, although additional contacts could be made if appropriate. In comparison with a control group, in which participants received only usual care (which included ready access to short-term psychotherapy), the AID intervention was not associated with statistically significant differences in recurrent suicidal behaviors [44]. Subgroup analyses examining adult participants aged 20–39 and 40 and older also did not find differences in recurrent suicidal behavior between groups [44].

The Baerum Model and OPAC

A municipal suicide prevention team that provides comprehensive social services to suicide attempters has operated in Baerum, Norway, since 1983 [45]. Under the Baerum model, patients who attempt suicide, can be discharged from the general hospital without psychiatric admission, and are determined to have a high level of need for support are connected by a hospital-based suicide prevention team to a community-based team consisting of nurses and a consulting psychologist, who subsequently engage patients in own their homes and through follow-up phone calls. The services they provide include care coordination, encouragement, activation of social networks, psychological first-aid, and counseling focused on problem-solving. The ostensible goal of the suicide prevention team is to provide a bridge between inpatient medical care and outpatient mental health treatment; however, the intervention lasts approximately 1 year regardless of whether the patient connects with a treatment program [45].

A retrospective comparison of outcomes between recipients of the original Baerum program and non-recipients failed to find a difference in suicide attempts or suicide deaths between groups [45]. However, this was not a controlled study, and suicide attempters were preferentially referred to the program based on whether they had a higher level of need at baseline. Hvid and Wang adapted this model to patients who presented to EDs and general hospitals in Amager, Denmark [46] and have since conducted a series of randomized controlled trials comparing their adaptation to usual care. The Danish version of the Baerum model, renamed OPAC (for “outreach, problem solving, adherence, continuity”), provides similar case management and counseling services but for a maximum of 6 months. In their studies, OPAC significantly reduced the number of patients with a repeat suicide attempt and the total number of repeat suicide attempts at a 1-year interval, and this effect on total number of suicide attempts was sustained at 5 years [47,48]. Although the OPAC protocol begins with a patient’s presentation to the ED, the intervention is initiated after admission to the general hospital. Therefore, while this may inspire a model that provides similar services directly from the ED to patients who do not require general hospital admission, the existing model is not entirely based in the ED.

Discussion

The needs of suicidal patients are often multidimensional, and in some cases their risks are driven by psychosocial problems in addition to, or instead of, medically modifiable psychiatric conditions [49]. However, developing an ED-based program to support patients who are at risk of suicide after they are discharged from the ED is possible. Many such programs that provide or facilitate caring contacts, family support, case management, and/or treatment engagement with discharged patients have demonstrated that similar strategies may have the potential to impact future suicidal behavior. Nonetheless, it would be a stretch to say that all hospital systems should immediately begin doing so.

A new post-discharge support program is an investment of financial resources, personnel, and sometimes technology. Successful delivery of support or messages in any format requires that the intended recipient be able to receive it via reliable access to a working address, telephone number, or electronic device. Nonetheless, programs that rely on BCIs alone (excluding those conducted via telephone) cost relatively little to implement and thus would require a smaller investment than programs that require synchronous telephone or face-to-face contacts with staff in addition to or instead of BCIs. Costs for synchronous programs will also vary depending on the frequency and duration of contacts and the licensure and training required of the staff who provide them.

A trend toward better outcomes associating with more resource-intensive programs is easy to imagine but has not been definitively demonstrated. The wide variation between protocols in all types of programs makes comparisons between those that do and do not include synchronous contacts, and between types of synchronous contacts, difficult. Meanwhile, the low cost of BCIs alone could increase their attractiveness as an investment regardless of the magnitude of outcome improvement.

Denchev et al constructed a cost/benefit comparison model that included the postcard BCI study conducted by Carter et al [20], the telephone outreach study conducted by Vaiva et al [23], and a study of cognitive behavioral therapy (CBT) [11], all of which showed a clinical benefit. This model relied upon some numeric estimations and did not account for variation in outcomes between individual studies of each intervention strategy. However, it concluded that both telephone outreach and CBT were likely to be cost-prohibitive compared to asynchronous BCIs, which were associated with a reduction in costs overall [28].

Conclusion

There remains much to learn regarding how best to reduce suicide risk among adult patients in the period after discharge from the ED, during which patients with an identified suicide risk are known to be vulnerable. However, providing psychosocial and emotional support to patients with an identified suicide risk after they are discharged from the ED is feasible and may reduce subsequent suicidal behaviors. Templates for providing supportive outreach using different modalities now exist, and these may help guide the ongoing development and widespread adoption of more effective and cost-effective solutions.

Corresponding author: David S. Kroll, MD, [email protected].

Financial disclosure: Dr. Kroll has received research funding from Brigham and Women’s Hospital to study and develop technological solutions for supporting suicidal patients after discharge from the emergency department. He has additionally received research funding and a speaking honorarium from Avasure.

From the Department of Psychiatry, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA.

Abstract

• Objective: To provide a review of emergency department (ED)-based psychosocial interventions that support adult patients with an identified suicide risk towards a goal of reducing subsequent suicidal behavior through the period after discharge, which is known to be a time of high risk for suicidal behavior.
• Methods: Non-systematic review of the literature.
• Results: Multiple methods of engaging patients after discharge from the ED have been shown to reduce subsequent suicidal behaviors. These methods include sending caring letters in the mail, facilitating supportive phone conversations, case management, and protocols that combine different services. Overall, the existing literature is insufficient to recommend widespread adoption of any individual strategy or protocol. However, providing psychosocial and emotional support to patients with an identified suicide risk after they are discharged from the ED is feasible and may reduce subsequent suicidal behaviors. Templates for providing supportive outreach using different modalities now exist, and these may help guide the ongoing development and widespread adoption of more effective and cost-effective solutions.
• Conclusion: Many ED–based interventions that provide enhanced support to patients with suicide risk after they are discharged have demonstrated a potential to reduce the risk of future suicidal behavior.

Key words: suicide; emergency department.

Despite the fact that emergency department (ED) providers often feel unprepared to manage suicide risk, patients with significant suicide risk frequently receive care in EDs, whether or not they have sustained physical injuries resulting from suicidal behavior [1,2]. Patients make greater than 400,000 visits to EDs in the United States each year for suicidal and self-injurious behaviors (suicide attempts and self-injurious behaviors are typically coded in ways that make them indistinguishable from each other in retrospective analyses) [3], and it is estimated that 6% to 10% of all patients in EDs endorse suicidal ideation when asked, regardless of their original chief complaints [4]. Meanwhile, suicide has become the 10th leading cause of death in the United States [5], and the Joint Commission has charged all accredited health care organizations with providing comprehensive treatment to suicidal patients, which may range from immediately containing an acute risk to ensuring continuity of care in follow-up [5].

When an acute suicide risk is identified in the ED, the provider’s immediate next steps should be to place the patient in a safe area under constant observation and to provide an emergency assessment [5,6]. Although psychiatric consultation and/or psychiatric admission may follow this assessment, suicide risk does not require admission in all cases; and some patients with suicide risk may be discharged to an outpatient setting even without receiving a psychiatric consultation [1]. Regardless of whether an outpatient disposition from the ED is appropriate, however, the period that immediately follows discharge is a time of high risk for repeated suicidal behavior and suicide death [7–9], and only 30% to 50% of patients who are discharged from EDs after a self-harm incident actually keep a follow-up mental health appointment [9,10]. Therefore, any support given to patients through this transition out of the emergency care setting could be especially high-yield.

The Joint Commission recommends that all patients with suicidal ideation receive, at minimum, a referral to treatment, telephone numbers for local and national crisis support resources (including the National Suicide Prevention Lifeline 1-800-273-TALK), collaborative safety planning, and counseling to restrict access to lethal means upon discharge [5]. However, some programs have demonstrated the capacity to provide enhanced support to patients beyond discharge from the ED, with some success in reducing the rates of subsequent suicidal behaviors. This non-systematic review describes interventions that can be initiated in the context of an ED encounter with the purpose of reducing future suicidal behavior among adult patients. They are primarily psychosocial rather than clinical. Clinical interventions that apply psychotherapy [11–13] psychopharmacology [14], and specialized inpatient treatments [15] have been studied as well but are beyond the scope of this review.

[polldaddy:10107269]

Interventions to Support Patients At Risk of Suicide After Discharge from the ED

Brief Contact Interventions

The idea that maintaining written correspondence with patients who have a known suicide risk after discharge can reduce subsequent suicide rates originated with a study of psychiatric inpatients conducted by Motto and Bostrom, in which patients who had been admitted for depression but had declined outpatient treatment were randomly assigned to periodically receive letters containing supportive messages from staff members over a period of 5 years [16]. This study remarkably found that these so-called brief contact interventions (BCIs), which were personalized to each recipient but did not contain psychotherapy per se, were associated with a reduced rate of suicide throughout the duration of the program compared with no written contacts [16].

BCIs have since been adapted to other communication formats and have been studied in patients who were discharged directly from the ED after an evaluation of suicide risk or suicidal behavior. Typically, BCIs consist of short, supportive messages that are delivered at regular intervals (often once every 1–2 months) over a period of 1 to 5 years [17,18]. They notably do not contain psychotherapy content, although they may reinforce coping strategies or remind recipients of how to access help if needed [17,19]. They may arrive as postcards [20,21], letters [22], telephone outreach [23–25], or a combination of modalities [26].

Protocols that rely on BCIs alone vary in their structure and have yielded mixed results [18]. A meta-analysis of 12 BCI protocols conducted by Milner et al found that, overall, BCIs administered after a presentation to the ED for self-harm have been associated with a significant reduction in repeat suicide attempts per recipient but not in total suicide deaths [27]. Milner’s group did not recommend large-scale promotion of BCIs based on the inadequacy of data so far, but suggested that this strategy may yet show promise upon further study [27]. A key advantage of BCIs is that they are inexpensive to implement, particularly if they do not include a telephone outreach component [28]. Thus, even if the potential benefit to patients is small, administering BCIs can be cost-effective [28].

It should not come as a surprise, therefore, that the potential for incorporation of BCIs into mobile smartphone technology is currently under investigation. Individuals who own mobile phones typically keep them on their persons and turned on continuously, and thus this is a reliable platform for maintaining contact with a wide range of patients in real-time [17,29]. Developers of at least 2 BCI smartphone programs that rely on mobile text messaging have published their protocols [17,30]. However, whether these programs will succeed in meaningfully reducing suicide rates remains to be determined by future research.

Green Cards

Morgan et al conducted a study in the United Kingdom in which individuals who presented to EDs after a self-harm event received a “green card,” which contained encouraging messages about seeking help and provided contact information for emergency services with 24-hour availability [31]. The green card also facilitated access to a crisis admission if necessary. The green card was distributed first in the ED and a second time by mail 3 weeks later. No suicides occurred in either the intervention or control group, which received usual care, and no statistically significant differences in suicide reattempt rate were found between groups after 1 year [31].

Evans et al studied an updated version of the green card intervention in which the green card facilitated access to an on-call psychiatrist with 24-hour availability by telephone [32]. The updated card included encouraging messages about seeking help similar to the original green card described by Morgan; however, the psychiatry consultation via telephone replaced the offer of hospital admission [32]. This second trial of green cards also failed to show a reduction in the rate of suicide reattempts among green card recipients at 6 months and 1 year [32,33].

Brief Intervention and Contact

The World Health Organization’s Brief Intervention and Contact (BIC) protocol is a standardized, multi-step suicide prevention program that has been studied primarily in patients who present to EDs after a suicide attempt in middle-income countries [34]. BIC includes a 1-hour information session that is administered shortly prior to discharge, and subsequently provides 9 follow-up contact interventions at specified intervals over an 18-month period. Unlike in a typical BCI, the contacts in BIC are conducted by a clinician either face-to-face or over the phone and include standardized assessments of the patient’s condition, although they still do not include psychotherapy. BIC has been shown to reduce suicide attempts, suicide deaths, or both in India [34–36], Iran [34,36,37], China [34,36], Brazil [34,36], and Sri Lanka [34,36] but was not found to directly improve clinical outcomes in a study conducted in French Polynesia [38]. A meta-analysis conducted by Riblet et al concluded that BIC is effective in reducing suicide risk overall [39].

ED-SAFE

The Emergency Department Safety Assessment and Follow-up Evaluation (ED-SAFE) protocol was validated in 8 EDs in 7 states in the US that did not already provide psychiatric services internally [40]. Under this model, all patients in the ED receive a screening for suicide risk, and those with an initial positive screen receive a secondary screen administered by the ED physician, a self-administered safety plan, and a series of up to 11 phone contacts over the following year that are administered by trained mental health clinicians in a central location. The ED-SAFE phone contacts follow the Coping Long Term with Active Suicide Program (CLASP) protocol [41] and provide support around safety planning and treatment engagement. They have the capacity to engage the patients’ significant others directly if a significant other is available and the patient chooses to involve that person.

In a single multicenter study, ED-SAFE reduced the absolute risk of suicide attempt by 5%, and the relative risk by 20% compared to usual treatment [40]. An intermediate phase of the study compared the universal suicide screening alone (ie, without the safety plan or follow-up contacts) with usual care and did not find this to improve outcomes [40].

Case Management

Kawanishi et al conducted a randomized controlled trial of assertive case management, the ACTION-J study, for patients with psychiatric diagnoses who presented with self-harm to 17 participating EDs in Japan [42]. In the ACTION-J study, case managers were mental health clinicians who provided clinical evaluations, treatment planning, encouragement, and care coordination over the course of 7 scheduled face-to-face or phone contacts in the first 18 months, and additional contacts at 6-month intervals until the completion of the trial (up to a total of 5 years) [43]. The comparison intervention, enhanced usual care, consisted of psychoeducation provided at the time of the encounter in the ED without case management services. The assertive case management intervention was associated with a decrease in suicidal behavior in the first 6 months but not for the duration of the study, except in women, for whom the benefit lasted the full 18 months [42]. A subsequent analysis also found a decrease in the total number of self-harm episodes per person-year compared to enhanced usual care, although there was not a difference in the number of participants who experienced a repeat self-harm episode [43]. The benefit was most strongly pronounced among patients who had presented with an index suicide attempt [43].

Morthorst et al applied an alternative case management model for the assertive intervention for deliberate self harm (AID) trial, which took place in Denmark [44]. Participants were aged 12 and older and could have been recruited from medical or pediatric inpatient units as well as the ED after a self-harm event. AID employed psychiatric nurses to provide crisis intervention, crisis planning, problem solving, motivational support, family mediation, and assistance with keeping appointments over a period of 6 months following discharge. Outreach took place over the phone, by text message, in participants’ homes, in cafes, and at health and social services appointments. The intervention required at least 4 contacts, although additional contacts could be made if appropriate. In comparison with a control group, in which participants received only usual care (which included ready access to short-term psychotherapy), the AID intervention was not associated with statistically significant differences in recurrent suicidal behaviors [44]. Subgroup analyses examining adult participants aged 20–39 and 40 and older also did not find differences in recurrent suicidal behavior between groups [44].

The Baerum Model and OPAC

A municipal suicide prevention team that provides comprehensive social services to suicide attempters has operated in Baerum, Norway, since 1983 [45]. Under the Baerum model, patients who attempt suicide, can be discharged from the general hospital without psychiatric admission, and are determined to have a high level of need for support are connected by a hospital-based suicide prevention team to a community-based team consisting of nurses and a consulting psychologist, who subsequently engage patients in own their homes and through follow-up phone calls. The services they provide include care coordination, encouragement, activation of social networks, psychological first-aid, and counseling focused on problem-solving. The ostensible goal of the suicide prevention team is to provide a bridge between inpatient medical care and outpatient mental health treatment; however, the intervention lasts approximately 1 year regardless of whether the patient connects with a treatment program [45].

A retrospective comparison of outcomes between recipients of the original Baerum program and non-recipients failed to find a difference in suicide attempts or suicide deaths between groups [45]. However, this was not a controlled study, and suicide attempters were preferentially referred to the program based on whether they had a higher level of need at baseline. Hvid and Wang adapted this model to patients who presented to EDs and general hospitals in Amager, Denmark [46] and have since conducted a series of randomized controlled trials comparing their adaptation to usual care. The Danish version of the Baerum model, renamed OPAC (for “outreach, problem solving, adherence, continuity”), provides similar case management and counseling services but for a maximum of 6 months. In their studies, OPAC significantly reduced the number of patients with a repeat suicide attempt and the total number of repeat suicide attempts at a 1-year interval, and this effect on total number of suicide attempts was sustained at 5 years [47,48]. Although the OPAC protocol begins with a patient’s presentation to the ED, the intervention is initiated after admission to the general hospital. Therefore, while this may inspire a model that provides similar services directly from the ED to patients who do not require general hospital admission, the existing model is not entirely based in the ED.

Discussion

The needs of suicidal patients are often multidimensional, and in some cases their risks are driven by psychosocial problems in addition to, or instead of, medically modifiable psychiatric conditions [49]. However, developing an ED-based program to support patients who are at risk of suicide after they are discharged from the ED is possible. Many such programs that provide or facilitate caring contacts, family support, case management, and/or treatment engagement with discharged patients have demonstrated that similar strategies may have the potential to impact future suicidal behavior. Nonetheless, it would be a stretch to say that all hospital systems should immediately begin doing so.

A new post-discharge support program is an investment of financial resources, personnel, and sometimes technology. Successful delivery of support or messages in any format requires that the intended recipient be able to receive it via reliable access to a working address, telephone number, or electronic device. Nonetheless, programs that rely on BCIs alone (excluding those conducted via telephone) cost relatively little to implement and thus would require a smaller investment than programs that require synchronous telephone or face-to-face contacts with staff in addition to or instead of BCIs. Costs for synchronous programs will also vary depending on the frequency and duration of contacts and the licensure and training required of the staff who provide them.

A trend toward better outcomes associating with more resource-intensive programs is easy to imagine but has not been definitively demonstrated. The wide variation between protocols in all types of programs makes comparisons between those that do and do not include synchronous contacts, and between types of synchronous contacts, difficult. Meanwhile, the low cost of BCIs alone could increase their attractiveness as an investment regardless of the magnitude of outcome improvement.

Denchev et al constructed a cost/benefit comparison model that included the postcard BCI study conducted by Carter et al [20], the telephone outreach study conducted by Vaiva et al [23], and a study of cognitive behavioral therapy (CBT) [11], all of which showed a clinical benefit. This model relied upon some numeric estimations and did not account for variation in outcomes between individual studies of each intervention strategy. However, it concluded that both telephone outreach and CBT were likely to be cost-prohibitive compared to asynchronous BCIs, which were associated with a reduction in costs overall [28].

Conclusion

There remains much to learn regarding how best to reduce suicide risk among adult patients in the period after discharge from the ED, during which patients with an identified suicide risk are known to be vulnerable. However, providing psychosocial and emotional support to patients with an identified suicide risk after they are discharged from the ED is feasible and may reduce subsequent suicidal behaviors. Templates for providing supportive outreach using different modalities now exist, and these may help guide the ongoing development and widespread adoption of more effective and cost-effective solutions.

Corresponding author: David S. Kroll, MD, [email protected].

Financial disclosure: Dr. Kroll has received research funding from Brigham and Women’s Hospital to study and develop technological solutions for supporting suicidal patients after discharge from the emergency department. He has additionally received research funding and a speaking honorarium from Avasure.

From the Department of Psychiatry, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA.

Abstract

• Objective: To provide a review of emergency department (ED)-based psychosocial interventions that support adult patients with an identified suicide risk towards a goal of reducing subsequent suicidal behavior through the period after discharge, which is known to be a time of high risk for suicidal behavior.
• Methods: Non-systematic review of the literature.
• Results: Multiple methods of engaging patients after discharge from the ED have been shown to reduce subsequent suicidal behaviors. These methods include sending caring letters in the mail, facilitating supportive phone conversations, case management, and protocols that combine different services. Overall, the existing literature is insufficient to recommend widespread adoption of any individual strategy or protocol. However, providing psychosocial and emotional support to patients with an identified suicide risk after they are discharged from the ED is feasible and may reduce subsequent suicidal behaviors. Templates for providing supportive outreach using different modalities now exist, and these may help guide the ongoing development and widespread adoption of more effective and cost-effective solutions.
• Conclusion: Many ED–based interventions that provide enhanced support to patients with suicide risk after they are discharged have demonstrated a potential to reduce the risk of future suicidal behavior.

Key words: suicide; emergency department.

Despite the fact that emergency department (ED) providers often feel unprepared to manage suicide risk, patients with significant suicide risk frequently receive care in EDs, whether or not they have sustained physical injuries resulting from suicidal behavior [1,2]. Patients make greater than 400,000 visits to EDs in the United States each year for suicidal and self-injurious behaviors (suicide attempts and self-injurious behaviors are typically coded in ways that make them indistinguishable from each other in retrospective analyses) [3], and it is estimated that 6% to 10% of all patients in EDs endorse suicidal ideation when asked, regardless of their original chief complaints [4]. Meanwhile, suicide has become the 10th leading cause of death in the United States [5], and the Joint Commission has charged all accredited health care organizations with providing comprehensive treatment to suicidal patients, which may range from immediately containing an acute risk to ensuring continuity of care in follow-up [5].

When an acute suicide risk is identified in the ED, the provider’s immediate next steps should be to place the patient in a safe area under constant observation and to provide an emergency assessment [5,6]. Although psychiatric consultation and/or psychiatric admission may follow this assessment, suicide risk does not require admission in all cases; and some patients with suicide risk may be discharged to an outpatient setting even without receiving a psychiatric consultation [1]. Regardless of whether an outpatient disposition from the ED is appropriate, however, the period that immediately follows discharge is a time of high risk for repeated suicidal behavior and suicide death [7–9], and only 30% to 50% of patients who are discharged from EDs after a self-harm incident actually keep a follow-up mental health appointment [9,10]. Therefore, any support given to patients through this transition out of the emergency care setting could be especially high-yield.

The Joint Commission recommends that all patients with suicidal ideation receive, at minimum, a referral to treatment, telephone numbers for local and national crisis support resources (including the National Suicide Prevention Lifeline 1-800-273-TALK), collaborative safety planning, and counseling to restrict access to lethal means upon discharge [5]. However, some programs have demonstrated the capacity to provide enhanced support to patients beyond discharge from the ED, with some success in reducing the rates of subsequent suicidal behaviors. This non-systematic review describes interventions that can be initiated in the context of an ED encounter with the purpose of reducing future suicidal behavior among adult patients. They are primarily psychosocial rather than clinical. Clinical interventions that apply psychotherapy [11–13] psychopharmacology [14], and specialized inpatient treatments [15] have been studied as well but are beyond the scope of this review.

[polldaddy:10107269]

Interventions to Support Patients At Risk of Suicide After Discharge from the ED

Brief Contact Interventions

The idea that maintaining written correspondence with patients who have a known suicide risk after discharge can reduce subsequent suicide rates originated with a study of psychiatric inpatients conducted by Motto and Bostrom, in which patients who had been admitted for depression but had declined outpatient treatment were randomly assigned to periodically receive letters containing supportive messages from staff members over a period of 5 years [16]. This study remarkably found that these so-called brief contact interventions (BCIs), which were personalized to each recipient but did not contain psychotherapy per se, were associated with a reduced rate of suicide throughout the duration of the program compared with no written contacts [16].

BCIs have since been adapted to other communication formats and have been studied in patients who were discharged directly from the ED after an evaluation of suicide risk or suicidal behavior. Typically, BCIs consist of short, supportive messages that are delivered at regular intervals (often once every 1–2 months) over a period of 1 to 5 years [17,18]. They notably do not contain psychotherapy content, although they may reinforce coping strategies or remind recipients of how to access help if needed [17,19]. They may arrive as postcards [20,21], letters [22], telephone outreach [23–25], or a combination of modalities [26].

Protocols that rely on BCIs alone vary in their structure and have yielded mixed results [18]. A meta-analysis of 12 BCI protocols conducted by Milner et al found that, overall, BCIs administered after a presentation to the ED for self-harm have been associated with a significant reduction in repeat suicide attempts per recipient but not in total suicide deaths [27]. Milner’s group did not recommend large-scale promotion of BCIs based on the inadequacy of data so far, but suggested that this strategy may yet show promise upon further study [27]. A key advantage of BCIs is that they are inexpensive to implement, particularly if they do not include a telephone outreach component [28]. Thus, even if the potential benefit to patients is small, administering BCIs can be cost-effective [28].

It should not come as a surprise, therefore, that the potential for incorporation of BCIs into mobile smartphone technology is currently under investigation. Individuals who own mobile phones typically keep them on their persons and turned on continuously, and thus this is a reliable platform for maintaining contact with a wide range of patients in real-time [17,29]. Developers of at least 2 BCI smartphone programs that rely on mobile text messaging have published their protocols [17,30]. However, whether these programs will succeed in meaningfully reducing suicide rates remains to be determined by future research.

Green Cards

Morgan et al conducted a study in the United Kingdom in which individuals who presented to EDs after a self-harm event received a “green card,” which contained encouraging messages about seeking help and provided contact information for emergency services with 24-hour availability [31]. The green card also facilitated access to a crisis admission if necessary. The green card was distributed first in the ED and a second time by mail 3 weeks later. No suicides occurred in either the intervention or control group, which received usual care, and no statistically significant differences in suicide reattempt rate were found between groups after 1 year [31].

Evans et al studied an updated version of the green card intervention in which the green card facilitated access to an on-call psychiatrist with 24-hour availability by telephone [32]. The updated card included encouraging messages about seeking help similar to the original green card described by Morgan; however, the psychiatry consultation via telephone replaced the offer of hospital admission [32]. This second trial of green cards also failed to show a reduction in the rate of suicide reattempts among green card recipients at 6 months and 1 year [32,33].

Brief Intervention and Contact

The World Health Organization’s Brief Intervention and Contact (BIC) protocol is a standardized, multi-step suicide prevention program that has been studied primarily in patients who present to EDs after a suicide attempt in middle-income countries [34]. BIC includes a 1-hour information session that is administered shortly prior to discharge, and subsequently provides 9 follow-up contact interventions at specified intervals over an 18-month period. Unlike in a typical BCI, the contacts in BIC are conducted by a clinician either face-to-face or over the phone and include standardized assessments of the patient’s condition, although they still do not include psychotherapy. BIC has been shown to reduce suicide attempts, suicide deaths, or both in India [34–36], Iran [34,36,37], China [34,36], Brazil [34,36], and Sri Lanka [34,36] but was not found to directly improve clinical outcomes in a study conducted in French Polynesia [38]. A meta-analysis conducted by Riblet et al concluded that BIC is effective in reducing suicide risk overall [39].

ED-SAFE

The Emergency Department Safety Assessment and Follow-up Evaluation (ED-SAFE) protocol was validated in 8 EDs in 7 states in the US that did not already provide psychiatric services internally [40]. Under this model, all patients in the ED receive a screening for suicide risk, and those with an initial positive screen receive a secondary screen administered by the ED physician, a self-administered safety plan, and a series of up to 11 phone contacts over the following year that are administered by trained mental health clinicians in a central location. The ED-SAFE phone contacts follow the Coping Long Term with Active Suicide Program (CLASP) protocol [41] and provide support around safety planning and treatment engagement. They have the capacity to engage the patients’ significant others directly if a significant other is available and the patient chooses to involve that person.

In a single multicenter study, ED-SAFE reduced the absolute risk of suicide attempt by 5%, and the relative risk by 20% compared to usual treatment [40]. An intermediate phase of the study compared the universal suicide screening alone (ie, without the safety plan or follow-up contacts) with usual care and did not find this to improve outcomes [40].

Case Management

Kawanishi et al conducted a randomized controlled trial of assertive case management, the ACTION-J study, for patients with psychiatric diagnoses who presented with self-harm to 17 participating EDs in Japan [42]. In the ACTION-J study, case managers were mental health clinicians who provided clinical evaluations, treatment planning, encouragement, and care coordination over the course of 7 scheduled face-to-face or phone contacts in the first 18 months, and additional contacts at 6-month intervals until the completion of the trial (up to a total of 5 years) [43]. The comparison intervention, enhanced usual care, consisted of psychoeducation provided at the time of the encounter in the ED without case management services. The assertive case management intervention was associated with a decrease in suicidal behavior in the first 6 months but not for the duration of the study, except in women, for whom the benefit lasted the full 18 months [42]. A subsequent analysis also found a decrease in the total number of self-harm episodes per person-year compared to enhanced usual care, although there was not a difference in the number of participants who experienced a repeat self-harm episode [43]. The benefit was most strongly pronounced among patients who had presented with an index suicide attempt [43].

Morthorst et al applied an alternative case management model for the assertive intervention for deliberate self harm (AID) trial, which took place in Denmark [44]. Participants were aged 12 and older and could have been recruited from medical or pediatric inpatient units as well as the ED after a self-harm event. AID employed psychiatric nurses to provide crisis intervention, crisis planning, problem solving, motivational support, family mediation, and assistance with keeping appointments over a period of 6 months following discharge. Outreach took place over the phone, by text message, in participants’ homes, in cafes, and at health and social services appointments. The intervention required at least 4 contacts, although additional contacts could be made if appropriate. In comparison with a control group, in which participants received only usual care (which included ready access to short-term psychotherapy), the AID intervention was not associated with statistically significant differences in recurrent suicidal behaviors [44]. Subgroup analyses examining adult participants aged 20–39 and 40 and older also did not find differences in recurrent suicidal behavior between groups [44].

The Baerum Model and OPAC

A municipal suicide prevention team that provides comprehensive social services to suicide attempters has operated in Baerum, Norway, since 1983 [45]. Under the Baerum model, patients who attempt suicide, can be discharged from the general hospital without psychiatric admission, and are determined to have a high level of need for support are connected by a hospital-based suicide prevention team to a community-based team consisting of nurses and a consulting psychologist, who subsequently engage patients in own their homes and through follow-up phone calls. The services they provide include care coordination, encouragement, activation of social networks, psychological first-aid, and counseling focused on problem-solving. The ostensible goal of the suicide prevention team is to provide a bridge between inpatient medical care and outpatient mental health treatment; however, the intervention lasts approximately 1 year regardless of whether the patient connects with a treatment program [45].

A retrospective comparison of outcomes between recipients of the original Baerum program and non-recipients failed to find a difference in suicide attempts or suicide deaths between groups [45]. However, this was not a controlled study, and suicide attempters were preferentially referred to the program based on whether they had a higher level of need at baseline. Hvid and Wang adapted this model to patients who presented to EDs and general hospitals in Amager, Denmark [46] and have since conducted a series of randomized controlled trials comparing their adaptation to usual care. The Danish version of the Baerum model, renamed OPAC (for “outreach, problem solving, adherence, continuity”), provides similar case management and counseling services but for a maximum of 6 months. In their studies, OPAC significantly reduced the number of patients with a repeat suicide attempt and the total number of repeat suicide attempts at a 1-year interval, and this effect on total number of suicide attempts was sustained at 5 years [47,48]. Although the OPAC protocol begins with a patient’s presentation to the ED, the intervention is initiated after admission to the general hospital. Therefore, while this may inspire a model that provides similar services directly from the ED to patients who do not require general hospital admission, the existing model is not entirely based in the ED.

Discussion

The needs of suicidal patients are often multidimensional, and in some cases their risks are driven by psychosocial problems in addition to, or instead of, medically modifiable psychiatric conditions [49]. However, developing an ED-based program to support patients who are at risk of suicide after they are discharged from the ED is possible. Many such programs that provide or facilitate caring contacts, family support, case management, and/or treatment engagement with discharged patients have demonstrated that similar strategies may have the potential to impact future suicidal behavior. Nonetheless, it would be a stretch to say that all hospital systems should immediately begin doing so.

A new post-discharge support program is an investment of financial resources, personnel, and sometimes technology. Successful delivery of support or messages in any format requires that the intended recipient be able to receive it via reliable access to a working address, telephone number, or electronic device. Nonetheless, programs that rely on BCIs alone (excluding those conducted via telephone) cost relatively little to implement and thus would require a smaller investment than programs that require synchronous telephone or face-to-face contacts with staff in addition to or instead of BCIs. Costs for synchronous programs will also vary depending on the frequency and duration of contacts and the licensure and training required of the staff who provide them.

A trend toward better outcomes associating with more resource-intensive programs is easy to imagine but has not been definitively demonstrated. The wide variation between protocols in all types of programs makes comparisons between those that do and do not include synchronous contacts, and between types of synchronous contacts, difficult. Meanwhile, the low cost of BCIs alone could increase their attractiveness as an investment regardless of the magnitude of outcome improvement.

Denchev et al constructed a cost/benefit comparison model that included the postcard BCI study conducted by Carter et al [20], the telephone outreach study conducted by Vaiva et al [23], and a study of cognitive behavioral therapy (CBT) [11], all of which showed a clinical benefit. This model relied upon some numeric estimations and did not account for variation in outcomes between individual studies of each intervention strategy. However, it concluded that both telephone outreach and CBT were likely to be cost-prohibitive compared to asynchronous BCIs, which were associated with a reduction in costs overall [28].

Conclusion

There remains much to learn regarding how best to reduce suicide risk among adult patients in the period after discharge from the ED, during which patients with an identified suicide risk are known to be vulnerable. However, providing psychosocial and emotional support to patients with an identified suicide risk after they are discharged from the ED is feasible and may reduce subsequent suicidal behaviors. Templates for providing supportive outreach using different modalities now exist, and these may help guide the ongoing development and widespread adoption of more effective and cost-effective solutions.

Corresponding author: David S. Kroll, MD, [email protected].

Financial disclosure: Dr. Kroll has received research funding from Brigham and Women’s Hospital to study and develop technological solutions for supporting suicidal patients after discharge from the emergency department. He has additionally received research funding and a speaking honorarium from Avasure.

Anxiety disorders are the most common psychiatric illnesses in the United States, with a prevalence of nearly 29%.¹ These disorders typically are treated with pharmacotherapy, psychotherapy, or a combination of both. Pharmacotherapy for anxiety has evolved considerably during the last 30 years, but medications are not efficacious for or tolerated by all patients. For example, selective serotonin reuptake inhibitors, which are frequently used for treating anxiety, can cause sexual dysfunction,² weight gain,² drug interactions,² coagulopathies,³ and gastrointestinal disturbances.⁴ Psychotherapeutic techniques, such as cognitive behavioral therapy (CBT) and interpersonal therapy (IPT), are efficacious for mild to moderate anxiety.^5-7

In addition to standard pharmacotherapy and psychotherapy, some evidence suggests that complementary therapies, such as yoga, massage, and relaxation techniques, may be beneficial as adjunctive treatments for anxiety. In placebo-controlled trials, several of these complementary therapies have been shown to decrease serum levels of the inflammatory biomarker cortisol. Anxiety is associated with inflammation,⁸ so therapies that reduce inflammation may help reduce symptoms of anxiety. Here, we describe the results of select positive randomized controlled trials (RCTs) of several complementary interventions for anxiety that might be useful as adjunctive treatments to psychotherapy or pharmacotherapy.

A look at RCTs that measured both anxiety and cortisol

We searched PubMed, Google Scholar, and Scopus to identify RCTs of complementary nonpharmacologic and nonpsychotherapeutic therapies for anxiety published from January 2010 to May 2017. We included only studies that:

• blindly assessed anxiety levels through a validated instrument (the State-Trait Anxiety Inventory [STAI])⁹
• measured cortisol concentrations before and after treatment.

Evaluating both STAI scores and cortisol levels is useful because doing so gives insight into both the clinical and biological efficacy of the therapies. Studies were excluded if they employed a pharmacologic agent in addition to the approach being evaluated.

We identified 26 studies, of which 14 met the inclusion/exclusion criteria. These studies found beneficial effects for yoga, massage therapy, aromatherapy massage, pet therapy, Qigong, auricular acupressure, reiki touch therapy, acupuncture, music therapy, and relaxation techniques.

Yoga

Yoga has become increasingly popular in the Western world during the last 2 decades.¹⁰ There are a variety of yoga practices; common forms include hatha yoga, power yoga, kripalu yoga, and forrest yoga.¹¹

A study of 92 depressed pregnant women monitored the effects of 20 minutes of yoga once a week for 12 weeks.¹² Half of the women were randomly assigned to the yoga intervention, which consisted of standing, kneeling, and seated poses, and half were assigned to a social support discussion group. After 12 weeks, both groups had significant decreases in STAI scores. Both groups also had statistically significant decreases in salivary cortisol levels immediately after each session.¹²

Hatha yoga consists of a combination of postural exercises, breathing techniques, relaxation, and meditation. In a 12-week study of 88 postmenopausal women, those who practiced hatha yoga for 75 minutes a day had significantly lower STAI scores compared with women who exercised for 75 minutes a day and those who performed no physical activity.¹³

Continue to: Massage therapy

Massage therapy

Receiving as little as 15 minutes of back massage has proven to be beneficial for individuals with anxiety. In an RCT conducted in Turkey, 44 caregivers of patients with cancer were assigned to receive a back massage or to rest quietly in a room for 15 minutes once each day for 1 week.¹⁴ By the end of the week, compared with those who quietly rested, those who received the back massage had a statistically significant reduction in serum cortisol levels and STAI scores.¹⁴

Aromatherapy massage

Aromatherapy is the use of essential oils from plants through distillation.¹⁵ The scent of the oils is purported to provide medical benefits. More than 60 essential oils are used therapeutically, including rose, lavender, lemon, and orange.¹⁶ These essential oils are frequently used in combination with a massage.

In South Korea, researchers investigated the effects of aromatherapy massage on 25 women who had children diagnosed with attention-deficit/hyperactivity disorder.¹⁷ Women assigned to the treatment group received a 40-minute aromatherapy massage using mixed essential oils that contained lavender and geranium twice a week for 4 weeks. Women in the control group received no treatment. Compared with those in the control group, women who received the aromatherapy massages had a statistically significant decrease in STAI scores and salivary cortisol levels. Plasma cortisol was not significantly different between groups.¹⁷

Pet therapy

The psychological benefits of animal-assisted therapy were not evident until World War II, when dogs were used to cheer up injured soldiers.¹⁸ Today, pet therapy has been used on many inpatient units.¹⁹

In a U.S. study, 48 healthy undergraduate students were assigned to a room with a dog, a room with a friend, or a room by themselves.²⁰ All participants were given the Trier Social Stress Test (TSST), a protocol that measures stress by having participants give a speech and perform mental arithmetic in front of an audience.The TSST is known to induce increases in cortisol levels. Although no differences in STAI scores were found among groups, students in the room with the dog had a lower spike in salivary cortisol after the TSST compared with participants who were in a room with a friend or in a room alone.²⁰

Continue to: Qigong

In Chinese medicine, Qi is known as a vital life force that flows through the body. The disruption of Qi is hypothesized to contri­bute to disease.²¹

Qigong is a medical therapy that focuses on uniting the body, breath, and mind to improve health.²¹ It consists of rhythmic, choreographed movements used to position the body into postures believed to help direct Qi to specific areas in the body. Qigong also uses sound exercises, in which an individual creates certain syllables while breathing. Six syllables are used, each of which is believed to affect a certain organ.²¹

Korean researchers randomly assigned 32 healthy men to a Qigong training group or a sham Qigong control group.²² Individuals in the training group performed 25 minutes of sound exercises, 20 minutes of meditation, and 15 minutes of movements. The control group learned the same movements as the experimental group, but without the conscious effort of moving Qi. After 3 sessions, those in the Qigong training group had significantly decreased STAI scores and serum cortisol levels compared with those in the sham group.²²

In a different Korean study, researchers randomly assigned 50 participants with elevated distress levels to a Qigong training group or a waitlist control group in which participants called a trainer to describe stressful events.²³ After 4 weeks, participants in the Qigong group had significant decreases in STAI scores compared with the control group. However, there were no changes in salivary cortisol levels.²³

Auricular acupressure

Auricular acupressure involves applying pressure on certain portions of the auricle (outer ear) to alleviate pain and disease.²⁴ Similar to Qigong, auricular acupressure focuses on reestablishing Qi in the body. Researchers randomly assigned 80 post-caesarean section women in Taiwan to 5 days of auricular acupressure or usual care.²⁵ The women who received auricular acupressure had significantly lower STAI scores and serum cortisol levels compared with women who received routine care.²⁵

Continue to: Reiki touch therapy

Reiki touch therapy originated in Japan. In this therapy, healers apply a light touch or hover their hands above an individual’s body to help direct energy.²⁶

The effects of reiki touch therapy were recently evaluated in a U.S. study.²⁷ Researchers randomly assigned 37 patients with human immunodeficiency virus to an experimental group that received 30 minutes of reiki touch therapy plus music therapy 6 times a week for 10 weeks, or to a music therapy–only control group. Patients who received reiki touch therapy had a significant decrease in STAI scores. Patients in this group also had a statistically significant drop in salivary cortisol levels after the first week.²⁷

Acupuncture

Acupuncture is the application of needles to specific areas on the body. Acupuncture has been proposed to activate pain receptors, thereby producing an analgesic response.²⁸

Researchers in Brazil randomly assigned 57 lactating women with preterm infants to an experimental group that received acupuncture or to a control group that received sham acupuncture.²⁹ Treatment was administered at 5 points on the ear unilaterally for 5 minutes once a week for 16 months. Custom-made needles that did not actually puncture the skin were used in the sham group; a toothpick was used to create the sensation of needle perforations. STAI scores were reduced in both groups, although there was no statistically significant difference in scores between the acupuncture and sham groups.²⁹

Music therapy

Music has been long believed to have beneficial psychological effects. In Turkey, researchers evaluated the effects of music therapy in 100 oncology patients who received port catheters.³⁰ Patients were randomly assigned to an experimental group that received music therapy throughout the procedure or to a control group that received normal care. Patients who listened to music during port catheter placement had significantly reduced STAI scores and serum cortisol levels compared with those in the control group.³⁰

Continue to: Relaxation techniques

A wide range of relaxation techniques are used for therapeutic purposes. In Switzerland, researchers evaluated the anxiolytic effects of 10 minutes of progressive muscle relaxation and guided imagery in 39 pregnant women.³¹ Women randomly assigned to progressive muscle relaxation were instructed to systematically tense and then release muscle groups throughout their body in sequential order. Women assigned to the guided imagery intervention were told to imagine a safe place and to think of someone who could confer security and reassurance. The remainder of the women were assigned to a control group, where they sat quietly without any formal instructions. Researchers found that each group had a decrease in STAI scores and salivary cortisol levels immediately after the intervention.³¹

The relaxation response was first described in 1975 by Herbert Benson, MD, as a deep meditative state characterized by a decrease in tension, heart rate, and breathing rate. Several techniques can induce this state, including hypnosis, progressive muscle relaxation, yoga, and transcendental meditation.³² In a study of 15 healthy older adults (age 65 to 80), researchers randomly assigned participants to a relaxation response training group or to a control group.³³ The relaxation response training included meditation, imagery, and relaxation techniques. After 5 weeks, participants who received the relaxation response training had marginally significant decreases in STAI scores compared with those in the control group.³³

Consider these therapies as adjuncts

Our review of select positive RCTs (Table^{12-14,17,20,22,23,25,27,29-31,33}) suggests that some nonpharmacologic/nonpsychotherapeutic adjunctive interventions may have beneficial effects for patients who have anxiety. Several of the controlled studies we reviewed demonstrated that these interventions are superior to placebo. The reductions in both anxiety severity as measured by the STAI and cortisol levels suggests that some of these complementary therapies deserve a second look as useful adjuncts to established anxiety treatments.

Bottom Line

A review of select randomized controlled trials suggests that some complementary therapies may be helpful as adjunctive therapy in patients with anxiety. These include yoga, massage therapy, aromatherapy massage, pet therapy, Qigong, auricular acupressure, reiki touch therapy, acupuncture, music therapy, and relaxation techniques.

Related Resources

• Bandelow B, Baldwin D, Abelli M, et al. Biological markers for anxiety disorders, OCD and PTSD: a consensus statement. Part II: neurochemistry, neurophysiology and neurocognition. World J Biol Psychiatry. 2017;18(3):162-214.
• National Institute of Mental Health. Anxiety disorders. https://www.nimh.nih.gov/health/topics/anxiety-disorders/index.shtml.

Anxiety disorders are the most common psychiatric illnesses in the United States, with a prevalence of nearly 29%.¹ These disorders typically are treated with pharmacotherapy, psychotherapy, or a combination of both. Pharmacotherapy for anxiety has evolved considerably during the last 30 years, but medications are not efficacious for or tolerated by all patients. For example, selective serotonin reuptake inhibitors, which are frequently used for treating anxiety, can cause sexual dysfunction,² weight gain,² drug interactions,² coagulopathies,³ and gastrointestinal disturbances.⁴ Psychotherapeutic techniques, such as cognitive behavioral therapy (CBT) and interpersonal therapy (IPT), are efficacious for mild to moderate anxiety.^5-7

In addition to standard pharmacotherapy and psychotherapy, some evidence suggests that complementary therapies, such as yoga, massage, and relaxation techniques, may be beneficial as adjunctive treatments for anxiety. In placebo-controlled trials, several of these complementary therapies have been shown to decrease serum levels of the inflammatory biomarker cortisol. Anxiety is associated with inflammation,⁸ so therapies that reduce inflammation may help reduce symptoms of anxiety. Here, we describe the results of select positive randomized controlled trials (RCTs) of several complementary interventions for anxiety that might be useful as adjunctive treatments to psychotherapy or pharmacotherapy.

A look at RCTs that measured both anxiety and cortisol

We searched PubMed, Google Scholar, and Scopus to identify RCTs of complementary nonpharmacologic and nonpsychotherapeutic therapies for anxiety published from January 2010 to May 2017. We included only studies that:

• blindly assessed anxiety levels through a validated instrument (the State-Trait Anxiety Inventory [STAI])⁹
• measured cortisol concentrations before and after treatment.

Evaluating both STAI scores and cortisol levels is useful because doing so gives insight into both the clinical and biological efficacy of the therapies. Studies were excluded if they employed a pharmacologic agent in addition to the approach being evaluated.

We identified 26 studies, of which 14 met the inclusion/exclusion criteria. These studies found beneficial effects for yoga, massage therapy, aromatherapy massage, pet therapy, Qigong, auricular acupressure, reiki touch therapy, acupuncture, music therapy, and relaxation techniques.

Yoga

Yoga has become increasingly popular in the Western world during the last 2 decades.¹⁰ There are a variety of yoga practices; common forms include hatha yoga, power yoga, kripalu yoga, and forrest yoga.¹¹

A study of 92 depressed pregnant women monitored the effects of 20 minutes of yoga once a week for 12 weeks.¹² Half of the women were randomly assigned to the yoga intervention, which consisted of standing, kneeling, and seated poses, and half were assigned to a social support discussion group. After 12 weeks, both groups had significant decreases in STAI scores. Both groups also had statistically significant decreases in salivary cortisol levels immediately after each session.¹²

Hatha yoga consists of a combination of postural exercises, breathing techniques, relaxation, and meditation. In a 12-week study of 88 postmenopausal women, those who practiced hatha yoga for 75 minutes a day had significantly lower STAI scores compared with women who exercised for 75 minutes a day and those who performed no physical activity.¹³

Continue to: Massage therapy

Massage therapy

Receiving as little as 15 minutes of back massage has proven to be beneficial for individuals with anxiety. In an RCT conducted in Turkey, 44 caregivers of patients with cancer were assigned to receive a back massage or to rest quietly in a room for 15 minutes once each day for 1 week.¹⁴ By the end of the week, compared with those who quietly rested, those who received the back massage had a statistically significant reduction in serum cortisol levels and STAI scores.¹⁴

Aromatherapy massage

Aromatherapy is the use of essential oils from plants through distillation.¹⁵ The scent of the oils is purported to provide medical benefits. More than 60 essential oils are used therapeutically, including rose, lavender, lemon, and orange.¹⁶ These essential oils are frequently used in combination with a massage.

In South Korea, researchers investigated the effects of aromatherapy massage on 25 women who had children diagnosed with attention-deficit/hyperactivity disorder.¹⁷ Women assigned to the treatment group received a 40-minute aromatherapy massage using mixed essential oils that contained lavender and geranium twice a week for 4 weeks. Women in the control group received no treatment. Compared with those in the control group, women who received the aromatherapy massages had a statistically significant decrease in STAI scores and salivary cortisol levels. Plasma cortisol was not significantly different between groups.¹⁷

Pet therapy

The psychological benefits of animal-assisted therapy were not evident until World War II, when dogs were used to cheer up injured soldiers.¹⁸ Today, pet therapy has been used on many inpatient units.¹⁹

In a U.S. study, 48 healthy undergraduate students were assigned to a room with a dog, a room with a friend, or a room by themselves.²⁰ All participants were given the Trier Social Stress Test (TSST), a protocol that measures stress by having participants give a speech and perform mental arithmetic in front of an audience.The TSST is known to induce increases in cortisol levels. Although no differences in STAI scores were found among groups, students in the room with the dog had a lower spike in salivary cortisol after the TSST compared with participants who were in a room with a friend or in a room alone.²⁰

Continue to: Qigong

In Chinese medicine, Qi is known as a vital life force that flows through the body. The disruption of Qi is hypothesized to contri­bute to disease.²¹

Qigong is a medical therapy that focuses on uniting the body, breath, and mind to improve health.²¹ It consists of rhythmic, choreographed movements used to position the body into postures believed to help direct Qi to specific areas in the body. Qigong also uses sound exercises, in which an individual creates certain syllables while breathing. Six syllables are used, each of which is believed to affect a certain organ.²¹

Korean researchers randomly assigned 32 healthy men to a Qigong training group or a sham Qigong control group.²² Individuals in the training group performed 25 minutes of sound exercises, 20 minutes of meditation, and 15 minutes of movements. The control group learned the same movements as the experimental group, but without the conscious effort of moving Qi. After 3 sessions, those in the Qigong training group had significantly decreased STAI scores and serum cortisol levels compared with those in the sham group.²²

In a different Korean study, researchers randomly assigned 50 participants with elevated distress levels to a Qigong training group or a waitlist control group in which participants called a trainer to describe stressful events.²³ After 4 weeks, participants in the Qigong group had significant decreases in STAI scores compared with the control group. However, there were no changes in salivary cortisol levels.²³

Auricular acupressure

Auricular acupressure involves applying pressure on certain portions of the auricle (outer ear) to alleviate pain and disease.²⁴ Similar to Qigong, auricular acupressure focuses on reestablishing Qi in the body. Researchers randomly assigned 80 post-caesarean section women in Taiwan to 5 days of auricular acupressure or usual care.²⁵ The women who received auricular acupressure had significantly lower STAI scores and serum cortisol levels compared with women who received routine care.²⁵

Continue to: Reiki touch therapy

Reiki touch therapy originated in Japan. In this therapy, healers apply a light touch or hover their hands above an individual’s body to help direct energy.²⁶

The effects of reiki touch therapy were recently evaluated in a U.S. study.²⁷ Researchers randomly assigned 37 patients with human immunodeficiency virus to an experimental group that received 30 minutes of reiki touch therapy plus music therapy 6 times a week for 10 weeks, or to a music therapy–only control group. Patients who received reiki touch therapy had a significant decrease in STAI scores. Patients in this group also had a statistically significant drop in salivary cortisol levels after the first week.²⁷

Acupuncture

Acupuncture is the application of needles to specific areas on the body. Acupuncture has been proposed to activate pain receptors, thereby producing an analgesic response.²⁸

Researchers in Brazil randomly assigned 57 lactating women with preterm infants to an experimental group that received acupuncture or to a control group that received sham acupuncture.²⁹ Treatment was administered at 5 points on the ear unilaterally for 5 minutes once a week for 16 months. Custom-made needles that did not actually puncture the skin were used in the sham group; a toothpick was used to create the sensation of needle perforations. STAI scores were reduced in both groups, although there was no statistically significant difference in scores between the acupuncture and sham groups.²⁹

Music therapy

Music has been long believed to have beneficial psychological effects. In Turkey, researchers evaluated the effects of music therapy in 100 oncology patients who received port catheters.³⁰ Patients were randomly assigned to an experimental group that received music therapy throughout the procedure or to a control group that received normal care. Patients who listened to music during port catheter placement had significantly reduced STAI scores and serum cortisol levels compared with those in the control group.³⁰

Continue to: Relaxation techniques

A wide range of relaxation techniques are used for therapeutic purposes. In Switzerland, researchers evaluated the anxiolytic effects of 10 minutes of progressive muscle relaxation and guided imagery in 39 pregnant women.³¹ Women randomly assigned to progressive muscle relaxation were instructed to systematically tense and then release muscle groups throughout their body in sequential order. Women assigned to the guided imagery intervention were told to imagine a safe place and to think of someone who could confer security and reassurance. The remainder of the women were assigned to a control group, where they sat quietly without any formal instructions. Researchers found that each group had a decrease in STAI scores and salivary cortisol levels immediately after the intervention.³¹

The relaxation response was first described in 1975 by Herbert Benson, MD, as a deep meditative state characterized by a decrease in tension, heart rate, and breathing rate. Several techniques can induce this state, including hypnosis, progressive muscle relaxation, yoga, and transcendental meditation.³² In a study of 15 healthy older adults (age 65 to 80), researchers randomly assigned participants to a relaxation response training group or to a control group.³³ The relaxation response training included meditation, imagery, and relaxation techniques. After 5 weeks, participants who received the relaxation response training had marginally significant decreases in STAI scores compared with those in the control group.³³

Consider these therapies as adjuncts

Our review of select positive RCTs (Table^{12-14,17,20,22,23,25,27,29-31,33}) suggests that some nonpharmacologic/nonpsychotherapeutic adjunctive interventions may have beneficial effects for patients who have anxiety. Several of the controlled studies we reviewed demonstrated that these interventions are superior to placebo. The reductions in both anxiety severity as measured by the STAI and cortisol levels suggests that some of these complementary therapies deserve a second look as useful adjuncts to established anxiety treatments.

Bottom Line

A review of select randomized controlled trials suggests that some complementary therapies may be helpful as adjunctive therapy in patients with anxiety. These include yoga, massage therapy, aromatherapy massage, pet therapy, Qigong, auricular acupressure, reiki touch therapy, acupuncture, music therapy, and relaxation techniques.

Related Resources

• Bandelow B, Baldwin D, Abelli M, et al. Biological markers for anxiety disorders, OCD and PTSD: a consensus statement. Part II: neurochemistry, neurophysiology and neurocognition. World J Biol Psychiatry. 2017;18(3):162-214.
• National Institute of Mental Health. Anxiety disorders. https://www.nimh.nih.gov/health/topics/anxiety-disorders/index.shtml.

Anxiety disorders are the most common psychiatric illnesses in the United States, with a prevalence of nearly 29%.¹ These disorders typically are treated with pharmacotherapy, psychotherapy, or a combination of both. Pharmacotherapy for anxiety has evolved considerably during the last 30 years, but medications are not efficacious for or tolerated by all patients. For example, selective serotonin reuptake inhibitors, which are frequently used for treating anxiety, can cause sexual dysfunction,² weight gain,² drug interactions,² coagulopathies,³ and gastrointestinal disturbances.⁴ Psychotherapeutic techniques, such as cognitive behavioral therapy (CBT) and interpersonal therapy (IPT), are efficacious for mild to moderate anxiety.^5-7

In addition to standard pharmacotherapy and psychotherapy, some evidence suggests that complementary therapies, such as yoga, massage, and relaxation techniques, may be beneficial as adjunctive treatments for anxiety. In placebo-controlled trials, several of these complementary therapies have been shown to decrease serum levels of the inflammatory biomarker cortisol. Anxiety is associated with inflammation,⁸ so therapies that reduce inflammation may help reduce symptoms of anxiety. Here, we describe the results of select positive randomized controlled trials (RCTs) of several complementary interventions for anxiety that might be useful as adjunctive treatments to psychotherapy or pharmacotherapy.

A look at RCTs that measured both anxiety and cortisol

We searched PubMed, Google Scholar, and Scopus to identify RCTs of complementary nonpharmacologic and nonpsychotherapeutic therapies for anxiety published from January 2010 to May 2017. We included only studies that:

• blindly assessed anxiety levels through a validated instrument (the State-Trait Anxiety Inventory [STAI])⁹
• measured cortisol concentrations before and after treatment.

Evaluating both STAI scores and cortisol levels is useful because doing so gives insight into both the clinical and biological efficacy of the therapies. Studies were excluded if they employed a pharmacologic agent in addition to the approach being evaluated.

We identified 26 studies, of which 14 met the inclusion/exclusion criteria. These studies found beneficial effects for yoga, massage therapy, aromatherapy massage, pet therapy, Qigong, auricular acupressure, reiki touch therapy, acupuncture, music therapy, and relaxation techniques.

Yoga

Yoga has become increasingly popular in the Western world during the last 2 decades.¹⁰ There are a variety of yoga practices; common forms include hatha yoga, power yoga, kripalu yoga, and forrest yoga.¹¹

A study of 92 depressed pregnant women monitored the effects of 20 minutes of yoga once a week for 12 weeks.¹² Half of the women were randomly assigned to the yoga intervention, which consisted of standing, kneeling, and seated poses, and half were assigned to a social support discussion group. After 12 weeks, both groups had significant decreases in STAI scores. Both groups also had statistically significant decreases in salivary cortisol levels immediately after each session.¹²

Hatha yoga consists of a combination of postural exercises, breathing techniques, relaxation, and meditation. In a 12-week study of 88 postmenopausal women, those who practiced hatha yoga for 75 minutes a day had significantly lower STAI scores compared with women who exercised for 75 minutes a day and those who performed no physical activity.¹³

Continue to: Massage therapy

Massage therapy

Receiving as little as 15 minutes of back massage has proven to be beneficial for individuals with anxiety. In an RCT conducted in Turkey, 44 caregivers of patients with cancer were assigned to receive a back massage or to rest quietly in a room for 15 minutes once each day for 1 week.¹⁴ By the end of the week, compared with those who quietly rested, those who received the back massage had a statistically significant reduction in serum cortisol levels and STAI scores.¹⁴

Aromatherapy massage

Aromatherapy is the use of essential oils from plants through distillation.¹⁵ The scent of the oils is purported to provide medical benefits. More than 60 essential oils are used therapeutically, including rose, lavender, lemon, and orange.¹⁶ These essential oils are frequently used in combination with a massage.

In South Korea, researchers investigated the effects of aromatherapy massage on 25 women who had children diagnosed with attention-deficit/hyperactivity disorder.¹⁷ Women assigned to the treatment group received a 40-minute aromatherapy massage using mixed essential oils that contained lavender and geranium twice a week for 4 weeks. Women in the control group received no treatment. Compared with those in the control group, women who received the aromatherapy massages had a statistically significant decrease in STAI scores and salivary cortisol levels. Plasma cortisol was not significantly different between groups.¹⁷

Pet therapy

The psychological benefits of animal-assisted therapy were not evident until World War II, when dogs were used to cheer up injured soldiers.¹⁸ Today, pet therapy has been used on many inpatient units.¹⁹

In a U.S. study, 48 healthy undergraduate students were assigned to a room with a dog, a room with a friend, or a room by themselves.²⁰ All participants were given the Trier Social Stress Test (TSST), a protocol that measures stress by having participants give a speech and perform mental arithmetic in front of an audience.The TSST is known to induce increases in cortisol levels. Although no differences in STAI scores were found among groups, students in the room with the dog had a lower spike in salivary cortisol after the TSST compared with participants who were in a room with a friend or in a room alone.²⁰

Continue to: Qigong

In Chinese medicine, Qi is known as a vital life force that flows through the body. The disruption of Qi is hypothesized to contri­bute to disease.²¹

Qigong is a medical therapy that focuses on uniting the body, breath, and mind to improve health.²¹ It consists of rhythmic, choreographed movements used to position the body into postures believed to help direct Qi to specific areas in the body. Qigong also uses sound exercises, in which an individual creates certain syllables while breathing. Six syllables are used, each of which is believed to affect a certain organ.²¹

Korean researchers randomly assigned 32 healthy men to a Qigong training group or a sham Qigong control group.²² Individuals in the training group performed 25 minutes of sound exercises, 20 minutes of meditation, and 15 minutes of movements. The control group learned the same movements as the experimental group, but without the conscious effort of moving Qi. After 3 sessions, those in the Qigong training group had significantly decreased STAI scores and serum cortisol levels compared with those in the sham group.²²

In a different Korean study, researchers randomly assigned 50 participants with elevated distress levels to a Qigong training group or a waitlist control group in which participants called a trainer to describe stressful events.²³ After 4 weeks, participants in the Qigong group had significant decreases in STAI scores compared with the control group. However, there were no changes in salivary cortisol levels.²³

Auricular acupressure

Auricular acupressure involves applying pressure on certain portions of the auricle (outer ear) to alleviate pain and disease.²⁴ Similar to Qigong, auricular acupressure focuses on reestablishing Qi in the body. Researchers randomly assigned 80 post-caesarean section women in Taiwan to 5 days of auricular acupressure or usual care.²⁵ The women who received auricular acupressure had significantly lower STAI scores and serum cortisol levels compared with women who received routine care.²⁵

Continue to: Reiki touch therapy

Reiki touch therapy originated in Japan. In this therapy, healers apply a light touch or hover their hands above an individual’s body to help direct energy.²⁶

The effects of reiki touch therapy were recently evaluated in a U.S. study.²⁷ Researchers randomly assigned 37 patients with human immunodeficiency virus to an experimental group that received 30 minutes of reiki touch therapy plus music therapy 6 times a week for 10 weeks, or to a music therapy–only control group. Patients who received reiki touch therapy had a significant decrease in STAI scores. Patients in this group also had a statistically significant drop in salivary cortisol levels after the first week.²⁷

Acupuncture

Acupuncture is the application of needles to specific areas on the body. Acupuncture has been proposed to activate pain receptors, thereby producing an analgesic response.²⁸

Researchers in Brazil randomly assigned 57 lactating women with preterm infants to an experimental group that received acupuncture or to a control group that received sham acupuncture.²⁹ Treatment was administered at 5 points on the ear unilaterally for 5 minutes once a week for 16 months. Custom-made needles that did not actually puncture the skin were used in the sham group; a toothpick was used to create the sensation of needle perforations. STAI scores were reduced in both groups, although there was no statistically significant difference in scores between the acupuncture and sham groups.²⁹

Music therapy

Music has been long believed to have beneficial psychological effects. In Turkey, researchers evaluated the effects of music therapy in 100 oncology patients who received port catheters.³⁰ Patients were randomly assigned to an experimental group that received music therapy throughout the procedure or to a control group that received normal care. Patients who listened to music during port catheter placement had significantly reduced STAI scores and serum cortisol levels compared with those in the control group.³⁰

Continue to: Relaxation techniques

A wide range of relaxation techniques are used for therapeutic purposes. In Switzerland, researchers evaluated the anxiolytic effects of 10 minutes of progressive muscle relaxation and guided imagery in 39 pregnant women.³¹ Women randomly assigned to progressive muscle relaxation were instructed to systematically tense and then release muscle groups throughout their body in sequential order. Women assigned to the guided imagery intervention were told to imagine a safe place and to think of someone who could confer security and reassurance. The remainder of the women were assigned to a control group, where they sat quietly without any formal instructions. Researchers found that each group had a decrease in STAI scores and salivary cortisol levels immediately after the intervention.³¹

The relaxation response was first described in 1975 by Herbert Benson, MD, as a deep meditative state characterized by a decrease in tension, heart rate, and breathing rate. Several techniques can induce this state, including hypnosis, progressive muscle relaxation, yoga, and transcendental meditation.³² In a study of 15 healthy older adults (age 65 to 80), researchers randomly assigned participants to a relaxation response training group or to a control group.³³ The relaxation response training included meditation, imagery, and relaxation techniques. After 5 weeks, participants who received the relaxation response training had marginally significant decreases in STAI scores compared with those in the control group.³³

Consider these therapies as adjuncts

Our review of select positive RCTs (Table^{12-14,17,20,22,23,25,27,29-31,33}) suggests that some nonpharmacologic/nonpsychotherapeutic adjunctive interventions may have beneficial effects for patients who have anxiety. Several of the controlled studies we reviewed demonstrated that these interventions are superior to placebo. The reductions in both anxiety severity as measured by the STAI and cortisol levels suggests that some of these complementary therapies deserve a second look as useful adjuncts to established anxiety treatments.

Bottom Line

A review of select randomized controlled trials suggests that some complementary therapies may be helpful as adjunctive therapy in patients with anxiety. These include yoga, massage therapy, aromatherapy massage, pet therapy, Qigong, auricular acupressure, reiki touch therapy, acupuncture, music therapy, and relaxation techniques.

Related Resources

• Bandelow B, Baldwin D, Abelli M, et al. Biological markers for anxiety disorders, OCD and PTSD: a consensus statement. Part II: neurochemistry, neurophysiology and neurocognition. World J Biol Psychiatry. 2017;18(3):162-214.
• National Institute of Mental Health. Anxiety disorders. https://www.nimh.nih.gov/health/topics/anxiety-disorders/index.shtml.

EVIDENCE SUMMARY

Three meta-analyses that included only randomized controlled trials (RCTs) compared various CBT delivery methods with controls (wait-listed for treatment or general sleep hygiene education) to assess sleep outcomes for adults with insomnia.^1-3 TABLE 1^1-3 summarizes the results.

CBT is comparable to pharmacotherapy

A 2002 comparative meta-analysis of 21 RCTs with a total of 470 patients examined the effectiveness of CBT (stimulus control and/or sleep restriction) compared with pharmacotherapy (benzodiazepines or benzodiazepine agonists) for treating primary insomnia of longer than one month’s duration in adults with no comorbid medical or psychiatric diagnoses.⁴ The CBT group received intervention over an average of 5 weeks, and the pharmacotherapy group received intervention over an average of 2 weeks.

CBT produced greater reductions in sleep onset latency than pharmacotherapy based on mean weighted effect size (1.05 vs 0.45 weighted effect size; 95% confidence interval, 0.17-1.04; P=.01). Although both CBT and pharmacotherapy improved sleep outcomes, no statistical differences were found in wake after sleep onset time, total sleep time, number of awakenings, or sleep quality ratings (TABLE 2⁴).

Continue to: CBT has significant benefit for comorbid insomnia

A 2015 meta-analysis of 23 studies enrolling a total of 1379 adults with a number of illnesses (chronic pain, alcohol dependence, breast cancer, psychiatric disorders, chronic obstructive pulmonary disease, fibromyalgia) and comorbid insomnia investigated the qualitative effectiveness of individual or group CBT therapy.⁵ Subjects received at least 4 face-to-face sessions and at least 2 components of CBT.

The primary outcome showed that sleep quality improved, as measured by a 6.36-point reduction in the Insomnia Severity Index (ISI; a 7-question scale on which 0=no insomnia and 28=severe insomnia) and a 3.3-point reduction in the Pittsburgh Sleep Quality Index (PSQI; a 7-category assessment tool on which 0=perfect quality and 21=poor quality). The effect size was large for both ISI and PSQI, as indicated by standard mean differences greater than 0.8 (1.22 and 0.88, respectively) and was sustained for as long as 18 months.

RECOMMENDATIONS

The American College of Physicians strongly recommends that all adult patients receive CBT as initial treatment for chronic insomnia disorder. It can be performed in multiple settings, including the primary care setting. Compared with hypnotics, CBT is unlikely to have any adverse effects.⁶

EVIDENCE SUMMARY

Three meta-analyses that included only randomized controlled trials (RCTs) compared various CBT delivery methods with controls (wait-listed for treatment or general sleep hygiene education) to assess sleep outcomes for adults with insomnia.^1-3 TABLE 1^1-3 summarizes the results.

CBT is comparable to pharmacotherapy

A 2002 comparative meta-analysis of 21 RCTs with a total of 470 patients examined the effectiveness of CBT (stimulus control and/or sleep restriction) compared with pharmacotherapy (benzodiazepines or benzodiazepine agonists) for treating primary insomnia of longer than one month’s duration in adults with no comorbid medical or psychiatric diagnoses.⁴ The CBT group received intervention over an average of 5 weeks, and the pharmacotherapy group received intervention over an average of 2 weeks.

CBT produced greater reductions in sleep onset latency than pharmacotherapy based on mean weighted effect size (1.05 vs 0.45 weighted effect size; 95% confidence interval, 0.17-1.04; P=.01). Although both CBT and pharmacotherapy improved sleep outcomes, no statistical differences were found in wake after sleep onset time, total sleep time, number of awakenings, or sleep quality ratings (TABLE 2⁴).

Continue to: CBT has significant benefit for comorbid insomnia

A 2015 meta-analysis of 23 studies enrolling a total of 1379 adults with a number of illnesses (chronic pain, alcohol dependence, breast cancer, psychiatric disorders, chronic obstructive pulmonary disease, fibromyalgia) and comorbid insomnia investigated the qualitative effectiveness of individual or group CBT therapy.⁵ Subjects received at least 4 face-to-face sessions and at least 2 components of CBT.

The primary outcome showed that sleep quality improved, as measured by a 6.36-point reduction in the Insomnia Severity Index (ISI; a 7-question scale on which 0=no insomnia and 28=severe insomnia) and a 3.3-point reduction in the Pittsburgh Sleep Quality Index (PSQI; a 7-category assessment tool on which 0=perfect quality and 21=poor quality). The effect size was large for both ISI and PSQI, as indicated by standard mean differences greater than 0.8 (1.22 and 0.88, respectively) and was sustained for as long as 18 months.

RECOMMENDATIONS

The American College of Physicians strongly recommends that all adult patients receive CBT as initial treatment for chronic insomnia disorder. It can be performed in multiple settings, including the primary care setting. Compared with hypnotics, CBT is unlikely to have any adverse effects.⁶

EVIDENCE SUMMARY

Three meta-analyses that included only randomized controlled trials (RCTs) compared various CBT delivery methods with controls (wait-listed for treatment or general sleep hygiene education) to assess sleep outcomes for adults with insomnia.^1-3 TABLE 1^1-3 summarizes the results.

CBT is comparable to pharmacotherapy

A 2002 comparative meta-analysis of 21 RCTs with a total of 470 patients examined the effectiveness of CBT (stimulus control and/or sleep restriction) compared with pharmacotherapy (benzodiazepines or benzodiazepine agonists) for treating primary insomnia of longer than one month’s duration in adults with no comorbid medical or psychiatric diagnoses.⁴ The CBT group received intervention over an average of 5 weeks, and the pharmacotherapy group received intervention over an average of 2 weeks.

CBT produced greater reductions in sleep onset latency than pharmacotherapy based on mean weighted effect size (1.05 vs 0.45 weighted effect size; 95% confidence interval, 0.17-1.04; P=.01). Although both CBT and pharmacotherapy improved sleep outcomes, no statistical differences were found in wake after sleep onset time, total sleep time, number of awakenings, or sleep quality ratings (TABLE 2⁴).

Continue to: CBT has significant benefit for comorbid insomnia

A 2015 meta-analysis of 23 studies enrolling a total of 1379 adults with a number of illnesses (chronic pain, alcohol dependence, breast cancer, psychiatric disorders, chronic obstructive pulmonary disease, fibromyalgia) and comorbid insomnia investigated the qualitative effectiveness of individual or group CBT therapy.⁵ Subjects received at least 4 face-to-face sessions and at least 2 components of CBT.

The primary outcome showed that sleep quality improved, as measured by a 6.36-point reduction in the Insomnia Severity Index (ISI; a 7-question scale on which 0=no insomnia and 28=severe insomnia) and a 3.3-point reduction in the Pittsburgh Sleep Quality Index (PSQI; a 7-category assessment tool on which 0=perfect quality and 21=poor quality). The effect size was large for both ISI and PSQI, as indicated by standard mean differences greater than 0.8 (1.22 and 0.88, respectively) and was sustained for as long as 18 months.

RECOMMENDATIONS

The American College of Physicians strongly recommends that all adult patients receive CBT as initial treatment for chronic insomnia disorder. It can be performed in multiple settings, including the primary care setting. Compared with hypnotics, CBT is unlikely to have any adverse effects.⁶

Continuous electronic fetal heart rate monitoring (EFM) is used in the vast majority of all labors in the United States. With the use of EFM categories and definitions from the American College of Obstetricians and Gynecologists, the National Institutes of Health, and the Society for Maternal-Fetal Medicine, clinicians can now better define and communicate tracing assessments. Except for reducing neonatal seizure activity, however, EFM use during labor has not been demonstrated to significantly improve fetal and neonatal outcomes, yet EFM is associated with an increase in cesarean deliveries and instrument-assisted vaginal births.¹

The negative predictive value of EFM for fetal hypoxia/acidosis is high, but its positive predictive value is only 30%, and the false-positive rate is as high as 60%.² Although a false-positive assessment may result in a potentially unnecessary operative vaginal or cesarean delivery, a falsely reassuring strip may produce devastating consequences in the newborn and, not infrequently, medical malpractice liability. One etiology associated with falsely reassuring assessments is that of EFM monitoring of the maternal heart rate and the failure to recognize the tracing as maternal.

In this article, I discuss the mechanisms and periods of labor that often are associated with the maternal heart rate masquerading as the fetal heart rate. I review common EFM patterns associated with the maternal heart rate so as to aid in recognizing the maternal heart rate. In addition, I provide 3 case scenarios that illustrate the simple yet critical steps that clinicians can take to remedy the situation. Being aware of the potential for a maternal heart rate recording, investigating the EFM signals, and correcting the monitoring can help prevent significant morbidity.

CASE 1 EFM shows seesaw decelerations and returns to baseline rate

A 29-year-old woman (G3P2) at 39 weeks’ gestation was admitted to the hospital with spontaneous labor. Continuous EFM external monitoring was initiated. After membranes spontaneously ruptured at 4 cm dilation, an epidural was placed. Throughout the active phase of labor, the fetus demonstrated intermittent mild variable decelerations, and the fetal heart rate baseline increased to 180 beats per minute (BPM). With complete dilation, the patient initiated pushing. During the first several pushes, the EFM demonstrated an initial heart rate deceleration, and a loss of signal, but the heart rate returned to a baseline rate of 150 BPM. With the patient’s continued pushing efforts, the EFM baseline increased to 180 BPM, with evidence of variable decelerations to a nadir of 120 BPM, although with some signal gaps (FIGURE 1, red arrow). The tracing then appeared to have a baseline of 120 BPM with variability or accelerations (FIGURE 1, green arrow) before shifting again to 170 to 180 BPM.

What was happening?

Why does the EFM record the maternal heart rate?

Most commonly, EFM recording of the maternal heart rate occurs during the second stage of labor. Early in labor, the normal fetal heart rate (110–160 BPM) typically exceeds the basal maternal heart rate. However, in the presence of chorioamnionitis and maternal fever or with the stress of maternal pushing, the maternal heart rate frequently approaches or exceeds that of the fetal heart rate. The maximum maternal heart rate can be estimated as 220 BPM minus the maternal age. Thus, the heart rate in a 20-year-old gravida may reach rates of 160 to 180 BPM, equivalent to 80% to 90% of her maximum heart rate during second-stage pushing.

The external Doppler fetal monitor, having a somewhat narrow acoustic window, may lose the focus on the fetal heart as a result of descent of the baby, the abdominal shape-altering effect of uterine contractions, and the patient’s pushing. During the second stage, the EFM may record the maternal heart rate from the uterine arteries. Although some clinicians claim to differentiate the maternal from the fetal heart rate by the “whooshing” maternal uterine artery signal as compared with the “thumping” fetal heart rate signal, this auditory assessment is unproven and likely unreliable.

CASE 1 Problem recognized and addressed

In this case, the obstetrician recognized that “slipping” from the fetal to the maternal heart rate recording occurred with the onset of maternal pushing. After the pushing ceased, the maternal heart rate slipped back to the fetal heart rate. With the next several contractions, only the maternal heart rate was recorded. A fetal scalp electrode was then placed, and fetal variable decelerations were recognized. In view of the category II EFM recording, a vacuum procedure was performed from +3 station and a female infant was delivered. She had Apgar scores of 6 and 8 at 1 and 5 minutes, respectively, and she did well in the nursery.

Read what happened in Case 2 when the EFM demonstrated breaks in the tracing

CASE 2 EFM tracings belie the clinical situation

A 20-year-old woman (G1P0) presented for induction of labor at 41 weeks’ gestation. Continuous EFM recording was initiated, and the patient was given dinoprostone and, subsequently, oxytocin. Rupture of membranes at 3 cm demonstrated a small amount of fluid with thick meconium. The patient progressed to complete dilation and developed a temperature of 38.5°C; the EFM baseline increased to 180 BPM. Throughout the first hour of the second stage of labor, the EFM demonstrated breaks in the tracing and a heart rate of 130 to 150 BPM with each pushing effort (FIGURE 2A). The Doppler monitor was subsequently adjusted to focus on the fetal heart and repetitive late decelerations were observed (FIGURE 2B). An emergent cesarean delivery was performed. A depressed newborn male was delivered, with Apgar scores of 2 and 4 at 1 and 5 minutes, respectively, and significant metabolic acidosis.

What happened?

Fetal versus maternal responses to pushing

The fetal variable deceleration pattern is well recognized by clinicians. As a result of umbilical cord occlusion (due to compression, stretching, or twisting of the cord), fetal variable decelerations have a typical pattern. An initial acceleration shoulder resulting from umbilical vein occlusion (due to reduced venous return) is followed by an umbilical artery occlusion–induced sharp deceleration. The relief of the occlusion allows the sharp return toward baseline with the secondary shoulder overshoot.

In some cases, partial umbilical cord occlusion that affects only the fetal umbilical vein may result in an acceleration, although these usually resolve or evolve into variable decelerations within 30 minutes. By contrast, the maternal heart rate typically increases with contractions and with maternal pushing efforts. Thus, a repetitive pattern of heart rate accelerations with each contraction should warn of a possible maternal heart rate recording.

How maternal heart rate responds to pushing. Maternal pushing is a Valsalva maneuver. Although there are 4 classic cardiovascular phases of Valsalva responses, the typical maternal pushing effort results in an increase in the maternal heart rate. With the common sequence of three 10-second pushes during each contraction, the maternal heart rate often exhibits 3 acceleration and deceleration responses. The maternal heart rate tracing looks similar to the shape of the Three Sisters mountain peaks in Oregon (FIGURE 3). Due to Valsalva physiology, the 3 peaks of the Sisters mirror the 3 uterine wave form peaks, although with a 5- to 10-second delay in the heart rate responses (mountain peaks) from the pushing efforts.

Pre- and postcontraction changes offer clues. Several classic findings aid in differentiating the maternal from the fetal heart rate. If the tracing is maternal, typically the heart rate gradually decreases following the end of the contraction/pushing and continues to decrease until the start of the next contraction/pushing, at which time it increases. During the push, the Three Sisters wave form, with the 5- to 10-second offset, should alert the clinician to possible maternal heart rate recordings. By contrast, the fetal heart rate variable deceleration typically increases following the end of the maternal contraction/pushing and is either stable or increases further (variable with slow recovery) prior to the next uterine contraction/pushing effort. These differences in the patterns of precontraction and postcontraction changes can be very valuable in differentiating periods of maternal versus fetal heart rate recordings.

With “slipping” between fetal and maternal recording, it is not uncommon to record fetal heart rate between contractions, slip to the maternal heart rate during the pushing effort, and return again to the fetal heart rate with the end of the contraction. When confounded with the potential for other EFM artifacts, including doubling of a low maternal or fetal heart rate, or halving of a tachycardic signal, it is not surprising that it is challenging to recognize an EFM maternal heart rate recording.

CASE 2 Check the monitor for accurate focus

A retrospective analysis of this case revealed that the maternal heart rate was recorded with each contraction throughout the second stage. The actual fetal heart rate pattern of decelerations was revealed with the refocusing of the Doppler monitor.

Read how subtle slipping manifested in the EFM tracing of Case 3

CASE 3 Low fetal heart rate and variability during contractions

A 22-year-old woman (G2P1) in spontaneous labor at term progressed to complete dilation. Fetal heart rate accelerations occurred for approximately 30 minutes. With the advent of pushing, the fetal heart rate showed a rate of 130 to 140 BPM and mild decelerations with each contraction (FIGURE 4A). As the second stage progressed, the tracing demonstrated an undulating baseline heart rate between 100 and 130 BPM with possible variability during contractions (FIGURE 4B). This pattern continued for an additional 60 minutes. At vaginal delivery, the ObGyn was surprised to deliver a depressed newborn with Apgar scores of 1 and 3 at 1 and 5 minutes, respectively.

Slipping from the fetal to the maternal heart rate may be imperceptible

In contrast to the breaks in the tracings seen in Case 1 and Case 2, the EFM tracing in Case 3 appears continuous. Yet, slipping from the fetal to the maternal recording was occurring.

As seen in FIGURE 4C, the maternal heart rate with variability was recorded during pushing efforts, and the fetal heart rate was seen rising back toward a baseline between contractions. Note that the fetal heart rate did not reach a level baseline, but rather decelerated with the next contraction. The slipping to the maternal heart rate occurred without a perceptible break in the recording, making this tracing extremely difficult to interpret.

CASE 3 Be ever vigilant

The lack of recognition that the EFM recording had slipped to the maternal heart rate resulted in fetal and newborn hypoxia and acidosis, accounting for the infant’s low Apgar scores.

Read how using 3 steps can help you distinguish fetal from maternal heart rate patterns

Follow 3 steps to discern fetal vs maternal heart rate

These cases illustrate the difficulties in recognizing maternal heart rate patterns on the fetal monitor tracing. The 3 simple steps described below can aid in differentiating maternal from fetal heart rate patterns.

1 Be aware and alert

Recognize that EFM monitoring of the maternal heart rate may occur during periods of monitoring, particularly in second-stage labor. Often, the recorded tracing is a mix of fetal and maternal patterns. Remember that the maternal heart rate may increase markedly during the second stage and rise even higher during pushing efforts. When presented with a tracing that ostensibly represents the fetus, it may be challenging for the clinician to question that assumption. Thus, be aware that tracings may not represent what they seem to be.

Often, clinicians view only the 10-minute portion of the tracing displayed on the monitor screen. I recommend, however, that clinicians review the tracing over the past 30 to 60 minutes, or since their last EFM assessment, for an understanding of the recent fetal baseline heart rate and decelerations.

2 Investigate

Although it is sometimes challenging to recognize EFM maternal heart rate recordings, this is relatively easy to investigate. Even without a pulse oximeter in place, carefully examine the EFM recording for maternal signs to determine if the maternal heart rate is within the range of the recording. You can confirm that the recording is maternal through 1 of 3 easy measures:

• First, check the maternal radial pulse and correlate it with the heart rate baseline.
• Second, place a maternal electrocardiographic (EKG) heart rate monitor.
• Last, and often the simplest approach for continuous tracings, place a finger pulse oximeter to provide a continuous maternal pulse reading. Should the maternal heart rate superimpose on the EFM recording, maternal patterns are likely being detected. However, since the pulse oximeter and EFM Doppler devices use different technologies, they will provide similar—but not precisely identical—heart rate numerical readings if both are assessing the maternal heart rate. In that case, take steps to assure that the EFM truly is recording the fetal heart rate.

3 Treat and correct

If the EFM is recording a maternal signal or if a significant question remains, place a fetal scalp electrode (unless contraindicated), as this may likely occur during the second stage. Alternatively, place a maternal surface fetal EKG monitor, or use ultrasonography to visually assess the fetal heart rate in real time.

Key point summary

The use of a maternal finger pulse oximeter, combined with a careful assessment of the EFM tracing, and/or a fetal scalp electrode are appropriate measures for confirming a fetal heart rate recording.

The 3 steps described (be aware and alert, investigate, treat and correct) can help you effectively monitor the fetal heart rate and avoid the potentially dangerous outcomes that might occur when the maternal heart rate masquerades as the fetal heart rate.

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Continuous electronic fetal heart rate monitoring (EFM) is used in the vast majority of all labors in the United States. With the use of EFM categories and definitions from the American College of Obstetricians and Gynecologists, the National Institutes of Health, and the Society for Maternal-Fetal Medicine, clinicians can now better define and communicate tracing assessments. Except for reducing neonatal seizure activity, however, EFM use during labor has not been demonstrated to significantly improve fetal and neonatal outcomes, yet EFM is associated with an increase in cesarean deliveries and instrument-assisted vaginal births.¹

The negative predictive value of EFM for fetal hypoxia/acidosis is high, but its positive predictive value is only 30%, and the false-positive rate is as high as 60%.² Although a false-positive assessment may result in a potentially unnecessary operative vaginal or cesarean delivery, a falsely reassuring strip may produce devastating consequences in the newborn and, not infrequently, medical malpractice liability. One etiology associated with falsely reassuring assessments is that of EFM monitoring of the maternal heart rate and the failure to recognize the tracing as maternal.

In this article, I discuss the mechanisms and periods of labor that often are associated with the maternal heart rate masquerading as the fetal heart rate. I review common EFM patterns associated with the maternal heart rate so as to aid in recognizing the maternal heart rate. In addition, I provide 3 case scenarios that illustrate the simple yet critical steps that clinicians can take to remedy the situation. Being aware of the potential for a maternal heart rate recording, investigating the EFM signals, and correcting the monitoring can help prevent significant morbidity.

CASE 1 EFM shows seesaw decelerations and returns to baseline rate

A 29-year-old woman (G3P2) at 39 weeks’ gestation was admitted to the hospital with spontaneous labor. Continuous EFM external monitoring was initiated. After membranes spontaneously ruptured at 4 cm dilation, an epidural was placed. Throughout the active phase of labor, the fetus demonstrated intermittent mild variable decelerations, and the fetal heart rate baseline increased to 180 beats per minute (BPM). With complete dilation, the patient initiated pushing. During the first several pushes, the EFM demonstrated an initial heart rate deceleration, and a loss of signal, but the heart rate returned to a baseline rate of 150 BPM. With the patient’s continued pushing efforts, the EFM baseline increased to 180 BPM, with evidence of variable decelerations to a nadir of 120 BPM, although with some signal gaps (FIGURE 1, red arrow). The tracing then appeared to have a baseline of 120 BPM with variability or accelerations (FIGURE 1, green arrow) before shifting again to 170 to 180 BPM.

What was happening?

Why does the EFM record the maternal heart rate?

Most commonly, EFM recording of the maternal heart rate occurs during the second stage of labor. Early in labor, the normal fetal heart rate (110–160 BPM) typically exceeds the basal maternal heart rate. However, in the presence of chorioamnionitis and maternal fever or with the stress of maternal pushing, the maternal heart rate frequently approaches or exceeds that of the fetal heart rate. The maximum maternal heart rate can be estimated as 220 BPM minus the maternal age. Thus, the heart rate in a 20-year-old gravida may reach rates of 160 to 180 BPM, equivalent to 80% to 90% of her maximum heart rate during second-stage pushing.

The external Doppler fetal monitor, having a somewhat narrow acoustic window, may lose the focus on the fetal heart as a result of descent of the baby, the abdominal shape-altering effect of uterine contractions, and the patient’s pushing. During the second stage, the EFM may record the maternal heart rate from the uterine arteries. Although some clinicians claim to differentiate the maternal from the fetal heart rate by the “whooshing” maternal uterine artery signal as compared with the “thumping” fetal heart rate signal, this auditory assessment is unproven and likely unreliable.

CASE 1 Problem recognized and addressed

In this case, the obstetrician recognized that “slipping” from the fetal to the maternal heart rate recording occurred with the onset of maternal pushing. After the pushing ceased, the maternal heart rate slipped back to the fetal heart rate. With the next several contractions, only the maternal heart rate was recorded. A fetal scalp electrode was then placed, and fetal variable decelerations were recognized. In view of the category II EFM recording, a vacuum procedure was performed from +3 station and a female infant was delivered. She had Apgar scores of 6 and 8 at 1 and 5 minutes, respectively, and she did well in the nursery.

Read what happened in Case 2 when the EFM demonstrated breaks in the tracing

CASE 2 EFM tracings belie the clinical situation

A 20-year-old woman (G1P0) presented for induction of labor at 41 weeks’ gestation. Continuous EFM recording was initiated, and the patient was given dinoprostone and, subsequently, oxytocin. Rupture of membranes at 3 cm demonstrated a small amount of fluid with thick meconium. The patient progressed to complete dilation and developed a temperature of 38.5°C; the EFM baseline increased to 180 BPM. Throughout the first hour of the second stage of labor, the EFM demonstrated breaks in the tracing and a heart rate of 130 to 150 BPM with each pushing effort (FIGURE 2A). The Doppler monitor was subsequently adjusted to focus on the fetal heart and repetitive late decelerations were observed (FIGURE 2B). An emergent cesarean delivery was performed. A depressed newborn male was delivered, with Apgar scores of 2 and 4 at 1 and 5 minutes, respectively, and significant metabolic acidosis.

What happened?

Fetal versus maternal responses to pushing

The fetal variable deceleration pattern is well recognized by clinicians. As a result of umbilical cord occlusion (due to compression, stretching, or twisting of the cord), fetal variable decelerations have a typical pattern. An initial acceleration shoulder resulting from umbilical vein occlusion (due to reduced venous return) is followed by an umbilical artery occlusion–induced sharp deceleration. The relief of the occlusion allows the sharp return toward baseline with the secondary shoulder overshoot.

In some cases, partial umbilical cord occlusion that affects only the fetal umbilical vein may result in an acceleration, although these usually resolve or evolve into variable decelerations within 30 minutes. By contrast, the maternal heart rate typically increases with contractions and with maternal pushing efforts. Thus, a repetitive pattern of heart rate accelerations with each contraction should warn of a possible maternal heart rate recording.

How maternal heart rate responds to pushing. Maternal pushing is a Valsalva maneuver. Although there are 4 classic cardiovascular phases of Valsalva responses, the typical maternal pushing effort results in an increase in the maternal heart rate. With the common sequence of three 10-second pushes during each contraction, the maternal heart rate often exhibits 3 acceleration and deceleration responses. The maternal heart rate tracing looks similar to the shape of the Three Sisters mountain peaks in Oregon (FIGURE 3). Due to Valsalva physiology, the 3 peaks of the Sisters mirror the 3 uterine wave form peaks, although with a 5- to 10-second delay in the heart rate responses (mountain peaks) from the pushing efforts.

Pre- and postcontraction changes offer clues. Several classic findings aid in differentiating the maternal from the fetal heart rate. If the tracing is maternal, typically the heart rate gradually decreases following the end of the contraction/pushing and continues to decrease until the start of the next contraction/pushing, at which time it increases. During the push, the Three Sisters wave form, with the 5- to 10-second offset, should alert the clinician to possible maternal heart rate recordings. By contrast, the fetal heart rate variable deceleration typically increases following the end of the maternal contraction/pushing and is either stable or increases further (variable with slow recovery) prior to the next uterine contraction/pushing effort. These differences in the patterns of precontraction and postcontraction changes can be very valuable in differentiating periods of maternal versus fetal heart rate recordings.

With “slipping” between fetal and maternal recording, it is not uncommon to record fetal heart rate between contractions, slip to the maternal heart rate during the pushing effort, and return again to the fetal heart rate with the end of the contraction. When confounded with the potential for other EFM artifacts, including doubling of a low maternal or fetal heart rate, or halving of a tachycardic signal, it is not surprising that it is challenging to recognize an EFM maternal heart rate recording.

CASE 2 Check the monitor for accurate focus

A retrospective analysis of this case revealed that the maternal heart rate was recorded with each contraction throughout the second stage. The actual fetal heart rate pattern of decelerations was revealed with the refocusing of the Doppler monitor.

Read how subtle slipping manifested in the EFM tracing of Case 3

CASE 3 Low fetal heart rate and variability during contractions

A 22-year-old woman (G2P1) in spontaneous labor at term progressed to complete dilation. Fetal heart rate accelerations occurred for approximately 30 minutes. With the advent of pushing, the fetal heart rate showed a rate of 130 to 140 BPM and mild decelerations with each contraction (FIGURE 4A). As the second stage progressed, the tracing demonstrated an undulating baseline heart rate between 100 and 130 BPM with possible variability during contractions (FIGURE 4B). This pattern continued for an additional 60 minutes. At vaginal delivery, the ObGyn was surprised to deliver a depressed newborn with Apgar scores of 1 and 3 at 1 and 5 minutes, respectively.

Slipping from the fetal to the maternal heart rate may be imperceptible

In contrast to the breaks in the tracings seen in Case 1 and Case 2, the EFM tracing in Case 3 appears continuous. Yet, slipping from the fetal to the maternal recording was occurring.

As seen in FIGURE 4C, the maternal heart rate with variability was recorded during pushing efforts, and the fetal heart rate was seen rising back toward a baseline between contractions. Note that the fetal heart rate did not reach a level baseline, but rather decelerated with the next contraction. The slipping to the maternal heart rate occurred without a perceptible break in the recording, making this tracing extremely difficult to interpret.

CASE 3 Be ever vigilant

The lack of recognition that the EFM recording had slipped to the maternal heart rate resulted in fetal and newborn hypoxia and acidosis, accounting for the infant’s low Apgar scores.

Read how using 3 steps can help you distinguish fetal from maternal heart rate patterns

Follow 3 steps to discern fetal vs maternal heart rate

These cases illustrate the difficulties in recognizing maternal heart rate patterns on the fetal monitor tracing. The 3 simple steps described below can aid in differentiating maternal from fetal heart rate patterns.

1 Be aware and alert

Recognize that EFM monitoring of the maternal heart rate may occur during periods of monitoring, particularly in second-stage labor. Often, the recorded tracing is a mix of fetal and maternal patterns. Remember that the maternal heart rate may increase markedly during the second stage and rise even higher during pushing efforts. When presented with a tracing that ostensibly represents the fetus, it may be challenging for the clinician to question that assumption. Thus, be aware that tracings may not represent what they seem to be.

Often, clinicians view only the 10-minute portion of the tracing displayed on the monitor screen. I recommend, however, that clinicians review the tracing over the past 30 to 60 minutes, or since their last EFM assessment, for an understanding of the recent fetal baseline heart rate and decelerations.

2 Investigate

Although it is sometimes challenging to recognize EFM maternal heart rate recordings, this is relatively easy to investigate. Even without a pulse oximeter in place, carefully examine the EFM recording for maternal signs to determine if the maternal heart rate is within the range of the recording. You can confirm that the recording is maternal through 1 of 3 easy measures:

• First, check the maternal radial pulse and correlate it with the heart rate baseline.
• Second, place a maternal electrocardiographic (EKG) heart rate monitor.
• Last, and often the simplest approach for continuous tracings, place a finger pulse oximeter to provide a continuous maternal pulse reading. Should the maternal heart rate superimpose on the EFM recording, maternal patterns are likely being detected. However, since the pulse oximeter and EFM Doppler devices use different technologies, they will provide similar—but not precisely identical—heart rate numerical readings if both are assessing the maternal heart rate. In that case, take steps to assure that the EFM truly is recording the fetal heart rate.

3 Treat and correct

If the EFM is recording a maternal signal or if a significant question remains, place a fetal scalp electrode (unless contraindicated), as this may likely occur during the second stage. Alternatively, place a maternal surface fetal EKG monitor, or use ultrasonography to visually assess the fetal heart rate in real time.

Key point summary

The use of a maternal finger pulse oximeter, combined with a careful assessment of the EFM tracing, and/or a fetal scalp electrode are appropriate measures for confirming a fetal heart rate recording.

The 3 steps described (be aware and alert, investigate, treat and correct) can help you effectively monitor the fetal heart rate and avoid the potentially dangerous outcomes that might occur when the maternal heart rate masquerades as the fetal heart rate.

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.

Continuous electronic fetal heart rate monitoring (EFM) is used in the vast majority of all labors in the United States. With the use of EFM categories and definitions from the American College of Obstetricians and Gynecologists, the National Institutes of Health, and the Society for Maternal-Fetal Medicine, clinicians can now better define and communicate tracing assessments. Except for reducing neonatal seizure activity, however, EFM use during labor has not been demonstrated to significantly improve fetal and neonatal outcomes, yet EFM is associated with an increase in cesarean deliveries and instrument-assisted vaginal births.¹

The negative predictive value of EFM for fetal hypoxia/acidosis is high, but its positive predictive value is only 30%, and the false-positive rate is as high as 60%.² Although a false-positive assessment may result in a potentially unnecessary operative vaginal or cesarean delivery, a falsely reassuring strip may produce devastating consequences in the newborn and, not infrequently, medical malpractice liability. One etiology associated with falsely reassuring assessments is that of EFM monitoring of the maternal heart rate and the failure to recognize the tracing as maternal.

In this article, I discuss the mechanisms and periods of labor that often are associated with the maternal heart rate masquerading as the fetal heart rate. I review common EFM patterns associated with the maternal heart rate so as to aid in recognizing the maternal heart rate. In addition, I provide 3 case scenarios that illustrate the simple yet critical steps that clinicians can take to remedy the situation. Being aware of the potential for a maternal heart rate recording, investigating the EFM signals, and correcting the monitoring can help prevent significant morbidity.

CASE 1 EFM shows seesaw decelerations and returns to baseline rate

A 29-year-old woman (G3P2) at 39 weeks’ gestation was admitted to the hospital with spontaneous labor. Continuous EFM external monitoring was initiated. After membranes spontaneously ruptured at 4 cm dilation, an epidural was placed. Throughout the active phase of labor, the fetus demonstrated intermittent mild variable decelerations, and the fetal heart rate baseline increased to 180 beats per minute (BPM). With complete dilation, the patient initiated pushing. During the first several pushes, the EFM demonstrated an initial heart rate deceleration, and a loss of signal, but the heart rate returned to a baseline rate of 150 BPM. With the patient’s continued pushing efforts, the EFM baseline increased to 180 BPM, with evidence of variable decelerations to a nadir of 120 BPM, although with some signal gaps (FIGURE 1, red arrow). The tracing then appeared to have a baseline of 120 BPM with variability or accelerations (FIGURE 1, green arrow) before shifting again to 170 to 180 BPM.

What was happening?

Why does the EFM record the maternal heart rate?

Most commonly, EFM recording of the maternal heart rate occurs during the second stage of labor. Early in labor, the normal fetal heart rate (110–160 BPM) typically exceeds the basal maternal heart rate. However, in the presence of chorioamnionitis and maternal fever or with the stress of maternal pushing, the maternal heart rate frequently approaches or exceeds that of the fetal heart rate. The maximum maternal heart rate can be estimated as 220 BPM minus the maternal age. Thus, the heart rate in a 20-year-old gravida may reach rates of 160 to 180 BPM, equivalent to 80% to 90% of her maximum heart rate during second-stage pushing.

The external Doppler fetal monitor, having a somewhat narrow acoustic window, may lose the focus on the fetal heart as a result of descent of the baby, the abdominal shape-altering effect of uterine contractions, and the patient’s pushing. During the second stage, the EFM may record the maternal heart rate from the uterine arteries. Although some clinicians claim to differentiate the maternal from the fetal heart rate by the “whooshing” maternal uterine artery signal as compared with the “thumping” fetal heart rate signal, this auditory assessment is unproven and likely unreliable.

CASE 1 Problem recognized and addressed

In this case, the obstetrician recognized that “slipping” from the fetal to the maternal heart rate recording occurred with the onset of maternal pushing. After the pushing ceased, the maternal heart rate slipped back to the fetal heart rate. With the next several contractions, only the maternal heart rate was recorded. A fetal scalp electrode was then placed, and fetal variable decelerations were recognized. In view of the category II EFM recording, a vacuum procedure was performed from +3 station and a female infant was delivered. She had Apgar scores of 6 and 8 at 1 and 5 minutes, respectively, and she did well in the nursery.

Read what happened in Case 2 when the EFM demonstrated breaks in the tracing

CASE 2 EFM tracings belie the clinical situation

A 20-year-old woman (G1P0) presented for induction of labor at 41 weeks’ gestation. Continuous EFM recording was initiated, and the patient was given dinoprostone and, subsequently, oxytocin. Rupture of membranes at 3 cm demonstrated a small amount of fluid with thick meconium. The patient progressed to complete dilation and developed a temperature of 38.5°C; the EFM baseline increased to 180 BPM. Throughout the first hour of the second stage of labor, the EFM demonstrated breaks in the tracing and a heart rate of 130 to 150 BPM with each pushing effort (FIGURE 2A). The Doppler monitor was subsequently adjusted to focus on the fetal heart and repetitive late decelerations were observed (FIGURE 2B). An emergent cesarean delivery was performed. A depressed newborn male was delivered, with Apgar scores of 2 and 4 at 1 and 5 minutes, respectively, and significant metabolic acidosis.

What happened?

Fetal versus maternal responses to pushing

The fetal variable deceleration pattern is well recognized by clinicians. As a result of umbilical cord occlusion (due to compression, stretching, or twisting of the cord), fetal variable decelerations have a typical pattern. An initial acceleration shoulder resulting from umbilical vein occlusion (due to reduced venous return) is followed by an umbilical artery occlusion–induced sharp deceleration. The relief of the occlusion allows the sharp return toward baseline with the secondary shoulder overshoot.

In some cases, partial umbilical cord occlusion that affects only the fetal umbilical vein may result in an acceleration, although these usually resolve or evolve into variable decelerations within 30 minutes. By contrast, the maternal heart rate typically increases with contractions and with maternal pushing efforts. Thus, a repetitive pattern of heart rate accelerations with each contraction should warn of a possible maternal heart rate recording.

How maternal heart rate responds to pushing. Maternal pushing is a Valsalva maneuver. Although there are 4 classic cardiovascular phases of Valsalva responses, the typical maternal pushing effort results in an increase in the maternal heart rate. With the common sequence of three 10-second pushes during each contraction, the maternal heart rate often exhibits 3 acceleration and deceleration responses. The maternal heart rate tracing looks similar to the shape of the Three Sisters mountain peaks in Oregon (FIGURE 3). Due to Valsalva physiology, the 3 peaks of the Sisters mirror the 3 uterine wave form peaks, although with a 5- to 10-second delay in the heart rate responses (mountain peaks) from the pushing efforts.

Pre- and postcontraction changes offer clues. Several classic findings aid in differentiating the maternal from the fetal heart rate. If the tracing is maternal, typically the heart rate gradually decreases following the end of the contraction/pushing and continues to decrease until the start of the next contraction/pushing, at which time it increases. During the push, the Three Sisters wave form, with the 5- to 10-second offset, should alert the clinician to possible maternal heart rate recordings. By contrast, the fetal heart rate variable deceleration typically increases following the end of the maternal contraction/pushing and is either stable or increases further (variable with slow recovery) prior to the next uterine contraction/pushing effort. These differences in the patterns of precontraction and postcontraction changes can be very valuable in differentiating periods of maternal versus fetal heart rate recordings.

With “slipping” between fetal and maternal recording, it is not uncommon to record fetal heart rate between contractions, slip to the maternal heart rate during the pushing effort, and return again to the fetal heart rate with the end of the contraction. When confounded with the potential for other EFM artifacts, including doubling of a low maternal or fetal heart rate, or halving of a tachycardic signal, it is not surprising that it is challenging to recognize an EFM maternal heart rate recording.

CASE 2 Check the monitor for accurate focus

A retrospective analysis of this case revealed that the maternal heart rate was recorded with each contraction throughout the second stage. The actual fetal heart rate pattern of decelerations was revealed with the refocusing of the Doppler monitor.

Read how subtle slipping manifested in the EFM tracing of Case 3

CASE 3 Low fetal heart rate and variability during contractions

A 22-year-old woman (G2P1) in spontaneous labor at term progressed to complete dilation. Fetal heart rate accelerations occurred for approximately 30 minutes. With the advent of pushing, the fetal heart rate showed a rate of 130 to 140 BPM and mild decelerations with each contraction (FIGURE 4A). As the second stage progressed, the tracing demonstrated an undulating baseline heart rate between 100 and 130 BPM with possible variability during contractions (FIGURE 4B). This pattern continued for an additional 60 minutes. At vaginal delivery, the ObGyn was surprised to deliver a depressed newborn with Apgar scores of 1 and 3 at 1 and 5 minutes, respectively.

Slipping from the fetal to the maternal heart rate may be imperceptible

In contrast to the breaks in the tracings seen in Case 1 and Case 2, the EFM tracing in Case 3 appears continuous. Yet, slipping from the fetal to the maternal recording was occurring.

As seen in FIGURE 4C, the maternal heart rate with variability was recorded during pushing efforts, and the fetal heart rate was seen rising back toward a baseline between contractions. Note that the fetal heart rate did not reach a level baseline, but rather decelerated with the next contraction. The slipping to the maternal heart rate occurred without a perceptible break in the recording, making this tracing extremely difficult to interpret.

CASE 3 Be ever vigilant

The lack of recognition that the EFM recording had slipped to the maternal heart rate resulted in fetal and newborn hypoxia and acidosis, accounting for the infant’s low Apgar scores.

Read how using 3 steps can help you distinguish fetal from maternal heart rate patterns

Follow 3 steps to discern fetal vs maternal heart rate

These cases illustrate the difficulties in recognizing maternal heart rate patterns on the fetal monitor tracing. The 3 simple steps described below can aid in differentiating maternal from fetal heart rate patterns.

1 Be aware and alert

Recognize that EFM monitoring of the maternal heart rate may occur during periods of monitoring, particularly in second-stage labor. Often, the recorded tracing is a mix of fetal and maternal patterns. Remember that the maternal heart rate may increase markedly during the second stage and rise even higher during pushing efforts. When presented with a tracing that ostensibly represents the fetus, it may be challenging for the clinician to question that assumption. Thus, be aware that tracings may not represent what they seem to be.

Often, clinicians view only the 10-minute portion of the tracing displayed on the monitor screen. I recommend, however, that clinicians review the tracing over the past 30 to 60 minutes, or since their last EFM assessment, for an understanding of the recent fetal baseline heart rate and decelerations.

2 Investigate

Although it is sometimes challenging to recognize EFM maternal heart rate recordings, this is relatively easy to investigate. Even without a pulse oximeter in place, carefully examine the EFM recording for maternal signs to determine if the maternal heart rate is within the range of the recording. You can confirm that the recording is maternal through 1 of 3 easy measures:

• First, check the maternal radial pulse and correlate it with the heart rate baseline.
• Second, place a maternal electrocardiographic (EKG) heart rate monitor.
• Last, and often the simplest approach for continuous tracings, place a finger pulse oximeter to provide a continuous maternal pulse reading. Should the maternal heart rate superimpose on the EFM recording, maternal patterns are likely being detected. However, since the pulse oximeter and EFM Doppler devices use different technologies, they will provide similar—but not precisely identical—heart rate numerical readings if both are assessing the maternal heart rate. In that case, take steps to assure that the EFM truly is recording the fetal heart rate.

3 Treat and correct

If the EFM is recording a maternal signal or if a significant question remains, place a fetal scalp electrode (unless contraindicated), as this may likely occur during the second stage. Alternatively, place a maternal surface fetal EKG monitor, or use ultrasonography to visually assess the fetal heart rate in real time.

Key point summary

The use of a maternal finger pulse oximeter, combined with a careful assessment of the EFM tracing, and/or a fetal scalp electrode are appropriate measures for confirming a fetal heart rate recording.

The 3 steps described (be aware and alert, investigate, treat and correct) can help you effectively monitor the fetal heart rate and avoid the potentially dangerous outcomes that might occur when the maternal heart rate masquerades as the fetal heart rate.

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.

In this Update I highlight 5 interesting investigations on infectious diseases. The first addresses the value of applying prophylactically a negative-pressure wound dressing to prevent surgical site infection (SSI) in obese women having cesarean delivery (CD). The second report assesses the effectiveness of a preoperative vaginal wash in reducing the frequency of postcesarean endometritis. The third investigation examines the role of systemic antibiotics, combined with surgical drainage, for patients who have subcutaneous abscesses ranging in size up to 5 cm. The fourth study presents new information about the major risk factors for Clostridium difficile infections in obstetric patients. The final study presents valuable sobering new data about the risks of congenital Zika virus infection.

Negative-pressure wound therapy after CD shows some benefit in preventing SSI

Yu L, Kronen RJ, Simon LE, Stoll CR, Colditz GA, Tuuli MG. Prophylactic negative-pressure wound therapy after cesarean is associated with reduced risk of surgical site infection: a systematic review and meta-analysis. Am J Obstet Gynecol. 2018;218(2):200-210.e1.

Illustration: Used with permission. Courtesy of KCI, an Acelity Company

Yu and colleagues sought to determine if the prophylactic use of negative-pressure devices, compared with standard wound dressing, was effective in reducing the frequency of SSI after CD.

The authors searched multiple databases and initially identified 161 randomized controlled trials and cohort studies for further assessment. After applying rigorous exclusion criteria, they ultimately selected 9 studies for systematic review and meta-analysis. Six studies were randomized controlled trials (RCTs), 2 were retrospective cohort studies, and 1 was a prospective cohort study. Five studies were considered high quality; 4 were of low quality. 

Details of the study

Several types of negative-pressure devices were used, but the 2 most common were the Prevena incision management system (KCI, San Antonio, Texas) and PICO negative- pressure wound therapy (Smith & Nephew, St. Petersburg, Florida). The majority of patients in all groups were at high risk for wound complications because of obesity.

The primary outcome of interest was the frequency of SSI. Secondary outcomes included dehiscence, seroma, endometritis, a composite measure for all wound complications, and hospital readmission.

The absolute risk of SSI in the intervention group was 5% (95% confidence interval [CI], 2.0%-7.0%) compared with 11% (95% CI, 7.0%-16.0%) in the standard dressing group. The pooled risk ratio was 0.45 (95% CI, 0.31-0.66). The absolute risk reduction was 6% (95% CI, -10.0% to -3.0%), and the number needed to treat was 17.

There were no significant differences in the rate of any of the secondary outcomes other than the composite of all wound complications. This difference was largely accounted for by the difference in the rate of SSI. 

Illustration: Used with permission. Courtesy of KCI, an Acelity Company

How negative-pressure devices aid wound healing

Yu and colleagues explained that negative-pressure devices exert their beneficial effects in various ways, including:

• shrinking the wound  
• inducing cellular stretch
• removing extracellular fluids
• creating a favorable environment for healing
• promoting angiogenesis and neurogenesis.

Multiple studies in nonobstetric patients have shown that prophylactic use of negative-pressure devices is beneficial in reducing the rate of SSI.¹ Yu and colleagues' systematic review and meta-analysis confirms those findings in a high-risk population of women having CD.

Study limitations

Before routinely adopting the use of negative-pressure devices for all women having CD, however, obstetricians should consider the following caveats:  

• The investigations included in the study by Yu and colleagues did not consistently distinguish between scheduled versus unscheduled CDs.
• The reports did not systematically consider other major risk factors for wound complications besides obesity, and they did not control for these confounders in the statistical analyses.
• The studies included in the meta-analysis did not provide full descriptions of other measures that might influence the rate of SSIs, such as timing and selection of prophylactic antibiotics, selection of suture material, preoperative skin preparation, and closure techniques for the deep subcutaneous tissue and skin.
• None of the included studies systematically considered the cost-effectiveness of the negative-pressure devices. This is an important consideration given that the acquisition cost of these devices ranges from $200 to $500.

Read about vaginal cleansing’s effect on post-CD endometritis

Vaginal cleansing before CD lowers risk of postop endometritis

Caissutti C, Saccone G, Zullo F, et al. Vaginal cleansing before cesarean delivery: a systematic review and meta-analysis. Obstet Gynecol. 2017;130(3):527-538.

Photo: Shutterstock

Caissutti and colleagues aimed to determine if cleansing the vagina with an antiseptic solution prior to surgery reduced the frequency of postcesarean endometritis. They included 16 RCTs (4,837 patients) in their systematic review and meta-analysis. The primary outcome was the frequency of postoperative endometritis.

Details of the study

The studies were conducted in several countries and included patients of various socioeconomic classes. Six trials included only patients having a scheduled CD; 9 included both scheduled and unscheduled cesareans; and 1 included only unscheduled cesareans. In 11 studies, povidone-iodine was the antiseptic solution used. Two trials used chlorhexidine diacetate 0.2%, and 1 used chlorhexidine diacetate 0.4%. One trial used metronidazole 0.5% gel, and another used the antiseptic cetrimide, which is a mixture of different quaternary ammonium salts, including cetrimonium bromide.

In all trials, patients received prophylactic antibiotics. The antibiotics were administered prior to the surgical incision in 6 trials; they were given after the umbilical cord was clamped in 6 trials. In 2 trials, the antibiotics were given at varying times, and in the final 2 trials, the timing of antibiotic administration was not reported. Of note, no trials described the method of placenta removal, a factor of considerable significance in influencing the rate of postoperative endometritis.^5,6

Endometritis frequency reduced with vaginal cleansing; benefit greater in certain groups. Overall, in the 15 trials in which vaginal cleansing was compared with placebo or with no treatment, women in the treatment group had a significantly lower rate of endometritis (4.5% compared with 8.8%; relative risk [RR], 0.52; 95% CI, 0.37-0.72). When only women in labor were considered, the frequency of endometritis was 8.1% in the intervention group compared with 13.8% in the control group (RR, 0.52; 95% CI, 0.28-0.97). In the women who were not in labor, the difference in the incidence of endometritis was not statistically significant (3.5% vs 6.6%; RR, 0.62; 95% CI, 0.34-1.15).

In the subgroup analysis of women with ruptured membranes at the time of surgery, the incidence of endometritis was 4.3% in the treatment group compared with 20.1% in the control group (RR, 0.23; 95% CI, 0.10-0.52). In women with intact membranes at the time of surgery, the incidence of endometritis was not significantly reduced in the treatment group.

Interestingly, in the subgroup analysis of the 10 trials that used povidone-iodine, the reduction in the frequency of postcesarean endometritis was statistically significant (2.8% vs 6.3%; RR, 0.42; 95% CI, 0.25-0.71). However, this same protective effect was not observed in the women treated with chlorhexidine. In the 1 trial that directly compared povidone-iodine with chlorhexidine, there was no statistically significant difference in outcome.

Simple intervention, solid benefit

Endometritis is the most common complication following CD. The infection is polymicrobial, with mixed aerobic and anaerobic organisms. The principal risk factors for postcesarean endometritis are low socioeconomic status, extended duration of labor and ruptured membranes, multiple vaginal examinations, internal fetal monitoring, and pre-existing vaginal infections (principally, bacterial vaginosis and group B streptococcal colonization).

Two interventions are clearly of value in reducing the incidence of endometritis: administration of prophylactic antibiotics prior to the surgical incision and removal of the placenta by traction on the cord as opposed to manual extraction.^5,6

The assessment by Caissutti and colleagues confirms that a third measure — preoperative vaginal cleansing — also helps reduce the incidence of postcesarean endometritis. The principal benefit is seen in women who have been in labor with ruptured membranes, although certainly it is not harmful in lower-risk patients. The intervention is simple and straightforward: a 30-second vaginal wash with a povidone-iodine solution just prior to surgery.

Read about management approaches for skin abscesses

Treat smaller skin abscesses with antibiotics after surgical drainage? Yes.

Daum RS, Miller LG, Immergluck L, et al; for the DMID 07-0051 Team. A placebo-controlled trial of antibiotics for smaller skin abscesses. N Engl J Med. 2017;376(26):2545-2555.

Photo: Shutterstock

For treatment of subcutaneous abscesses that were 5 cm or smaller in diameter, investigators sought to determine if surgical drainage alone was equivalent to surgical drainage plus systemic antibiotics. After their abscess was drained, patients were randomly assigned to receive either clindamycin (300 mg 3 times daily) or trimethoprim-sulfamethoxazole (80 mg/400 mg twice daily) or placebo for 10 days. The primary outcome was clinical cure 7 to 10 days after treatment.

Details of the study

Daum and colleagues enrolled 786 participants (505 adults, 281 children) in the prospective double-blind study. Staphylococcus aureus was isolated from 527 patients (67.0%); methicillin-resistant S aureus (MRSA) was isolated from 388 (49.4%). The cure rate was similar in patients in the clindamycin group (83.1%) and the trimethoprim-sulfamethoxazole group (81.7%), and the cure rate in each antibiotic group was significantly higher than that in the placebo group (68.9%; P<.001 for both comparisons). The difference in treatment effect was specifically limited to patients who had S aureus isolated from their lesions.

Findings at follow-up. At 1 month of  follow-up, new infections were less common in the clindamycin group (6.8%) than in the trimethoprim-sulfamethoxazole group (13.5%; P = .03) or the placebo group (12.4%; P = .06). However, the highest frequency of adverse effects occurred in the patients who received clindamycin (21.9% vs 11.1% vs 12.5%). No adverse effects were judged to be serious, and all resolved without sequela.

Controversy remains on antibiotic use after drainage

This study is important for 2 major reasons. First, soft tissue infections are quite commonand can evolve into serious problems, especially when the offending pathogen is MRSA. Second, controversy exists about whether systemic antibiotics are indicated if the subcutaneous abscess is relatively small and is adequately drained. For example, Talan and colleagues demonstrated that, in settings with a high prevalence of MRSA, surgical drainage combined with trimethoprim-sulfamethoxazole (1 double-strength tablet orally twice daily) was superior to drainage plus placebo.⁸ However, Daum and Gold recently debated the issue of drainage plus antibiotics in a case vignette and reached opposite conclusions.⁹

Read how to avoid C difficile infections in pregnant patients

Antibiotic use, common in the obstetric population, raises risk for C difficile infection

Ruiter-Ligeti J, Vincent S, Czuzoj-Shulman N, Abenhaim HA. Risk factors, incidence, and morbidity associated with obstetric Clostridium difficile infection. Obstet Gynecol. 2018;131(2):387-391.

Photo: Shutterstock

The objective of this investigation was to identify risk factors for Clostridium difficile infection (previously termed pseudomembranous enterocolitis) in obstetric patients. The authors performed a retrospective cohort study using information from a large database maintained by the Agency for Healthcare Research and Quality. This database provides information about inpatient hospital stays in the United States, and it is the largest repository of its kind. It includes data from a sample of 1,000 US hospitals.

Details of the study

Ruiter-Ligeti and colleagues reviewed 13,881,592 births during 1999-2013 and identified 2,757 (0.02%) admissions for delivery complicated by C difficile infection, a rate of 20 admissions per 100,000 deliveries per year (95% CI, 19.13-20.62). The rate of admissions with this diagnosis doubled from 1999 (15 per 100,000) to 2013 (30 per 100,000, P<.001).

Among these obstetric patients, the principal risk factors for C difficile infection were older age, multiple gestation, long-term antibiotic use (not precisely defined), and concurrent diagnosis of inflammatory bowel disease. In addition, patients with pyelonephritis, perineal or cesarean wound infections, or pneumonia also were at increased risk, presumably because those patients required longer courses of broad-spectrum antibiotics.

Of additional note, when compared with women who did not have C difficile infection, patients with infection were more likely to develop a thromboembolic event (38.4 per 1,000), paralytic ileus (58.0 per 1,000), sepsis (46.4 per 1,000), and death (8.0 per 1,000).

Be on guard for C difficile infection in antibiotic-treated obstetric patients

C difficile infection is an uncommon but potentially very serious complication of antibiotic therapy. Given that approximately half of all women admitted for delivery are exposed to antibiotics because of prophylaxis for group B streptococcus infection, prophylaxis for CD, and treatment of chorioamnionitis and puerperal endometritis, clinicians constantly need to be vigilant for this complication.¹¹

Affected patients typically present with frequent loose, watery stools and lower abdominal cramping. In severe cases, blood may be present in the stool, and signs of intestinal distention and even acute peritonitis may be evident. The diagnosis can be established by documenting a positive culture or polymerase chain reaction (PCR) assay for C difficile and a positive cytotoxin assay for toxins A and/or B. In addition, if endoscopy is performed, the characteristic gray membranous plaques can be visualized on the rectal and colonic mucosa.¹¹

Discontinue antibiotic therapy. The first step in managing affected patients is to stop all antibiotics, if possible, or at least the one most likely to be the causative agent of C difficile infection. Patients with relatively mild clinical findings should be treated with oral metronidazole, 500 mg every 8 hours for 10 to 14 days. Patients with severe findings should be treated with oral vancomycin, 500 mg every 6 hours, plus IV metronidazole, 500 mg every 8 hours. The more seriously ill patient must be observed carefully for signs of bowel obstruction, intestinal perforation, peritonitis, and sepsis.

Read about pregnancy outcomes and trimester of maternal Zika infection

Danger for birth defects with maternal Zika infection present in all trimesters, but greatest in first

Hoen B, Schaub B, Funk AL, et al. Pregnancy outcomes after ZIKV infection in French territories in the Americas. N Engl J Med. 2018;378(11):985-994.

Photo: Shutterstock

To estimate the risk of congenital neurologic defects associated with Zika virus infection, Hoen and colleagues conducted a prospective cohort study of pregnant women with symptomatic Zika virus infection who were enrolled during March through November 2016 in French Guiana, Guadeloupe, and Martinique. All women had Zika virus infection confirmed by PCR assay.

Details of the study

The investigators reviewed 546 pregnancies, which resulted in the birth of 555 fetuses and infants. Thirty-nine fetuses and neonates (7%; 95% CI, 5.0-9.5) had neurologic and ocular findings known to be associated with Zika virus infection. Of these, 10 pregnancies were terminated, 1 fetus was stillborn, and 28 were live-born.

Microcephaly (defined as head circumference more than 2 SD below the mean) was present in 32 fetuses and infants (5.8%); 9 had severe microcephaly, defined as head circumference more than 3 SD below the mean. Neurologic and ocular abnormalities were more common when maternal infection occurred during the first trimester (24 of 189 fetuses and infants, 12.7%) compared with infection during the second trimester (9 of 252, 3.6%) or third trimester (6 of 114, 5.3%) (P = .001). 

Studies report similar rates of fetal injury

Zika virus infection primarily is caused by a bite from the Aedes aegypti mosquito. The infection also can be transmitted by sexual contact, laboratory accident, and blood transfusion. Eighty percent of infected persons are asymptomatic. In symptomatic patients, the most common clinical manifestations are low-grade fever, a disseminated maculopapular rash, arthralgias, swelling of the hands and feet, and nonpurulent conjunctivitis.

The most ominous manifestation of congenital Zika virus infection is microcephaly. Other important manifestations include lissencephaly, pachygyria, cortical atrophy, ventriculomegaly, subcortical calcifications, ocular abnormalities, and arthrogryposis. Although most of these abnormalities are immediately visible in the neonate, some may not appear until the child is older.

The present study is an excellent complement to 2 recent reports that defined the risk of Zika virus-related fetal injury in patients in the United States and its territories. Based on an analysis of data from the US Zika Pregnancy Registry, Honein and colleagues reported an overall rate of congenital infection of 6%.¹² The rate of fetal injury was 11% when the mother was infected in the first trimester and 0% when the infection occurred in the second or third trimester. The overall rate of infection and the first trimester rate of infection were similar to those reported by Hoen and colleagues.

Conversely, Shapiro-Mendoza and colleagues evaluated rates of infection in US territories (American Samoa, Puerto Rico, and the US Virgin Islands) and observed cases of fetal injury associated with second- and third-trimester maternal infection.¹³ These authors reported an overall rate of infection of 5% and an 8% rate of infection with first-trimester maternal infection. When maternal infection occurred in the second and third trimesters, the rates of fetal injury were 5% and 4%, respectively, figures almost identical to those reported by Hoen and colleagues. Of note, the investigations by Honein and Shapiro-Mendoza included women with both symptomatic and asymptomatic infection. 

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.

In this Update I highlight 5 interesting investigations on infectious diseases. The first addresses the value of applying prophylactically a negative-pressure wound dressing to prevent surgical site infection (SSI) in obese women having cesarean delivery (CD). The second report assesses the effectiveness of a preoperative vaginal wash in reducing the frequency of postcesarean endometritis. The third investigation examines the role of systemic antibiotics, combined with surgical drainage, for patients who have subcutaneous abscesses ranging in size up to 5 cm. The fourth study presents new information about the major risk factors for Clostridium difficile infections in obstetric patients. The final study presents valuable sobering new data about the risks of congenital Zika virus infection.

Negative-pressure wound therapy after CD shows some benefit in preventing SSI

Yu L, Kronen RJ, Simon LE, Stoll CR, Colditz GA, Tuuli MG. Prophylactic negative-pressure wound therapy after cesarean is associated with reduced risk of surgical site infection: a systematic review and meta-analysis. Am J Obstet Gynecol. 2018;218(2):200-210.e1.

Illustration: Used with permission. Courtesy of KCI, an Acelity Company

Yu and colleagues sought to determine if the prophylactic use of negative-pressure devices, compared with standard wound dressing, was effective in reducing the frequency of SSI after CD.

The authors searched multiple databases and initially identified 161 randomized controlled trials and cohort studies for further assessment. After applying rigorous exclusion criteria, they ultimately selected 9 studies for systematic review and meta-analysis. Six studies were randomized controlled trials (RCTs), 2 were retrospective cohort studies, and 1 was a prospective cohort study. Five studies were considered high quality; 4 were of low quality. 

Details of the study

Several types of negative-pressure devices were used, but the 2 most common were the Prevena incision management system (KCI, San Antonio, Texas) and PICO negative- pressure wound therapy (Smith & Nephew, St. Petersburg, Florida). The majority of patients in all groups were at high risk for wound complications because of obesity.

The primary outcome of interest was the frequency of SSI. Secondary outcomes included dehiscence, seroma, endometritis, a composite measure for all wound complications, and hospital readmission.

The absolute risk of SSI in the intervention group was 5% (95% confidence interval [CI], 2.0%-7.0%) compared with 11% (95% CI, 7.0%-16.0%) in the standard dressing group. The pooled risk ratio was 0.45 (95% CI, 0.31-0.66). The absolute risk reduction was 6% (95% CI, -10.0% to -3.0%), and the number needed to treat was 17.

There were no significant differences in the rate of any of the secondary outcomes other than the composite of all wound complications. This difference was largely accounted for by the difference in the rate of SSI. 

Illustration: Used with permission. Courtesy of KCI, an Acelity Company

How negative-pressure devices aid wound healing

Yu and colleagues explained that negative-pressure devices exert their beneficial effects in various ways, including:

• shrinking the wound  
• inducing cellular stretch
• removing extracellular fluids
• creating a favorable environment for healing
• promoting angiogenesis and neurogenesis.

Multiple studies in nonobstetric patients have shown that prophylactic use of negative-pressure devices is beneficial in reducing the rate of SSI.¹ Yu and colleagues' systematic review and meta-analysis confirms those findings in a high-risk population of women having CD.

Study limitations

Before routinely adopting the use of negative-pressure devices for all women having CD, however, obstetricians should consider the following caveats:  

• The investigations included in the study by Yu and colleagues did not consistently distinguish between scheduled versus unscheduled CDs.
• The reports did not systematically consider other major risk factors for wound complications besides obesity, and they did not control for these confounders in the statistical analyses.
• The studies included in the meta-analysis did not provide full descriptions of other measures that might influence the rate of SSIs, such as timing and selection of prophylactic antibiotics, selection of suture material, preoperative skin preparation, and closure techniques for the deep subcutaneous tissue and skin.
• None of the included studies systematically considered the cost-effectiveness of the negative-pressure devices. This is an important consideration given that the acquisition cost of these devices ranges from $200 to $500.

Read about vaginal cleansing’s effect on post-CD endometritis

Vaginal cleansing before CD lowers risk of postop endometritis

Caissutti C, Saccone G, Zullo F, et al. Vaginal cleansing before cesarean delivery: a systematic review and meta-analysis. Obstet Gynecol. 2017;130(3):527-538.

Photo: Shutterstock

Caissutti and colleagues aimed to determine if cleansing the vagina with an antiseptic solution prior to surgery reduced the frequency of postcesarean endometritis. They included 16 RCTs (4,837 patients) in their systematic review and meta-analysis. The primary outcome was the frequency of postoperative endometritis.

Details of the study

The studies were conducted in several countries and included patients of various socioeconomic classes. Six trials included only patients having a scheduled CD; 9 included both scheduled and unscheduled cesareans; and 1 included only unscheduled cesareans. In 11 studies, povidone-iodine was the antiseptic solution used. Two trials used chlorhexidine diacetate 0.2%, and 1 used chlorhexidine diacetate 0.4%. One trial used metronidazole 0.5% gel, and another used the antiseptic cetrimide, which is a mixture of different quaternary ammonium salts, including cetrimonium bromide.

In all trials, patients received prophylactic antibiotics. The antibiotics were administered prior to the surgical incision in 6 trials; they were given after the umbilical cord was clamped in 6 trials. In 2 trials, the antibiotics were given at varying times, and in the final 2 trials, the timing of antibiotic administration was not reported. Of note, no trials described the method of placenta removal, a factor of considerable significance in influencing the rate of postoperative endometritis.^5,6

Endometritis frequency reduced with vaginal cleansing; benefit greater in certain groups. Overall, in the 15 trials in which vaginal cleansing was compared with placebo or with no treatment, women in the treatment group had a significantly lower rate of endometritis (4.5% compared with 8.8%; relative risk [RR], 0.52; 95% CI, 0.37-0.72). When only women in labor were considered, the frequency of endometritis was 8.1% in the intervention group compared with 13.8% in the control group (RR, 0.52; 95% CI, 0.28-0.97). In the women who were not in labor, the difference in the incidence of endometritis was not statistically significant (3.5% vs 6.6%; RR, 0.62; 95% CI, 0.34-1.15).

In the subgroup analysis of women with ruptured membranes at the time of surgery, the incidence of endometritis was 4.3% in the treatment group compared with 20.1% in the control group (RR, 0.23; 95% CI, 0.10-0.52). In women with intact membranes at the time of surgery, the incidence of endometritis was not significantly reduced in the treatment group.

Interestingly, in the subgroup analysis of the 10 trials that used povidone-iodine, the reduction in the frequency of postcesarean endometritis was statistically significant (2.8% vs 6.3%; RR, 0.42; 95% CI, 0.25-0.71). However, this same protective effect was not observed in the women treated with chlorhexidine. In the 1 trial that directly compared povidone-iodine with chlorhexidine, there was no statistically significant difference in outcome.

Simple intervention, solid benefit

Endometritis is the most common complication following CD. The infection is polymicrobial, with mixed aerobic and anaerobic organisms. The principal risk factors for postcesarean endometritis are low socioeconomic status, extended duration of labor and ruptured membranes, multiple vaginal examinations, internal fetal monitoring, and pre-existing vaginal infections (principally, bacterial vaginosis and group B streptococcal colonization).

Two interventions are clearly of value in reducing the incidence of endometritis: administration of prophylactic antibiotics prior to the surgical incision and removal of the placenta by traction on the cord as opposed to manual extraction.^5,6

The assessment by Caissutti and colleagues confirms that a third measure — preoperative vaginal cleansing — also helps reduce the incidence of postcesarean endometritis. The principal benefit is seen in women who have been in labor with ruptured membranes, although certainly it is not harmful in lower-risk patients. The intervention is simple and straightforward: a 30-second vaginal wash with a povidone-iodine solution just prior to surgery.

Read about management approaches for skin abscesses

Treat smaller skin abscesses with antibiotics after surgical drainage? Yes.

Daum RS, Miller LG, Immergluck L, et al; for the DMID 07-0051 Team. A placebo-controlled trial of antibiotics for smaller skin abscesses. N Engl J Med. 2017;376(26):2545-2555.

Photo: Shutterstock

For treatment of subcutaneous abscesses that were 5 cm or smaller in diameter, investigators sought to determine if surgical drainage alone was equivalent to surgical drainage plus systemic antibiotics. After their abscess was drained, patients were randomly assigned to receive either clindamycin (300 mg 3 times daily) or trimethoprim-sulfamethoxazole (80 mg/400 mg twice daily) or placebo for 10 days. The primary outcome was clinical cure 7 to 10 days after treatment.

Details of the study

Daum and colleagues enrolled 786 participants (505 adults, 281 children) in the prospective double-blind study. Staphylococcus aureus was isolated from 527 patients (67.0%); methicillin-resistant S aureus (MRSA) was isolated from 388 (49.4%). The cure rate was similar in patients in the clindamycin group (83.1%) and the trimethoprim-sulfamethoxazole group (81.7%), and the cure rate in each antibiotic group was significantly higher than that in the placebo group (68.9%; P<.001 for both comparisons). The difference in treatment effect was specifically limited to patients who had S aureus isolated from their lesions.

Findings at follow-up. At 1 month of  follow-up, new infections were less common in the clindamycin group (6.8%) than in the trimethoprim-sulfamethoxazole group (13.5%; P = .03) or the placebo group (12.4%; P = .06). However, the highest frequency of adverse effects occurred in the patients who received clindamycin (21.9% vs 11.1% vs 12.5%). No adverse effects were judged to be serious, and all resolved without sequela.

Controversy remains on antibiotic use after drainage

This study is important for 2 major reasons. First, soft tissue infections are quite commonand can evolve into serious problems, especially when the offending pathogen is MRSA. Second, controversy exists about whether systemic antibiotics are indicated if the subcutaneous abscess is relatively small and is adequately drained. For example, Talan and colleagues demonstrated that, in settings with a high prevalence of MRSA, surgical drainage combined with trimethoprim-sulfamethoxazole (1 double-strength tablet orally twice daily) was superior to drainage plus placebo.⁸ However, Daum and Gold recently debated the issue of drainage plus antibiotics in a case vignette and reached opposite conclusions.⁹

Read how to avoid C difficile infections in pregnant patients

Antibiotic use, common in the obstetric population, raises risk for C difficile infection

Ruiter-Ligeti J, Vincent S, Czuzoj-Shulman N, Abenhaim HA. Risk factors, incidence, and morbidity associated with obstetric Clostridium difficile infection. Obstet Gynecol. 2018;131(2):387-391.

Photo: Shutterstock

The objective of this investigation was to identify risk factors for Clostridium difficile infection (previously termed pseudomembranous enterocolitis) in obstetric patients. The authors performed a retrospective cohort study using information from a large database maintained by the Agency for Healthcare Research and Quality. This database provides information about inpatient hospital stays in the United States, and it is the largest repository of its kind. It includes data from a sample of 1,000 US hospitals.

Details of the study

Ruiter-Ligeti and colleagues reviewed 13,881,592 births during 1999-2013 and identified 2,757 (0.02%) admissions for delivery complicated by C difficile infection, a rate of 20 admissions per 100,000 deliveries per year (95% CI, 19.13-20.62). The rate of admissions with this diagnosis doubled from 1999 (15 per 100,000) to 2013 (30 per 100,000, P<.001).

Among these obstetric patients, the principal risk factors for C difficile infection were older age, multiple gestation, long-term antibiotic use (not precisely defined), and concurrent diagnosis of inflammatory bowel disease. In addition, patients with pyelonephritis, perineal or cesarean wound infections, or pneumonia also were at increased risk, presumably because those patients required longer courses of broad-spectrum antibiotics.

Of additional note, when compared with women who did not have C difficile infection, patients with infection were more likely to develop a thromboembolic event (38.4 per 1,000), paralytic ileus (58.0 per 1,000), sepsis (46.4 per 1,000), and death (8.0 per 1,000).

Be on guard for C difficile infection in antibiotic-treated obstetric patients

C difficile infection is an uncommon but potentially very serious complication of antibiotic therapy. Given that approximately half of all women admitted for delivery are exposed to antibiotics because of prophylaxis for group B streptococcus infection, prophylaxis for CD, and treatment of chorioamnionitis and puerperal endometritis, clinicians constantly need to be vigilant for this complication.¹¹

Affected patients typically present with frequent loose, watery stools and lower abdominal cramping. In severe cases, blood may be present in the stool, and signs of intestinal distention and even acute peritonitis may be evident. The diagnosis can be established by documenting a positive culture or polymerase chain reaction (PCR) assay for C difficile and a positive cytotoxin assay for toxins A and/or B. In addition, if endoscopy is performed, the characteristic gray membranous plaques can be visualized on the rectal and colonic mucosa.¹¹

Discontinue antibiotic therapy. The first step in managing affected patients is to stop all antibiotics, if possible, or at least the one most likely to be the causative agent of C difficile infection. Patients with relatively mild clinical findings should be treated with oral metronidazole, 500 mg every 8 hours for 10 to 14 days. Patients with severe findings should be treated with oral vancomycin, 500 mg every 6 hours, plus IV metronidazole, 500 mg every 8 hours. The more seriously ill patient must be observed carefully for signs of bowel obstruction, intestinal perforation, peritonitis, and sepsis.

Read about pregnancy outcomes and trimester of maternal Zika infection

Danger for birth defects with maternal Zika infection present in all trimesters, but greatest in first

Hoen B, Schaub B, Funk AL, et al. Pregnancy outcomes after ZIKV infection in French territories in the Americas. N Engl J Med. 2018;378(11):985-994.

Photo: Shutterstock

To estimate the risk of congenital neurologic defects associated with Zika virus infection, Hoen and colleagues conducted a prospective cohort study of pregnant women with symptomatic Zika virus infection who were enrolled during March through November 2016 in French Guiana, Guadeloupe, and Martinique. All women had Zika virus infection confirmed by PCR assay.

Details of the study

The investigators reviewed 546 pregnancies, which resulted in the birth of 555 fetuses and infants. Thirty-nine fetuses and neonates (7%; 95% CI, 5.0-9.5) had neurologic and ocular findings known to be associated with Zika virus infection. Of these, 10 pregnancies were terminated, 1 fetus was stillborn, and 28 were live-born.

Microcephaly (defined as head circumference more than 2 SD below the mean) was present in 32 fetuses and infants (5.8%); 9 had severe microcephaly, defined as head circumference more than 3 SD below the mean. Neurologic and ocular abnormalities were more common when maternal infection occurred during the first trimester (24 of 189 fetuses and infants, 12.7%) compared with infection during the second trimester (9 of 252, 3.6%) or third trimester (6 of 114, 5.3%) (P = .001). 

Studies report similar rates of fetal injury

Zika virus infection primarily is caused by a bite from the Aedes aegypti mosquito. The infection also can be transmitted by sexual contact, laboratory accident, and blood transfusion. Eighty percent of infected persons are asymptomatic. In symptomatic patients, the most common clinical manifestations are low-grade fever, a disseminated maculopapular rash, arthralgias, swelling of the hands and feet, and nonpurulent conjunctivitis.

The most ominous manifestation of congenital Zika virus infection is microcephaly. Other important manifestations include lissencephaly, pachygyria, cortical atrophy, ventriculomegaly, subcortical calcifications, ocular abnormalities, and arthrogryposis. Although most of these abnormalities are immediately visible in the neonate, some may not appear until the child is older.

The present study is an excellent complement to 2 recent reports that defined the risk of Zika virus-related fetal injury in patients in the United States and its territories. Based on an analysis of data from the US Zika Pregnancy Registry, Honein and colleagues reported an overall rate of congenital infection of 6%.¹² The rate of fetal injury was 11% when the mother was infected in the first trimester and 0% when the infection occurred in the second or third trimester. The overall rate of infection and the first trimester rate of infection were similar to those reported by Hoen and colleagues.

Conversely, Shapiro-Mendoza and colleagues evaluated rates of infection in US territories (American Samoa, Puerto Rico, and the US Virgin Islands) and observed cases of fetal injury associated with second- and third-trimester maternal infection.¹³ These authors reported an overall rate of infection of 5% and an 8% rate of infection with first-trimester maternal infection. When maternal infection occurred in the second and third trimesters, the rates of fetal injury were 5% and 4%, respectively, figures almost identical to those reported by Hoen and colleagues. Of note, the investigations by Honein and Shapiro-Mendoza included women with both symptomatic and asymptomatic infection. 

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.

In this Update I highlight 5 interesting investigations on infectious diseases. The first addresses the value of applying prophylactically a negative-pressure wound dressing to prevent surgical site infection (SSI) in obese women having cesarean delivery (CD). The second report assesses the effectiveness of a preoperative vaginal wash in reducing the frequency of postcesarean endometritis. The third investigation examines the role of systemic antibiotics, combined with surgical drainage, for patients who have subcutaneous abscesses ranging in size up to 5 cm. The fourth study presents new information about the major risk factors for Clostridium difficile infections in obstetric patients. The final study presents valuable sobering new data about the risks of congenital Zika virus infection.

Negative-pressure wound therapy after CD shows some benefit in preventing SSI

Yu L, Kronen RJ, Simon LE, Stoll CR, Colditz GA, Tuuli MG. Prophylactic negative-pressure wound therapy after cesarean is associated with reduced risk of surgical site infection: a systematic review and meta-analysis. Am J Obstet Gynecol. 2018;218(2):200-210.e1.

Illustration: Used with permission. Courtesy of KCI, an Acelity Company

Yu and colleagues sought to determine if the prophylactic use of negative-pressure devices, compared with standard wound dressing, was effective in reducing the frequency of SSI after CD.

The authors searched multiple databases and initially identified 161 randomized controlled trials and cohort studies for further assessment. After applying rigorous exclusion criteria, they ultimately selected 9 studies for systematic review and meta-analysis. Six studies were randomized controlled trials (RCTs), 2 were retrospective cohort studies, and 1 was a prospective cohort study. Five studies were considered high quality; 4 were of low quality. 

Details of the study

Several types of negative-pressure devices were used, but the 2 most common were the Prevena incision management system (KCI, San Antonio, Texas) and PICO negative- pressure wound therapy (Smith & Nephew, St. Petersburg, Florida). The majority of patients in all groups were at high risk for wound complications because of obesity.

The primary outcome of interest was the frequency of SSI. Secondary outcomes included dehiscence, seroma, endometritis, a composite measure for all wound complications, and hospital readmission.

The absolute risk of SSI in the intervention group was 5% (95% confidence interval [CI], 2.0%-7.0%) compared with 11% (95% CI, 7.0%-16.0%) in the standard dressing group. The pooled risk ratio was 0.45 (95% CI, 0.31-0.66). The absolute risk reduction was 6% (95% CI, -10.0% to -3.0%), and the number needed to treat was 17.

There were no significant differences in the rate of any of the secondary outcomes other than the composite of all wound complications. This difference was largely accounted for by the difference in the rate of SSI. 

Illustration: Used with permission. Courtesy of KCI, an Acelity Company

How negative-pressure devices aid wound healing

Yu and colleagues explained that negative-pressure devices exert their beneficial effects in various ways, including:

• shrinking the wound  
• inducing cellular stretch
• removing extracellular fluids
• creating a favorable environment for healing
• promoting angiogenesis and neurogenesis.

Multiple studies in nonobstetric patients have shown that prophylactic use of negative-pressure devices is beneficial in reducing the rate of SSI.¹ Yu and colleagues' systematic review and meta-analysis confirms those findings in a high-risk population of women having CD.

Study limitations

Before routinely adopting the use of negative-pressure devices for all women having CD, however, obstetricians should consider the following caveats:  

• The investigations included in the study by Yu and colleagues did not consistently distinguish between scheduled versus unscheduled CDs.
• The reports did not systematically consider other major risk factors for wound complications besides obesity, and they did not control for these confounders in the statistical analyses.
• The studies included in the meta-analysis did not provide full descriptions of other measures that might influence the rate of SSIs, such as timing and selection of prophylactic antibiotics, selection of suture material, preoperative skin preparation, and closure techniques for the deep subcutaneous tissue and skin.
• None of the included studies systematically considered the cost-effectiveness of the negative-pressure devices. This is an important consideration given that the acquisition cost of these devices ranges from $200 to $500.

Read about vaginal cleansing’s effect on post-CD endometritis

Vaginal cleansing before CD lowers risk of postop endometritis

Caissutti C, Saccone G, Zullo F, et al. Vaginal cleansing before cesarean delivery: a systematic review and meta-analysis. Obstet Gynecol. 2017;130(3):527-538.

Photo: Shutterstock

Caissutti and colleagues aimed to determine if cleansing the vagina with an antiseptic solution prior to surgery reduced the frequency of postcesarean endometritis. They included 16 RCTs (4,837 patients) in their systematic review and meta-analysis. The primary outcome was the frequency of postoperative endometritis.

Details of the study

The studies were conducted in several countries and included patients of various socioeconomic classes. Six trials included only patients having a scheduled CD; 9 included both scheduled and unscheduled cesareans; and 1 included only unscheduled cesareans. In 11 studies, povidone-iodine was the antiseptic solution used. Two trials used chlorhexidine diacetate 0.2%, and 1 used chlorhexidine diacetate 0.4%. One trial used metronidazole 0.5% gel, and another used the antiseptic cetrimide, which is a mixture of different quaternary ammonium salts, including cetrimonium bromide.

In all trials, patients received prophylactic antibiotics. The antibiotics were administered prior to the surgical incision in 6 trials; they were given after the umbilical cord was clamped in 6 trials. In 2 trials, the antibiotics were given at varying times, and in the final 2 trials, the timing of antibiotic administration was not reported. Of note, no trials described the method of placenta removal, a factor of considerable significance in influencing the rate of postoperative endometritis.^5,6

Endometritis frequency reduced with vaginal cleansing; benefit greater in certain groups. Overall, in the 15 trials in which vaginal cleansing was compared with placebo or with no treatment, women in the treatment group had a significantly lower rate of endometritis (4.5% compared with 8.8%; relative risk [RR], 0.52; 95% CI, 0.37-0.72). When only women in labor were considered, the frequency of endometritis was 8.1% in the intervention group compared with 13.8% in the control group (RR, 0.52; 95% CI, 0.28-0.97). In the women who were not in labor, the difference in the incidence of endometritis was not statistically significant (3.5% vs 6.6%; RR, 0.62; 95% CI, 0.34-1.15).

In the subgroup analysis of women with ruptured membranes at the time of surgery, the incidence of endometritis was 4.3% in the treatment group compared with 20.1% in the control group (RR, 0.23; 95% CI, 0.10-0.52). In women with intact membranes at the time of surgery, the incidence of endometritis was not significantly reduced in the treatment group.

Interestingly, in the subgroup analysis of the 10 trials that used povidone-iodine, the reduction in the frequency of postcesarean endometritis was statistically significant (2.8% vs 6.3%; RR, 0.42; 95% CI, 0.25-0.71). However, this same protective effect was not observed in the women treated with chlorhexidine. In the 1 trial that directly compared povidone-iodine with chlorhexidine, there was no statistically significant difference in outcome.

Simple intervention, solid benefit

Endometritis is the most common complication following CD. The infection is polymicrobial, with mixed aerobic and anaerobic organisms. The principal risk factors for postcesarean endometritis are low socioeconomic status, extended duration of labor and ruptured membranes, multiple vaginal examinations, internal fetal monitoring, and pre-existing vaginal infections (principally, bacterial vaginosis and group B streptococcal colonization).

Two interventions are clearly of value in reducing the incidence of endometritis: administration of prophylactic antibiotics prior to the surgical incision and removal of the placenta by traction on the cord as opposed to manual extraction.^5,6

The assessment by Caissutti and colleagues confirms that a third measure — preoperative vaginal cleansing — also helps reduce the incidence of postcesarean endometritis. The principal benefit is seen in women who have been in labor with ruptured membranes, although certainly it is not harmful in lower-risk patients. The intervention is simple and straightforward: a 30-second vaginal wash with a povidone-iodine solution just prior to surgery.

Read about management approaches for skin abscesses

Treat smaller skin abscesses with antibiotics after surgical drainage? Yes.

Daum RS, Miller LG, Immergluck L, et al; for the DMID 07-0051 Team. A placebo-controlled trial of antibiotics for smaller skin abscesses. N Engl J Med. 2017;376(26):2545-2555.

Photo: Shutterstock

For treatment of subcutaneous abscesses that were 5 cm or smaller in diameter, investigators sought to determine if surgical drainage alone was equivalent to surgical drainage plus systemic antibiotics. After their abscess was drained, patients were randomly assigned to receive either clindamycin (300 mg 3 times daily) or trimethoprim-sulfamethoxazole (80 mg/400 mg twice daily) or placebo for 10 days. The primary outcome was clinical cure 7 to 10 days after treatment.

Details of the study

Daum and colleagues enrolled 786 participants (505 adults, 281 children) in the prospective double-blind study. Staphylococcus aureus was isolated from 527 patients (67.0%); methicillin-resistant S aureus (MRSA) was isolated from 388 (49.4%). The cure rate was similar in patients in the clindamycin group (83.1%) and the trimethoprim-sulfamethoxazole group (81.7%), and the cure rate in each antibiotic group was significantly higher than that in the placebo group (68.9%; P<.001 for both comparisons). The difference in treatment effect was specifically limited to patients who had S aureus isolated from their lesions.

Findings at follow-up. At 1 month of  follow-up, new infections were less common in the clindamycin group (6.8%) than in the trimethoprim-sulfamethoxazole group (13.5%; P = .03) or the placebo group (12.4%; P = .06). However, the highest frequency of adverse effects occurred in the patients who received clindamycin (21.9% vs 11.1% vs 12.5%). No adverse effects were judged to be serious, and all resolved without sequela.

Controversy remains on antibiotic use after drainage

This study is important for 2 major reasons. First, soft tissue infections are quite commonand can evolve into serious problems, especially when the offending pathogen is MRSA. Second, controversy exists about whether systemic antibiotics are indicated if the subcutaneous abscess is relatively small and is adequately drained. For example, Talan and colleagues demonstrated that, in settings with a high prevalence of MRSA, surgical drainage combined with trimethoprim-sulfamethoxazole (1 double-strength tablet orally twice daily) was superior to drainage plus placebo.⁸ However, Daum and Gold recently debated the issue of drainage plus antibiotics in a case vignette and reached opposite conclusions.⁹

Read how to avoid C difficile infections in pregnant patients

Antibiotic use, common in the obstetric population, raises risk for C difficile infection

Ruiter-Ligeti J, Vincent S, Czuzoj-Shulman N, Abenhaim HA. Risk factors, incidence, and morbidity associated with obstetric Clostridium difficile infection. Obstet Gynecol. 2018;131(2):387-391.

Photo: Shutterstock

The objective of this investigation was to identify risk factors for Clostridium difficile infection (previously termed pseudomembranous enterocolitis) in obstetric patients. The authors performed a retrospective cohort study using information from a large database maintained by the Agency for Healthcare Research and Quality. This database provides information about inpatient hospital stays in the United States, and it is the largest repository of its kind. It includes data from a sample of 1,000 US hospitals.

Details of the study

Ruiter-Ligeti and colleagues reviewed 13,881,592 births during 1999-2013 and identified 2,757 (0.02%) admissions for delivery complicated by C difficile infection, a rate of 20 admissions per 100,000 deliveries per year (95% CI, 19.13-20.62). The rate of admissions with this diagnosis doubled from 1999 (15 per 100,000) to 2013 (30 per 100,000, P<.001).

Among these obstetric patients, the principal risk factors for C difficile infection were older age, multiple gestation, long-term antibiotic use (not precisely defined), and concurrent diagnosis of inflammatory bowel disease. In addition, patients with pyelonephritis, perineal or cesarean wound infections, or pneumonia also were at increased risk, presumably because those patients required longer courses of broad-spectrum antibiotics.

Of additional note, when compared with women who did not have C difficile infection, patients with infection were more likely to develop a thromboembolic event (38.4 per 1,000), paralytic ileus (58.0 per 1,000), sepsis (46.4 per 1,000), and death (8.0 per 1,000).

Be on guard for C difficile infection in antibiotic-treated obstetric patients

C difficile infection is an uncommon but potentially very serious complication of antibiotic therapy. Given that approximately half of all women admitted for delivery are exposed to antibiotics because of prophylaxis for group B streptococcus infection, prophylaxis for CD, and treatment of chorioamnionitis and puerperal endometritis, clinicians constantly need to be vigilant for this complication.¹¹

Affected patients typically present with frequent loose, watery stools and lower abdominal cramping. In severe cases, blood may be present in the stool, and signs of intestinal distention and even acute peritonitis may be evident. The diagnosis can be established by documenting a positive culture or polymerase chain reaction (PCR) assay for C difficile and a positive cytotoxin assay for toxins A and/or B. In addition, if endoscopy is performed, the characteristic gray membranous plaques can be visualized on the rectal and colonic mucosa.¹¹

Discontinue antibiotic therapy. The first step in managing affected patients is to stop all antibiotics, if possible, or at least the one most likely to be the causative agent of C difficile infection. Patients with relatively mild clinical findings should be treated with oral metronidazole, 500 mg every 8 hours for 10 to 14 days. Patients with severe findings should be treated with oral vancomycin, 500 mg every 6 hours, plus IV metronidazole, 500 mg every 8 hours. The more seriously ill patient must be observed carefully for signs of bowel obstruction, intestinal perforation, peritonitis, and sepsis.

Read about pregnancy outcomes and trimester of maternal Zika infection

Danger for birth defects with maternal Zika infection present in all trimesters, but greatest in first

Hoen B, Schaub B, Funk AL, et al. Pregnancy outcomes after ZIKV infection in French territories in the Americas. N Engl J Med. 2018;378(11):985-994.

Photo: Shutterstock

To estimate the risk of congenital neurologic defects associated with Zika virus infection, Hoen and colleagues conducted a prospective cohort study of pregnant women with symptomatic Zika virus infection who were enrolled during March through November 2016 in French Guiana, Guadeloupe, and Martinique. All women had Zika virus infection confirmed by PCR assay.

Details of the study

The investigators reviewed 546 pregnancies, which resulted in the birth of 555 fetuses and infants. Thirty-nine fetuses and neonates (7%; 95% CI, 5.0-9.5) had neurologic and ocular findings known to be associated with Zika virus infection. Of these, 10 pregnancies were terminated, 1 fetus was stillborn, and 28 were live-born.

Microcephaly (defined as head circumference more than 2 SD below the mean) was present in 32 fetuses and infants (5.8%); 9 had severe microcephaly, defined as head circumference more than 3 SD below the mean. Neurologic and ocular abnormalities were more common when maternal infection occurred during the first trimester (24 of 189 fetuses and infants, 12.7%) compared with infection during the second trimester (9 of 252, 3.6%) or third trimester (6 of 114, 5.3%) (P = .001). 

Studies report similar rates of fetal injury

Zika virus infection primarily is caused by a bite from the Aedes aegypti mosquito. The infection also can be transmitted by sexual contact, laboratory accident, and blood transfusion. Eighty percent of infected persons are asymptomatic. In symptomatic patients, the most common clinical manifestations are low-grade fever, a disseminated maculopapular rash, arthralgias, swelling of the hands and feet, and nonpurulent conjunctivitis.

The most ominous manifestation of congenital Zika virus infection is microcephaly. Other important manifestations include lissencephaly, pachygyria, cortical atrophy, ventriculomegaly, subcortical calcifications, ocular abnormalities, and arthrogryposis. Although most of these abnormalities are immediately visible in the neonate, some may not appear until the child is older.

The present study is an excellent complement to 2 recent reports that defined the risk of Zika virus-related fetal injury in patients in the United States and its territories. Based on an analysis of data from the US Zika Pregnancy Registry, Honein and colleagues reported an overall rate of congenital infection of 6%.¹² The rate of fetal injury was 11% when the mother was infected in the first trimester and 0% when the infection occurred in the second or third trimester. The overall rate of infection and the first trimester rate of infection were similar to those reported by Hoen and colleagues.

Conversely, Shapiro-Mendoza and colleagues evaluated rates of infection in US territories (American Samoa, Puerto Rico, and the US Virgin Islands) and observed cases of fetal injury associated with second- and third-trimester maternal infection.¹³ These authors reported an overall rate of infection of 5% and an 8% rate of infection with first-trimester maternal infection. When maternal infection occurred in the second and third trimesters, the rates of fetal injury were 5% and 4%, respectively, figures almost identical to those reported by Hoen and colleagues. Of note, the investigations by Honein and Shapiro-Mendoza included women with both symptomatic and asymptomatic infection. 

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.

Photo: Shutterstock

Despite increasing media coverage of human trafficking and the gravity of its many ramifications, I am struck by how often trainees and other clinicians present to me patients for which trafficking is a real potential concern—yet who give me a blank expression when I ask if anyone has screened these patients for being victims of trafficking. I suspect that few of us anticipated, during medical training, that we would be providing care to women who are enslaved.

How large is the problem?

It is impossible to comprehend the true scope of human trafficking. Estimates are that 20.9 million men, women, and children globally are forced into work that they are not free to leave.¹

Although human trafficking is recognized as a global phenomenon, its prevalence in the United States is significant enough that it should prompt the health care community to engage in helping identify and assist victims/survivors: From January until June of 2017, the National Human Trafficking Hotline received 13,807 telephone calls, resulting in reporting of 4,460 cases.² Indeed, from 2015 to 2016 there was a 35.7% increase in the number of hotline cases reported, for a total of 7,572 (6,340—more than 80%—of which regarded females). California had the most cases reported (1,323), followed by Texas (670) and Florida (550); those 3 states also reported an increase in trafficking crime. Vermont (5), Rhode Island (9), and Alaska (10) reported the fewest calls.³

How is trafficking defined?

The United Nations Office on Drugs and Crime defines “trafficking in persons” as:

… recruitment, transportation, transfer, harbouring or receipt of persons, by means of the threat or use of force or other forms of coercion, of abduction, of fraud, of deception, of the abuse of power or of a position of vulnerability or of the giving or receiving of payments or benefits to achieve the consent of a person having control over another person, for the purpose of exploitation. Exploitation shall include, at a minimum, the exploitation of the prostitution of others or other forms of sexual exploitation, forced labour or services, slavery or practices similar to slavery, servitude or the removal of organs.⁴

Traffickers prey on potentially vulnerable people. Girls and young women who have experienced poverty, homelessness, childhood sexual abuse, substance abuse, gender nonconformity, mental illness, or developmental delay are at particular risk.⁵ Children who have had interactions with Child Protective Services, come from a dysfunctional family, or have lived in a community with high crime, political or social unrest, corruption, or gender bias and discrimination are also at increased risk.⁶

Read about clues that raise clinical suspicion

Clues that raise clinical suspicion

A number of potential signs should make providers suspicious about potential human trafficking. Some of those signs are similar to the red flags we see in intimate partner violence, such as:

• having a difficult time talking to the patient alone
• having the accompanying person answer the patient’s questions
• body language that suggests fear, anxiety, or distrust (eg, shifting positions, looking away, appearing withdrawn)
• physical examination inconsistent with the history
• physical injury (especially multiple injuries or injuries in various stages of healing)
• refusal of interpreter services.

Trafficked girls or women may appear overly familiar with sex, have unexpected material possessions, or appear to be giving scripted or memorized answers to queries.⁷ Traffickers often confiscate their victims’ personal identification. They try to prevent victims from knowing their geographic locales: Patients might not have any documentation or awareness of exact surroundings (eg, their home address). Patients may be wearing clothes considered inappropriate for the weather or venue. They may have tattoos that are marks of branding.⁸

Medical consequences of being trafficked are obvious, numerous, and serious

Many medical sequelae that result from trafficking are obvious, given the nature of work that victims are forced to do. For example, overcrowding can lead to infectious disease, such as tuberculosis.⁹ Inadequate access to preventive or basic medical services can result in weight loss, poor dentition, and untreated chronic medical conditions.

If victims are experiencing physical or sexual abuse, they can present with evidence of blunt trauma, ligature marks, skin burns, wounds inflicted by weapons, and vaginal lacerations.¹⁰ A study found that 63% of survivors reported at least 10 somatic symptoms, including headache, fatigue, dizziness, back pain, abdominal or pelvic pain, memory loss, and symptoms of genital infectious disease.¹¹

Girls and women being trafficked for sex may experience many of the sequelae of unprotected intercourse: irregular bleeding, unintended pregnancy, unwanted or unsafe pregnancy termination, vaginal trauma, and sexually transmitted infection (STI).¹² In a study of trafficking survivors, 38% were HIV-positive.¹³

Trafficking survivors can suffer myriad mental health conditions, with high rates of depression, anxiety, posttraumatic stress, and suicidal ideation.¹⁴ A study of 387 survivors found that 12% had attempted to harm themselves or commit suicide the month before they were interviewed.¹⁵

Substance abuse is also a common problem among trafficking victims.¹⁶ One survivor interviewed in a recent study said:

It was much more difficult to work sober because I was dealing with emotions or the pain that I was feeling during intercourse, because when you have sex with people 8, 9, 10 times a day, even more than that, it starts to hurt a lot. And being high made it easier to deal with that and also it made it easier for me to get away from my body while it was happening, place my brain somewhere else.¹⁷

Because of the substantial risk of mental health problems, including substance abuse, among trafficking survivors, the physical exam of a patient should include careful assessment of demeanor and mental health status. Of course, comprehensive inspection for signs of physical or blunt trauma is paramount.

Read about Patient and staff safety during the visit

Patient and staff safety during the visit

Providers should be aware of potential safety concerns, both for the patient and for the staff. Creative strategies should be utilized to screen the patient in private. The use of interpreter services—either in person or over the telephone—should be presented and facilitated as being a routine part of practice. Any person who accompanies the patient should be asked to leave the examining room, either as a statement of practice routine or under the guise of having him (or her) step out to obtain paperwork or provide documentation.

Care of victims

Trauma-informed care should be a guiding principle for trafficking survivors. This involves empowering the patient, who may feel victimized again if asked to undress and undergo multiple physical examinations. Macias-Konstantopoulos noted: “A trauma-informed approach to care acknowledges the pervasiveness and effect of trauma across the life span of the individual, recognizes the vulnerabilities and emotional triggers of trauma survivors, minimizes repeated traumatization and fosters physical, psychological, and emotional safety, recovery, health and well-being.”¹⁸

The patient should be counseled that she has control over her body and can guide different aspects of the examination. For example the provider should discuss: 1) the amount of clothing deemed optimal for an examination, 2) the availability of a support person during the exam (for instance, a nurse or a social worker) if the patient requests one, and 3) utilization of whatever strategies the patient deems optimal for her to be most comfortable during the exam (such as leaving the door slightly ajar or having a mutually agreed-on signal to interrupt the exam).

Routine health care maintenance should be offered, including an assessment of overall physical and dental health and screening for STI and mental health. Screening for substances of abuse should be considered. If indicated, emergency contraception, postexposure HIV prophylaxis, immunizations, and empiric antibiotics for STI should be offered.¹⁹

Screening when indicated by evidence, suspicion, or concern

Unlike the case with intimate partner violence, experts do not recommend universal screening for human trafficking. Clinicians should be comfortable, however, trying to elicit that history when a concern arises, either because of identified risk factors, red flags, or concerns that arise from the findings of the history or physical. Ideally, clinicians should consider becoming comfortable choosing a few screening questions to regularly incorporate into their assessment. The US Department of Health & Human Services (HHS) offers a list of questions that can be utilized (TABLE).²⁰

In January 2018, the Office on Trafficking in Persons, a unit of the HHS Administration for Children and Families, released an “Adult Human Trafficking Screening Tool and Guide.” The document includes 2 excellent tools²¹ that clinicians can utilize to identify patients who should be screened and how to identify and assist survivors (FIGURE 1 and FIGURE 2).

Clinicians, in their encounters with patients, are particularly well-positioned to intersect with, and identify, survivors. Regrettably, such opportunities are often missed—and victims thus remain unidentified and trapped in their circumstances. A study revealed that one-half of survivors who were interviewed reported seeing a physician while they were being trafficked.²² Even more alarming, another study showed that 87.8% of survivors had received health care during their captivity.²³ It is dismaying to know that these patients left those health care settings without receiving the assistance they truly need and with their true circumstances remaining unidentified.

Read about Finding assistance and support

Finding assistance and support

Centers in the United States now provide trauma-informed care for trafficking survivors in a confidential setting (see “Specialized care is increasingly available”).²⁴ A physician who works at a center in New York City noted: “Our survivors told us that more than fear or pain, the feelings that sat with them most often were worthlessness and invisibility. We can do better as physicians and as educators to expose this epidemic and care for its victims.”²⁴

Most clinicians practice in settings that do not have easy access to such subspecialized centers, however. For them, the National Human Trafficking Hotline can be an invaluable resource (see “Hotline is a valuable resource”).²⁵ Law enforcement and social services colleagues also can be useful allies.

Let’s turn our concern and awareness into results

We, as providers of women’s health care, are uniquely positioned to help these most vulnerable of people, many of whom have been stripped of personal documents and denied access to financial resources and community support. As a medical community, we should strive to combat this tragic epidemic, 1 patient at a time.

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.

Photo: Shutterstock

Despite increasing media coverage of human trafficking and the gravity of its many ramifications, I am struck by how often trainees and other clinicians present to me patients for which trafficking is a real potential concern—yet who give me a blank expression when I ask if anyone has screened these patients for being victims of trafficking. I suspect that few of us anticipated, during medical training, that we would be providing care to women who are enslaved.

How large is the problem?

It is impossible to comprehend the true scope of human trafficking. Estimates are that 20.9 million men, women, and children globally are forced into work that they are not free to leave.¹

Although human trafficking is recognized as a global phenomenon, its prevalence in the United States is significant enough that it should prompt the health care community to engage in helping identify and assist victims/survivors: From January until June of 2017, the National Human Trafficking Hotline received 13,807 telephone calls, resulting in reporting of 4,460 cases.² Indeed, from 2015 to 2016 there was a 35.7% increase in the number of hotline cases reported, for a total of 7,572 (6,340—more than 80%—of which regarded females). California had the most cases reported (1,323), followed by Texas (670) and Florida (550); those 3 states also reported an increase in trafficking crime. Vermont (5), Rhode Island (9), and Alaska (10) reported the fewest calls.³

How is trafficking defined?

The United Nations Office on Drugs and Crime defines “trafficking in persons” as:

… recruitment, transportation, transfer, harbouring or receipt of persons, by means of the threat or use of force or other forms of coercion, of abduction, of fraud, of deception, of the abuse of power or of a position of vulnerability or of the giving or receiving of payments or benefits to achieve the consent of a person having control over another person, for the purpose of exploitation. Exploitation shall include, at a minimum, the exploitation of the prostitution of others or other forms of sexual exploitation, forced labour or services, slavery or practices similar to slavery, servitude or the removal of organs.⁴

Traffickers prey on potentially vulnerable people. Girls and young women who have experienced poverty, homelessness, childhood sexual abuse, substance abuse, gender nonconformity, mental illness, or developmental delay are at particular risk.⁵ Children who have had interactions with Child Protective Services, come from a dysfunctional family, or have lived in a community with high crime, political or social unrest, corruption, or gender bias and discrimination are also at increased risk.⁶

Read about clues that raise clinical suspicion

Clues that raise clinical suspicion

A number of potential signs should make providers suspicious about potential human trafficking. Some of those signs are similar to the red flags we see in intimate partner violence, such as:

• having a difficult time talking to the patient alone
• having the accompanying person answer the patient’s questions
• body language that suggests fear, anxiety, or distrust (eg, shifting positions, looking away, appearing withdrawn)
• physical examination inconsistent with the history
• physical injury (especially multiple injuries or injuries in various stages of healing)
• refusal of interpreter services.

Trafficked girls or women may appear overly familiar with sex, have unexpected material possessions, or appear to be giving scripted or memorized answers to queries.⁷ Traffickers often confiscate their victims’ personal identification. They try to prevent victims from knowing their geographic locales: Patients might not have any documentation or awareness of exact surroundings (eg, their home address). Patients may be wearing clothes considered inappropriate for the weather or venue. They may have tattoos that are marks of branding.⁸

Medical consequences of being trafficked are obvious, numerous, and serious

Many medical sequelae that result from trafficking are obvious, given the nature of work that victims are forced to do. For example, overcrowding can lead to infectious disease, such as tuberculosis.⁹ Inadequate access to preventive or basic medical services can result in weight loss, poor dentition, and untreated chronic medical conditions.

If victims are experiencing physical or sexual abuse, they can present with evidence of blunt trauma, ligature marks, skin burns, wounds inflicted by weapons, and vaginal lacerations.¹⁰ A study found that 63% of survivors reported at least 10 somatic symptoms, including headache, fatigue, dizziness, back pain, abdominal or pelvic pain, memory loss, and symptoms of genital infectious disease.¹¹

Girls and women being trafficked for sex may experience many of the sequelae of unprotected intercourse: irregular bleeding, unintended pregnancy, unwanted or unsafe pregnancy termination, vaginal trauma, and sexually transmitted infection (STI).¹² In a study of trafficking survivors, 38% were HIV-positive.¹³

Trafficking survivors can suffer myriad mental health conditions, with high rates of depression, anxiety, posttraumatic stress, and suicidal ideation.¹⁴ A study of 387 survivors found that 12% had attempted to harm themselves or commit suicide the month before they were interviewed.¹⁵

Substance abuse is also a common problem among trafficking victims.¹⁶ One survivor interviewed in a recent study said:

It was much more difficult to work sober because I was dealing with emotions or the pain that I was feeling during intercourse, because when you have sex with people 8, 9, 10 times a day, even more than that, it starts to hurt a lot. And being high made it easier to deal with that and also it made it easier for me to get away from my body while it was happening, place my brain somewhere else.¹⁷

Because of the substantial risk of mental health problems, including substance abuse, among trafficking survivors, the physical exam of a patient should include careful assessment of demeanor and mental health status. Of course, comprehensive inspection for signs of physical or blunt trauma is paramount.

Read about Patient and staff safety during the visit

Patient and staff safety during the visit

Providers should be aware of potential safety concerns, both for the patient and for the staff. Creative strategies should be utilized to screen the patient in private. The use of interpreter services—either in person or over the telephone—should be presented and facilitated as being a routine part of practice. Any person who accompanies the patient should be asked to leave the examining room, either as a statement of practice routine or under the guise of having him (or her) step out to obtain paperwork or provide documentation.

Care of victims

Trauma-informed care should be a guiding principle for trafficking survivors. This involves empowering the patient, who may feel victimized again if asked to undress and undergo multiple physical examinations. Macias-Konstantopoulos noted: “A trauma-informed approach to care acknowledges the pervasiveness and effect of trauma across the life span of the individual, recognizes the vulnerabilities and emotional triggers of trauma survivors, minimizes repeated traumatization and fosters physical, psychological, and emotional safety, recovery, health and well-being.”¹⁸

The patient should be counseled that she has control over her body and can guide different aspects of the examination. For example the provider should discuss: 1) the amount of clothing deemed optimal for an examination, 2) the availability of a support person during the exam (for instance, a nurse or a social worker) if the patient requests one, and 3) utilization of whatever strategies the patient deems optimal for her to be most comfortable during the exam (such as leaving the door slightly ajar or having a mutually agreed-on signal to interrupt the exam).

Routine health care maintenance should be offered, including an assessment of overall physical and dental health and screening for STI and mental health. Screening for substances of abuse should be considered. If indicated, emergency contraception, postexposure HIV prophylaxis, immunizations, and empiric antibiotics for STI should be offered.¹⁹

Screening when indicated by evidence, suspicion, or concern

Unlike the case with intimate partner violence, experts do not recommend universal screening for human trafficking. Clinicians should be comfortable, however, trying to elicit that history when a concern arises, either because of identified risk factors, red flags, or concerns that arise from the findings of the history or physical. Ideally, clinicians should consider becoming comfortable choosing a few screening questions to regularly incorporate into their assessment. The US Department of Health & Human Services (HHS) offers a list of questions that can be utilized (TABLE).²⁰

In January 2018, the Office on Trafficking in Persons, a unit of the HHS Administration for Children and Families, released an “Adult Human Trafficking Screening Tool and Guide.” The document includes 2 excellent tools²¹ that clinicians can utilize to identify patients who should be screened and how to identify and assist survivors (FIGURE 1 and FIGURE 2).

Clinicians, in their encounters with patients, are particularly well-positioned to intersect with, and identify, survivors. Regrettably, such opportunities are often missed—and victims thus remain unidentified and trapped in their circumstances. A study revealed that one-half of survivors who were interviewed reported seeing a physician while they were being trafficked.²² Even more alarming, another study showed that 87.8% of survivors had received health care during their captivity.²³ It is dismaying to know that these patients left those health care settings without receiving the assistance they truly need and with their true circumstances remaining unidentified.

Read about Finding assistance and support

Finding assistance and support

Centers in the United States now provide trauma-informed care for trafficking survivors in a confidential setting (see “Specialized care is increasingly available”).²⁴ A physician who works at a center in New York City noted: “Our survivors told us that more than fear or pain, the feelings that sat with them most often were worthlessness and invisibility. We can do better as physicians and as educators to expose this epidemic and care for its victims.”²⁴

Most clinicians practice in settings that do not have easy access to such subspecialized centers, however. For them, the National Human Trafficking Hotline can be an invaluable resource (see “Hotline is a valuable resource”).²⁵ Law enforcement and social services colleagues also can be useful allies.

Let’s turn our concern and awareness into results

We, as providers of women’s health care, are uniquely positioned to help these most vulnerable of people, many of whom have been stripped of personal documents and denied access to financial resources and community support. As a medical community, we should strive to combat this tragic epidemic, 1 patient at a time.

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.

Photo: Shutterstock

Despite increasing media coverage of human trafficking and the gravity of its many ramifications, I am struck by how often trainees and other clinicians present to me patients for which trafficking is a real potential concern—yet who give me a blank expression when I ask if anyone has screened these patients for being victims of trafficking. I suspect that few of us anticipated, during medical training, that we would be providing care to women who are enslaved.

How large is the problem?

It is impossible to comprehend the true scope of human trafficking. Estimates are that 20.9 million men, women, and children globally are forced into work that they are not free to leave.¹

Although human trafficking is recognized as a global phenomenon, its prevalence in the United States is significant enough that it should prompt the health care community to engage in helping identify and assist victims/survivors: From January until June of 2017, the National Human Trafficking Hotline received 13,807 telephone calls, resulting in reporting of 4,460 cases.² Indeed, from 2015 to 2016 there was a 35.7% increase in the number of hotline cases reported, for a total of 7,572 (6,340—more than 80%—of which regarded females). California had the most cases reported (1,323), followed by Texas (670) and Florida (550); those 3 states also reported an increase in trafficking crime. Vermont (5), Rhode Island (9), and Alaska (10) reported the fewest calls.³

How is trafficking defined?

The United Nations Office on Drugs and Crime defines “trafficking in persons” as:

… recruitment, transportation, transfer, harbouring or receipt of persons, by means of the threat or use of force or other forms of coercion, of abduction, of fraud, of deception, of the abuse of power or of a position of vulnerability or of the giving or receiving of payments or benefits to achieve the consent of a person having control over another person, for the purpose of exploitation. Exploitation shall include, at a minimum, the exploitation of the prostitution of others or other forms of sexual exploitation, forced labour or services, slavery or practices similar to slavery, servitude or the removal of organs.⁴

Traffickers prey on potentially vulnerable people. Girls and young women who have experienced poverty, homelessness, childhood sexual abuse, substance abuse, gender nonconformity, mental illness, or developmental delay are at particular risk.⁵ Children who have had interactions with Child Protective Services, come from a dysfunctional family, or have lived in a community with high crime, political or social unrest, corruption, or gender bias and discrimination are also at increased risk.⁶

Read about clues that raise clinical suspicion

Clues that raise clinical suspicion

A number of potential signs should make providers suspicious about potential human trafficking. Some of those signs are similar to the red flags we see in intimate partner violence, such as:

• having a difficult time talking to the patient alone
• having the accompanying person answer the patient’s questions
• body language that suggests fear, anxiety, or distrust (eg, shifting positions, looking away, appearing withdrawn)
• physical examination inconsistent with the history
• physical injury (especially multiple injuries or injuries in various stages of healing)
• refusal of interpreter services.

Trafficked girls or women may appear overly familiar with sex, have unexpected material possessions, or appear to be giving scripted or memorized answers to queries.⁷ Traffickers often confiscate their victims’ personal identification. They try to prevent victims from knowing their geographic locales: Patients might not have any documentation or awareness of exact surroundings (eg, their home address). Patients may be wearing clothes considered inappropriate for the weather or venue. They may have tattoos that are marks of branding.⁸

Medical consequences of being trafficked are obvious, numerous, and serious

Many medical sequelae that result from trafficking are obvious, given the nature of work that victims are forced to do. For example, overcrowding can lead to infectious disease, such as tuberculosis.⁹ Inadequate access to preventive or basic medical services can result in weight loss, poor dentition, and untreated chronic medical conditions.

If victims are experiencing physical or sexual abuse, they can present with evidence of blunt trauma, ligature marks, skin burns, wounds inflicted by weapons, and vaginal lacerations.¹⁰ A study found that 63% of survivors reported at least 10 somatic symptoms, including headache, fatigue, dizziness, back pain, abdominal or pelvic pain, memory loss, and symptoms of genital infectious disease.¹¹

Girls and women being trafficked for sex may experience many of the sequelae of unprotected intercourse: irregular bleeding, unintended pregnancy, unwanted or unsafe pregnancy termination, vaginal trauma, and sexually transmitted infection (STI).¹² In a study of trafficking survivors, 38% were HIV-positive.¹³

Trafficking survivors can suffer myriad mental health conditions, with high rates of depression, anxiety, posttraumatic stress, and suicidal ideation.¹⁴ A study of 387 survivors found that 12% had attempted to harm themselves or commit suicide the month before they were interviewed.¹⁵

Substance abuse is also a common problem among trafficking victims.¹⁶ One survivor interviewed in a recent study said:

It was much more difficult to work sober because I was dealing with emotions or the pain that I was feeling during intercourse, because when you have sex with people 8, 9, 10 times a day, even more than that, it starts to hurt a lot. And being high made it easier to deal with that and also it made it easier for me to get away from my body while it was happening, place my brain somewhere else.¹⁷

Because of the substantial risk of mental health problems, including substance abuse, among trafficking survivors, the physical exam of a patient should include careful assessment of demeanor and mental health status. Of course, comprehensive inspection for signs of physical or blunt trauma is paramount.

Read about Patient and staff safety during the visit

Patient and staff safety during the visit

Providers should be aware of potential safety concerns, both for the patient and for the staff. Creative strategies should be utilized to screen the patient in private. The use of interpreter services—either in person or over the telephone—should be presented and facilitated as being a routine part of practice. Any person who accompanies the patient should be asked to leave the examining room, either as a statement of practice routine or under the guise of having him (or her) step out to obtain paperwork or provide documentation.

Care of victims

Trauma-informed care should be a guiding principle for trafficking survivors. This involves empowering the patient, who may feel victimized again if asked to undress and undergo multiple physical examinations. Macias-Konstantopoulos noted: “A trauma-informed approach to care acknowledges the pervasiveness and effect of trauma across the life span of the individual, recognizes the vulnerabilities and emotional triggers of trauma survivors, minimizes repeated traumatization and fosters physical, psychological, and emotional safety, recovery, health and well-being.”¹⁸

The patient should be counseled that she has control over her body and can guide different aspects of the examination. For example the provider should discuss: 1) the amount of clothing deemed optimal for an examination, 2) the availability of a support person during the exam (for instance, a nurse or a social worker) if the patient requests one, and 3) utilization of whatever strategies the patient deems optimal for her to be most comfortable during the exam (such as leaving the door slightly ajar or having a mutually agreed-on signal to interrupt the exam).

Routine health care maintenance should be offered, including an assessment of overall physical and dental health and screening for STI and mental health. Screening for substances of abuse should be considered. If indicated, emergency contraception, postexposure HIV prophylaxis, immunizations, and empiric antibiotics for STI should be offered.¹⁹

Screening when indicated by evidence, suspicion, or concern

Unlike the case with intimate partner violence, experts do not recommend universal screening for human trafficking. Clinicians should be comfortable, however, trying to elicit that history when a concern arises, either because of identified risk factors, red flags, or concerns that arise from the findings of the history or physical. Ideally, clinicians should consider becoming comfortable choosing a few screening questions to regularly incorporate into their assessment. The US Department of Health & Human Services (HHS) offers a list of questions that can be utilized (TABLE).²⁰

In January 2018, the Office on Trafficking in Persons, a unit of the HHS Administration for Children and Families, released an “Adult Human Trafficking Screening Tool and Guide.” The document includes 2 excellent tools²¹ that clinicians can utilize to identify patients who should be screened and how to identify and assist survivors (FIGURE 1 and FIGURE 2).

Clinicians, in their encounters with patients, are particularly well-positioned to intersect with, and identify, survivors. Regrettably, such opportunities are often missed—and victims thus remain unidentified and trapped in their circumstances. A study revealed that one-half of survivors who were interviewed reported seeing a physician while they were being trafficked.²² Even more alarming, another study showed that 87.8% of survivors had received health care during their captivity.²³ It is dismaying to know that these patients left those health care settings without receiving the assistance they truly need and with their true circumstances remaining unidentified.

Read about Finding assistance and support

Finding assistance and support

Centers in the United States now provide trauma-informed care for trafficking survivors in a confidential setting (see “Specialized care is increasingly available”).²⁴ A physician who works at a center in New York City noted: “Our survivors told us that more than fear or pain, the feelings that sat with them most often were worthlessness and invisibility. We can do better as physicians and as educators to expose this epidemic and care for its victims.”²⁴

Most clinicians practice in settings that do not have easy access to such subspecialized centers, however. For them, the National Human Trafficking Hotline can be an invaluable resource (see “Hotline is a valuable resource”).²⁵ Law enforcement and social services colleagues also can be useful allies.

Let’s turn our concern and awareness into results

We, as providers of women’s health care, are uniquely positioned to help these most vulnerable of people, many of whom have been stripped of personal documents and denied access to financial resources and community support. As a medical community, we should strive to combat this tragic epidemic, 1 patient at a time.

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.

Hepatitis C virus (HCV) infection is a major public health problem in the US. Following the 2010 report of the Institute of Medicine/National Academies of Sciences, Engineering, and Medicine (NASEM) on hepatitis and liver cancer, the US Department of Health and Human Services (HHS) released the first National Viral Hepatitis Action Plan in 2011 with subsequent action plan updates for 2014-2016 and 2017-2020.^1-3 A NASEM phase 2 report and the 2017-2020 HHS action plan outline a national strategy to prevent new viral hepatitis infections; reduce deaths and improve the health of people living with viral hepatitis; reduce viral hepatitis health disparities; and coordinate, monitor, and report on implementation of viral hepatitis activities.^3,4 The Department of Veterans Affairs (VA) is the single largest HCV care provider in the US with about 165,000 veterans in care diagnosed with HCV in the beginning of 2014 and is a national leader in the testing and treatment of HCV.^5,6

The VA’s recommendations for screening for HCV infection are in alignment with the United States Preventive Services Task Force (USPSTF) and Centers for Disease Control and Prevention (CDC) recommendations to test all veterans born between 1945 and 1965 and anyone with risk factors such as injection drug use.7-9 As of January 1, 2018, the VA had screened more than 80% of veterans in care within this highest risk birth cohort. As of January 1, 2018, more than 100,000 veterans in VA care have initiated treatment for HCV with direct-acting antivirals (DAAs) (Figure 1). 

Several critical factors contributed to the VA success with HCV testing and treatment, including congressional appropriation of funding from fiscal year (FY) 2016 through FY 2018, unrestricted access to interferon-free DAA HCV treatments, and dedicated resources from the VA National Viral Hepatitis Program within the HIV, Hepatitis, and Related Conditions Programs (HHRC) in the Office of Specialty Care Services.⁵ In 2014, HHRC created and supported the Hepatitis Innovation Team (HIT) Collaborative, a VA process improvement initiative enabling
Veterans Integrated Service Network (VISN) -based, multidisciplinary teams to increase veterans’ access to HCV testing and treatment.

As the VA makes consistent progress toward eliminating HCV in veterans in VA care, it has become clear that achieving a cure is only a starting point in improving HCV care. Many patients with HCV infection also have advanced liver disease (ALD), or cirrhosis, which is a condition of permanent liver fibrosis that remains after the patient has been cured of HCV infection. In addition to hepatitis C, ALD also can be caused by excessive alcohol use, hepatitis B virus (HBV) infection, nonalcoholic fatty liver diseases, and several other inherited diseases. Advanced liver disease affects more than 80,000 veterans in VA care, and the HIT infrastructure provides an excellent framework to better understand and address facility-level and systemwide challenges in diagnosing, caring for, and treating veterans with ALD across the Veterans Health Administration (VHA) system.

This report will describe the elements that contributed to the success of the HIT Collaborative in redesigning care for patients affected by HCV in the VA and how these elements can be applied to improve the system of care for VHA ALD care.

Hepatitis Innovation Teams Collaborative Leadership

After the US Food and Drug Administration (FDA) approved new DAA medications to treat HCV, the VA recognized the need to mobilize the health care system quickly and allocate resources for these new, minimally toxic, and highly effective medications. Early in 2014, HHRC established the National Hepatitis C Resource Center (NHCRC), a successor program to the 4 regional hepatitis C resource centers that had addressed HCV care across the system.10 The NHCRC was charged with developing an operational strategy for VA to respond rapidly to the availability of DAAs. In collaboration with representatives from the Office of Strategic Integration | Veterans Engineering Resource Center (OSI|VERC), the NHCRC formed the HIT Collaborative Leadership Team (CLT).

The HIT CLT is responsible for executing the HIT Collaborative and uses a Lean process improvement framework focused on eliminating waste and maximizing value. Members of the CLT with expertise in facilitation, Lean process improvement, leadership, clinical knowledge, and population health management act as coaches for the VISN HITs. The CLT works to build and support the VISN HITs, identify opportunities for individual teams to improve and assist in finding the right local mix of “players” to be successful. The HIT CLT ensures all teams are functioning and working toward achieving their goals. The CLT obtains data from VA national databases, which are provided to the VISN HITs to inform and encourage continuous improvement of their strategies. Annual VA-wide aspirational goals are developed and disseminated to encourage a unified mission.

Catchment areas for each VISN include between 6 and 10 medical centers as well as outpatient and ambulatory care centers. Multidisciplinary HITs are composed of physicians, nurses, pharmacists, nurse practitioners, physician assistants, social workers, mental health and substance use providers, peer support specialists, administrators, information technology experts, and systems redesign professionals from medical centers within each VISN. Teams develop strong relationships across medical centers, implement context-specific strategies applicable to rural
and urban centers, and share expertise. In addition to intra-VISN process improvement, HITs collaborate monthly across VISNs via a virtual platform. They share strong practices, seek advice from one another, and compare outcomes on an established set of goals.

The HITs use process improvement tools to systematically assess the current steps involved in care. At the close of each year, the HITs analyze the current state of operations and set goals to improve over the following year guided by a target state map. Seed funding is provided to every VISN HIT annually to launch change initiatives. Many VISN HITs use these funds to support a VISN HIT coordinator, and HITs also use this financial support to conduct 2- to 3-day process improvement workshops and to purchase supplies, such as point-of-care testing kits. The HIT communication and work are predominantly executed virtually.

Each year, teams worked toward achieving goals set nationally. These included increasing HCV birth cohort testing and improving the percentage of patients who had SVR12 testing
(Table). 

The HITs also set specific local VISN and medical center goals, prioritizing projects that could have the greatest impact on local patient access and quality of care and build on existing strengths and address barriers. These projects encompass a wide range of areas that contribute to the overall national goals.

Focus on Lean

Lean process improvement is based on 2 key pillars: respect for people (those seeking service as customers and patients and those providing service as frontline staff and stakeholders) and continuous improvement. With Lean, personnel providing care should work to identify and eliminate waste in the system and to streamline care delivery to maximize process steps that are most valued by patients (eg, interaction with a clinical provider) and minimize those that are not valued (eg, time spent waiting to see a provider). With the knowledge that HHRC fully supports their work, HITs were encouraged to innovate based on local resources, context, and culture.

Teams receive basic training in Lean from the HIT CLT and local systems redesign specialists if available. The HITs apply the A3 structured approach to problem solving.¹¹ The HITs follow prescribed problemsolving steps that help identify where to focus process improvement efforts, including analyzing the current state of care, outlining the target state, and prioritizing solution
approaches based on what will have the highest impact for patients. 

Innovations

Over the course of the HIT Collaborative, numerous innovations have emerged to address and mitigate barriers to HCV screening and treatment. Examples of successful innovations include the following:

• To address transportation issues, several teams developed programs specific to patients with HCV in rural locations or with limited mobility. Mobile vans and units traditionally used as mobile cardiology clinics were transformed into HCV clinics, bringing testing and treatment services directly to veterans;
• Pharmacists and social workers developed outreach strategies to locate homeless veterans, provide point-of-care testing and utilize mobile technology to concurrently enroll and link veterans to care; and
• Many liver care teams partnered with inpatient and outpatient substance use treatment clinics to provide patient education and coordinate HCV treatment.

Inter-VISN working groups developed systemwide tools to address common needs. In the program’s first year, a few medical facilities across a handful of VISNs shared local population health management systems, programming, and best practices. Over time, this working group combined the virtual networking capacity of the HIT Collaborative with technical expertise to promote rapid dissemination and uptake of a population health management system. Providers at medical centers across VA use the tools to identify veterans who should be screened and treated for HCV with the ability to continuously update information, identifying patients who do not respond to treatment or patients overdue for SVR12 testing.

Providers with experience using telehepatology formed another inter-VISN working group. These subject matter experts provided guidance to care teams interested in implementing telehealth in areas where limited local resources or knowledge had prevented them from moving forward. The ability to build a strong coalition across content areas fostered a collaborative learning environment, adaptable to implementing new processes and technologies.

In 2017, the VA made significant efforts to reach out to veterans eligible for VA care who had not yet been screened or remained untreated. In May, Hepatitis Awareness Month, HITs held HCV testing and community outreach events and participated in veteran stand-downs and veteran service organization activities.

Evaluation

Since 2014, the VA has increased its HCV treatment and screening rates. To assess the components contributing to these achievements and the role of the HIT Collaborative in driving this success, a team of implementation scientists have been working with the CLT to conduct a HIT program evaluation. The goal of the evaluation is to establish the impact of the HIT Collaborative. The evaluation team catalogs the activities of the Collaborative and the HITs and assesses implementation strategies (use of specific techniques) to increase the uptake of evidence-based practices specifically related to HCV treatment.¹²

At the close of each FY, HCV providers and members of the HIT Collaborative are queried through an online survey to determine which strategies have been used to improve HCV care and how these strategies were associated with the HIT Collaborative. The use of more strategies was associated with more HCV treatment initiations.¹³ All utilized strategies were identified whether or not they were associated with treatment starts. These data are being used to understand which combinations of strategies are most effective at increasing treatment for HCV in the VA and to inform future initiatives.

Expanding the Scope

Inspired by the successful results of the HIT work in HCV and in the spirit of continuously improving health care delivery, HHRC expanded the scope of the HIT Collaborative in FY 2018 to include ALD. There are about 80,000 veterans in VA care with advanced scarring of the liver and between 10,000 to 15,000 new diagnoses each year. In addition to HCV as an etiology for ALD, cases of cirrhosis are projected to increase among veterans in care due to metabolic syndrome and alcohol use. A recent review of VA data from fiscal year 2016 found that 88.6% of ALD patients had been seen in primary care within the past 2 years, with about half (51%) seen in a gastroenterology (GI) or hepatology clinic (Personal communication, HIV, Hepatitis, and Related Conditions Program Office March 16, 2018). For patients in VA care with ALD, GI visits are associated with a lower 5-year mortality.14 Annual mortality for all ALD patients in VA is 6.2%, and of those with a hospital admission, mortality rises to 31%.15 In FY 2016, there were about 52,000 ALD-related discharges (more than 2 per patient). Of those discharges, 24% were readmitted within 30 days, with an average length of stay of 1.9 days and an estimated cost per patient of $47,000 over 3 years.¹⁶

Hepatologists from across the VA convened to identify critical opportunities for improvement for patients with ALD. Base on available evidence presented in the literature and their clinical expertise, these subject matter experts identified several areas for quality improvement, with the overarching goal to improve identification of patients with early cirrhosis and ensure appropriate linkage to care for all cirrhotic patients, thus improving quality of life and reducing mortality. Although not finalized, candidate improvement targets include consistent linkage to care and treatment for HCV and HBV, comprehensive case management, post-discharge patient follow-up, and adherence to evidence-based standards of care.

Conclusion

The VA has made great strides in nearly eliminating HCV among veterans in VA care. The national effort to redesign hepatitis care using Lean management strategies and develop local and regional teams and centralized support allowed VA to maximize available resources to achieve higher rates of HCV birth cohort testing and treatment of patients infected with HCV than has any other health care system in the US.

The HIT Collaborative has been a unique and innovative mechanism to promote directed, patient-outcome driven change in a large and dynamic health care system. It has allowed rural and urban providers to work together to develop and spread quality improvement innovations and as an integrated system to achieve national priorities. The focus of this foundational HIT structure is expanding to identifying, treat, and care for VA’s ALD population.

Hepatitis C virus (HCV) infection is a major public health problem in the US. Following the 2010 report of the Institute of Medicine/National Academies of Sciences, Engineering, and Medicine (NASEM) on hepatitis and liver cancer, the US Department of Health and Human Services (HHS) released the first National Viral Hepatitis Action Plan in 2011 with subsequent action plan updates for 2014-2016 and 2017-2020.^1-3 A NASEM phase 2 report and the 2017-2020 HHS action plan outline a national strategy to prevent new viral hepatitis infections; reduce deaths and improve the health of people living with viral hepatitis; reduce viral hepatitis health disparities; and coordinate, monitor, and report on implementation of viral hepatitis activities.^3,4 The Department of Veterans Affairs (VA) is the single largest HCV care provider in the US with about 165,000 veterans in care diagnosed with HCV in the beginning of 2014 and is a national leader in the testing and treatment of HCV.^5,6

The VA’s recommendations for screening for HCV infection are in alignment with the United States Preventive Services Task Force (USPSTF) and Centers for Disease Control and Prevention (CDC) recommendations to test all veterans born between 1945 and 1965 and anyone with risk factors such as injection drug use.7-9 As of January 1, 2018, the VA had screened more than 80% of veterans in care within this highest risk birth cohort. As of January 1, 2018, more than 100,000 veterans in VA care have initiated treatment for HCV with direct-acting antivirals (DAAs) (Figure 1). 

Several critical factors contributed to the VA success with HCV testing and treatment, including congressional appropriation of funding from fiscal year (FY) 2016 through FY 2018, unrestricted access to interferon-free DAA HCV treatments, and dedicated resources from the VA National Viral Hepatitis Program within the HIV, Hepatitis, and Related Conditions Programs (HHRC) in the Office of Specialty Care Services.⁵ In 2014, HHRC created and supported the Hepatitis Innovation Team (HIT) Collaborative, a VA process improvement initiative enabling
Veterans Integrated Service Network (VISN) -based, multidisciplinary teams to increase veterans’ access to HCV testing and treatment.

As the VA makes consistent progress toward eliminating HCV in veterans in VA care, it has become clear that achieving a cure is only a starting point in improving HCV care. Many patients with HCV infection also have advanced liver disease (ALD), or cirrhosis, which is a condition of permanent liver fibrosis that remains after the patient has been cured of HCV infection. In addition to hepatitis C, ALD also can be caused by excessive alcohol use, hepatitis B virus (HBV) infection, nonalcoholic fatty liver diseases, and several other inherited diseases. Advanced liver disease affects more than 80,000 veterans in VA care, and the HIT infrastructure provides an excellent framework to better understand and address facility-level and systemwide challenges in diagnosing, caring for, and treating veterans with ALD across the Veterans Health Administration (VHA) system.

This report will describe the elements that contributed to the success of the HIT Collaborative in redesigning care for patients affected by HCV in the VA and how these elements can be applied to improve the system of care for VHA ALD care.

Hepatitis Innovation Teams Collaborative Leadership

After the US Food and Drug Administration (FDA) approved new DAA medications to treat HCV, the VA recognized the need to mobilize the health care system quickly and allocate resources for these new, minimally toxic, and highly effective medications. Early in 2014, HHRC established the National Hepatitis C Resource Center (NHCRC), a successor program to the 4 regional hepatitis C resource centers that had addressed HCV care across the system.10 The NHCRC was charged with developing an operational strategy for VA to respond rapidly to the availability of DAAs. In collaboration with representatives from the Office of Strategic Integration | Veterans Engineering Resource Center (OSI|VERC), the NHCRC formed the HIT Collaborative Leadership Team (CLT).

The HIT CLT is responsible for executing the HIT Collaborative and uses a Lean process improvement framework focused on eliminating waste and maximizing value. Members of the CLT with expertise in facilitation, Lean process improvement, leadership, clinical knowledge, and population health management act as coaches for the VISN HITs. The CLT works to build and support the VISN HITs, identify opportunities for individual teams to improve and assist in finding the right local mix of “players” to be successful. The HIT CLT ensures all teams are functioning and working toward achieving their goals. The CLT obtains data from VA national databases, which are provided to the VISN HITs to inform and encourage continuous improvement of their strategies. Annual VA-wide aspirational goals are developed and disseminated to encourage a unified mission.

Catchment areas for each VISN include between 6 and 10 medical centers as well as outpatient and ambulatory care centers. Multidisciplinary HITs are composed of physicians, nurses, pharmacists, nurse practitioners, physician assistants, social workers, mental health and substance use providers, peer support specialists, administrators, information technology experts, and systems redesign professionals from medical centers within each VISN. Teams develop strong relationships across medical centers, implement context-specific strategies applicable to rural
and urban centers, and share expertise. In addition to intra-VISN process improvement, HITs collaborate monthly across VISNs via a virtual platform. They share strong practices, seek advice from one another, and compare outcomes on an established set of goals.

The HITs use process improvement tools to systematically assess the current steps involved in care. At the close of each year, the HITs analyze the current state of operations and set goals to improve over the following year guided by a target state map. Seed funding is provided to every VISN HIT annually to launch change initiatives. Many VISN HITs use these funds to support a VISN HIT coordinator, and HITs also use this financial support to conduct 2- to 3-day process improvement workshops and to purchase supplies, such as point-of-care testing kits. The HIT communication and work are predominantly executed virtually.

Each year, teams worked toward achieving goals set nationally. These included increasing HCV birth cohort testing and improving the percentage of patients who had SVR12 testing
(Table). 

The HITs also set specific local VISN and medical center goals, prioritizing projects that could have the greatest impact on local patient access and quality of care and build on existing strengths and address barriers. These projects encompass a wide range of areas that contribute to the overall national goals.

Focus on Lean

Lean process improvement is based on 2 key pillars: respect for people (those seeking service as customers and patients and those providing service as frontline staff and stakeholders) and continuous improvement. With Lean, personnel providing care should work to identify and eliminate waste in the system and to streamline care delivery to maximize process steps that are most valued by patients (eg, interaction with a clinical provider) and minimize those that are not valued (eg, time spent waiting to see a provider). With the knowledge that HHRC fully supports their work, HITs were encouraged to innovate based on local resources, context, and culture.

Teams receive basic training in Lean from the HIT CLT and local systems redesign specialists if available. The HITs apply the A3 structured approach to problem solving.¹¹ The HITs follow prescribed problemsolving steps that help identify where to focus process improvement efforts, including analyzing the current state of care, outlining the target state, and prioritizing solution
approaches based on what will have the highest impact for patients. 

Innovations

Over the course of the HIT Collaborative, numerous innovations have emerged to address and mitigate barriers to HCV screening and treatment. Examples of successful innovations include the following:

• To address transportation issues, several teams developed programs specific to patients with HCV in rural locations or with limited mobility. Mobile vans and units traditionally used as mobile cardiology clinics were transformed into HCV clinics, bringing testing and treatment services directly to veterans;
• Pharmacists and social workers developed outreach strategies to locate homeless veterans, provide point-of-care testing and utilize mobile technology to concurrently enroll and link veterans to care; and
• Many liver care teams partnered with inpatient and outpatient substance use treatment clinics to provide patient education and coordinate HCV treatment.

Inter-VISN working groups developed systemwide tools to address common needs. In the program’s first year, a few medical facilities across a handful of VISNs shared local population health management systems, programming, and best practices. Over time, this working group combined the virtual networking capacity of the HIT Collaborative with technical expertise to promote rapid dissemination and uptake of a population health management system. Providers at medical centers across VA use the tools to identify veterans who should be screened and treated for HCV with the ability to continuously update information, identifying patients who do not respond to treatment or patients overdue for SVR12 testing.

Providers with experience using telehepatology formed another inter-VISN working group. These subject matter experts provided guidance to care teams interested in implementing telehealth in areas where limited local resources or knowledge had prevented them from moving forward. The ability to build a strong coalition across content areas fostered a collaborative learning environment, adaptable to implementing new processes and technologies.

In 2017, the VA made significant efforts to reach out to veterans eligible for VA care who had not yet been screened or remained untreated. In May, Hepatitis Awareness Month, HITs held HCV testing and community outreach events and participated in veteran stand-downs and veteran service organization activities.

Evaluation

Since 2014, the VA has increased its HCV treatment and screening rates. To assess the components contributing to these achievements and the role of the HIT Collaborative in driving this success, a team of implementation scientists have been working with the CLT to conduct a HIT program evaluation. The goal of the evaluation is to establish the impact of the HIT Collaborative. The evaluation team catalogs the activities of the Collaborative and the HITs and assesses implementation strategies (use of specific techniques) to increase the uptake of evidence-based practices specifically related to HCV treatment.¹²

At the close of each FY, HCV providers and members of the HIT Collaborative are queried through an online survey to determine which strategies have been used to improve HCV care and how these strategies were associated with the HIT Collaborative. The use of more strategies was associated with more HCV treatment initiations.¹³ All utilized strategies were identified whether or not they were associated with treatment starts. These data are being used to understand which combinations of strategies are most effective at increasing treatment for HCV in the VA and to inform future initiatives.

Expanding the Scope

Inspired by the successful results of the HIT work in HCV and in the spirit of continuously improving health care delivery, HHRC expanded the scope of the HIT Collaborative in FY 2018 to include ALD. There are about 80,000 veterans in VA care with advanced scarring of the liver and between 10,000 to 15,000 new diagnoses each year. In addition to HCV as an etiology for ALD, cases of cirrhosis are projected to increase among veterans in care due to metabolic syndrome and alcohol use. A recent review of VA data from fiscal year 2016 found that 88.6% of ALD patients had been seen in primary care within the past 2 years, with about half (51%) seen in a gastroenterology (GI) or hepatology clinic (Personal communication, HIV, Hepatitis, and Related Conditions Program Office March 16, 2018). For patients in VA care with ALD, GI visits are associated with a lower 5-year mortality.14 Annual mortality for all ALD patients in VA is 6.2%, and of those with a hospital admission, mortality rises to 31%.15 In FY 2016, there were about 52,000 ALD-related discharges (more than 2 per patient). Of those discharges, 24% were readmitted within 30 days, with an average length of stay of 1.9 days and an estimated cost per patient of $47,000 over 3 years.¹⁶

Hepatologists from across the VA convened to identify critical opportunities for improvement for patients with ALD. Base on available evidence presented in the literature and their clinical expertise, these subject matter experts identified several areas for quality improvement, with the overarching goal to improve identification of patients with early cirrhosis and ensure appropriate linkage to care for all cirrhotic patients, thus improving quality of life and reducing mortality. Although not finalized, candidate improvement targets include consistent linkage to care and treatment for HCV and HBV, comprehensive case management, post-discharge patient follow-up, and adherence to evidence-based standards of care.

Conclusion

The VA has made great strides in nearly eliminating HCV among veterans in VA care. The national effort to redesign hepatitis care using Lean management strategies and develop local and regional teams and centralized support allowed VA to maximize available resources to achieve higher rates of HCV birth cohort testing and treatment of patients infected with HCV than has any other health care system in the US.

The HIT Collaborative has been a unique and innovative mechanism to promote directed, patient-outcome driven change in a large and dynamic health care system. It has allowed rural and urban providers to work together to develop and spread quality improvement innovations and as an integrated system to achieve national priorities. The focus of this foundational HIT structure is expanding to identifying, treat, and care for VA’s ALD population.

Hepatitis C virus (HCV) infection is a major public health problem in the US. Following the 2010 report of the Institute of Medicine/National Academies of Sciences, Engineering, and Medicine (NASEM) on hepatitis and liver cancer, the US Department of Health and Human Services (HHS) released the first National Viral Hepatitis Action Plan in 2011 with subsequent action plan updates for 2014-2016 and 2017-2020.^1-3 A NASEM phase 2 report and the 2017-2020 HHS action plan outline a national strategy to prevent new viral hepatitis infections; reduce deaths and improve the health of people living with viral hepatitis; reduce viral hepatitis health disparities; and coordinate, monitor, and report on implementation of viral hepatitis activities.^3,4 The Department of Veterans Affairs (VA) is the single largest HCV care provider in the US with about 165,000 veterans in care diagnosed with HCV in the beginning of 2014 and is a national leader in the testing and treatment of HCV.^5,6

The VA’s recommendations for screening for HCV infection are in alignment with the United States Preventive Services Task Force (USPSTF) and Centers for Disease Control and Prevention (CDC) recommendations to test all veterans born between 1945 and 1965 and anyone with risk factors such as injection drug use.7-9 As of January 1, 2018, the VA had screened more than 80% of veterans in care within this highest risk birth cohort. As of January 1, 2018, more than 100,000 veterans in VA care have initiated treatment for HCV with direct-acting antivirals (DAAs) (Figure 1). 

Several critical factors contributed to the VA success with HCV testing and treatment, including congressional appropriation of funding from fiscal year (FY) 2016 through FY 2018, unrestricted access to interferon-free DAA HCV treatments, and dedicated resources from the VA National Viral Hepatitis Program within the HIV, Hepatitis, and Related Conditions Programs (HHRC) in the Office of Specialty Care Services.⁵ In 2014, HHRC created and supported the Hepatitis Innovation Team (HIT) Collaborative, a VA process improvement initiative enabling
Veterans Integrated Service Network (VISN) -based, multidisciplinary teams to increase veterans’ access to HCV testing and treatment.

As the VA makes consistent progress toward eliminating HCV in veterans in VA care, it has become clear that achieving a cure is only a starting point in improving HCV care. Many patients with HCV infection also have advanced liver disease (ALD), or cirrhosis, which is a condition of permanent liver fibrosis that remains after the patient has been cured of HCV infection. In addition to hepatitis C, ALD also can be caused by excessive alcohol use, hepatitis B virus (HBV) infection, nonalcoholic fatty liver diseases, and several other inherited diseases. Advanced liver disease affects more than 80,000 veterans in VA care, and the HIT infrastructure provides an excellent framework to better understand and address facility-level and systemwide challenges in diagnosing, caring for, and treating veterans with ALD across the Veterans Health Administration (VHA) system.

This report will describe the elements that contributed to the success of the HIT Collaborative in redesigning care for patients affected by HCV in the VA and how these elements can be applied to improve the system of care for VHA ALD care.

Hepatitis Innovation Teams Collaborative Leadership

After the US Food and Drug Administration (FDA) approved new DAA medications to treat HCV, the VA recognized the need to mobilize the health care system quickly and allocate resources for these new, minimally toxic, and highly effective medications. Early in 2014, HHRC established the National Hepatitis C Resource Center (NHCRC), a successor program to the 4 regional hepatitis C resource centers that had addressed HCV care across the system.10 The NHCRC was charged with developing an operational strategy for VA to respond rapidly to the availability of DAAs. In collaboration with representatives from the Office of Strategic Integration | Veterans Engineering Resource Center (OSI|VERC), the NHCRC formed the HIT Collaborative Leadership Team (CLT).

The HIT CLT is responsible for executing the HIT Collaborative and uses a Lean process improvement framework focused on eliminating waste and maximizing value. Members of the CLT with expertise in facilitation, Lean process improvement, leadership, clinical knowledge, and population health management act as coaches for the VISN HITs. The CLT works to build and support the VISN HITs, identify opportunities for individual teams to improve and assist in finding the right local mix of “players” to be successful. The HIT CLT ensures all teams are functioning and working toward achieving their goals. The CLT obtains data from VA national databases, which are provided to the VISN HITs to inform and encourage continuous improvement of their strategies. Annual VA-wide aspirational goals are developed and disseminated to encourage a unified mission.

Catchment areas for each VISN include between 6 and 10 medical centers as well as outpatient and ambulatory care centers. Multidisciplinary HITs are composed of physicians, nurses, pharmacists, nurse practitioners, physician assistants, social workers, mental health and substance use providers, peer support specialists, administrators, information technology experts, and systems redesign professionals from medical centers within each VISN. Teams develop strong relationships across medical centers, implement context-specific strategies applicable to rural
and urban centers, and share expertise. In addition to intra-VISN process improvement, HITs collaborate monthly across VISNs via a virtual platform. They share strong practices, seek advice from one another, and compare outcomes on an established set of goals.

The HITs use process improvement tools to systematically assess the current steps involved in care. At the close of each year, the HITs analyze the current state of operations and set goals to improve over the following year guided by a target state map. Seed funding is provided to every VISN HIT annually to launch change initiatives. Many VISN HITs use these funds to support a VISN HIT coordinator, and HITs also use this financial support to conduct 2- to 3-day process improvement workshops and to purchase supplies, such as point-of-care testing kits. The HIT communication and work are predominantly executed virtually.

Each year, teams worked toward achieving goals set nationally. These included increasing HCV birth cohort testing and improving the percentage of patients who had SVR12 testing
(Table). 

The HITs also set specific local VISN and medical center goals, prioritizing projects that could have the greatest impact on local patient access and quality of care and build on existing strengths and address barriers. These projects encompass a wide range of areas that contribute to the overall national goals.

Focus on Lean

Lean process improvement is based on 2 key pillars: respect for people (those seeking service as customers and patients and those providing service as frontline staff and stakeholders) and continuous improvement. With Lean, personnel providing care should work to identify and eliminate waste in the system and to streamline care delivery to maximize process steps that are most valued by patients (eg, interaction with a clinical provider) and minimize those that are not valued (eg, time spent waiting to see a provider). With the knowledge that HHRC fully supports their work, HITs were encouraged to innovate based on local resources, context, and culture.

Teams receive basic training in Lean from the HIT CLT and local systems redesign specialists if available. The HITs apply the A3 structured approach to problem solving.¹¹ The HITs follow prescribed problemsolving steps that help identify where to focus process improvement efforts, including analyzing the current state of care, outlining the target state, and prioritizing solution
approaches based on what will have the highest impact for patients. 

Innovations

Over the course of the HIT Collaborative, numerous innovations have emerged to address and mitigate barriers to HCV screening and treatment. Examples of successful innovations include the following:

• To address transportation issues, several teams developed programs specific to patients with HCV in rural locations or with limited mobility. Mobile vans and units traditionally used as mobile cardiology clinics were transformed into HCV clinics, bringing testing and treatment services directly to veterans;
• Pharmacists and social workers developed outreach strategies to locate homeless veterans, provide point-of-care testing and utilize mobile technology to concurrently enroll and link veterans to care; and
• Many liver care teams partnered with inpatient and outpatient substance use treatment clinics to provide patient education and coordinate HCV treatment.

Inter-VISN working groups developed systemwide tools to address common needs. In the program’s first year, a few medical facilities across a handful of VISNs shared local population health management systems, programming, and best practices. Over time, this working group combined the virtual networking capacity of the HIT Collaborative with technical expertise to promote rapid dissemination and uptake of a population health management system. Providers at medical centers across VA use the tools to identify veterans who should be screened and treated for HCV with the ability to continuously update information, identifying patients who do not respond to treatment or patients overdue for SVR12 testing.

Providers with experience using telehepatology formed another inter-VISN working group. These subject matter experts provided guidance to care teams interested in implementing telehealth in areas where limited local resources or knowledge had prevented them from moving forward. The ability to build a strong coalition across content areas fostered a collaborative learning environment, adaptable to implementing new processes and technologies.

In 2017, the VA made significant efforts to reach out to veterans eligible for VA care who had not yet been screened or remained untreated. In May, Hepatitis Awareness Month, HITs held HCV testing and community outreach events and participated in veteran stand-downs and veteran service organization activities.

Evaluation

Since 2014, the VA has increased its HCV treatment and screening rates. To assess the components contributing to these achievements and the role of the HIT Collaborative in driving this success, a team of implementation scientists have been working with the CLT to conduct a HIT program evaluation. The goal of the evaluation is to establish the impact of the HIT Collaborative. The evaluation team catalogs the activities of the Collaborative and the HITs and assesses implementation strategies (use of specific techniques) to increase the uptake of evidence-based practices specifically related to HCV treatment.¹²

At the close of each FY, HCV providers and members of the HIT Collaborative are queried through an online survey to determine which strategies have been used to improve HCV care and how these strategies were associated with the HIT Collaborative. The use of more strategies was associated with more HCV treatment initiations.¹³ All utilized strategies were identified whether or not they were associated with treatment starts. These data are being used to understand which combinations of strategies are most effective at increasing treatment for HCV in the VA and to inform future initiatives.

Expanding the Scope

Inspired by the successful results of the HIT work in HCV and in the spirit of continuously improving health care delivery, HHRC expanded the scope of the HIT Collaborative in FY 2018 to include ALD. There are about 80,000 veterans in VA care with advanced scarring of the liver and between 10,000 to 15,000 new diagnoses each year. In addition to HCV as an etiology for ALD, cases of cirrhosis are projected to increase among veterans in care due to metabolic syndrome and alcohol use. A recent review of VA data from fiscal year 2016 found that 88.6% of ALD patients had been seen in primary care within the past 2 years, with about half (51%) seen in a gastroenterology (GI) or hepatology clinic (Personal communication, HIV, Hepatitis, and Related Conditions Program Office March 16, 2018). For patients in VA care with ALD, GI visits are associated with a lower 5-year mortality.14 Annual mortality for all ALD patients in VA is 6.2%, and of those with a hospital admission, mortality rises to 31%.15 In FY 2016, there were about 52,000 ALD-related discharges (more than 2 per patient). Of those discharges, 24% were readmitted within 30 days, with an average length of stay of 1.9 days and an estimated cost per patient of $47,000 over 3 years.¹⁶

Hepatologists from across the VA convened to identify critical opportunities for improvement for patients with ALD. Base on available evidence presented in the literature and their clinical expertise, these subject matter experts identified several areas for quality improvement, with the overarching goal to improve identification of patients with early cirrhosis and ensure appropriate linkage to care for all cirrhotic patients, thus improving quality of life and reducing mortality. Although not finalized, candidate improvement targets include consistent linkage to care and treatment for HCV and HBV, comprehensive case management, post-discharge patient follow-up, and adherence to evidence-based standards of care.

Conclusion

The VA has made great strides in nearly eliminating HCV among veterans in VA care. The national effort to redesign hepatitis care using Lean management strategies and develop local and regional teams and centralized support allowed VA to maximize available resources to achieve higher rates of HCV birth cohort testing and treatment of patients infected with HCV than has any other health care system in the US.

The HIT Collaborative has been a unique and innovative mechanism to promote directed, patient-outcome driven change in a large and dynamic health care system. It has allowed rural and urban providers to work together to develop and spread quality improvement innovations and as an integrated system to achieve national priorities. The focus of this foundational HIT structure is expanding to identifying, treat, and care for VA’s ALD population.

ABSTRACT

Pain control following hip arthroscopy presents a significant clinical challenge, with postoperative pain requiring considerable opioid use. Peripheral nerve blocks (PNBs) have emerged as one option to improve pain and limit the consequences of opioid use. The purpose of this study is to provide a comprehensive review of outcomes associated with PNB in hip arthroscopy. We hypothesize that the use of PNB in hip arthroscopy leads to improved outcomes and is associated with few complications. A systematic review of PubMed, Medline, Scopus, and Embase databases was conducted through January 2015 for English-language articles reporting outcome data, with 2 reviewers independently reviewing studies for inclusion. When available, similar outcomes were combined to generate frequency-weighted means. Six studies met the inclusion criteria for this review, reporting on 710 patients undergoing hip arthroscopy. The mean ages were 37.0 and 37.7 years for the PNB and comparator groups, respectively, with a reported total of 281 (40.5%) male and 412 (59.5%) female patients. Postoperative post-anesthesia care unit (PACU) pain was consistently reduced in the PNB group, with the use of a lower morphine equivalent dose and lower rates of inpatient admission, compared with that in the control groups. Postoperative nausea and/or vomiting as well as PACU discharge time showed mixed results. High satisfaction and few complications were reported. In conclusion, PNB is associated with reductions in postoperative pain, analgesic use, and the rate of inpatient admissions, though similar rates of nausea/vomiting and time to discharge were reported. Current PNB techniques are varied, and future research efforts should focus on examining which of these methods provides the optimal risk-benefit profile in hip arthroscopy.

Continue to: Hip arthroscopy has emerged...

Hip arthroscopy has emerged as a useful procedure in the diagnosis and treatment of hip pathology,^1-8 experiencing a substantial rise in popularity in recent years, with the number of procedures growing by a factor of 18 from 1999 to 2009⁹ and 25 from 2006 to 2013.¹⁰ Though hip arthroscopy is beneficial in many cases, marked postoperative pain has presented a substantial challenge, with patients requiring considerable doses of opiate-based medications in the post-anesthesia care unit (PACU).^11,12 Increased narcotic use carries increased side effects, including postoperative nausea and vomiting,¹³ and poorly managed pain leads to increased unplanned admissions.¹⁴ Furthermore, patients with chronic hip pain and long-term opioid use may experience heightened and prolonged pain following the procedure, owing to medication tolerance and reduced opioid efficacy in this setting.¹⁵

Several pain control strategies have been employed in patients undergoing hip arthroscopy. General anesthesia^16,17 and combined spinal epidural (CSE)¹⁸ are commonly used. However, such techniques rely heavily on opioids for postoperative pain control,¹¹ and epidural anesthesia commonly requires adjunctive treatments (eg, neuromuscular blockade) to ensure muscle relaxation for joint distraction.¹⁹ One technique that has been employed recently is peripheral nerve block (PNB), which has been associated with a significant decrease in postoperative opioid use and nausea and vomiting.^13,20 This method has proven successful in other fields of arthroscopy, including shoulder arthroscopy, in which it resulted in faster recovery, reduced opioid consumption,²¹ and demonstrated cost-effectiveness²² compared with general anesthesia and knee arthroscopy.^23-26 As it is a relatively new field, little is known about the use of PNB in hip arthroscopy.

The goal of this systematic review was to comprehensively review the studies reporting on PNB in hip arthroscopy. We specifically focused on outcomes, including postoperative pain; analgesic use; nausea, vomiting, and antiemetic use; discharge time; inpatient admission; and patient satisfaction, as well as the complications associated with the use of PNB. Our knowledge of outcomes associated with PNB in hip arthroscopy is based on a few individual studies that have reported on small groups of patients using a variety of outcome measures and other findings. Furthermore, each of these studies commonly reflects the experience of an individual surgeon at a single institution and, when taken alone, may not be an accurate representation of the more general outcomes associated with PNB. A comprehensive review of such studies will provide surgeons, anesthesiologists, and patients with a better understanding of the anticipated outcomes of using PNB in hip arthroscopy. We hypothesize that the use of PNB in hip arthroscopy leads to improved outcomes and is associated with few complications.

MATERIALS AND METHODS

A systematic review of outcomes associated with PNB in hip arthroscopy was performed using the available English-language literature in accordance with the guidelines laid out by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and included studies retrieved from the PubMed, Medline, Scopus, and Embase computerized literature databases. Searches were executed comprising all years from database inception through January 2015. Articles were retrieved by an electronic search of medical subject headings and keyword terms and their respective combinations (Table 1). The inclusion criteria for studies in this systematic review were studies that (1) were written in the English language and (2) reported explicit outcome data. The exclusion criteria were (1) review articles, meta-analyses, case reports, abstracts/conference papers, comments/letters, or technique articles without reported patient data and (2) basic research, biomechanics, or animal/cadaveric studies without reported patient data.

Table 1. Search Terms Entered to Identify English-Language Studies Through January 2015

The literature search strategy is outlined in the Figure. The initial title search yielded a subset of possible articles that were then further included or excluded on the basis of the contents of the article’s abstract, wherein articles were again selected on the basis of the aforementioned inclusion and exclusion criteria. Articles selected in both the title and abstract phases underwent full-text review, during which the full text of each qualifying article was reviewed. In addition, the reference sections from articles undergoing full-text review were scanned to identify any additional studies that had not been identified in the original literature search. Appropriate studies for final inclusion were then selected at this stage. The title, abstract, and full-text selection process were performed by 2 of the study authors (Dr. Steinhaus and Dr. Lynch), with any discrepancies being discussed and resolved by mutual agreement.

Continue to: For all 6 included studies...

For all 6 included studies,^16-18,27-29 data were collected regarding the study specifics, patients included, and outcomes measured in the study. The journal of publication, type of study, level of evidence, and type of PNB, as well as the presence of a comparator group were noted (Table 2). Patient information included the number of patients at baseline and follow-up, mean age, gender, weight, height, body mass index, American Society of Anesthesiologists (ASA) status, and the specific procedures performed. In addition, data were collected on outcomes, including postoperative pain, as well as secondary outcomes and additional findings reported by the studies (Table 3). Where possible, weighted averages were calculated across all studies to obtain aggregate data.

RESULTS

STUDY INCLUSION

Six studies, all published between 2012 and 2014, were included in this systematic review (Table 2). Three studies involved lumbar plexus block, 2 studies involved femoral nerve block, and 1 study evaluated fascia iliaca block. Two studies used a control group of patients who received only general anesthesia (compared with the treatment group who received both general anesthesia and PNB); another study compared intravenous morphine with PNB; and 1 study compared CSE alone with PNB in addition to epidural.

DEMOGRAPHIC DATA

Demographic data from the included studies are presented in Table 2. In total, 710 and 549 patients were evaluated at baseline and final follow-up, respectively, which represents a follow-up rate of 77%. The frequency-weighted mean age of patients receiving PNB was 37.0 years compared with 37.7 years in the comparison groups, and the studies reported a total of 281 (40.5%) male and 412 (59.5%) female patients. The procedures performed were heterogeneously reported; therefore, totals were not tabulated, although the reported procedures included osteochondroplasty, labral débridement, labral and/or capsular repair, gluteus minimus repair, and synovectomy.

POSTOPERATIVE PAIN

Four studies reported on postoperative pain, and these data are presented in Table 3. In a retrospective study of patients receiving femoral nerve block in addition to general anesthesia, Dold and colleagues¹⁶ noted postoperative pain at 0, 15, 30, 45, and 60 minutes following arrival in the PACU, and discovered a statistically significantly lower level of pain at 60 minutes compared with inpatients receiving general anesthesia alone. YaDeau and colleagues¹⁸ found a significantly lower level of pain at rest in the PACU for those receiving CSE and lumbar plexus blockade compared with those receiving CSE alone. This significant difference did not persist at 24 hours or 6 months after the procedure, nor did it exist for pain with movement at any time point. Similarly, Schroeder and colleagues¹⁷ examined patients receiving general anesthesia and lumbar plexus block and found a significant reduction in pain immediately postoperatively in the PACU, though these effects disappeared the day following the procedure. Krych and colleagues²⁷ also reported on postoperative pain in patients undergoing fascia iliaca blockade, although they did not include a comparator group. Outcome comparison between patients who received PNB and controls in the PACU and 1 day following the procedure are presented in Table 4.

ANALGESIC USE

Four studies reported on analgesic use after PNB, and these data are presented in Table 3. Dold and colleagues¹⁶ noted analgesic use intraoperatively, in the PACU, and in the surgical day care unit (SDCU). These authors found a significant reduction in morphine equivalent dose given in the operating room and in the PACU in the group receiving PNB, with a nonsignificant trend toward lower use of oxycodone in the SDCU. Schroeder and colleagues¹⁷ similarly reported significant reductions in morphine equivalent dose intraoperatively and in Phase I recovery for patients receiving PNB, and these differences disappeared in Phase II recovery as well as intraoperatively if the block dose was considered. In addition, these authors found a significant reduction in the use of fentanyl and hydromorphone in the operating room in the PNB group, as well as a significant reduction in the proportion of patients receiving ketorolac in the operating room or PACU. Finally, YaDeau and colleagues¹⁸ reported total analgesic usage in the PACU among PNB patients compared with those receiving CSE alone and showed a strong trend toward reduced use in the PNB group, although this difference was not significant (P = .051). PACU analgesic use is presented in Table 4.

Continue to: Postoperative nausea...

POSTOPERATIVE NAUSEA/VOMITING AND ANTIEMETIC USE

Five studies presented data on nausea, vomiting, or antiemetic use following PNB and are shown in Table 3. YaDeau and colleagues¹⁸ reported nausea among 34% of patients in the PNB group, compared with 20% in the control group, vomiting in 2% and 7%, respectively, and antiemetic use in 12% of both groups. Dold and colleagues¹⁶ identified a similar trend, with 41.1% of patients in the PNB group and 32.5% of patients in the control group experiencing postoperative nausea or vomiting, while Krych and colleagues²⁷ noted only 10% of PNB patients with mild nausea and none requiring antiemetic use. In their study of patients receiving PNB, Schroeder and colleagues¹⁷ found a significant reduction in antiemetic use among PNB patients compared with those receiving general anesthesia alone. Similarly, Ward and colleagues²⁹ noted a significant difference in postoperative nausea, with 10% of patients in the PNB group experiencing postoperative nausea compared with 75% of those in the comparator group who received intravenous morphine. The mean percentage of patients experiencing postoperative nausea and/or vomiting is shown in Table 4.

DISCHARGE TIME

Four studies presented data on discharge time from the PACU and are summarized in Table 3. Three of these studies included a comparator group. Both Dold and colleagues¹⁶ and YaDeau and colleagues¹⁸ reported an increase in the time to discharge for patients receiving PNB, although these differences were not significant. The study by Ward and colleagues,²⁹ on the other hand, noted a significant reduction in the time to discharge for the PNB group. In addition to these studies, Krych and colleagues²⁷ examined the time from skin closure to discharge for patients receiving PNB, noting a mean 199 minutes for the patients in their study. Mean times to discharge for the PNB and control groups are presented in Table 4.

INPATIENT ADMISSION

Four studies presented data on the proportion of study participants who were admitted as inpatients, and these data are shown in Table 3. Dold and colleagues¹⁶ reported no inpatient admissions in their PNB group compared with 5.0% for the control group (both cases of pain control), while YaDeau and colleagues¹⁸ found that 3 admissions occurred, with 2 in the control group (1 for oxygen desaturation and the other for intractable pain and nausea) and 1 from the PNB group (epidural spread and urinary retention). Two additional studies reported data on PNB groups alone. Krych and colleagues²⁷ observed no overnight admissions in their study, while Nye and colleagues²⁸ reported 1 readmission for bilateral leg numbness and weakness due to epidural spread, which resolved following discontinuation of the block. The mean proportion of inpatient admissions is presented in Table 4.

SATISFACTION

A total of 3 studies examined patient satisfaction, and these data are presented in Table 3. In their study, Ward and colleagues²⁹ reported a significantly greater rate of satisfaction at 1 day postoperatively among the patients in the PNB group (90%) than among patients who received intravenous morphine (25%) (P < .0001). Similarly, YaDeau and colleagues¹⁸ noted greater satisfaction among the PNB group than among the control group, with PNB patients rating their satisfaction at a mean of 8.6 and control patients at a mean of 7.9 on a 10-point scale (0-10) 24 hours postoperatively, although this difference was not significant. Finally, Krych and colleagues²⁷ found that 67% of patients were “very satisfied” and 33% were “satisfied”, based on a Likert scale.

COMPLICATIONS

Four studies presented data on complications, and these findings are summarized in Table 3. In their work, Nye and colleagues²⁸ reported most extensively on complications associated with PNB. Overall, the authors found a rate of significant complications of 3.8%. In terms of specific complications, they noted local anesthetic systemic toxicity (0.9%), epidural spread (0.5%), sensory or motor deficits (9.4%), falls (0.5%), and catheter issues. In their study of patients receiving PNB and CSE, YaDeau and colleagues¹⁸ identified 1 patient in the PNB group with epidural spread and urinary retention, while they noted 1 case of oxygen desaturation and another case of intractable pain and nausea in the group receiving CSE alone, all 3 of which required inpatient admission. They found no permanent adverse events attributable to the PNB. In another study, Dold and colleagues¹⁶ observed no complications in patients receiving PNB compared with those in 2 admissions in the control group for inadequate pain control. Similarly, Krych and colleagues²⁷ identified no complications in patients who received PNB in their study.

DISCUSSION

Hip arthroscopy has experienced a substantial gain in popularity in recent years, emerging as a beneficial technique for both the diagnosis and treatment of diverse hip pathologies in patients spanning a variety of demographics. Nevertheless, postoperative pain control, as well as medication side effects and unwanted patient admissions, present major challenges to the treating surgeon. As an adjuvant measure, peripheral nerve block represents one option to improve postoperative pain management, while at the same time addressing the adverse effects of considerable opioid use, which is commonly seen in these patients. Early experience with this method in hip arthroscopy was reported in a case series by Lee and colleagues.¹² In an attempt to reduce postoperative pain, as well as limit the adverse effects and delay in discharge associated with considerable opioid use in the PACU, the authors used preoperative paravertebral blocks of L1 and L2 in 2 patients requiring hip arthroscopy with encouraging results. Since then, a number of studies have attempted the use of PNB in hip arthroscopy.^16-18,27-29 However, we were unable to identify any prior reviews reporting on peripheral nerve blockade in hip arthroscopy, and thus this study is unique in providing a greater understanding of the outcomes associated with PNB use.

In general, we found that PNB was associated with improved outcomes. Based on the studies included in this review, there was a statistically significantly lower level of pain in the PACU for femoral nerve block (compared with general anesthesia alone)¹⁶ and lumbar plexus blockade (compared with general anesthesia¹⁷ and CSE¹⁸ alone). Nevertheless, these effects are likely short-lived, with differences disappearing the day following the procedure. In terms of analgesic use, 2 studies report significant reductions in analgesic use intraoperatively and in the PACU/Phase I recovery,^16,17 with a third reporting a strong trend toward reduced analgesic use in the PACU (P = .051).¹⁸ Finally, we report fewer admissions for the PNB group, as well as high rates of satisfaction and few complications across these studies.

Continue to: Unlike these measures...

Unlike these measures, postoperative nausea, vomiting, and antiemetic use, as well as time to discharge, showed more mixed results. With regard to nausea/vomiting, 2 studies^16,18 reported nonsignificantly increased rates in the PNB group, whereas others reported significant reductions in nausea/vomiting²⁹ and in the proportion of patients receiving antiemetics.¹⁷ Similarly, mixed results were seen in terms of patient discharge time from the PACU. Two studies^16,18 reported a nonsignificant increase in time to discharge for the PNB group, while another²⁹ noted a significant reduction for the PNB group compared with those receiving intravenous morphine. These mixed results were surprising, as we expected reductions in opioid use to result in fewer instances of nausea/vomiting and a quicker time to discharge. The reasons underlying these findings are not clear, although it has been suggested that current discharge guidelines and clinical pathways limit the ability to take advantage of the accelerated timeline offered by regional anesthesia.^16,30 As experience with PNB grows, our guidelines and pathways are likely to adapt to capitalize on these advantages, and future studies may show more reliable improvements in these measures.

While rare, the risk of bleeding requiring blood transfusion following hip arthroscopy is one of the most common complications of this procedure. Though the studies included in this review did not report on the need for transfusion, a recent study by Cvetanovich and colleagues¹⁰ used a national database and found that, of patients undergoing hip arthroscopy (n = 1338), 0.4% (n = 5) had bleeding requiring a transfusion, with 0.3% (n = 4) requiring return to the operating room, similar to an earlier study by Clarke and colleagues,³¹ who noted bleeding from the portal site in 0.4% of hip arthroscopy patients. In terms of risk factors, Cvetanovich and colleagues¹⁰ found that ASA class, older age, and prior cardiac surgery were significantly associated with minor and overall complications, whereas both regional anesthesia/monitored anesthesia care and alcohol consumption of >2 drinks a day were significantly associated with minor complications, including bleeding requiring transfusions. They noted, however, that these risk factors accounted for only 5% of the variance in complication rates, indicating that other unidentified variables better explained the variance in complication rates. These authors concluded that complications associated with hip arthroscopy are so rare that we may not be able to predict which risk factors or anesthesia types are more likely to cause them. Further characterization of bleeding following hip arthroscopy and its associated risk factors is a valuable area for future research.

LIMITATIONS

Our study contains a number of limitations. This review included studies whose level of evidence varied from I to IV; therefore, our study is limited by any bias or heterogeneity introduced in patient recruitment, selection, variability of technique, data collection, and analysis used in these studies. This heterogeneity is most apparent in the block types and comparator groups. Furthermore, several different outcome measures were reported across the 6 studies used in this review, which decreased the relevance of any one of these individual outcomes. Finally, given the limited data that currently exist for the use of PNB in hip arthroscopy, we are unable to note meaningful differences between various types of PNBs, such as differences in postoperative pain or other measures such as quadriceps weakness, which can accompany femoral nerve block.¹² While it is important to read our work with these limitations in mind, this systematic review is, to our knowledge, the only comprehensive review to date of studies reporting on PNB in hip arthroscopy, providing clinicians and patients with a greater understanding of the associated outcomes across these studies.

CONCLUSION

This systematic review shows improved outcomes and few complications with PNB use in hip arthroscopy, with reductions in postoperative pain, analgesic use, and the rate of inpatient admissions. Although opioid use was reduced in these studies, we found similar rates of postoperative nausea/vomiting as well as similar time to discharge from the PACU, which may reflect our continued reliance on outdated discharge guidelines and clinical pathways. Current attempts to provide peripheral nerve blockade are quite varied, with studies targeting femoral nerve, fascia iliaca, L1/L2 paravertebral, and lumbar plexus blockade. Future research efforts with a large prospective trial investigating these techniques should focus on which of these PNBs presents the optimal risk-benefit profile for hip arthroscopy patients and thus appropriately address the clinical questions at hand.

This paper will be judged for the Resident Writer’s Award.

ABSTRACT

Pain control following hip arthroscopy presents a significant clinical challenge, with postoperative pain requiring considerable opioid use. Peripheral nerve blocks (PNBs) have emerged as one option to improve pain and limit the consequences of opioid use. The purpose of this study is to provide a comprehensive review of outcomes associated with PNB in hip arthroscopy. We hypothesize that the use of PNB in hip arthroscopy leads to improved outcomes and is associated with few complications. A systematic review of PubMed, Medline, Scopus, and Embase databases was conducted through January 2015 for English-language articles reporting outcome data, with 2 reviewers independently reviewing studies for inclusion. When available, similar outcomes were combined to generate frequency-weighted means. Six studies met the inclusion criteria for this review, reporting on 710 patients undergoing hip arthroscopy. The mean ages were 37.0 and 37.7 years for the PNB and comparator groups, respectively, with a reported total of 281 (40.5%) male and 412 (59.5%) female patients. Postoperative post-anesthesia care unit (PACU) pain was consistently reduced in the PNB group, with the use of a lower morphine equivalent dose and lower rates of inpatient admission, compared with that in the control groups. Postoperative nausea and/or vomiting as well as PACU discharge time showed mixed results. High satisfaction and few complications were reported. In conclusion, PNB is associated with reductions in postoperative pain, analgesic use, and the rate of inpatient admissions, though similar rates of nausea/vomiting and time to discharge were reported. Current PNB techniques are varied, and future research efforts should focus on examining which of these methods provides the optimal risk-benefit profile in hip arthroscopy.

Continue to: Hip arthroscopy has emerged...

Hip arthroscopy has emerged as a useful procedure in the diagnosis and treatment of hip pathology,^1-8 experiencing a substantial rise in popularity in recent years, with the number of procedures growing by a factor of 18 from 1999 to 2009⁹ and 25 from 2006 to 2013.¹⁰ Though hip arthroscopy is beneficial in many cases, marked postoperative pain has presented a substantial challenge, with patients requiring considerable doses of opiate-based medications in the post-anesthesia care unit (PACU).^11,12 Increased narcotic use carries increased side effects, including postoperative nausea and vomiting,¹³ and poorly managed pain leads to increased unplanned admissions.¹⁴ Furthermore, patients with chronic hip pain and long-term opioid use may experience heightened and prolonged pain following the procedure, owing to medication tolerance and reduced opioid efficacy in this setting.¹⁵

Several pain control strategies have been employed in patients undergoing hip arthroscopy. General anesthesia^16,17 and combined spinal epidural (CSE)¹⁸ are commonly used. However, such techniques rely heavily on opioids for postoperative pain control,¹¹ and epidural anesthesia commonly requires adjunctive treatments (eg, neuromuscular blockade) to ensure muscle relaxation for joint distraction.¹⁹ One technique that has been employed recently is peripheral nerve block (PNB), which has been associated with a significant decrease in postoperative opioid use and nausea and vomiting.^13,20 This method has proven successful in other fields of arthroscopy, including shoulder arthroscopy, in which it resulted in faster recovery, reduced opioid consumption,²¹ and demonstrated cost-effectiveness²² compared with general anesthesia and knee arthroscopy.^23-26 As it is a relatively new field, little is known about the use of PNB in hip arthroscopy.

The goal of this systematic review was to comprehensively review the studies reporting on PNB in hip arthroscopy. We specifically focused on outcomes, including postoperative pain; analgesic use; nausea, vomiting, and antiemetic use; discharge time; inpatient admission; and patient satisfaction, as well as the complications associated with the use of PNB. Our knowledge of outcomes associated with PNB in hip arthroscopy is based on a few individual studies that have reported on small groups of patients using a variety of outcome measures and other findings. Furthermore, each of these studies commonly reflects the experience of an individual surgeon at a single institution and, when taken alone, may not be an accurate representation of the more general outcomes associated with PNB. A comprehensive review of such studies will provide surgeons, anesthesiologists, and patients with a better understanding of the anticipated outcomes of using PNB in hip arthroscopy. We hypothesize that the use of PNB in hip arthroscopy leads to improved outcomes and is associated with few complications.

MATERIALS AND METHODS

A systematic review of outcomes associated with PNB in hip arthroscopy was performed using the available English-language literature in accordance with the guidelines laid out by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and included studies retrieved from the PubMed, Medline, Scopus, and Embase computerized literature databases. Searches were executed comprising all years from database inception through January 2015. Articles were retrieved by an electronic search of medical subject headings and keyword terms and their respective combinations (Table 1). The inclusion criteria for studies in this systematic review were studies that (1) were written in the English language and (2) reported explicit outcome data. The exclusion criteria were (1) review articles, meta-analyses, case reports, abstracts/conference papers, comments/letters, or technique articles without reported patient data and (2) basic research, biomechanics, or animal/cadaveric studies without reported patient data.

Table 1. Search Terms Entered to Identify English-Language Studies Through January 2015

The literature search strategy is outlined in the Figure. The initial title search yielded a subset of possible articles that were then further included or excluded on the basis of the contents of the article’s abstract, wherein articles were again selected on the basis of the aforementioned inclusion and exclusion criteria. Articles selected in both the title and abstract phases underwent full-text review, during which the full text of each qualifying article was reviewed. In addition, the reference sections from articles undergoing full-text review were scanned to identify any additional studies that had not been identified in the original literature search. Appropriate studies for final inclusion were then selected at this stage. The title, abstract, and full-text selection process were performed by 2 of the study authors (Dr. Steinhaus and Dr. Lynch), with any discrepancies being discussed and resolved by mutual agreement.

Continue to: For all 6 included studies...

For all 6 included studies,^16-18,27-29 data were collected regarding the study specifics, patients included, and outcomes measured in the study. The journal of publication, type of study, level of evidence, and type of PNB, as well as the presence of a comparator group were noted (Table 2). Patient information included the number of patients at baseline and follow-up, mean age, gender, weight, height, body mass index, American Society of Anesthesiologists (ASA) status, and the specific procedures performed. In addition, data were collected on outcomes, including postoperative pain, as well as secondary outcomes and additional findings reported by the studies (Table 3). Where possible, weighted averages were calculated across all studies to obtain aggregate data.

RESULTS

STUDY INCLUSION

Six studies, all published between 2012 and 2014, were included in this systematic review (Table 2). Three studies involved lumbar plexus block, 2 studies involved femoral nerve block, and 1 study evaluated fascia iliaca block. Two studies used a control group of patients who received only general anesthesia (compared with the treatment group who received both general anesthesia and PNB); another study compared intravenous morphine with PNB; and 1 study compared CSE alone with PNB in addition to epidural.

DEMOGRAPHIC DATA

Demographic data from the included studies are presented in Table 2. In total, 710 and 549 patients were evaluated at baseline and final follow-up, respectively, which represents a follow-up rate of 77%. The frequency-weighted mean age of patients receiving PNB was 37.0 years compared with 37.7 years in the comparison groups, and the studies reported a total of 281 (40.5%) male and 412 (59.5%) female patients. The procedures performed were heterogeneously reported; therefore, totals were not tabulated, although the reported procedures included osteochondroplasty, labral débridement, labral and/or capsular repair, gluteus minimus repair, and synovectomy.

POSTOPERATIVE PAIN

Four studies reported on postoperative pain, and these data are presented in Table 3. In a retrospective study of patients receiving femoral nerve block in addition to general anesthesia, Dold and colleagues¹⁶ noted postoperative pain at 0, 15, 30, 45, and 60 minutes following arrival in the PACU, and discovered a statistically significantly lower level of pain at 60 minutes compared with inpatients receiving general anesthesia alone. YaDeau and colleagues¹⁸ found a significantly lower level of pain at rest in the PACU for those receiving CSE and lumbar plexus blockade compared with those receiving CSE alone. This significant difference did not persist at 24 hours or 6 months after the procedure, nor did it exist for pain with movement at any time point. Similarly, Schroeder and colleagues¹⁷ examined patients receiving general anesthesia and lumbar plexus block and found a significant reduction in pain immediately postoperatively in the PACU, though these effects disappeared the day following the procedure. Krych and colleagues²⁷ also reported on postoperative pain in patients undergoing fascia iliaca blockade, although they did not include a comparator group. Outcome comparison between patients who received PNB and controls in the PACU and 1 day following the procedure are presented in Table 4.

ANALGESIC USE

Four studies reported on analgesic use after PNB, and these data are presented in Table 3. Dold and colleagues¹⁶ noted analgesic use intraoperatively, in the PACU, and in the surgical day care unit (SDCU). These authors found a significant reduction in morphine equivalent dose given in the operating room and in the PACU in the group receiving PNB, with a nonsignificant trend toward lower use of oxycodone in the SDCU. Schroeder and colleagues¹⁷ similarly reported significant reductions in morphine equivalent dose intraoperatively and in Phase I recovery for patients receiving PNB, and these differences disappeared in Phase II recovery as well as intraoperatively if the block dose was considered. In addition, these authors found a significant reduction in the use of fentanyl and hydromorphone in the operating room in the PNB group, as well as a significant reduction in the proportion of patients receiving ketorolac in the operating room or PACU. Finally, YaDeau and colleagues¹⁸ reported total analgesic usage in the PACU among PNB patients compared with those receiving CSE alone and showed a strong trend toward reduced use in the PNB group, although this difference was not significant (P = .051). PACU analgesic use is presented in Table 4.

Continue to: Postoperative nausea...

POSTOPERATIVE NAUSEA/VOMITING AND ANTIEMETIC USE

Five studies presented data on nausea, vomiting, or antiemetic use following PNB and are shown in Table 3. YaDeau and colleagues¹⁸ reported nausea among 34% of patients in the PNB group, compared with 20% in the control group, vomiting in 2% and 7%, respectively, and antiemetic use in 12% of both groups. Dold and colleagues¹⁶ identified a similar trend, with 41.1% of patients in the PNB group and 32.5% of patients in the control group experiencing postoperative nausea or vomiting, while Krych and colleagues²⁷ noted only 10% of PNB patients with mild nausea and none requiring antiemetic use. In their study of patients receiving PNB, Schroeder and colleagues¹⁷ found a significant reduction in antiemetic use among PNB patients compared with those receiving general anesthesia alone. Similarly, Ward and colleagues²⁹ noted a significant difference in postoperative nausea, with 10% of patients in the PNB group experiencing postoperative nausea compared with 75% of those in the comparator group who received intravenous morphine. The mean percentage of patients experiencing postoperative nausea and/or vomiting is shown in Table 4.

DISCHARGE TIME

Four studies presented data on discharge time from the PACU and are summarized in Table 3. Three of these studies included a comparator group. Both Dold and colleagues¹⁶ and YaDeau and colleagues¹⁸ reported an increase in the time to discharge for patients receiving PNB, although these differences were not significant. The study by Ward and colleagues,²⁹ on the other hand, noted a significant reduction in the time to discharge for the PNB group. In addition to these studies, Krych and colleagues²⁷ examined the time from skin closure to discharge for patients receiving PNB, noting a mean 199 minutes for the patients in their study. Mean times to discharge for the PNB and control groups are presented in Table 4.

INPATIENT ADMISSION

Four studies presented data on the proportion of study participants who were admitted as inpatients, and these data are shown in Table 3. Dold and colleagues¹⁶ reported no inpatient admissions in their PNB group compared with 5.0% for the control group (both cases of pain control), while YaDeau and colleagues¹⁸ found that 3 admissions occurred, with 2 in the control group (1 for oxygen desaturation and the other for intractable pain and nausea) and 1 from the PNB group (epidural spread and urinary retention). Two additional studies reported data on PNB groups alone. Krych and colleagues²⁷ observed no overnight admissions in their study, while Nye and colleagues²⁸ reported 1 readmission for bilateral leg numbness and weakness due to epidural spread, which resolved following discontinuation of the block. The mean proportion of inpatient admissions is presented in Table 4.

SATISFACTION

A total of 3 studies examined patient satisfaction, and these data are presented in Table 3. In their study, Ward and colleagues²⁹ reported a significantly greater rate of satisfaction at 1 day postoperatively among the patients in the PNB group (90%) than among patients who received intravenous morphine (25%) (P < .0001). Similarly, YaDeau and colleagues¹⁸ noted greater satisfaction among the PNB group than among the control group, with PNB patients rating their satisfaction at a mean of 8.6 and control patients at a mean of 7.9 on a 10-point scale (0-10) 24 hours postoperatively, although this difference was not significant. Finally, Krych and colleagues²⁷ found that 67% of patients were “very satisfied” and 33% were “satisfied”, based on a Likert scale.

COMPLICATIONS

Four studies presented data on complications, and these findings are summarized in Table 3. In their work, Nye and colleagues²⁸ reported most extensively on complications associated with PNB. Overall, the authors found a rate of significant complications of 3.8%. In terms of specific complications, they noted local anesthetic systemic toxicity (0.9%), epidural spread (0.5%), sensory or motor deficits (9.4%), falls (0.5%), and catheter issues. In their study of patients receiving PNB and CSE, YaDeau and colleagues¹⁸ identified 1 patient in the PNB group with epidural spread and urinary retention, while they noted 1 case of oxygen desaturation and another case of intractable pain and nausea in the group receiving CSE alone, all 3 of which required inpatient admission. They found no permanent adverse events attributable to the PNB. In another study, Dold and colleagues¹⁶ observed no complications in patients receiving PNB compared with those in 2 admissions in the control group for inadequate pain control. Similarly, Krych and colleagues²⁷ identified no complications in patients who received PNB in their study.

DISCUSSION

Hip arthroscopy has experienced a substantial gain in popularity in recent years, emerging as a beneficial technique for both the diagnosis and treatment of diverse hip pathologies in patients spanning a variety of demographics. Nevertheless, postoperative pain control, as well as medication side effects and unwanted patient admissions, present major challenges to the treating surgeon. As an adjuvant measure, peripheral nerve block represents one option to improve postoperative pain management, while at the same time addressing the adverse effects of considerable opioid use, which is commonly seen in these patients. Early experience with this method in hip arthroscopy was reported in a case series by Lee and colleagues.¹² In an attempt to reduce postoperative pain, as well as limit the adverse effects and delay in discharge associated with considerable opioid use in the PACU, the authors used preoperative paravertebral blocks of L1 and L2 in 2 patients requiring hip arthroscopy with encouraging results. Since then, a number of studies have attempted the use of PNB in hip arthroscopy.^16-18,27-29 However, we were unable to identify any prior reviews reporting on peripheral nerve blockade in hip arthroscopy, and thus this study is unique in providing a greater understanding of the outcomes associated with PNB use.

In general, we found that PNB was associated with improved outcomes. Based on the studies included in this review, there was a statistically significantly lower level of pain in the PACU for femoral nerve block (compared with general anesthesia alone)¹⁶ and lumbar plexus blockade (compared with general anesthesia¹⁷ and CSE¹⁸ alone). Nevertheless, these effects are likely short-lived, with differences disappearing the day following the procedure. In terms of analgesic use, 2 studies report significant reductions in analgesic use intraoperatively and in the PACU/Phase I recovery,^16,17 with a third reporting a strong trend toward reduced analgesic use in the PACU (P = .051).¹⁸ Finally, we report fewer admissions for the PNB group, as well as high rates of satisfaction and few complications across these studies.

Continue to: Unlike these measures...

Unlike these measures, postoperative nausea, vomiting, and antiemetic use, as well as time to discharge, showed more mixed results. With regard to nausea/vomiting, 2 studies^16,18 reported nonsignificantly increased rates in the PNB group, whereas others reported significant reductions in nausea/vomiting²⁹ and in the proportion of patients receiving antiemetics.¹⁷ Similarly, mixed results were seen in terms of patient discharge time from the PACU. Two studies^16,18 reported a nonsignificant increase in time to discharge for the PNB group, while another²⁹ noted a significant reduction for the PNB group compared with those receiving intravenous morphine. These mixed results were surprising, as we expected reductions in opioid use to result in fewer instances of nausea/vomiting and a quicker time to discharge. The reasons underlying these findings are not clear, although it has been suggested that current discharge guidelines and clinical pathways limit the ability to take advantage of the accelerated timeline offered by regional anesthesia.^16,30 As experience with PNB grows, our guidelines and pathways are likely to adapt to capitalize on these advantages, and future studies may show more reliable improvements in these measures.

While rare, the risk of bleeding requiring blood transfusion following hip arthroscopy is one of the most common complications of this procedure. Though the studies included in this review did not report on the need for transfusion, a recent study by Cvetanovich and colleagues¹⁰ used a national database and found that, of patients undergoing hip arthroscopy (n = 1338), 0.4% (n = 5) had bleeding requiring a transfusion, with 0.3% (n = 4) requiring return to the operating room, similar to an earlier study by Clarke and colleagues,³¹ who noted bleeding from the portal site in 0.4% of hip arthroscopy patients. In terms of risk factors, Cvetanovich and colleagues¹⁰ found that ASA class, older age, and prior cardiac surgery were significantly associated with minor and overall complications, whereas both regional anesthesia/monitored anesthesia care and alcohol consumption of >2 drinks a day were significantly associated with minor complications, including bleeding requiring transfusions. They noted, however, that these risk factors accounted for only 5% of the variance in complication rates, indicating that other unidentified variables better explained the variance in complication rates. These authors concluded that complications associated with hip arthroscopy are so rare that we may not be able to predict which risk factors or anesthesia types are more likely to cause them. Further characterization of bleeding following hip arthroscopy and its associated risk factors is a valuable area for future research.

LIMITATIONS

Our study contains a number of limitations. This review included studies whose level of evidence varied from I to IV; therefore, our study is limited by any bias or heterogeneity introduced in patient recruitment, selection, variability of technique, data collection, and analysis used in these studies. This heterogeneity is most apparent in the block types and comparator groups. Furthermore, several different outcome measures were reported across the 6 studies used in this review, which decreased the relevance of any one of these individual outcomes. Finally, given the limited data that currently exist for the use of PNB in hip arthroscopy, we are unable to note meaningful differences between various types of PNBs, such as differences in postoperative pain or other measures such as quadriceps weakness, which can accompany femoral nerve block.¹² While it is important to read our work with these limitations in mind, this systematic review is, to our knowledge, the only comprehensive review to date of studies reporting on PNB in hip arthroscopy, providing clinicians and patients with a greater understanding of the associated outcomes across these studies.

CONCLUSION

This systematic review shows improved outcomes and few complications with PNB use in hip arthroscopy, with reductions in postoperative pain, analgesic use, and the rate of inpatient admissions. Although opioid use was reduced in these studies, we found similar rates of postoperative nausea/vomiting as well as similar time to discharge from the PACU, which may reflect our continued reliance on outdated discharge guidelines and clinical pathways. Current attempts to provide peripheral nerve blockade are quite varied, with studies targeting femoral nerve, fascia iliaca, L1/L2 paravertebral, and lumbar plexus blockade. Future research efforts with a large prospective trial investigating these techniques should focus on which of these PNBs presents the optimal risk-benefit profile for hip arthroscopy patients and thus appropriately address the clinical questions at hand.

This paper will be judged for the Resident Writer’s Award.

ABSTRACT

Pain control following hip arthroscopy presents a significant clinical challenge, with postoperative pain requiring considerable opioid use. Peripheral nerve blocks (PNBs) have emerged as one option to improve pain and limit the consequences of opioid use. The purpose of this study is to provide a comprehensive review of outcomes associated with PNB in hip arthroscopy. We hypothesize that the use of PNB in hip arthroscopy leads to improved outcomes and is associated with few complications. A systematic review of PubMed, Medline, Scopus, and Embase databases was conducted through January 2015 for English-language articles reporting outcome data, with 2 reviewers independently reviewing studies for inclusion. When available, similar outcomes were combined to generate frequency-weighted means. Six studies met the inclusion criteria for this review, reporting on 710 patients undergoing hip arthroscopy. The mean ages were 37.0 and 37.7 years for the PNB and comparator groups, respectively, with a reported total of 281 (40.5%) male and 412 (59.5%) female patients. Postoperative post-anesthesia care unit (PACU) pain was consistently reduced in the PNB group, with the use of a lower morphine equivalent dose and lower rates of inpatient admission, compared with that in the control groups. Postoperative nausea and/or vomiting as well as PACU discharge time showed mixed results. High satisfaction and few complications were reported. In conclusion, PNB is associated with reductions in postoperative pain, analgesic use, and the rate of inpatient admissions, though similar rates of nausea/vomiting and time to discharge were reported. Current PNB techniques are varied, and future research efforts should focus on examining which of these methods provides the optimal risk-benefit profile in hip arthroscopy.

Continue to: Hip arthroscopy has emerged...

Hip arthroscopy has emerged as a useful procedure in the diagnosis and treatment of hip pathology,^1-8 experiencing a substantial rise in popularity in recent years, with the number of procedures growing by a factor of 18 from 1999 to 2009⁹ and 25 from 2006 to 2013.¹⁰ Though hip arthroscopy is beneficial in many cases, marked postoperative pain has presented a substantial challenge, with patients requiring considerable doses of opiate-based medications in the post-anesthesia care unit (PACU).^11,12 Increased narcotic use carries increased side effects, including postoperative nausea and vomiting,¹³ and poorly managed pain leads to increased unplanned admissions.¹⁴ Furthermore, patients with chronic hip pain and long-term opioid use may experience heightened and prolonged pain following the procedure, owing to medication tolerance and reduced opioid efficacy in this setting.¹⁵

Several pain control strategies have been employed in patients undergoing hip arthroscopy. General anesthesia^16,17 and combined spinal epidural (CSE)¹⁸ are commonly used. However, such techniques rely heavily on opioids for postoperative pain control,¹¹ and epidural anesthesia commonly requires adjunctive treatments (eg, neuromuscular blockade) to ensure muscle relaxation for joint distraction.¹⁹ One technique that has been employed recently is peripheral nerve block (PNB), which has been associated with a significant decrease in postoperative opioid use and nausea and vomiting.^13,20 This method has proven successful in other fields of arthroscopy, including shoulder arthroscopy, in which it resulted in faster recovery, reduced opioid consumption,²¹ and demonstrated cost-effectiveness²² compared with general anesthesia and knee arthroscopy.^23-26 As it is a relatively new field, little is known about the use of PNB in hip arthroscopy.

The goal of this systematic review was to comprehensively review the studies reporting on PNB in hip arthroscopy. We specifically focused on outcomes, including postoperative pain; analgesic use; nausea, vomiting, and antiemetic use; discharge time; inpatient admission; and patient satisfaction, as well as the complications associated with the use of PNB. Our knowledge of outcomes associated with PNB in hip arthroscopy is based on a few individual studies that have reported on small groups of patients using a variety of outcome measures and other findings. Furthermore, each of these studies commonly reflects the experience of an individual surgeon at a single institution and, when taken alone, may not be an accurate representation of the more general outcomes associated with PNB. A comprehensive review of such studies will provide surgeons, anesthesiologists, and patients with a better understanding of the anticipated outcomes of using PNB in hip arthroscopy. We hypothesize that the use of PNB in hip arthroscopy leads to improved outcomes and is associated with few complications.

MATERIALS AND METHODS

A systematic review of outcomes associated with PNB in hip arthroscopy was performed using the available English-language literature in accordance with the guidelines laid out by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and included studies retrieved from the PubMed, Medline, Scopus, and Embase computerized literature databases. Searches were executed comprising all years from database inception through January 2015. Articles were retrieved by an electronic search of medical subject headings and keyword terms and their respective combinations (Table 1). The inclusion criteria for studies in this systematic review were studies that (1) were written in the English language and (2) reported explicit outcome data. The exclusion criteria were (1) review articles, meta-analyses, case reports, abstracts/conference papers, comments/letters, or technique articles without reported patient data and (2) basic research, biomechanics, or animal/cadaveric studies without reported patient data.

Table 1. Search Terms Entered to Identify English-Language Studies Through January 2015

The literature search strategy is outlined in the Figure. The initial title search yielded a subset of possible articles that were then further included or excluded on the basis of the contents of the article’s abstract, wherein articles were again selected on the basis of the aforementioned inclusion and exclusion criteria. Articles selected in both the title and abstract phases underwent full-text review, during which the full text of each qualifying article was reviewed. In addition, the reference sections from articles undergoing full-text review were scanned to identify any additional studies that had not been identified in the original literature search. Appropriate studies for final inclusion were then selected at this stage. The title, abstract, and full-text selection process were performed by 2 of the study authors (Dr. Steinhaus and Dr. Lynch), with any discrepancies being discussed and resolved by mutual agreement.

Continue to: For all 6 included studies...

For all 6 included studies,^16-18,27-29 data were collected regarding the study specifics, patients included, and outcomes measured in the study. The journal of publication, type of study, level of evidence, and type of PNB, as well as the presence of a comparator group were noted (Table 2). Patient information included the number of patients at baseline and follow-up, mean age, gender, weight, height, body mass index, American Society of Anesthesiologists (ASA) status, and the specific procedures performed. In addition, data were collected on outcomes, including postoperative pain, as well as secondary outcomes and additional findings reported by the studies (Table 3). Where possible, weighted averages were calculated across all studies to obtain aggregate data.

RESULTS

STUDY INCLUSION

Six studies, all published between 2012 and 2014, were included in this systematic review (Table 2). Three studies involved lumbar plexus block, 2 studies involved femoral nerve block, and 1 study evaluated fascia iliaca block. Two studies used a control group of patients who received only general anesthesia (compared with the treatment group who received both general anesthesia and PNB); another study compared intravenous morphine with PNB; and 1 study compared CSE alone with PNB in addition to epidural.

DEMOGRAPHIC DATA

Demographic data from the included studies are presented in Table 2. In total, 710 and 549 patients were evaluated at baseline and final follow-up, respectively, which represents a follow-up rate of 77%. The frequency-weighted mean age of patients receiving PNB was 37.0 years compared with 37.7 years in the comparison groups, and the studies reported a total of 281 (40.5%) male and 412 (59.5%) female patients. The procedures performed were heterogeneously reported; therefore, totals were not tabulated, although the reported procedures included osteochondroplasty, labral débridement, labral and/or capsular repair, gluteus minimus repair, and synovectomy.

POSTOPERATIVE PAIN

Four studies reported on postoperative pain, and these data are presented in Table 3. In a retrospective study of patients receiving femoral nerve block in addition to general anesthesia, Dold and colleagues¹⁶ noted postoperative pain at 0, 15, 30, 45, and 60 minutes following arrival in the PACU, and discovered a statistically significantly lower level of pain at 60 minutes compared with inpatients receiving general anesthesia alone. YaDeau and colleagues¹⁸ found a significantly lower level of pain at rest in the PACU for those receiving CSE and lumbar plexus blockade compared with those receiving CSE alone. This significant difference did not persist at 24 hours or 6 months after the procedure, nor did it exist for pain with movement at any time point. Similarly, Schroeder and colleagues¹⁷ examined patients receiving general anesthesia and lumbar plexus block and found a significant reduction in pain immediately postoperatively in the PACU, though these effects disappeared the day following the procedure. Krych and colleagues²⁷ also reported on postoperative pain in patients undergoing fascia iliaca blockade, although they did not include a comparator group. Outcome comparison between patients who received PNB and controls in the PACU and 1 day following the procedure are presented in Table 4.

ANALGESIC USE

Four studies reported on analgesic use after PNB, and these data are presented in Table 3. Dold and colleagues¹⁶ noted analgesic use intraoperatively, in the PACU, and in the surgical day care unit (SDCU). These authors found a significant reduction in morphine equivalent dose given in the operating room and in the PACU in the group receiving PNB, with a nonsignificant trend toward lower use of oxycodone in the SDCU. Schroeder and colleagues¹⁷ similarly reported significant reductions in morphine equivalent dose intraoperatively and in Phase I recovery for patients receiving PNB, and these differences disappeared in Phase II recovery as well as intraoperatively if the block dose was considered. In addition, these authors found a significant reduction in the use of fentanyl and hydromorphone in the operating room in the PNB group, as well as a significant reduction in the proportion of patients receiving ketorolac in the operating room or PACU. Finally, YaDeau and colleagues¹⁸ reported total analgesic usage in the PACU among PNB patients compared with those receiving CSE alone and showed a strong trend toward reduced use in the PNB group, although this difference was not significant (P = .051). PACU analgesic use is presented in Table 4.

Continue to: Postoperative nausea...

POSTOPERATIVE NAUSEA/VOMITING AND ANTIEMETIC USE

Five studies presented data on nausea, vomiting, or antiemetic use following PNB and are shown in Table 3. YaDeau and colleagues¹⁸ reported nausea among 34% of patients in the PNB group, compared with 20% in the control group, vomiting in 2% and 7%, respectively, and antiemetic use in 12% of both groups. Dold and colleagues¹⁶ identified a similar trend, with 41.1% of patients in the PNB group and 32.5% of patients in the control group experiencing postoperative nausea or vomiting, while Krych and colleagues²⁷ noted only 10% of PNB patients with mild nausea and none requiring antiemetic use. In their study of patients receiving PNB, Schroeder and colleagues¹⁷ found a significant reduction in antiemetic use among PNB patients compared with those receiving general anesthesia alone. Similarly, Ward and colleagues²⁹ noted a significant difference in postoperative nausea, with 10% of patients in the PNB group experiencing postoperative nausea compared with 75% of those in the comparator group who received intravenous morphine. The mean percentage of patients experiencing postoperative nausea and/or vomiting is shown in Table 4.

DISCHARGE TIME

Four studies presented data on discharge time from the PACU and are summarized in Table 3. Three of these studies included a comparator group. Both Dold and colleagues¹⁶ and YaDeau and colleagues¹⁸ reported an increase in the time to discharge for patients receiving PNB, although these differences were not significant. The study by Ward and colleagues,²⁹ on the other hand, noted a significant reduction in the time to discharge for the PNB group. In addition to these studies, Krych and colleagues²⁷ examined the time from skin closure to discharge for patients receiving PNB, noting a mean 199 minutes for the patients in their study. Mean times to discharge for the PNB and control groups are presented in Table 4.

INPATIENT ADMISSION

Four studies presented data on the proportion of study participants who were admitted as inpatients, and these data are shown in Table 3. Dold and colleagues¹⁶ reported no inpatient admissions in their PNB group compared with 5.0% for the control group (both cases of pain control), while YaDeau and colleagues¹⁸ found that 3 admissions occurred, with 2 in the control group (1 for oxygen desaturation and the other for intractable pain and nausea) and 1 from the PNB group (epidural spread and urinary retention). Two additional studies reported data on PNB groups alone. Krych and colleagues²⁷ observed no overnight admissions in their study, while Nye and colleagues²⁸ reported 1 readmission for bilateral leg numbness and weakness due to epidural spread, which resolved following discontinuation of the block. The mean proportion of inpatient admissions is presented in Table 4.

SATISFACTION

A total of 3 studies examined patient satisfaction, and these data are presented in Table 3. In their study, Ward and colleagues²⁹ reported a significantly greater rate of satisfaction at 1 day postoperatively among the patients in the PNB group (90%) than among patients who received intravenous morphine (25%) (P < .0001). Similarly, YaDeau and colleagues¹⁸ noted greater satisfaction among the PNB group than among the control group, with PNB patients rating their satisfaction at a mean of 8.6 and control patients at a mean of 7.9 on a 10-point scale (0-10) 24 hours postoperatively, although this difference was not significant. Finally, Krych and colleagues²⁷ found that 67% of patients were “very satisfied” and 33% were “satisfied”, based on a Likert scale.

COMPLICATIONS

Four studies presented data on complications, and these findings are summarized in Table 3. In their work, Nye and colleagues²⁸ reported most extensively on complications associated with PNB. Overall, the authors found a rate of significant complications of 3.8%. In terms of specific complications, they noted local anesthetic systemic toxicity (0.9%), epidural spread (0.5%), sensory or motor deficits (9.4%), falls (0.5%), and catheter issues. In their study of patients receiving PNB and CSE, YaDeau and colleagues¹⁸ identified 1 patient in the PNB group with epidural spread and urinary retention, while they noted 1 case of oxygen desaturation and another case of intractable pain and nausea in the group receiving CSE alone, all 3 of which required inpatient admission. They found no permanent adverse events attributable to the PNB. In another study, Dold and colleagues¹⁶ observed no complications in patients receiving PNB compared with those in 2 admissions in the control group for inadequate pain control. Similarly, Krych and colleagues²⁷ identified no complications in patients who received PNB in their study.

DISCUSSION

Hip arthroscopy has experienced a substantial gain in popularity in recent years, emerging as a beneficial technique for both the diagnosis and treatment of diverse hip pathologies in patients spanning a variety of demographics. Nevertheless, postoperative pain control, as well as medication side effects and unwanted patient admissions, present major challenges to the treating surgeon. As an adjuvant measure, peripheral nerve block represents one option to improve postoperative pain management, while at the same time addressing the adverse effects of considerable opioid use, which is commonly seen in these patients. Early experience with this method in hip arthroscopy was reported in a case series by Lee and colleagues.¹² In an attempt to reduce postoperative pain, as well as limit the adverse effects and delay in discharge associated with considerable opioid use in the PACU, the authors used preoperative paravertebral blocks of L1 and L2 in 2 patients requiring hip arthroscopy with encouraging results. Since then, a number of studies have attempted the use of PNB in hip arthroscopy.^16-18,27-29 However, we were unable to identify any prior reviews reporting on peripheral nerve blockade in hip arthroscopy, and thus this study is unique in providing a greater understanding of the outcomes associated with PNB use.

In general, we found that PNB was associated with improved outcomes. Based on the studies included in this review, there was a statistically significantly lower level of pain in the PACU for femoral nerve block (compared with general anesthesia alone)¹⁶ and lumbar plexus blockade (compared with general anesthesia¹⁷ and CSE¹⁸ alone). Nevertheless, these effects are likely short-lived, with differences disappearing the day following the procedure. In terms of analgesic use, 2 studies report significant reductions in analgesic use intraoperatively and in the PACU/Phase I recovery,^16,17 with a third reporting a strong trend toward reduced analgesic use in the PACU (P = .051).¹⁸ Finally, we report fewer admissions for the PNB group, as well as high rates of satisfaction and few complications across these studies.

Continue to: Unlike these measures...

Unlike these measures, postoperative nausea, vomiting, and antiemetic use, as well as time to discharge, showed more mixed results. With regard to nausea/vomiting, 2 studies^16,18 reported nonsignificantly increased rates in the PNB group, whereas others reported significant reductions in nausea/vomiting²⁹ and in the proportion of patients receiving antiemetics.¹⁷ Similarly, mixed results were seen in terms of patient discharge time from the PACU. Two studies^16,18 reported a nonsignificant increase in time to discharge for the PNB group, while another²⁹ noted a significant reduction for the PNB group compared with those receiving intravenous morphine. These mixed results were surprising, as we expected reductions in opioid use to result in fewer instances of nausea/vomiting and a quicker time to discharge. The reasons underlying these findings are not clear, although it has been suggested that current discharge guidelines and clinical pathways limit the ability to take advantage of the accelerated timeline offered by regional anesthesia.^16,30 As experience with PNB grows, our guidelines and pathways are likely to adapt to capitalize on these advantages, and future studies may show more reliable improvements in these measures.

While rare, the risk of bleeding requiring blood transfusion following hip arthroscopy is one of the most common complications of this procedure. Though the studies included in this review did not report on the need for transfusion, a recent study by Cvetanovich and colleagues¹⁰ used a national database and found that, of patients undergoing hip arthroscopy (n = 1338), 0.4% (n = 5) had bleeding requiring a transfusion, with 0.3% (n = 4) requiring return to the operating room, similar to an earlier study by Clarke and colleagues,³¹ who noted bleeding from the portal site in 0.4% of hip arthroscopy patients. In terms of risk factors, Cvetanovich and colleagues¹⁰ found that ASA class, older age, and prior cardiac surgery were significantly associated with minor and overall complications, whereas both regional anesthesia/monitored anesthesia care and alcohol consumption of >2 drinks a day were significantly associated with minor complications, including bleeding requiring transfusions. They noted, however, that these risk factors accounted for only 5% of the variance in complication rates, indicating that other unidentified variables better explained the variance in complication rates. These authors concluded that complications associated with hip arthroscopy are so rare that we may not be able to predict which risk factors or anesthesia types are more likely to cause them. Further characterization of bleeding following hip arthroscopy and its associated risk factors is a valuable area for future research.

LIMITATIONS

Our study contains a number of limitations. This review included studies whose level of evidence varied from I to IV; therefore, our study is limited by any bias or heterogeneity introduced in patient recruitment, selection, variability of technique, data collection, and analysis used in these studies. This heterogeneity is most apparent in the block types and comparator groups. Furthermore, several different outcome measures were reported across the 6 studies used in this review, which decreased the relevance of any one of these individual outcomes. Finally, given the limited data that currently exist for the use of PNB in hip arthroscopy, we are unable to note meaningful differences between various types of PNBs, such as differences in postoperative pain or other measures such as quadriceps weakness, which can accompany femoral nerve block.¹² While it is important to read our work with these limitations in mind, this systematic review is, to our knowledge, the only comprehensive review to date of studies reporting on PNB in hip arthroscopy, providing clinicians and patients with a greater understanding of the associated outcomes across these studies.

CONCLUSION

This systematic review shows improved outcomes and few complications with PNB use in hip arthroscopy, with reductions in postoperative pain, analgesic use, and the rate of inpatient admissions. Although opioid use was reduced in these studies, we found similar rates of postoperative nausea/vomiting as well as similar time to discharge from the PACU, which may reflect our continued reliance on outdated discharge guidelines and clinical pathways. Current attempts to provide peripheral nerve blockade are quite varied, with studies targeting femoral nerve, fascia iliaca, L1/L2 paravertebral, and lumbar plexus blockade. Future research efforts with a large prospective trial investigating these techniques should focus on which of these PNBs presents the optimal risk-benefit profile for hip arthroscopy patients and thus appropriately address the clinical questions at hand.

This paper will be judged for the Resident Writer’s Award.

ABSTRACT

This study was performed to compare outcomes of open, arthroscopic, and percutaneous surgical techniques for lateral epicondylitis. We searched PubMed (MEDLINE) for literature published between January 1, 2004 and May 23, 2015 using these key words: lateral epicondylitis AND (surgery OR operative OR surgical OR open OR arthroscopic OR percutaneous). Meta-analyses were performed for outcomes reported in 3 studies using 2-sample and 2-proportion Z-tests. Thirty-five studies including 1640 elbows (1055 open, 401 arthroscopic, 184 percutaneous) met the inclusion criteria. There were no differences between groups regarding duration to return to work, complication rate, or patient satisfaction. A greater proportion of patients were pain free in the open group than in the arthroscopic group (70% vs 60%). Despite the absence of a difference among techniques regarding return to work and subjective function, we recommend open débridement as the technique most likely to achieve a pain-free outcome.

Continue to: Lateral epicondylitis affects...

Lateral epicondylitis affects 1% to 3% of adults each year. Although common, symptoms of lateral epicondylitis resolve spontaneously within a year of symptom onset in 80% of cases, and only 3% of patients who seek medical treatment ultimately require surgical intervention within 2 years of symptom onset.¹ Despite a relatively low percentage of patients who require surgery, Sanders and colleagues¹ noted a significant increase in the rate of surgical intervention from 1.1% to 3.2% of cases in the last 15 years. Surgical intervention is generally indicated when pain and functional disability persist after 6 to 12 months of nonsurgical treatment. Traditional surgical treatment involves open release/débridement of the extensor carpi radialis (ECRB) origin; however, with the increasing prevalence of surgical intervention, surgeons have demonstrated a rising interest in less invasive techniques like arthroscopic release/débridement and percutaneous tenotomy as alternatives to traditional open débridement. While favorable results have been reported for all 3 techniques, there is no current consensus regarding the optimal surgical technique. In 2007, Lo and Safran² reported no difference in the results of open, percutaneous, and arthroscopic techniques regarding any outcome measure in a systematic review of 33 papers. We conducted a repeat systematic review of the current literature to update Lo and Safran’s² review and to ascertain if more recent literature demonstrates superiority of 1 technique regarding pain relief, subjective questionnaire data, subjective satisfaction, restoration of strength, and return to work. We hypothesized that return to work would be accelerated, pain decreased, and function improved in the early postoperative period in the arthroscopic and percutaneous groups, but there would be no difference in ultimate pain, functional outcome, or subjective satisfaction.

METHODS

SEARCH STRATEGY AND STUDY SELECTION

We conducted a systematic review of the literature to update the topic of surgical intervention with lateral epicondylitis since the publication of the most recent review by Lo and Safran² in 2007, which included all relevant studies published up to 2004. To include all relevant studies published since that time, we searched PubMed (MEDLINE) for all literature published from January 1, 2004 to May 23, 2015 using the following key words: lateral epicondylitis AND (surgery OR operative OR surgical OR open OR arthroscopic OR percutaneous). General search terms were utilized to avoid unintentional exclusion of relevant studies. Two authors reviewed the abstracts of all resultant citations. Table 1 outlines the inclusion and exclusion criteria for the search. References from all included studies were reviewed for applicable articles that were not captured by the initial broad search strategy. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) trial flow chart shows the study selection algorithm (Figure 1).

Table 1. Inclusion and Exclusion Criteria for the Analyzed Studies

DATA EXTRACTION AND ANALYSIS

Data were extracted from the included studies by 2 reviewers using data abstraction forms. All study, subject, and surgery parameters were collected. The study and subject demographic parameters analyzed included year of publication, level of evidence, presence of study financial conflict of interest, number of subjects and elbows, gender, age, proportion in whom the dominant extremity was involved, proportion who were laborers, proportion who had a workman’s compensation claim, duration of symptoms prior to surgical intervention, and surgical technique employed (open, arthroscopic, or percutaneous). We recorded the following clinical outcomes: proportion of patients with complete pain relief, proportion who were partially or completely satisfied, proportion who were improved, duration to return to work, grip strength, Disabilities of the Arm, Shoulder, and Hand (DASH) score, visual analog scale (VAS) pain score, and complication rate.

Continue to: Statistical analysis...

STATISTICAL ANALYSIS

Data from all studies were pooled and descriptive statistics were reported as weighted mean ± weighted standard deviation for continuous variables and frequency with percentage for categorical variables. A meta-analysis was performed for all outcome measures that were reported in 3 or more studies within a specific treatment cohort. Data were analyzed using 2-sample and 2-proportion Z-tests. Results were considered statistically significant at P < .05.

RESULTS

LITERATURE RESEARCH

Using the aforementioned search strategy, 154 studies were identified. Following application of the inclusion and exclusion criteria, 35 studies were included in the analysis (Figure 1). One study compared open and percutaneous techniques, and another compared arthroscopic and percutaneous techniques, rendering a total of 19 studies examining open surgical techniques for treatment of lateral epicondylitis,^3-21 12 studies examining arthroscopic techniques,^14,22-32 and 6 studies reporting percutaneous surgical treatment of lateral epicondylitis^29,33-37 (Table 2). There was1 level I study (3%), 6 level III studies (17%), and 28 level IV studies (80%).

Table 2. Study Demographic Data for Open, Arthroscopic, and Percutaneous Lateral Epicondylectomy

Abbreviations: AJO, The American Journal of Orthopedics; AJSM, American Journal of Sports Medicine; Arthroscopy, The Journal of Arthroscopy and Related Surgery; CORR, Clinical Orthopaedics & Related Research; JHS, Journal of Hand Surgery; JOS, Journal of Orthopaedic Surgery; JSES, Journal of Shoulder and Elbow Surgery; KSSTA, Knee Surgery, Sports Traumatology, and Arthroscopy.

SUBJECT DEMOGRAPHICS

The 35 included studies comprised 1579 patients and 1640 elbows. Among these, 1055 (64%) elbows underwent open (O), 401 (25%) underwent arthroscopic (A), and 184 (11%) underwent percutaneous (P) treatment. The average age was 45.7 years, 47% of the patients were male, 43% were laborers, 31% had worker’s compensation claims, and the dominant extremity was involved in 62% of patients. The percutaneous cohort was older than the open cohort (P = 46.9, O = 45.4, A = 45.8; P = .036). The duration of symptoms was shorter in the percutaneous cohort than in the other 2 groups and shorter in the arthroscopic cohort than in the open cohort (P = 8 months, O = 23 months, A = 18 months; P < .001). There were no significant differences between groups regarding gender, occupation, worker’s compensation status, or involvement of the dominant extremity (Table 3).

Table 3. Subject Demographics for Open, Arthroscopic, and Percutaneous Groups

MATA-ANALYSIS CLINICAL OUTCOMES

Clinical outcome results were pooled for all studies reporting the same outcome measure for the same technique (open, arthroscopic, or percutaneous). A meta-analysis was performed for all outcome measures that were reported in a minimum of 3 studies utilizing the same surgical technique (Table 4).

PAIN RELIEF

Thirteen open studies,^{3,5,7,8,11-16,18,19,21} 7 arthroscopic studies^{14,22-24,26,27,31} and 0 percutaneous studies reported the proportion of patients who were pain free at final follow-up. The proportion of patients who were pain free following open débridement was greater than that in the arthroscopic cohort (O = 70%, A = 60%; P = .009) (Table 4).

Continue to: Subjective improvement and satisfaction...

SUBJECTIVE IMPROVEMENT AND SATISFACTION

Nine open studies, 6 arthroscopic studies, and 1 percutaneous study reported the proportion of patients who felt that their condition had been improved as a result of surgery. There was no difference in the proportion of patients who experienced improvement between the open and arthroscopic cohorts. Four open studies,^3,11,12 5 arthroscopic studies,^{22,26,28,29,32} and 2 percutaneous studies^29,36 reported the proportion of patients who were satisfied or partially satisfied with the results of the procedure. There was no difference between the open and arthroscopic groups in the proportion of patients who were satisfied or partially satisfied (Table 4).

RETURN TO WORK

The duration to return to work following surgery was reported in 5 open studies,^4,5,10,13,14 9 arthroscopic studies,^14,23-29,32 and 2 percutaneous studies.^29,36 There was no statistically significant difference between the open and arthroscopic groups with regard to duration to return to work (O = 6.5 weeks, A = 6 weeks; P = .601). The percutaneous technique could not be included in the meta-analysis due to the presence of only 2 studies, but the pooled mean duration to return to work in these 2 studies was 5.5 weeks (Table 4).

GRIP STRENGTH

Postoperative grip strength was reported in 2 open studies,^10,19 4 arthroscopic studies,^28,30,32 and 2 percutaneous studies.^35-36 A meta-analysis could not be performed on all the groups due to the presence of only 2 open and 2 percutaneous studies reporting grip strength. The pooled averages were O = 38.3 kg, A = 34.8 kg, and P = 27.1 kg (Table 4).

DASH SCORE

The postoperative DASH score was reported in 4 open studies,^{4,15,17,19,20} 5 arthroscopic studies,^28-31 and 3 percutaneous studies.^29,33,36 At final follow-up, the mean DASH score was higher in the arthroscopic group than in the open and percutaneous groups (A = 12.8, O = 19.5, P = 25.3; P < .001 for both comparisons), and the mean DASH score was significantly higher in the open group than in the percutaneous group (P = .029). The reporting of DASH scores in the early postoperative period was not sufficiently consistent to allow us to test our hypothesis that there would be early differences in function between groups (Table 4).

VAS PAIN SCORE

Postoperative VAS pain scores were reported in 11 open studies,^{6,8-10,12,15,19-21} 8 arthroscopic studies,^24-26,29-32 and 5 percutaneous studies.^29,33,35-37 At final follow-up, there was a lower mean VAS score in the arthroscopic group than in the open and percutaneous groups (A = 1.1, O = 1.9, and P = 2.5; P < .001 for both comparisons) and a lower mean VAS score in the open group than in the percutaneous group (P = .002) (Table 4). Reporting of VAS scores in the early postoperative period in the included studies wan not sufficiently consistent to allow us to test our hypothesis that there would be early differences in pain between groups.

COMPLICATIONS

The complication rate was reported in 15 open studies, 10 arthroscopic studies, and 3 percutaneous studies. There was no difference in the complication rate between the open and arthroscopic techniques (O = 2.4%, A = 1.9%; P = .629) (Table 4). Complications noted in the open cohort included superficial wound infection (6), hematoma (5), synovial fistula (2), seroma (2), and posterior interosseous nerve palsy (1). Complications noted in the arthroscopic cohort included superficial infection (3), hematoma (1), and transient paresthesia (1). Of note, there were no complications in the percutaneous group.

Continue to: Discussion...

DISCUSSION

The primary purpose of this review was to determine if definitive evidence suggests that any 1 of open, percutaneous, or arthroscopic surgical treatment is superior to the other 2 for relieving pain, improving functionality, restoring strength, or accelerating return to work. The most striking finding of this study was a significantly higher proportion of patients who were pain free at final follow-up in the open group than in the arthroscopic group (70% vs 60%, P = .009) (Table 4). At final follow-up, there were no significant differences between groups regarding duration to return to work, proportion who were improved, proportion who were satisfied or partially satisfied, and complication rate. Average VAS and DASH scores at final follow-up were lower in the arthroscopic group than in the open and percutaneous groups (Figure 2). However, although the difference between mean DASH scores in the arthroscopic and open groups (6.7 points) was statistically significant, it is likely not clinically significant, as the minimal clinically important difference (MCID) for the DASH score is 10 points, as demonstrated by Sorensen and colleagues.³⁸ Although it has not been specifically defined for lateral epicondylitis, the MCID for VAS pain has been reported in the literature to range from 1.0 to 1.4.^39-40 Therefore, as for the DASH score, the difference witnessed between the open and arthroscopic groups (0.8) is likely not clinically significant. Of note, the differences between values for arthroscopic and percutaneous techniques are greater than the MCID.

In light of a recent increase in the prevalence of surgical intervention for lateral epicondylitis, many authors have promoted arthroscopic and percutaneous techniques as alternatives to traditional open débridement with the goal of achieving the same results with decreased morbidity and accelerated return to work. Given the increased proportion of patients who were pain free at final follow-up in the open cohort, it is our contention that open release/débridement of the common extensor/ECRB origin allows the surgeon to fully appreciate the extent of tendinotic tissue that is contributing to the patient’s symptoms and to address the pathology in its entirety. Other authors have also questioned whether the full extent of extra-articular tendinosis can be accurately identified arthroscopically. Cummins⁴¹ demonstrated, in a series of 18 patients who underwent arthroscopic ECRB débridement, that 6 patients had residual tendinosis upon open evaluation and 10 had residual tendinosis on histologic assessment. Additionally, in the same series, residual tendinopathy was associated with poorer clinical outcomes.

The improved visualization associated with an open technique comes at minimal expense, as the incision was only 1.5 cm to 5 cm in 13 of 15 papers reporting incision length.^{3,4,6,8-11,13,15,18-20} This increased exposure may not translate into increased morbidity, as there was no increase in the duration to return to work nor the complication rate. As a result of the extensive instrumentation necessary for arthroscopic techniques, open techniques also appear to be less expensive. Analyses in the literature have suggested increased expenditures associated with arthroscopic treatment ranging from 23%⁴² to 100%⁴³ greater than those of open treatment.

Although obvious, it should be noted that a percutaneous tenotomy does not permit assessment of the extent of pathologic tendinosis. As a result of an inability to visualize and débride pathologic tissue, percutaneous tenotomy rendered inferior outcomes to open and arthroscopic techniques in terms of both postoperative VAS pain score and DASH score. Nonetheless, it is a relatively rapid and simple technique and resulted in zero complications in 184 elbows. Overall, percutaneous tenotomy appears to be an inferior technique to open and arthroscopic techniques in terms of achieving complete pain relief and optimal functional recovery; however, it may be useful in those who wish to avoid a more invasive intervention.

LIMITATIONS

The most significant limitation of this study was the heterogeneity in the techniques utilized in each group. Among the 19 papers in the open cohort, 11 used techniques aimed at lengthening or release of the extensor origin, 7 performed débridement of tendinotic tissue at the ECRB origin, and 1 compared these approaches. Exposures ranged from 1.5 cm to 8 cm in length, 3 techniques added tendon repair following débridement, and 2 utilized a radiofrequency device.

Among the 12 papers in the arthroscopic cohort, 8 performed arthroscopic (inside-out) débridement of the tendinotic tissue at the ECRB origin, 3 performed arthroscopic release of the ECRB tendon, and 1 performed endoscopic ECRB release in an outside-in fashion. Four techniques added posterior synovial plica excision and 4 added decortication of the lateral epicondyle débridement or release. Some authors advocate for arthroscopic intervention on the grounds that it permits evaluation and correction of other intra-articular pathology. With this in mind, some authors have suggested that a synovial fold (plica) adjacent to the radiocapitellar joint may contribute to lateral elbow pain.^27,44 Nevertheless, in the only comparative trial in the literature, Rhyou and Kim³⁰ demonstrated that excision of posterior synovial fold failed to enhance pain relief or function in a retrospective cohort study comparing arthroscopic débridement with and without plica excision.

Continue to: Some authors advocate...

Some authors advocate decorticating the non-articular, lateral epicondyle with a shaver to stimulate bleeding and promote a healing response. However, 1 study in our review compared arthroscopic ECRB release with and without decortication and found that decortication significantly increased pain up to 4 weeks postoperatively, increased duration to return to work, and did not improve the ultimate clinical result.²⁵ Of note, others have used a similar rationale to advocate drilling the lateral epicondyle when utilizing an open technique. However, Dunn and colleagues⁸ note that they have modified the Nirschl technique to eliminate drilling because they feel it increases postoperative pain and may damage the extensor digitorum communis origin.

Among the 6 papers in the percutaneous tenotomy cohort, 2 performed tenotomy with a hypodermic needle, 2 with a scalpel through a limited incision (0.5 cm-1 cm), 1 using a TX1 tissue removal system (Tenex Health), and 1 with a percutaneous radiofrequency probe. In 3 techniques, ultrasound was used to direct the tenotomy.

The quality of this review is also limited by the studies included for analysis, as with any systematic review. Because 28 of the 35 included studies were classified as evidence level IV, the likelihood of methodological bias is increased. The majority of studies contained ≥1 demonstrable biases, including selection, detection, attrition biases, or a combination. Selection bias is prevalent among predominantly level IV studies, in which the authors have selected their preferred surgical technique. There was heterogeneity in the reporting of preoperative variables and the outcome measures that were utilized. Scoring systems, such as the Nirschl Tennis Elbow Score and the Mayo Elbow Performance Index, would have been valuable in comparing the groups had they been more consistently reported. The heterogeneity in clinical outcome tools and the lack of reported outcome variance or standard deviations prevented a formal meta-analysis of some of these outcome measures. Due to inconsistent reporting, we were also unable to test our hypothesis that there would be less pain and improved function in the arthroscopic and/or percutaneous cohorts in the early postoperative period compared to the open cohort due to the less invasive techniques used. Although the differences in DASH and VAS scores at final follow-up likely did not meet the MCID threshold, these differences may have been greater and more clinically relevant in the early postoperative period.

CONCLUSION

We hypothesized that the arthroscopic and percutaneous groups would experience accelerated return to work and reduced pain in the early postoperative period but no difference in ultimate pain, functional outcome, or subjective satisfaction. There is no difference between open, arthroscopic, and percutaneous surgical treatment for lateral epicondylitis regarding return to work and subjective satisfaction; however, open treatment led to a greater percentage of patients being pain free at final follow-up. While arthroscopic treatment led to better pain and functional scores at final follow-up, the absolute differences were quite small and likely not clinically significant. In light of the available evidence, we recommend open débridement as the best means of minimizing cost and achieving a pain-free outcome in the long term. For future investigators, it would be useful to perform a randomized clinical study directly comparing open, arthroscopic, and percutaneous techniques, including assessment of pain and functional scores in the early postoperative period, and to further evaluate differences in cost among the various techniques.

This paper will be judged for the Resident Writer’s Award.

ABSTRACT

This study was performed to compare outcomes of open, arthroscopic, and percutaneous surgical techniques for lateral epicondylitis. We searched PubMed (MEDLINE) for literature published between January 1, 2004 and May 23, 2015 using these key words: lateral epicondylitis AND (surgery OR operative OR surgical OR open OR arthroscopic OR percutaneous). Meta-analyses were performed for outcomes reported in 3 studies using 2-sample and 2-proportion Z-tests. Thirty-five studies including 1640 elbows (1055 open, 401 arthroscopic, 184 percutaneous) met the inclusion criteria. There were no differences between groups regarding duration to return to work, complication rate, or patient satisfaction. A greater proportion of patients were pain free in the open group than in the arthroscopic group (70% vs 60%). Despite the absence of a difference among techniques regarding return to work and subjective function, we recommend open débridement as the technique most likely to achieve a pain-free outcome.

Continue to: Lateral epicondylitis affects...

Lateral epicondylitis affects 1% to 3% of adults each year. Although common, symptoms of lateral epicondylitis resolve spontaneously within a year of symptom onset in 80% of cases, and only 3% of patients who seek medical treatment ultimately require surgical intervention within 2 years of symptom onset.¹ Despite a relatively low percentage of patients who require surgery, Sanders and colleagues¹ noted a significant increase in the rate of surgical intervention from 1.1% to 3.2% of cases in the last 15 years. Surgical intervention is generally indicated when pain and functional disability persist after 6 to 12 months of nonsurgical treatment. Traditional surgical treatment involves open release/débridement of the extensor carpi radialis (ECRB) origin; however, with the increasing prevalence of surgical intervention, surgeons have demonstrated a rising interest in less invasive techniques like arthroscopic release/débridement and percutaneous tenotomy as alternatives to traditional open débridement. While favorable results have been reported for all 3 techniques, there is no current consensus regarding the optimal surgical technique. In 2007, Lo and Safran² reported no difference in the results of open, percutaneous, and arthroscopic techniques regarding any outcome measure in a systematic review of 33 papers. We conducted a repeat systematic review of the current literature to update Lo and Safran’s² review and to ascertain if more recent literature demonstrates superiority of 1 technique regarding pain relief, subjective questionnaire data, subjective satisfaction, restoration of strength, and return to work. We hypothesized that return to work would be accelerated, pain decreased, and function improved in the early postoperative period in the arthroscopic and percutaneous groups, but there would be no difference in ultimate pain, functional outcome, or subjective satisfaction.

METHODS

SEARCH STRATEGY AND STUDY SELECTION

We conducted a systematic review of the literature to update the topic of surgical intervention with lateral epicondylitis since the publication of the most recent review by Lo and Safran² in 2007, which included all relevant studies published up to 2004. To include all relevant studies published since that time, we searched PubMed (MEDLINE) for all literature published from January 1, 2004 to May 23, 2015 using the following key words: lateral epicondylitis AND (surgery OR operative OR surgical OR open OR arthroscopic OR percutaneous). General search terms were utilized to avoid unintentional exclusion of relevant studies. Two authors reviewed the abstracts of all resultant citations. Table 1 outlines the inclusion and exclusion criteria for the search. References from all included studies were reviewed for applicable articles that were not captured by the initial broad search strategy. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) trial flow chart shows the study selection algorithm (Figure 1).

Table 1. Inclusion and Exclusion Criteria for the Analyzed Studies

DATA EXTRACTION AND ANALYSIS

Data were extracted from the included studies by 2 reviewers using data abstraction forms. All study, subject, and surgery parameters were collected. The study and subject demographic parameters analyzed included year of publication, level of evidence, presence of study financial conflict of interest, number of subjects and elbows, gender, age, proportion in whom the dominant extremity was involved, proportion who were laborers, proportion who had a workman’s compensation claim, duration of symptoms prior to surgical intervention, and surgical technique employed (open, arthroscopic, or percutaneous). We recorded the following clinical outcomes: proportion of patients with complete pain relief, proportion who were partially or completely satisfied, proportion who were improved, duration to return to work, grip strength, Disabilities of the Arm, Shoulder, and Hand (DASH) score, visual analog scale (VAS) pain score, and complication rate.

Continue to: Statistical analysis...

STATISTICAL ANALYSIS

Data from all studies were pooled and descriptive statistics were reported as weighted mean ± weighted standard deviation for continuous variables and frequency with percentage for categorical variables. A meta-analysis was performed for all outcome measures that were reported in 3 or more studies within a specific treatment cohort. Data were analyzed using 2-sample and 2-proportion Z-tests. Results were considered statistically significant at P < .05.

RESULTS

LITERATURE RESEARCH

Using the aforementioned search strategy, 154 studies were identified. Following application of the inclusion and exclusion criteria, 35 studies were included in the analysis (Figure 1). One study compared open and percutaneous techniques, and another compared arthroscopic and percutaneous techniques, rendering a total of 19 studies examining open surgical techniques for treatment of lateral epicondylitis,^3-21 12 studies examining arthroscopic techniques,^14,22-32 and 6 studies reporting percutaneous surgical treatment of lateral epicondylitis^29,33-37 (Table 2). There was1 level I study (3%), 6 level III studies (17%), and 28 level IV studies (80%).

Table 2. Study Demographic Data for Open, Arthroscopic, and Percutaneous Lateral Epicondylectomy