Stronger, longer, better opioid antagonists? Nalmefene is NOT a naloxone replacement.

The fatal overdose crisis claims nearly 200 lives daily in the United States (U.S). Evolutions in the illicit drug supply, such as the addition of sedative adulterants and a shift to synthetic opioids such as fentanyl, have driven increasing rates of both fatal and non-fatal overdose. Specifically, synthetic opioid usage of fentanyl was implicated in 68 % of the U.S. drug overdose deaths in 2022 alone. This has placed tremendous burden on communities, emergency medical services, and healthcare systems, and contributed to tragedy and grief both in the U.S. and worldwide. Despite the availability of effective opioid antagonist medications and standards of care, there has been increased interest in research and development of alternative opioid overdose reversal agents by the National Institutes of Health (NIH) in partnership with pharmaceutical manufacturers over the last decade. The U.S. Food and Drug Administration (FDA) recently approved nalmefene (Opvee) a mu-opioid receptor antagonist that boasts an extended half-life and stronger mu-receptor affinity compared to the standard of care use of naloxone for opioid reversal. In this article, we explore the medical need and ramifications of the introduction of longer-acting opioid antagonists in the current opioid overdose landscape. Existing data highlight the effectiveness of already available naloxone products as a safe and effective standard of care. These data support the notion that stronger, longer-acting agents may be unnecessary, and their existence may cause undue harm, such as more severe and/or prolonged withdrawal symptoms, lead to challenging patient interactions, and complicate the initiation of medications for opioid use disorder. More evidence is needed before healthcare professionals should implement the use of stronger, longer-acting opioid antagonists for reversing opioid overdose over evidence-based, cost-effective naloxone.

Hypoglycemic Events in the Emergency Department.

BACKGROUND: In the United States, hypoglycemic events contribute to 100 000 emergency department (ED) visits, costing $120 million annually. Hypoglycemia hinders glycemic management in people living with diabetes. Glucagon is the first line of treatment for severe hypoglycemia that is administrable by a caregiver in a nonclinical setting. However, there is a paucity of evidence on how frequently glucagon is prescribed for the anticipatory management of hypoglycemia, especially in ED. METHODS: A retrospective study of patients seen with hypoglycemic events in an urban ED between 2016 and 2018 was performed to characterize gaps in prescription and use of glucagon for the anticipatory management of severe hypoglycemia. RESULTS: We identified 232 patients with a documented history of type 1 diabetes mellitus or type 2 diabetes mellitus who were seen in the ED with hypoglycemia. The majority of the patients were women (59%), African American (57%), and covered by public insurance (76%). Eighty-four percent of the patients had type 2 diabetes mellitus, 75% were receiving treatment with hypoglycemic medications, and 61% were receiving treatment with insulin. The prevalence of glucagon prescription was only 3% in this sample, and only 12% of the patients had received formal diabetes education in the year before the ED visit. CONCLUSION: Despite its proven efficacy in the management of severe hypoglycemia, glucagon is underused. This may be due to the lack of awareness, education, or training among both providers and patients. ED providers should be educated on prescribing glucagon and its use as a tool for the self-management of hypoglycemia. Patients at risk of hypoglycemia and their families need to be educated on the efficacy and use of glucagon.

Poor guideline adherence in a real-world evaluation of hypertensive emergency management.

BACKGROUND: The American College of Cardiology and American Heart Association define hypertensive emergency (HTN-E) as a systolic blood pressure greater than 180 mmHg or a diastolic blood pressure greater than 120 mmHg with evidence of end-organ damage (EOD). Based on expert opinion, current guidelines recommend antihypertensive therapy to reduce blood pressure (BP) at specific hourly rates to reduce progression of EOD, outlined by four criteria. Our goal was to describe compliance with guideline recommendations for early management of HTN-E and to analyze safety outcomes related to pharmacologic intervention. METHODS: This was a retrospective chart review including patients presenting to the emergency department with HTN-E between September 2016 and August 2020. We excluded patients with a compelling indication for altered therapeutic goals (e.g. acute aortic dissection, hemorrhagic or ischemic stroke, and pheochromocytoma). The primary outcome was complete adherence with guideline recommendations in the first 24 h. RESULTS: Of 758 screened records, 402 were included. Mean age was 54 years and majority Black race (72%). Overall, total adherence was poor (<1%): 30% received intravenous therapy within 1 h, 64% achieved 1-h BP goals, 44% achieved 6-h goals, and 9% had appropriate 24-h maintenance BP. Hypotensive events (N = 67) were common and antihypertensive-associated EOD (N = 21) did occur. Predictors of hypotension include treatment within 1 h and management with continuous infusion medication. CONCLUSIONS: Current practice is poorly compliant with guideline criteria and there are risks associated with recommended treatments. Our results favor relaxing the expert opinion-based recommendations.

Effect of an emergency department education and empowerment intervention on uncontrolled hypertension in a predominately minority population: The AHEAD2 randomized clinical pilot trial.

OBJECTIVE: To determine whether an emergency department (ED) education and empowerment intervention coupled with early risk assessment can help improve blood pressure (BP) in a high-risk population. METHODS: A hypertension emergency department intervention aimed at decreasing disparities (AHEAD2) is a 3-arm, single-site randomized pilot trial for feasibility in an urban academic ED. A total of 150 predominantly ethnic minorities with no primary care provider and severely elevated blood pressure (BP) (≥160/100 mm Hg) were enrolled over 10 months. Participants were randomized into 1 of 3 study arms: (1) enhanced usual care (EUC), (2) ED-initiated screening, brief intervention, and referral for treatment (ED-SBIRT), or (3) ED- SBIRT plus a 48-72 hours post-acute care hypertension transition clinic (ED-SBIRT+PACHT-c). Primary outcomes were change in systolic and diastolic BP (SBP and DBP) from baseline to 9 months. Secondary outcomes were BP control (BP <140/90 mm Hg), changes in hypertension knowledge, medication adherence, and limited bedside echocardiogram (LBE) findings. RESULTS: SBP reduction from baseline to month 9 was -26.8 (95% confidence interval [CI]: -32.8, -20.7) mm Hg for ED-SBIRT, -23.4 (95% CI: -29.5, -17.3) mm Hg for ED-SBIRT+PACHT-c, and -18.9 (95% CI: -24.9, -12.9) mm Hg for EUC. DBP decreased by -12.5 (95% CI: -16.1, -9.0) mm Hg for ED-SBIRT, -11.3 (95% CI: -14.8, -7.7) mm Hg for ED-SBIRT+PACHT-c, and -8.4 (95% CI: -11.9, -4.9) mm Hg for EUC. A multicomponent intervention compared with EUC resulted in SBP decrease of -7.9 mm Hg (95% CI: -16.4, 0.6). At 9 months, hypertension was controlled for 29.3% (95% CI: 20.3, 38.3) of intervention and 23.5% (95% CI: 11.9, 35.2) of EUC participants. All groups saw improvements in hypertension knowledge, medication adherence, and LBEs, with greater improvements in intervention groups. CONCLUSIONS: The study findings suggest that a multicomponent intervention comprising of ED education and empowerment coupled with early risk assessment may help improve BP in a high-risk population.

Factors Influencing Emergency Department Utilization and Hospital Re-Admissions in a Predominantly Obese, Racially Diverse Urban Renal Transplant Population.

INTRODUCTION: Early emergency department and hospital re-admissions are common in renal transplant recipients, but data are lacking in unique populations. Study Aim: The purpose of this study was to identify patient risk factors for multiple acute care utilization events within the first year of renal transplantation. DESIGN: This was a single-center, retrospective cohort study of adult renal transplant recipients between 9/2013-9/2016. Patients were compared across number of emergency department visits and by hospital re-admissions. Diagnoses were categorized. Univariate and multivariate logistic regression was used to assess risk for multiple acute care utilization events within the first 12 months post-transplant. RESULTS: A total of 216 patients were analyzed and were on average 50.5 (SD 13.9) years old, redominantly Black (49.77%) with an average body mass index of 33.33 (9.8) and were recipients of deceased donor renal transplants (61.11%). A total of 105 (48.6%) patients visited the emergency epartment and 119 (55.1%) patients had a hospital readmission. Patients having a body mass index >35 kg/m2 did not differ across emergency department visit or hospitalization groups. Delayed graft function (OR 2.86, 95% CI 1.07-7.65) and previous renal transplant (OR 2.77, 95% CI 1.04-7.39) were significantly associated with multiple acute care utilizations. DISCUSSION: Acute care utilization following renal transplantation was similar to previously reported experiences. Obesity did not impact use of acute care resources or patient outcomes. Strategies addressing potential preventable emergency visits and hospital re-dmissions should be promoted.

Rhabdomyolysis Secondary to Clenbuterol Use and Exercise.

BACKGROUND: The literature regarding rhabdomyolysis secondary to illicit drug use is sparse. Clenbuterol is a bronchodilator approved for veterinary use, which in high doses can increase protein deposition and lipolysis similarly to anabolic steroids, and is thereby abused for bodybuilding and weight loss effects. Clenbuterol has previously been described in case reports to be cardiotoxic, with patient presentations similar to overdoses of sympathomimetic substances, but reports of rhabdomyolysis are limited to a single case series in horses. CASE REPORT: We report the first case of rhabdomyolysis secondary to clenbuterol in a human. Our patient used clenbuterol for muscle-building effects in addition to exercise for multiple days prior to presentation. The patient's chief complaint at Emergency Department (ED) presentation was discolored urine. Workup for rhabdomyolysis was initiated, and an initial creatine kinase was measured at 122,933 units/L. Our patient's rhabdomyolysis was successfully treated with supportive therapy, and the patient was eventually discharged to home with no identifiable disability. The patient's kidney function remained at baseline, and no acute kidney injury was experienced secondary to rhabdomyolysis. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Patients presenting to the ED may have been unintentionally exposed through cutting of illicit substances or through intentional use in bodybuilding. Clenbuterol has well-described cardiotoxic effects, and we report the additional toxicity of rhabdomyolysis with its use.