Opioid Overdose Deaths with Buprenorphine Detected in Postmortem Toxicology: a Retrospective Analysis.

BACKGROUND: Buprenorphine is a unique µ-opioid receptor partial agonist with avid receptor binding, nominal euphoric reward, and a ceiling effect on sedation and respiratory depression. Despite a pharmacologic profile that enhances safety, cases of fatal opioid overdose with buprenorphine on postmortem toxicology are reported, but details of these cases in the literature are limited. METHODS: A retrospective review of opioid-involved drug overdose fatalities in Rhode Island (RI) from 2016 to 2018 using the RI Department of Health State Unintentional Drug Overdose Reporting System (SUDORS) database. Deaths with buprenorphine on toxicology testing versus opioid-involved overdose deaths without buprenorphine were compared to assess the type and number of co-exposures. RESULTS: Of 534 opioid-involved deaths, 29 (5.4%) included buprenorphine and/or norbuprenorphine on toxicology. Most frequent co-exposures are as follows: fentanyl (75.9%), norfentanyl (72.4%), cocaine (41.4%), benzoylecgonine (41.4%), cannabinoids (31.0%), ethanol (31.0%), levamisole (31.0%), and free morphine (31.0%). An average number of co-exposures for fatalities with buprenorphine were 9.24 versus 6.68 in those without buprenorphine. In one case buprenorphine was the only drug listed to cause death; all other fatalities with buprenorphine on toxicology reported additional drugs contributing to death. CONCLUSION: Decedents with buprenorphine detected on toxicology testing commonly had documented polysubstance use. Although data are limited, buprenorphine may provide some risk mitigation against full agonist opioid overdose including fentanyl. Further work should explore the use of postmortem concentrations of buprenorphine, norbuprenorphine, and other opioid metabolites to determine the role of buprenorphine in fatal overdose pharmacology.

Incidence of Treatment for Opioid Use Disorder Following Nonfatal Overdose in Commercially Insured Patients.

Importance: Timely initiation and referral to treatment for patients with opioid use disorder seen in the emergency department is associated with reduced mortality. It is not known how often commercially insured adults obtain follow-up treatment after nonfatal opioid overdose. Objective: To investigate the incidence of follow-up treatment following emergency department discharge after nonfatal opioid overdose and patient characteristics associated with receipt of follow-up treatment. Design, Setting, and Participants: A retrospective cohort study was conducted using an administrative claims database for a large US commercial insurer, from October 1, 2011, to September 30, 2016. Data analysis was performed from May 1, 2019, to September 26, 2019. Adult patients discharged from the emergency department after an index opioid overdose (no overdose in the preceding 90 days) were included. Patients with cancer and without continuous insurance enrollment were excluded. Main Outcomes and Measures: The primary outcome was follow-up treatment in the 90 days following overdose, defined as a combined outcome of claims for treatment encounters or medications for opioid use disorder (buprenorphine and naltrexone). Analysis was stratified by whether patients received treatment for opioid use disorder in the 90 days before the overdose. Logistic regression models were used to identify patient characteristics associated with receipt of follow-up treatment. Marginal effects were used to report the average adjusted probability and absolute risk differences (ARDs) in follow-up for different patient characteristics. Results: A total of 6451 patients were identified with nonfatal opioid overdose; the mean (SD) age was 45.0 (19.3) years, 3267 were women (50.6%), and 4676 patients (72.5%) reported their race as non-Hispanic white. A total of 1069 patients (16.6%; 95% CI, 15.7%-17.5%) obtained follow-up treatment within 90 days after the overdose. In adjusted analysis of patients who did not receive treatment before the overdose, black patients were half as likely to obtain follow-up compared with non-Hispanic white patients (ARD, -5.9%; 95% CI, -8.6% to -3.6%). Women (ARD, -1.7%; 95% CI, -3.3% to -0.5%) and Hispanic patients (ARD, -3.5%; 95% CI, -6.1% to -0.9%) were also less likely to obtain follow-up. For each additional year of age, patients were 0.2% less likely to obtain follow-up (95% CI, -0.3% to -0.1%). Conclusions and Relevance: Efforts to improve the low rate of timely follow-up treatment following opioid overdose may seek to address sex, race/ethnicity, and age disparities.

Opioid Prescribing in a Cross Section of US Emergency Departments.

STUDY OBJECTIVE: Opioid pain reliever prescribing at emergency department (ED) discharge has increased in the past decade but specific prescription details are lacking. Previous ED opioid pain reliever prescribing estimates relied on national survey extrapolation or prescription databases. The main goal of this study is to use a research consortium to analyze the characteristics of patients and opioid prescriptions, using a national sample of ED patients. We also aim to examine the indications for opioid pain reliever prescribing, characteristics of opioids prescribed both in the ED and at discharge, and characteristics of patients who received opioid pain relievers compared with those who did not. METHODS: This observational, multicenter, retrospective, cohort study assessed opioid pain reliever prescribing to consecutive patients presenting to the consortium EDs during 1 week in October 2012. The consortium study sites consisted of 19 EDs representing 1.4 million annual visits, varied geographically, and were predominantly academic centers. Medical records of all patients aged 18 to 90 years and discharged with an opioid pain reliever (excluding tramadol) were individually abstracted by standardized chart review by investigators for detailed analysis. Descriptive statistics were generated. RESULTS: During the study week, 27,516 patient visits were evaluated in the consortium EDs; 19,321 patients (70.2%) were discharged and 3,284 (11.9% of all patients and 17.0% of discharged patients) received an opioid pain reliever prescription. For patients prescribed an opioid pain reliever, mean age was 41 years (SD 14 years) and 1,694 (51.6%) were women. Mean initial pain score was 7.7 (SD 2.4). The most common diagnoses associated with opioid pain reliever prescribing were back pain (10.2%), abdominal pain (10.1%), and extremity fracture (7.1%) or sprain (6.5%). The most common opioid pain relievers prescribed were oxycodone (52.3%), hydrocodone (40.9%), and codeine (4.8%). Greater than 99% of pain relievers were immediate release and 90.0% were combination preparations, and the mean and median number of pills was 16.6 (SD 7.6) and 15 (interquartile range 12 to 20), respectively. CONCLUSION: In a study of ED patients treated during a single week across the country, 17% of discharged patients were prescribed opioid pain relievers. The majority of the prescriptions had small pill counts and almost exclusively immediate-release formulations.

A review of emergency cardiopulmonary bypass for severe poisoning by cardiotoxic drugs.

Cardiovascular collapse remains a leading cause of death in severe acute drug intoxication. Commonly prescribed medications such as antidysrhythmics, calcium channel antagonists, and beta adrenergic receptor antagonists can cause refractory cardiovascular collapse in massive overdose. Emergency cardiopulmonary bypass (ECPB), a modality originating in cardiac surgery, is a rescue technique that has been successfully implemented in the treatment of refractory cardiogenic shock and cardiac arrest unresponsive to traditional medical interventions. More recently a growing number of animal studies, case reports, and case series have documented its use in refractory hemodynamic collapse in poisoned patients. This article will review current ECPB techniques and explore its growing role in the treatment of severely hemodynamically compromised poisoned patients.

A 52-year-old man with malaise and a petechial rash.

BACKGROUND: Capnocytophaga canimorsus is a Gram-negative, fusiform, rod-shaped organism that is part of the normal oral flora of dogs, cats, and other animals. A significant number of Emergency Department (ED) patients are surgically or functionally asplenic and may be at marked risk for overwhelming post-splenectomy infection (OPSI). OPSI has a mortality rate estimated to be up to 70%. The risk of sepsis is estimated to be 30-60 times greater after splenectomy, and C. canimorsus is one of the organisms that can cause catastrophic OPSI. OBJECTIVES: To describe a case of C. canimorsus septic shock in a post-splenectomy patient and review the epidemiology of OPSI, the role of the spleen in protecting the body from infection, and the potential role of early goal-directed therapy in the resuscitation of patients with OPSI. CASE REPORT: A 52 year-old man with a past medical history significant for idiopathic thrombocytopenic purpura (status post-splenectomy), and non-Hodgkin lymphoma (treated for cure), was brought to the ED with the chief complaints of light-headedness, malaise, and a rapidly spreading rash. He was found to be hypotensive, tachycardic, and tachypneic, and had a marked lactic acidosis. He was aggressively resuscitated with large volume fluid resuscitation and treated empirically with broad-spectrum antibiotics for septic shock of unclear etiology. His clinical course was complicated by acute lung injury and renal failure. Blood cultures grew C. canimorsus; he was extubated on hospital day 7 and discharged home several days later in good condition. CONCLUSIONS: Patients status-post-splenectomy are at greatly increased risk for infection from encapsulated organisms and other organisms, including C. canimorsus, which is part of the normal oral flora of dogs, cats, and other animals. It can be spread to humans by bites, scratches, or less invasive forms of animal-human contact. C. canimorsus infection can lead to OPSI. Early recognition and aggressive clinical management, including early goal-directed therapy and rapid administration of antibiotics, may minimize the morbidity and mortality of this condition and other etiologies of severe sepsis and septic shock.

Acetaminophen-induced nephrotoxicity: pathophysiology, clinical manifestations, and management.

UNLABELLED: Acetaminophen-induced liver necrosis has been studied extensively, but the extrahepatic manifestations of acetaminophen toxicity are currently not described well in the literature. Renal insufficiency occurs in approximately 1-2% of patients with acetaminophen overdose. The pathophysiology of renal toxicity in acetaminophen poisoning has been attributed to cytochrome P-450 mixed function oxidase isoenzymes present in the kidney, although other mechanisms have been elucidated, including the role of prostaglandin synthetase and N-deacetylase enzymes. Paradoxically, glutathione is considered an important element in the detoxification of acetaminophen and its metabolites; however, its conjugates have been implicated in the formation of nephrotoxic compounds. Acetaminophen-induced renal failure becomes evident after hepatotoxicity in most cases, but can be differentiated from the hepatorenal syndrome, which may complicate fulminant hepatic failure. The role of N-acetylcysteine therapy in the setting of acetaminophen-induced renal failure is unclear. This review will focus on the pathophysiology, clinical features, and management of renal insufficiency in the setting of acute acetaminophen toxicity. CASE: A 47-year-old female was found lethargic at home and brought by ambulance to an emergency department. History from family members suggested an inadvertent acetaminophen overdose, and she had last been seen a few hours earlier. She reportedly ingested 18 tablets of 500 mg acetaminophen (APAP) over the previous two days because she had run out of her prescription pain medication. Her past medical history was significant for fibromyalgia, arthritis, and a prior gastric bypass procedure. She had no history of alcohol abuse or renal insufficiency. She was lethargic. Vital signs: BP 128/96 mmHg, pulse 112/min, respirations 32/min; pulse oximetry 98% on 2L nasal cannula oxygen. Laboratory studies: BUN 9 mg/dL, creatinine 0.9 mg/dl, acetaminophen 12 mcg/mL, AST 5409 u/L and ALT 1085 u/L. A urinalysis was negative for blood with trace protein and ketones. A urine drug screen was positive for marijuana and opioid metabolites. At the initial hospital, she was treated with N-acetylcysteine (NAC) orally. Subsequently, she developed fulminant hepatic failure with elevated transaminases, hypoglycemia, and coagulopathy (Tables 1A and 1B). She was transferred to our facility two days after initial presentation for liver transplant evaluation. At that time, her APAP level was 2.0 mg/L. Oral NAC therapy was continued after transfer. The patient's liver function subsequently improved and she ultimately did not require transplantation. She did develop acute renal failure during the course of her hospitalization, with a creatinine of 2.3 mg/dL on transfer, which increased to 8.1 mg/dL nine days later (approximately 11-13 days post-ingestion). Medical toxicology was consulted by the intensive care unit team to address whether this was acetaminophen-induced renal failure and if there was a role for NAC in this setting.

Torsade de pointes caused by polypharmacy and substance abuse in a patient with human immunodeficiency virus.

Drug-induced QT prolongation is a potentially dangerous adverse effect of some medication combinations. When QT prolongation progresses to torsade de pointes, life-threatening or fatal outcomes may result. A 57-year-old man with a history of human immunodeficiency syndrome on abacavir, nevirapine, tenofovir, voriconazole, and methadone presented to the emergency department with a chief complaint of new-onset seizures. The physical exam was unremarkable. The electrocardiogram demonstrated sinus bradycardia and a prolonged QT(c) interval of 690 ms. In the emergency department, he had several episodes of torsade de pointes (TdP) and ventricular tachycardia that resolved spontaneously. These episodes were accompanied by an alteration in mentation and generalized twitching. Magnesium and amiodarone were effective in terminating the dysrhythmia. The patient had multiple risk factors for prolonged QT syndrome including human immunodeficiency virus infection, methadone therapy, and polypharmacy leading to potential drug interactions. Physicians must be aware of multidrug interactions potentiating QT prolongation and leading to torsade de pointes.

Emergency Department evaluation of patients with fever and chemotherapy-induced neutropenia.

We sought to describe the common causes of infection in patients presenting to the Emergency Department (ED) with elevated temperature and chemotherapy-induced neutropenia and to determine the frequency with which the ED diagnosis of infection is consistent with the final hospital discharge diagnosis. We performed a structured restrospective chart review of ED patients with fever (T > 38 degrees C) and neutropenia (absolute neutrophil count < 1000/mm(3)) over a 2-year period. Fifty-five episodes of neutropenic fever occurred in 52 patients (mean age 52 years, range 18-86 years; 53% men). Twenty-six patients (47%) were found to have a specific infection identified. Of these, 21/26 (81%; 95% CI, 70-91%) had the source of infection identified while in the ED. All patients who had a focal site of infection identified during their hospitalization were diagnosed in the ED (100%; 95% CI, 86-100%). The other 5 patients, without a source identified in the ED, were found to have bacteremia. The 29 patients without a source identified in the ED were hospitalized and had negative blood and urine cultures and were discharged to home after resolution of fever. A thorough history, physical examination, chest radiograph and urinalysis in the ED identified all patients with a focus of infection. Meticulous ED evaluation of patients with neutropenia and fever may be sufficient to diagnose most sources of infection; however, a significant number of patients without an identifiable focus may have bacteremia.