Treatment of acute naloxone-precipitated opioid withdrawal with buprenorphine

Naloxone is a frequently utilized and effective treatment to reverse the life-threatening effects of illicit opioid intoxication. Excessive naloxone dosing in these circumstances, however, may lead to naloxone-precipitated opioid withdrawal in individuals with opioid dependence. Buprenorphine, a partial mu-opioid agonist, is increasingly utilized in the Emergency Department (ED) for the treatment of opioid withdrawal syndrome but little is known regarding its utility in cases of naloxone-precipitated opioid withdrawal. We report a case of naloxone-precipitated opioid withdrawal that was effectively treated with sublingual buprenorphine. An older male was brought into the ED with signs and symptoms of opioid toxicity that was successfully treated with pre-hospital naloxone by Emergency Medical Services. He had a clinical opioid withdrawal scale (COWS) or 10 with abdominal cramping and unintentional defecation. After a discussion of treatment options and possible adverse effects with the patient, the decision was made to administer 4 mg/1 mg of sublingual buprenorphine/naloxone film. The patient reported a rapid improvement in symptoms and at 30 min posttreatment, his COWS was 4. His COWS decreased to 3 at 1 h and this was sustained for 4 h of observation. The patient was subsequently discharged to a treatment facility for opioid use disorder. This case highlights the potential of buprenorphine as a treatment modality for acute naloxone-precipitated opioid withdrawal. Due to the risks of worsening or sustained buprenorphine-precipitated opioid withdrawal, further research is warranted to identify patients who may benefit from this therapy.     

One million screened: Scaling up SBIRT and buprenorphine treatment in hospital emergency departments across Maryland

PurposeIdentification of problematic alcohol use and substance use in the population has been a clinical challenge, especially during the heightened years of the opioid epidemic. Bringing Screening, Brief Intervention, and Referral to Treatment (SBIRT) to scale in medical settings, such as hospital emergency departments (EDs) could facilitate broad identification of substance use disorders, timely delivery of brief interventions, and successful linkages to treatment.ProceduresThis large-scale data analysis pulled electronic health record (EHR) data from 23 hospitals in the state of Maryland for over 1 million patient visits between July 2014 and November 2018.FindingsOf the 1,097,142 ED patients screened, 17.2% screened positive for problematic alcohol or any drug use in the previous 12 months. During this same period, 79,899 brief interventions were delivered, 15,961 referrals to outpatient treatment were made and 38.3% of those were successfully linked to treatment. Of the 950 patients exhibiting withdrawal symptoms, over two-thirds patients (70.1%; n = 666) were administered buprenorphine, 94.6% (n = 630) accepted a referral to buprenorphine treatment in the community, and 64.6% (n = 430) attended their first outpatient buprenorphine treatment visit. A total of 2382 patients presented to the ED with a suspected opioid overdose, over half were referred to the intervention program (53.8%) and 63.2% were successfully engaged by the PRCs in the ED.ConclusionsThis analysis supports the scalability of SBIRT in hospital EDs and presents an implementation model that can be replicated in EDs nationwide.     

Comparison of phenobarbital-adjunct versus benzodiazepine-only approach for alcohol withdrawal syndrome in the ED

ObjectivesTo compare a phenobarbital-adjunct versus benzodiazepine-only approach for the management of alcohol withdrawal syndrome in the emergency department (ED) with regard to the need for intensive care unit (ICU) admission, severity of symptoms on ED discharge, and complications.MethodsThis was a retrospective cohort study conducted in two academic EDs in the United States. Adult patients seen in the ED with a diagnosis of alcohol withdrawal syndrome were included. Patients were categorized into two groups based on whether phenobarbital was administered in the ED: 1) phenobarbital group (with or without benzodiazepines) or 2) non-phenobarbital group. The primary outcome measure was the need for ICU admission. Secondary outcomes included Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scores at ED discharge, and complications. Complications were a composite of death, need for intubation, hypotension or vasopressor use, seizures, and hospital acquired pneumonia.ResultsThe study cohort included 209 patients (phenobarbital = 97, non-phenobarbital = 112). The mean (standard deviation) age was 49 (12) years and 85% (n = 178) were male. A similar proportion of patients in the phenobarbital (14%, n = 14) and non-phenobarbital (11%, n = 12) groups required ICU admission (p = 0.529). The median CIWA-Ar score on ED discharge was 7 (IQR 4–12) points in the phenobarbital group and 7 (IQR 4–14) points in the non-phenobarbital group (p = 0.752). The occurrence of complications was also similar in the phenobarbital (9%, n = 9) and non-phenobarbital groups (11%, n = 10).ConclusionAdjunctive phenobarbital use in the ED for alcohol withdrawal syndrome did not result in decreased ICU admission, severity of symptoms, or complications.     

Phenobarbital for Acute Alcohol Withdrawal: A Prospective Randomized Double-blind Placebo-controlled Study

Background

Acute alcohol withdrawal syndrome (AAWS) is encountered in patients presenting acutely to the Emergency Department (ED) and often requires pharmacologic management.

Objective

We investigated whether a single dose of intravenous (i.v.) phenobarbital combined with a standardized lorazepam-based alcohol withdrawal protocol decreases intensive care unit (ICU) admission in ED patients with acute alcohol withdrawal.

Methods

This was a prospective, randomized, double-blind, placebo-controlled study. Patients were randomized to receive either a single dose of i.v. phenobarbital (10 mg/kg in 100 mL normal saline) or placebo (100 mL normal saline). All patients were placed on the institutional symptom-guided lorazepam-based alcohol withdrawal protocol. The primary outcome was initial level of hospital admission (ICU vs. telemetry vs. floor ward).

Results

There were 198 patients enrolled in the study, and 102 met inclusion criteria for analysis. Fifty-one patients received phenobarbital and 51 received placebo. Baseline characteristics and severity were similar in both groups. Patients that received phenobarbital had fewer ICU admissions (8% vs. 25%, 95% confidence interval 4–32). There were no differences in adverse events.

Conclusions

A single dose of i.v. phenobarbital combined with a symptom-guided lorazepam-based alcohol withdrawal protocol resulted in decreased ICU admission and did not cause increased adverse outcomes.     

Sedation - Effects of disorders of abuse on therapeutic efficacy (SEDATE): A retrospective cohort study

BackgroundThe impact of alcohol or opioid use disorders on medication dosing for procedural sedation in the emergency department (ED) is unclear, as most of the literature is from gastrointestinal endoscopy. Exploring how these patient factors affect sedative and analgesic medications may inform more nuanced sedation strategies in the emergency department.MethodsThis was a retrospective chart-review cohort study across five EDs from 2015 to 2020. Included were adult patients who underwent procedural sedation in the ED, categorized into three a priori groups: alcohol use disorder (AUD), opioid use disorder (OUD), and individuals with neither (non-SUD). Wilcoxon test was used to compare the time-averaged dose of agents between groups. Logistic regression was used to model multi-agent sedations. The propofol time-averaged dose was the primary outcome. Secondary outcomes included other agents, sedation duration, and switching to other agents.Results2725 sedations were included in the analysis. 59 patients had a history of AUD, and 40 had a history of OUD. Time-averaged doses of medications did not differ significantly between AUD and non-SUD patients. Likewise, patients with OUD did not receive different doses of medications compared to non-SUD. The propofol doses for non-SUD, AUD, and OUD were 0.033 IQR 0.04; 0.042 IQR 0.05; and 0.058 IQR 0.04 mg/kg*min, respectively. Sedation duration was not different across groups. Having AUD or OUD is not associated with increased odds of requiring multiple sedative agents.ConclusionAlthough sedation in patients with AUD or OUD may be associated with significant case bias, these patient factors did not significantly alter outcomes compared to the general population. This study suggests there is no evidence to proactively adjust medication strategy in ED patients with AUD or OUD.     

Use of buprenorphine in the treatment of opioid addiction. II. Physiologic and behavioral effects of daily and alternate-day administration and abrupt withdrawal

Nineteen heroin-dependent male volunteers were administered buprenorphine sublingually, in ascending daily doses of 2, 4, and 8 mg. They were maintained on 8 mg daily through study day 18. On study days 19 through 36, subjects in group 1 continued to receive burprenorphine daily; subjects in group 2 received buprenorphine or placebo on alternate days. On days 37 through 52, all subjects received placebo. Subjects receiving buprenorphine on alternate days reported significantly greater urge for an opioid, increased dysphoria scores, and pupillary dilation on placebo days. After abrupt termination of buprenorphine, no withdrawal signs were detected with the Himmelsbach scale. However, subjects reported mild-to-moderate opioid withdrawal symptoms, peaking at 3 to 5 and lasting for 8 to 10 days. Daily administration of buprenorphine provided greater control of subtle opioid withdrawal symptoms, but subjects could tolerate a between-dose interval of 48 hours.     

Rates of substance use disorder treatment seeking visits after emergency department-initiated buprenorphine

BackgroundEmergency department-initiated buprenorphine (EDIB) programs have been shown to improve treatment outcomes for patients with opioid use disorders (OUD); however, little is known about how EDIB implementation impacts the patient census at participating hospitals.ObjectivesTo determine if implementation of an EDIB program was associated with changes in the number of patients presenting to the ED seeking treatment for substance use disorder (SUD).MethodsWe conducted a retrospective evaluation at a single academic ED that began offering EDIB in December 2017. Data span the period of December 2016 to April 2019, All ED visits with a chief complaint of addiction problem, detoxification, drug/alcohol assessment, drug problem, or withdrawal charted by nursing at the time of triage were eligible for inclusion. Charts were reviewed to determine: (1) treatment status and (2) substance(s) for which the patient was seeking treatment. An interrupted time series analysis was used to compare the pre- and post-EDIB rates for all-substance, as well as opioid-specific, treatment-seeking visits.ResultsFor all-substance visits, the predicted level change in the treatment-seeking rate after EDIB was implemented was positive but not significant (0.000497, p = 0.53); the trend change after EDIB was also not significant (−0.00004, p = 0.73). For visits involving opioids, the predicted level change was (0.000638, p = 0.21); and the trend change was (0.000047, p = 0.49).ConclusionImplementation of an EDIB program was not associated with increased rates of presentation by patients requesting treatment for a substance use disorder in the participating ED setting.     

A novel social work approach to emergency department buprenorphine induction and warm hand-off to community providers

Study objectiveMedications for opioid use disorder (MOUD) is considered gold standard treatment for persons with an opioid use disorder and can be successfully initiated in emergency departments (EDBUP). Perceived provider barriers to EDBUP adoption include increased provider work, lack of provider knowledge about outpatient MOUD resources, and a lack of viable MOUD treatment options within health systems. We evaluated the feasibility of a novel EDBUP institutional design that utilizes the social work team to drive ED care for patients with OUD and coordinate MOUD referral to existing community resources.MethodsThis is a retrospective, cohort, single-center study describing patient outcomes in a social work driven EDBUP program with referral to community MOUD providers. ED patients with OUD were identified via patient request, standardized nurse screening, or ED provider concern. All identified patients received an urgent social work consult to explore willingness to seek treatment for OUD. Social workers developed individualized follow up plans with participating patients. Clinical data was abstracted from the Electronic Health Record. Social workers tracked continuity with outpatient MOUD services in a clinical care database.ResultsFrom June 1, 2018 through August 31, 2019, 120 patients opted for ED buprenorphine induction. 61% presented to initial outpatient intake appointment and 39% remained engaged in treatment after 30 days.ConclusionsEDs can effectively utilize the expertise of social workers to drive EDBUP and coordinate outpatient MOUD referrals. Our interdisciplinary EDBUP program structure is feasible and has the potential to yield meaningful reductions in physician workload and ED cost.     

Single dose phenobarbital in addition to symptom-triggered lorazepam in alcohol withdrawal

ObjectiveThe purpose of this study was to evaluate the safety and efficacy of a single parenteral dose of phenobarbital in addition to symptom-triggered lorazepam for the acute management of alcohol withdrawal syndrome (AWS).MethodsThis was a retrospective chart review of adult patients who presented to the Emergency Department with moderate or severe symptoms of alcohol withdrawal. Patients were included if they received at least 4 mg of lorazepam through the hospital's Alcohol Withdrawal Order Set on hospital day one. Patients who received a single parenteral dose of phenobarbital on hospital day one were compared to those who did not.ResultsForty patients received phenobarbital and 38 patients received lorazepam only. Median daily lorazepam requirements, disposition, hospital length of stay, and median maximum daily CIWA-Ar scores were not statistically significant different between the groups. Significantly more patients in the phenobarbital group were discharged within three days in comparison to the lorazepam only group (9 patients vs. 2 patients, respectively, p < 0.05). In the lorazepam only group, two patients were intubated, one patient had delirium tremens, and no patients seized. In the phenobarbital group no adverse events were observed.ConclusionsMore patients were discharged within three days if they received a single parenteral dose of phenobarbital on hospital day one, in addition to symptom-triggered lorazepam for the acute management of AWS. Emergency Medicine physicians should consider ordering one parenteral phenobarbital dose on hospital day one to patients presenting with AWS.     

Assessment of benzodiazepine dosing strategies for the management of status epilepticus in the emergency department

PurposeAlthough guidelines recommend specific benzodiazepine doses for the treatment of generalized convulsive status epilepticus (GCSE), underdosing appears to be common. The purpose of this investigation was to assess benzodiazepine dosing strategies for the initial management of GCSE in patients presenting to the Emergency Department (ED).MethodsThis was a retrospective review of adult patients who received benzodiazepines in the ED for treatment of GCSE. Characteristics of those achieving seizure cessation following initial benzodiazepine therapy were assessed.Results222 patients presented to the ED and received 403 doses of benzodiazepines, of which 1.5% conformed with recommendations. First-line therapy was successful in 86.8% of patients with an average dose of 1.6 mg (0.02 mg/kg). No difference in dosing was noted between those experiencing early cessation and those that did not (p = 0.132). Patients experiencing early cessation were significantly less likely to receive further doses, be intubated, or be admitted to the intensive care unit (ICU) or hospital (p < 0.05 for all comparisons). Those that received early antiepileptic drug therapy were significantly less likely to receive additional benzodiazepine doses, be intubated, or be admitted to the ICU or hospital (p < 0.05 for all comparisons).ConclusionsAccording to guideline recommendations, there was consistent underdosing of benzodiazepines noted in both prehospital and ED settings. Early seizure cessation and the early receipt of an antiepileptic drug were found to be associated with multiple significant clinical outcomes. Future investigations should explore optimal dosing strategies for benzodiazepines as well as the impact of early antiepileptic drug administration.     

A strategy of escalating doses of benzodiazepines and phenobarbital administration reduces the need for mechanical ventilation in delirium tremens

OBJECTIVE: Patients with severe alcohol withdrawal and delirium tremens are frequently resistant to standard doses of benzodiazepines. Case reports suggest that these patients have a high incidence of requiring intensive care and many require mechanical ventilation. However, few data exist on treatment strategies and outcomes for these subjects in the medical intensive care unit (ICU). Our goal was a) to describe the outcomes of patients admitted to the medical ICU solely for treatment of severe alcohol withdrawal and b) to determine whether a strategy of escalating doses of benzodiazepines in combination with phenobarbital would improve outcomes. DESIGN: Retrospective cohort study. SETTING: Inner-city municipal hospital. PATIENTS: Subjects admitted to the medical ICU solely for the treatment of severe alcohol withdrawal. INTERVENTIONS: Institution of guidelines emphasizing escalating doses of diazepam in combination with phenobarbital. MEASUREMENTS AND MAIN RESULTS: Preguideline (n = 54) all subjects were treated with intermittent boluses of diazepam with an average total and maximal individual dose of 248 mg and 32 mg, respectively; 17% were treated with phenobarbital. Forty-seven percent required intubation due to inability to achieve adequate sedation and need for constant infusion of sedative-hypnotics. Intubated subjects had longer length of stay (5.6 vs. 3.4 days; p = .09) and higher incidence of nosocomial pneumonia (42 vs. 21% p = .08). Postguideline (n = 41) there were increases in maximum individual dose of diazepam (32 vs. 86 mg; p = .001), total amount of diazepam (248 vs. 562 mg; p = .001), and phenobarbital use (17 vs. 58%; p = .01). This was associated with a reduction in the need for mechanical ventilation (47 vs. 22%; p = .008), with trends toward reductions in ICU length of stay and nosocomial pneumonia. CONCLUSIONS: Patients admitted to a medical ICU solely for treatment of severe alcohol withdrawal have a high incidence of requiring mechanical ventilation. Guidelines emphasizing escalating bolus doses of diazepam, and barbiturates if necessary, significantly reduced the need for mechanical ventilation and showed trends toward reductions in ICU length of stay and nosocomial infections.     

Oral phenobarbital loading: a safe and effective method of withdrawing patients with headache from butalbital compounds

BACKGROUND: The overuse of short-acting barbiturate medications for the acute treatment of headache is a common problem in the United States. Most experts agree that withdrawal from these medications is necessary for subsequent headache treatment to be successful, yet there are few published articles outlining effective methods of drug withdrawal. OBJECTIVE: To evaluate the safety and effectiveness of phenobarbital loading for withdrawal from overuse of short-acting barbiturate compounds in inpatients with headache. DESIGN AND METHODS: We performed a retrospective chart review of 18 consecutive patients in an inpatient pain rehabilitation program who were withdrawn from overuse of butalbital-combination medications using a phenobarbital-loading protocol. RESULTS: Eighteen patients with headache hospitalized in an inpatient pain unit for withdrawal from overuse of combination butalbital preparations underwent a phenobarbital-loading protocol. Short-acting barbiturate medications were discontinued, and patients received 120 mg of oral phenobarbital until their score on a predetermined scale reached target levels, and the drug was then discontinued. All patients were effectively treated with no serious adverse events. The median number of doses required varied significantly, and could not be predicted by the patient's prior intake. CONCLUSIONS: Management of butalbital withdrawal can be simplified by using a phenobarbital-loading protocol, taking advantage of the natural tapering afforded by the drug's long half-life. This method possesses most of the characteristics of an ideal drug withdrawal program for patients with headache who are overusing medications.     

Opioid substitution therapy or hidden opioids are a minefield for nalmefene: an atypical case series of 11 patients in Lorraine

Opioid antagonists such as naltrexone and nalmefene are used in drug therapy for alcoholism. Nalmefene, approved in Europe in February 2013 for the reduction of alcohol consumption, is used in patients with alcohol dependence. We report 11 cases of opioid withdrawal syndrome after a single dose of nalmefene in patients usually treated with methadone, buprenorphine, but also with fentanyl or loperamide. Nalmefene is both a partial agonist and an antagonist of opioid receptors. Regarding to its opioid antagonist activity, nalmefene is contraindicated in patients with an opioid treatment. Therefore, when prescribing or delivering nalmefene, healthcare professionals need to be vigilant about any type of opioid exposure, even masked or hidden, to avoid these potential life‐threatening syndromes.