High-Dose Buprenorphine Induction in the Emergency Department for Treatment of Opioid Use Disorder

Abstract

Importance: Emergency departments (EDs) sporadically use a high-dose buprenorphine induction strategy for the treatment of opioid use disorder (OUD) in response to the increasing potency of the illicit opioid drug supply and commonly encountered delays in access to follow-up care.

Objective: To examine the safety and tolerability of high-dose (>12 mg) buprenorphine induction for patients with OUD presenting to an ED.

Design, setting, and participants: In this case series of ED encounters, data were manually abstracted from electronic health records for all ED patients with OUD treated with buprenorphine at a single, urban, safety-net hospital in Oakland, California, for the calendar year 2018. Data analysis was performed from April 2020 to March 2021.

Interventions: ED physicians and advanced practice practitioners were trained on a high-dose sublingual buprenorphine induction protocol, which was then clinically implemented.

Main outcomes and measures: Vital signs; use of supplemental oxygen; the presence of precipitated withdrawal, sedation, and respiratory depression; adverse events; length of stay; and hospitalization during and 24 hours after the ED visit were reported according to total sublingual buprenorphine dose (range, 2 to >28 mg).

Results: Among a total of 391 unique patients (median [interquartile range] age, 36 [29-48] years), representing 579 encounters, 267 (68.3%) were male and 170 were (43.5%) Black. Homelessness (88 patients [22.5%]) and psychiatric disorders (161 patients [41.2%]) were common. A high dose of sublingual buprenorphine (>12 mg) was administered by 54 unique clinicians during 366 (63.2%) encounters, including 138 doses (23.8%) greater than or equal to 28 mg. No cases of respiratory depression or sedation were reported. All 5 (0.8%) cases of precipitated withdrawal had no association with dose; 4 cases occurred after doses of 8 mg of buprenorphine. Three serious adverse events unrelated to buprenorphine were identified. Nausea or vomiting was rare (2%-6% of cases). The median (interquartile range) length of stay was 2.4 (1.6-3.75) hours.

Conclusions and relevance: These findings suggest that high-dose buprenorphine induction, adopted by multiple clinicians in a single-site urban ED, was safe and well tolerated in patients with untreated OUD. Further prospective investigations conducted in multiple sites would enhance these findings.

Figure 1.. High-Dose Buprenorphine Treatment Pathway

^aComplicating factors include age 65 years or older; altered mental status; viable pregnancy; methadone use; intoxication with alcohol, benzodiazepines, or other sedatives; postoverdose reversal with naloxone; anticipated surgery; long-term opioid therapy for pain; or any serious acute medical illness, such as heart failure, liver failure, kidney failure, or respiratory distress. ^bWithdrawal is a clinical determination based on the Clinical Opiate Withdrawal Scale (COWS): mild, 5-12; moderate, 13-24; severe, greater than 25. A starting dose of 8 mg sublingual should be considered in moderate-to-severe withdrawal. ^cBuprenorphine, sublingual monoproduct was used. ^dStandard dose induction (8-12 mg) is associated with a lower risk of sedation, respiratory depression, and adverse effects, such as nausea and headache, particularly in patients with complicating factors; the duration and magnitude of withdrawal suppression is less. High doses may produce sedation, respiratory depression, nausea, and headache; the duration and magnitude of withdrawal suppression is greater.

Figure 2.. Minimum Respiratory Rate and Oxygen Saturation (SpO₂) Following Initial Dose by Buprenorphine Dose

Boxes correspond to 25th and 75th percentiles, with lines in boxes denoting medians. Dots denote outliers. Error bars denote 95% CIs. Kruskal-Wallis test compares distributions of respiratory rate and oxygen saturation across buprenorphine dose categories.

Figure 3.. Buprenorphine Doses Administered by Physicians (MDs) and Advanced Practice Practitioners (APPs)

A, Total doses are shown. Each dot represents a unique patient encounter. Boxes correspond to 25th and 75th percentiles, with lines in boxes denoting medians. Error bars denote 95% CIs. Kruskal-Wallis test compares distributions of respiratory rate and oxygen saturation across buprenorphine dose categories. MDs provided high-dose buprenorphine in 71 of 220 patient encounters (32%), and APPs provided high-dose buprenorphine in 181 of 359 encounters (50%). B, Total buprenorphine dose administered per encounter by calendar time (in quarter years) of encounter. Red line indicates the best fit line. Error bars denote 95% CIs. The Spearman correlation of dose administered by time was 0.23 (P < .001) overall, 0.19 (P = .005) for MDs, and 0.22 (P < .001) for APPs. Dots denote outliers. Two patients received higher dosing. One patient in the MD group received 36 mg as the inpatient team ordered an additional buprenorphine 20 hours into the admission while the patient boarded in the ED. They did well and followed-up in the hospital bridge clinic. The second patient in the APP group who received 48 mg was experiencing homelessness, used excessively high amounts of opioids daily, and insisted they needed large buprenorphine doses for symptom control. They were seen previously in the ED, with demonstrated tolerance to high dosing. They went to an inpatient substance treatment program.