Acute Opioid Withdrawal Following Intramuscular Administration of Naloxone 1.6 mg: A Prospective Out-Of-Hospital Series

Abstract

Study objective: Large doses of intramuscular (IM) naloxone are commonly used in out-of-hospital settings to reverse opioid toxicity; however, they are used less commonly in hospitals because of concerns about opioid withdrawal, particularly agitation. We aimed to determine the frequency of severe agitation following a single 1.6 mg IM naloxone dose.

Methods: We undertook a prospective study of adult (>15 years) patients treated by an Australian state ambulance service with 1.6 mg IM administration of naloxone for respiratory depression (respiratory rate <11 breaths/min and/or oxygen saturation <93% in room air) caused by presumed opioid poisoning. The primary outcome was the proportion of presentations with severe agitation (Sedation Assessment Tool score >1) within 1 hour of naloxone administration. Secondary outcomes were the proportion of presentations with acute opioid withdrawal (tachycardia [pulse rate >100 beats/min], hypertension [systolic >140 mm Hg], vomiting, agitation, seizure, myocardial infarction, arrhythmia, or pulmonary edema), and reversal of respiratory depression (respiratory rate >10 breaths/min and saturation >92% or Glasgow Coma Scale score 15).

Results: From October 2019 to July 2021, there were 197 presentations in 171 patients, with a median age of 41 years (range, 18 to 80 years); of the total patients, 119 were men (70%). The most common opioids were heroin (131 [66%]), oxycodone (14 [7%]), and morphine (11 [6%]). Severe agitation occurred in 14 (7% [95% confidence interval {CI} 4% to 12%]) presentations. Opioid withdrawal occurred in 76 presentations (39% [95% CI 32% to 46%]), most commonly in the form of tachycardia (18%), mild agitation/anxiety (18%) and hypertension (14%). Three presentations (1.5%) received chemical sedation for severe agitation within 1 hour of naloxone administration. A single 1.6 mg dose of naloxone reversed respiratory depression in 192 (97% [95% CI: 94% to 99%]) presentations.

Conclusion: Severe agitation was uncommon following the administration of 1.6 mg IM naloxone and rarely required chemical sedation.