Systematic Review of Naloxone Dosing and Adverse Events in the Emergency Department

Experts recommend using the lowest effective dose of naloxone to balance the reversal of opioid-induced respiratory depression and avoid precipitated opioid withdrawal, however, there is no established dosing standards within the emergency department (ED). The aim of this review was to determine current naloxone dosing practice in the ED and their association with adverse events. We conducted a systematic review by searching PubMed, Cochrane, Embase, and EBSCO from 2000–2021. Articles containing patient-level data for initial ED dose and patient outcome had data abstracted by two independent reviewers. Patients were divided into subgroups depending on the initial dose of i.v. naloxone: low dose ([LD], < 0.4 mg), standard dose ([SD], 0.4–2 mg), or high dose ([HD], > 2 mg). Our outcomes were the dose range administered and adverse events per dose. We compared groups using chi-squared difference of proportions or Fisher's exact test. The review included 13 articles with 209 patients in the results analysis: 111 patients in LD (0.04–0.1 mg), 95 in SD (0.4–2 mg), and 3 in HD (4–12 mg). At least one adverse event was reported in 37 SD patients (38.9%), compared with 14 in LD (12.6%, p < 0.0001) and 2 in HD (100.0%, p = 0.16). At least one additional dose was administered to 53 SD patients (55.8%), compared with 55 in LD (49.5%, p < 0.0001), and 3 in HD (100.0%, p = 0.48). Lower doses of naloxone in the ED may help reduce related adverse events without increasing the need for additional doses. Future studies should evaluate the effectiveness of lower doses of naloxone to reverse opioid-induced respiratory depression without causing precipitated opioid withdrawal.