The need for multiple naloxone administrations for opioid overdose reversals: A review of the literature.

A growing challenge in the opioid epidemic is the rise of highly potent synthetic opioids, (i.e., illicitly manufactured fentanyl [IMF]) entering the US non-prescription opioid market. Successful reversal may require multiple doses of naloxone, the standard of care for opioid overdose. We conducted a narrative literature review to summarize the rates of multiple naloxone administrations (MNA) for opioid overdose reversal. : A MEDLINE search was conducted for published articles using MESH search terms: opioid overdose, naloxone and multiple naloxone administration. Of the 2,101 studies identified, articles meeting inclusion/exclusion criteria were reviewed, categorized by primary and secondary outcomes of interest and summarized by data source and study design. : A total of 24 articles meeting eligibility criteria were included. Among EMS-based studies, MNA rates ranged from 9% to 53%; in general, bystander-reported studies were notably higher, from 16% to 89%. Variation in study design, data sources, year and geography, may have contributed to these ranges. Three studies that included longitudinal results reported a significant percent increase between 26% and 43% in annual MNA rates or a significant increase in mean naloxone doses over time ( < .001). : This summary found that multiple naloxone administrations during opioid overdose encounters vary widely, have occurred in up to 89% of all opioid overdoses, and have significantly increased over time. Higher naloxone formulations may fulfill an unmet need in opioid overdose reversals, given the rising rates of overdoses involving IMF. Further studies are needed to gain a better understanding of MNA during opioid overdose encounters, particularly across a wider geographic region in the US in order to inform continuing efforts to combat the opioid epidemic.