Administering naloxone for opioid overdose reversal in out-of-hospital settings appears to be safe and effective

1. For reversing opioid overdose, intranasal naloxone of a higher concentration (2 mg/mL) seems to have a similar efficacy to intramuscular naloxone.

2. Lack of transport to a health care facility after successful naloxone reversal seems to be associated with low serious adverse events and death rates, but no comparisons were made to a transport group.

Evidence Rating Level: 1 (Excellent)

Study Rundown: In the United States, opioid overdose is the top cause of death related to injury.  Outside the hospital, naloxone is often used to treat opioid overdose.  Although guidelines for such use exists, there still remain some uncertainties, which this systematic review sought to address.  Researchers aimed to synthetize data regarding the effects on mortality of naloxone administration routes and dosages on people suspected to have overdosed on opioids in a nonhospital setting.  The authors also evaluated the necessity for transport to a facility for care after an overdose was reversed with naloxone.  After reviewing 13 eligible studies, researchers found that for reversing opioid overdose, intranasal naloxone of a higher concentration (2 mg/mL) had a similar efficacy to intramuscular naloxone.  Lack of transport after naloxone reversal appeared to be linked to a low rate of severe harm.  However, no study assessed the risk of lack of transport versus transport.  The authors suggest that further research is required to determine the best administration route and optimal dose of naloxone.

A strength of this study is that it may assist with emergency medical services (EMS) naloxone use guidelines. Limitations of the study include the low number of studies, some methodological inadequacies, and lack of studies assessing highly concentrated intranasal reformulations or autoinjectors that have been recently approved by the U.S. Food and Drug Administration (FDA).

Click to read the study in Annals of Internal Medicine

Relevant Reading: Review of naloxone safety for opioid overdose: practical considerations for new technology and expanded public access

In-Depth [systematic review]: In this study, researchers used the Cochrane Central Register of Controlled Trials, Ovid MEDLINE, PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), materials from the FDA, and reference lists to find randomized trials and cohort studies that compared various doses of naloxone, routes of administration, and lack of transport versus transport after naloxone reversal.  The authors found 13 eligible studies, including 4 cohort studies and 3 randomized controlled trials that evaluated various routes of administration. Of these, 1 trial found that for reversing opioid overdose, intranasal naloxone of a higher concentration (2 mg/mL) had a similar efficacy (with no adverse event differences) to intramuscular naloxone.  Another trial found that intranasal naloxone at a lower concentration (2 mg/5 mL) was not as effective as intramuscular naloxone but was linked to a reduced agitation risk.  Both trials had the same total dose of 2 mg.  There was not enough evidence to make conclusions about other administration routes.  Six studies reported low serious adverse events and death rates (0% to 1.25%) in patients who were not transported after successful naloxone reversal.  However, there was no transported patient group for comparison.  Considering that people who were not transported probably are at a decreased risk for complications related to opioid overdose compared to patients who were transported, this makes interpretation of this data difficult.

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