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TOPLINE:

In a study of adults treated by emergency medical services (EMS) following 9-1-1 calls, intramuscular (IM) naloxone administration was associated with lower odds of repeat naloxone dosing and faster recovery of mental status and respiratory function than intranasal (IN) naloxone administration, without an observed increase in precipitated withdrawal symptoms.

METHODOLOGY:

• Researchers conducted a retrospective observational analysis of 16,550 adults (median age, 40 years; 32% women; 55% White, nonHispanic individuals; 36% treated in a public location) who received bag-valve-mask ventilation and either IM (n = 3286) or IN (n = 13,264) naloxone following a 9-1-1 call.
• Patients with cardiac arrest, a respiratory rate > 12 breaths/min, or a Glasgow Coma Scale (GCS) score > 12 before naloxone administration as well as those who received naloxone before the arrival of EMS were excluded.
• Researchers compared initial naloxone administration routes and evaluated outcomes such as postnaloxone cardiac arrest, hypoxia, recovery of the respiratory rate and mental status, repeat naloxone dosing, signs of precipitated withdrawal, and transportation by EMS.

TAKEAWAY:

• Initial IM naloxone administration was associated with lower odds of additional naloxone dosing than initial IN naloxone administration (adjusted odds ratio [aOR], 0.39; 95% CI, 0.35-0.44), and patients who were initially administered IM naloxone received a lower total prehospital naloxone dose than those who were initially administered IN naloxone (2.0 vs 2.4 mg).
• Initial IM naloxone administration was associated with higher odds of recovery to a GCS score > 12 (aOR, 1.15; 95% CI, 1.01-1.30) and lower odds of transportation by EMS (aOR, 0.82; 95% CI, 0.71-0.95) than initial IN naloxone administration.
• Patients who received IM naloxone achieved a respiratory rate > 12 breaths/min and a GCS score > 12 faster than those who received IN naloxone (9.3 vs 10.4 minutes and 11.9 vs 14.9 minutes, respectively; P < .001 for both).
• The initial route of naloxone administration was not associated with postnaloxone cardiac arrest, hypoxia, return to a respiratory rate > 12 breaths/min, treatment for nausea/vomiting or agitation, or other indicators of precipitated opioid withdrawal.

IN PRACTICE:

"In this national cohort, a strategy of initial IM naloxone was associated with decreased odds of postnaloxone hypoxia, decreased odds of repeat naloxone dosing, and more rapid resolution of altered mental status and respiratory depression in comparison to initial IN naloxone," the authors wrote. "EMS protocols and medication deployment strategies should consider both effectiveness and patient tolerability when selecting first-line naloxone routes," they added.

SOURCE:

The study was led by Tanner Smida, Division of Prehospital Care, West Virginia University, School of Medicine, Morgantown, West Virginia. It was published online on June 3, 2026, in Prehospital Emergency Care.

LIMITATIONS:

The study was limited by the inability to confirm opioid overdose as the cause of altered mental status and respiratory depression in all patients, unmeasured confounding inherent to observational analyses, the use of GCS scores as a proxy for neurologic recovery, and reliance on treatment for withdrawal symptoms rather than validated withdrawal scales to identify precipitated withdrawal.

DISCLOSURES:

The study was supported by the West Virginia Clinical and Translational Science Institute through a National Institute of General Medical Sciences award. The authors reported no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.