Prehospital naloxone administration – what influences choice of dose and route of administration?

Abstract

Introduction:Amidst the ongoing opioid crisis there are debates regarding the optimal route of administration and dosages of naloxone. This applies both for lay people administration and emergency medical services, and in the development of new naloxone products.We examined the characteristics of naloxone administration, including predictors of dosages and multiple doses during patient treatment by emergency medical service staff in order enlighten this debate.Methods: This was a prospective observational study of patients administered naloxone by the Oslo City Center emergency medical service, Norway (2014-2018). Cases were linked to The National Cause of Death Registry. We investigated the route of administration and dosage of naloxone, clinical and demographic variables relating to initial naloxone dose and use of multiple naloxone doses and one-week mortality.Results: Overall, 2,215 cases were included, and the majority (91.9%) were administered intramuscular naloxone. Initial doses were 0.4 or 0.8 mg, and 15% of patients received multiple dosages. Unconscious patients or those in respiratory arrest were more likely to be treated with 0.8 mg naloxone and to receive multiple doses. The one-week mortality from drug-related deaths was 4.1 per 1000 episodes, with no deaths due to rebound toxicity.Conclusions: Intramuscular naloxone doses of 0.4 and 0.8 mg were effective and safe in the treatment of opioid overdose in the prehospital setting. Emergency medical staff appear to titrate naloxone based on clinical presentation.

Comparison of intranasal and intramuscular naloxone in opioid overdoses managed by ambulance staff: a double‐dummy, randomised, controlled trial

“…The inclusion criteria ensured that the overdoses studied were severe, and that the participants were in deep coma with inadequate spontaneous respiration. Compared to those in a non‐selected sample in Oslo, the participants had lower median respiratory rates (3 vs 7/min) and Glasgow Coma Score (3 vs 4/15) [36]. The nasal dose was chosen based on several pharmacokinetic studies of volunteers, including a study in which volunteers were exposed to an opioid [10, 17, 19].…”

“…The nasal dose was chosen based on several pharmacokinetic studies of volunteers, including a study in which volunteers were exposed to an opioid [10, 17, 19]. The comparator dose exceeded the 0.4 mg IM dose required for regulatory purposes and was chosen based on a field study and recommendations of the WHO [5, 36]. The trial conformed to contemporary standards of clinical trial study design and conductance according to the Good Clinical Practice guidelines, including the registration, classification and publication of adverse events, such as recurrence of overdose in the 12 hours post‐inclusion.…”