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Background : Naloxone is widely available to bystanders and first responders to treat patients with suspected opioid overdose. In these patients, the prognostic factors and potential benefits associated with additional naloxone administered by emergency medical services (EMS) are uncertain. Objectives : We sought to identify prognostic factors for admission to the hospital following prehospital administration of naloxone for suspected opioid overdose by bystanders and first responders. We secondarily examined whether administration of additional naloxone by paramedics after initial treatment by non-EMS personnel was associated with improvement in level of consciousness prior to hospital arrival. Methods : This is a retrospective cross-sectional study of patients treated within a single urban EMS system from 2013 to 2016. Inclusion criteria were administration of naloxone by bystanders or first responders and transport to one of three academic medical centers. For the secondary analysis, only patients with a Glasgow Coma Scale (GCS) score ≤12 on paramedic arrival were included. We performed univariate and multivariable analyses examining a primary outcome of hospital admission and secondary outcome of improvement in consciousness as defined by GCS >12 in patients with initial GCS ≤12. Results : Of 359 patients identified for the primary analysis, 60 were admitted to the hospital. Factors associated with increased rate of admission included higher total naloxone dosage (OR 1.36, 95% CI 1.09-1.70) and presence of alternate/additional non-opioid central nervous system (CNS) depressants (OR 2.51, 95% CI 1.13-5.56). Among 178 patients who had poor neurologic status (GCS ≤12) on paramedic arrival following naloxone administered by bystander or first responder, administration of additional naloxone was not associated with a better rate of neurologic improvement prior to hospital arrival (77% improved with additional naloxone, 81% improved without additional naloxone; OR 0.82, 95% CI 0.39-1.76). Conclusions : Among patients with suspected opioid overdose treated with naloxone by bystanders and first responders, a higher total dose of naloxone and polysubstance intoxication with additional CNS depressants were predictors of admission. Administration of additional naloxone by paramedics was not associated with a higher rate of neurologic improvement prior to hospital arrival, suggesting a ceiling effect on naloxone efficacy in opioid overdose.

Study Objective: We aim to determine whether administration of higher doses of naloxone for the treatment of opioid overdose is associated with increased pulmonary complications., Methods: This was a retrospective, observational, cross-sectional study of 1,831 patients treated with naloxone by the City of Pittsburgh Bureau of Emergency Medical Services. Emergency medical services and hospital records were abstracted for data in regard to naloxone dosing, route of administration, and clinical outcomes, including the development of complications such as pulmonary edema, aspiration pneumonia, and aspiration pneumonitis. For the purposes of this investigation, we defined high-dose naloxone as total administration exceeding 4.4 mg. Multivariable analysis was used to attempt to account for confounders such as route of administration and pretreatment morbidity., Results: Patients receiving out-of-hospital naloxone in doses exceeding 4.4 mg were 62% more likely to have a pulmonary complication after opioid overdose (42% versus 26% absolute risk; odds ratio 2.14; 95% confidence interval 1.44 to 3.18). This association remained statistically significant after multivariable analysis with logistic regression (odds ratio 1.85; 95% confidence interval 1.12 to 3.04). A secondary analysis showed an increased risk of 27% versus 13% (odds ratio 2.57; 95% confidence interval 1.45 to 4.54) when initial naloxone dosing exceeded 0.4 mg. Pulmonary edema occurred in 1.1% of patients., Conclusion: Higher doses of naloxone in the out-of-hospital treatment of opioid overdose are associated with a higher rate of pulmonary complications. Furthermore, prospective study is needed to determine the causality of this relationship., (Copyright © 2019 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)