Naloxone and Clinical Outcomes in Opioid-Associated Out-of-Hospital Cardiac Arrests in California

The incidence of opioid-associated out-of-hospital cardiac arrest (OA-OHCA) has increased over the past two decades, with recent studies attributing up to 17% of OHCA to drug overdose. Although naloxone has been clearly shown to be effective in reversing the respiratory depression caused by opioid overdose, its role in OA-OHCA remains unclear. No clinical trials of naloxone in OA-OHCA exist and the retrospective studies evaluating the topic have been conducted in smaller populations. Our aim is to assess the association between emergency medical services (EMS)-administered naloxone and clinical outcomes in patients at high risk of OA-OHCA in a California-wide cohort.

We conducted a retrospective cohort study of adults with EMS-treated OHCA using 2021–2022 data from the California Resuscitation Outcomes Consortium, a network of 173 California EMS agencies. The primary cohort is patients identified as high risk for OA-OHCA using the Naloxone Cardiac Arrest Decision Instrument (NACARDI), with additional analyses conducted in EMS-presumed drug-related OHCA and all OHCA patients. An a priori sensitivity analysis was conducted in a cohort restricted to patients who received epinephrine. The primary outcome was survival-to-hospital discharge. Secondary outcomes included neurologic outcome at discharge and sustained return of spontaneous circulation (ROSC). Inverse probability weighted regression was used to estimate naloxone treatment effects.

Among 3,811 patients meeting NACARDI criteria, 1,251 (32.8%) received naloxone. Receipt of naloxone in this cohort was associated with increased survival-to-hospital discharge (adjusted absolute risk difference [ARD]: 2.6%; 95% CI, 1.3%–4.3%), good neurologic outcome (ARD, 3.2%; 95% CI, 1.8%–4.6%), and increased ROSC (]ARD, 3.3%; 95% CI, 1.1%–5.4%). A sensitivity analysis among patients who received epinephrine showed no association between naloxone and the primary outcome of survival, though a positive association with favorable neurological outcome persisted.

In this retrospective cohort study, among patients with OHCA at high risk for opioid involvement EMS-administered naloxone was associated with higher rates of survival and favorable neurological status. These findings support the need for a randomized trial to determine the causal effects of naloxone in opioid-associated cardiac arrest.