Naloxone Administration in Out-of-Hospital Cardiac Arrest

Out-of-hospital cardiac (OHCA) arrest remains a leading cause of mortality, with opioid-related arrests representing a potentially reversible subset. Naloxone administration may be considered during resuscitation when overdose is suspected, however its impact on clinically meaningful outcomes remains uncertain. Prior observational studies have evaluated the association between naloxone administration during OHCA and outcomes including survival and return of spontaneous circulation (ROSC), with mixed results. This study aimed to evaluate the association between naloxone administration and outcomes after OHCA within a large urban emergency medical services (EMS) system to better understand the role of naloxone during cardiac arrest.

This was a retrospective cohort study of non-traumatic OHCA patients treated by a single urban EMS system from 2018–2025. Patients were grouped by naloxone administration. Primary outcome was survival to discharge; secondary outcomes included ROSC. Unadjusted odds ratios were calculated, with multivariable logistic regression adjusting for arrest and resuscitation characteristics.

A total of 3,772 patients met inclusion criteria, of whom 680 (18%) received naloxone during resuscitation. Overall, survival to hospital discharge occurred in 331 (10.1%) patients. Survival occurred in 59 (9.6%) patients who received naloxone compared with 272 (10.2%) who did not (OR 0.94; 95% CI 0.70-1.26). ROSC occurred in 200 (38.9%) naloxone-treated patients versus 1036 (43.9%) untreated patients (OR 0.81; 95% CI 0.67-0.99). Among 269 suspected drug-related OHCA, survival to hospital discharge occurred in 21 (11.8%) naloxone-treated patients versus 4 (5.6%) untreated patients (OR 2.27; 95% CI 0.75–6.88), and ROSC occurred in 57 (39.0%) versus 16 (31.4%) patients, respectively (OR 1.40; 95% CI 0.71–2.76). Results for naloxone were similar after multivariable regression; propensity weighted analysis is ongoing.

In this large EMS system cohort of patients with OHCA, naloxone administration was associated with decreased odds of ROSC and no difference in survival to hospital discharge. In patients with suspected drug-related etiology of OHCA, naloxone administration was not associated with improved outcomes. These results highlight the need for further studies to inform patient selection and optimize naloxone use during OHCA.