NAloxone CARdiac Arrest Decision Instruments (NACARDI) for targeted antidotal therapy in occult opioid overdose precipitated cardiac arrest

We have recently demonstrated that a significant proportion of fatal out-of-hospital cardiac arrests (OHCAs) are precipitated by occult overdose, which could benefit from antidote therapy administered adjunctively with other cardiac resuscitation measures. We sought to develop simple decision instruments that EMS providers and other first responders can use to rapidly identify occult opioid overdose-associated OHCAs. We examined data from February 2011 through December 2017 in the Postmortem Systematic Investigation of Sudden Cardiac Death study, in which San Francisco (California) County EMS-attended OHCA deaths received autopsy and expert panel adjudication of cause of death. Using classification tree analyses, we derived highly sensitive and specific decision instruments that predicted our primary outcome of occult opioid OD-associated OHCA. We then calculated screening performance characteristics of these instruments. Of 767 OHCA deaths, 80 (10.4%) were associated with occult opioid overdose. Of the eight models with 100% sensitivity for opioid overdose-associated cardiac arrest, the highest specificity model (23.4%, 95% confidence interval [CI] 20.3−26.7%) was age < 60 years OR race = black or non-Latinx white OR arrest in public place. The highest specificity instrument (96.3%, 95% CI 94.6–97.5%) consisting of age < 60 years AND race = black or non-Latinx white AND unwitnessed arrest AND female sex had 25% (95% CI 16–35.9%) sensitivity. We have derived simple decision instruments that can identify patients whose OHCA precipitant was occult opioid overdose. These instruments may be used to guide selective administration of the antidote naloxone in OHCA resuscitations.