Drug Overdoses Leading to Cardiac Arrest Rising, Particularly With Stimulant-Opioid Combination

Substance use disorder contributes to over 100,000 deaths annually in the United States, and substances such as opioids, stimulants, and benzodiazepines are important causes of OD-related OHCA.

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Incidence of out-of-hospital cardiac arrest (OHCA) resulting from drug overdose (OD) dramatically increased from 2015 to 2021, according to a population-based cohort study published in JAMA Network Open.

Additionally, the most common drug-specific profile that led to ODs was a combination of stimulants and opioids, rather than either substance on their own. The study sought to evaluate the temporal pattern, clinical presentation, care, and outcomes of adults with OHCA overall as well as the patients’ drug-specific profiles.

“While there has been deserved focus on public health measures and resuscitation guidelines for opioid-related OD, our study underscores the need for investment in public health infrastructure and prevention for these alternative drug profiles,” the authors emphasized.

Substance use disorder contributes to over 100,000 deaths annually in the United States, and substances such as opioids, stimulants, and benzodiazepines are important causes of OD-related OHCA. In addition to cardiac arrest, use of these substances has been associated with several other cardiopulmonary pathophysiological conditions, including arrhythmogenesis, vascular dysfunction, atherosclerosis, and respiratory depression.

Although opioid-associated OHCA has traditionally been the most common substance contributing to OD-OHCA, drug use patterns are shifting as the prevalence of synthetic opioids and stimulants and subsequent mortality among individuals with substance use disorder have increased.

In the past, studies evaluating OD-OHCA have either solely focused on opioid-related OD-OHCA or grouped substances together without distinguishing drug-specific profiles. They also have relied on nonsystematic toxicology screens or inferential evidence for OD, impacting the ability to determine OHCA etiology. The lack of true understanding of the drug-specific characteristics of OD-OHCA has implications for acute resuscitation treatment, postresuscitation care, and public health efforts to reduce morbidity and mortality related to substance use disorder.

The present analysis looked at data from adult patients with emergency medical services-treated OHCA in King County, Washington. The study was conducted from January 1, 2015, to December 31, 2021. OHCA etiology was determined using records from emergency medical services, hospitals, and medical examiners. The statistical analysis was performed on July 1, 2023.

Drug-specific profiles were categorized as:

  • Opioid without stimulant
  • Stimulant without opioid
  • Opioid and stimulant
  • All other nonstimulant, nonopioid drugs

During the 7-year period, there were 6790 OHCA events, of which 702 were caused by OD. Among the patients with OD-OHCA, the mean (IQR) age of the patients was 41 (29-53) years, and 36% (n = 252) were women. For those who had a non–OD-OHCA, the mean age was 66 (56-77) years, and 35% (n = 2144) were women.

Additionally, the incidence of OD-OHCA rose from 5.2 per 100,000 person-years in 2015 (95% CI, 3.8-6.6) to 13.0 per 100,000 person-years in 2021(95% CI, 10.9-15.1; P < .001), whereas no significant termporal change in the incidence of non–OD-OHCA (P = .30).

Compared with non–OD-OHCAs, OD-OHCA events were more likely to be unwitnessed (41% vs 66%, respectively) and less likely to be considered shockable (25% vs 8%). Unadjusted survival was not different between OD- and non–OD-OHCA (20% vs 18%).

Of the 702 OD-OHSA incidents, 295 were attributed to opioids only, 129 were considered stimulant only, 205 were from a combination of opioids and stimulants, and 73 were caused by other drugs. The opioid-stimulant combination category experienced the greatest relative increase in incidence over time.

Patients with stimulant-only OHCA were more likely have a shockable rhythm compared with patients with opioid-only OHCA or opioid-stimulant OHCA (24% vs 4% vs 5%). Stimulant-only OHCAs were also more likely to have a witness compared to opioid-only and opioid-stimulant OHCAs (50% vs 19% vs 23%).

Additionally, patients with an OHCA caused by a combination of opioids and stimulants had the lowest survival to hospital discharge (10%) compared with patients with stimulant-only OHCA (22%) or OHCA due to other drugs (26%).

“Although the precise basis for increased OHCA mortality in this combined OD profile is not certain, the cumulative consequences of untoward respiratory and cardiac effects may combine to challenge heart resuscitation and brain recovery and ultimately increase case fatality. For those with long-term stimulant use, it is also possible that an underlying cardiac pathology may further reduce cardiac reserve and challenge resuscitation efforts following OHCA in the setting of combined opioid and stimulant overdose,” the authors noted.

The observational retrospective study design, focus on a single electronic medical record system, lack of race and ethnicity data, and potential misclassification of drug-specific information were cited at limitations of the analysis.


Yogeswaran V, Drucker C, Kume K, et al. Presentation and outcomes of adults with overdose-related out-of-hosppital cardiac arrest. JAMA Netw Open. 2023;6(11):e2341921. doi:10.1001/jamanetworkopen.2023.41921

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