Comprehensive Summary
This cohort study evaluated whether non-cardiac depolarization-blocking (DB) drugs affect initial heart rhythm and survival in out-of-hospital cardiac arrest (OHCA). Between 2001 and 2020, 54,370 OHCA patients from the Danish Cardiac Arrest registry were included. Non-cardiac DB drug use was defined by a prescription within 90 days prior to OHCA. Primary and secondary outcomes were the presence of a non-shockable heart rhythm and 30-day survival, respectively. After adjustment for comorbidities and resuscitation characteristics, non-cardiac DB drug users had 62% higher odds of non-shockable rhythm versus non-users (OR 1.62, 95% CI 1.48-1.79), with associations consistent across all ages and sexes. Among drug classes, antiepileptics showed the strongest association (OR 2.28, 95% CI 1.80-2.93), followed by antidepressants (OR 1.62) and tramadol (OR 1.51). Non-cardiac DB drug use also demonstrated lower 30-day survival following OHCA (OR 0.81, 95 % CI: 0.69–0.95).
Outcomes and Implications
This study provides evidence that non-cardiac DB drugs, including commonly prescribed antidepressants, antiepileptics, and tramadol, are associated with worse outcomes in OHCA. These medications block cardiac sodium channels off-target, potentially impairing action potential generation and impulse conduction, which may promote progression from shockable to non-shockable rhythms during arrest. For emergency clinicians, awareness of non-cardiac DB drug use may inform post-resuscitation management and prognostication. With 11.6% of OHCA patients in this cohort using these medications, the clinical impact is substantial. Limitations include the study’s observational nature, the inability to adjust for lifestyle factors, the unavailability of important clinical variables like imaging findings and the potential for misclassification of OHCA due to lack of detailed cause-of-death information.