Time to Administration of Epinephrine and Outcome After in-Hospital Cardiac Arrest With Nonshockable Rhythms: Retrospective Analysis of Large In-Hospital Data Registry

Each year, about 200,000 in-hospital patients have a cardiac arrest, with survival rates of 7% to 26%. The majority of these cardiac arrests have nonshockable (asystole or pulseless electrical activity) initial cardiac rhythms. No intervention has been shown to be efficacious in patients with nonshockable cardiac arrest, apart from cardiopulmonary resuscitation (CPR). This retrospective study of 25,095 patients aimed to determine if earlier administration of epinephrine to in-hospital patients with nonshockable cardiac arrest rhythms was associated with increased return of spontaneous circulation, survival, and neurologically intact survival. There are currently no well-controlled trials of epinephrine to assess such endpoints. The primary exposure of interest was time to administration of epinephrine. The median time to epinephrine administration was 3 min, with a median of three doses administered. Time to administration was analyzed in 3-min intervals, which found a significant stepwise decrease in in-hospital survival, with increasing time interval. Unadjusted and adjusted odds ratio per category were 1.0 for 1 to 3 min, 0.91 for 4 to 6 min, 0.74 for 7 to 9 min, and 0.63 for > 9 min. The stepwise decrease in outcomes was conserved across all outcome variables. Three sensitivity analyses using multivariable regression models were constructed with adjustment for patients with delays in initiation of CPR, patients who received CPR within the first minute of recognition of cardiac arrest, and patients categorized by quarters of delivery of epinephrine. All demonstrated that time to epinephrine administration remained independently associated with survival to hospital discharge after multivariable adjustments. In patients who experience a cardiac arrest in-hospital, earlier administration of epinephrine was strongly associated with increased probability of return of spontaneous circulation, 24-h survival, in-hospital survival, and overall neurologically intact survival.