Immediate Intravenous Epinephrine Versus Early Intravenous Epinephrine for Inhospital Cardiopulmonary Arrest

Abdullah Bakhsh; Maha Safhi; Ashwaq Alghamdi; Amjad Alharazi; Bedoor Alshabibi; Rajwa Alobaidi; Maryam Alnashri


BMC Anesthesiol. 2021;21(147) 

In This Article


Our findings reveal that immediate administration of intravenous epinephrine is associated with increased sustained return of spontaneous circulation (ROSC) (20-min – 24-h). There had been some controversy on the ability of epinephrine to increase ROSC rates. However, there is a strong evidence from large number of clinical studies that epinephrine use improves the chances of ROSC, but does not benefit survival.[19–21] Notably, some studies suggest that epinephrine might actually worsen the neurologic outcome with increasing cumulative dose of epinephrine.[22] Early epinephrine administration is practically achievable for in-hospital cardiac arrest as opposed to out-of-hospital settings. Our study reveals that median epinephrine administration time is 2.00 min. A study by Hansen at al.[23] conducted a secondary analysis on 26,755 patients in the out-of-hospital setting. A 10-min cut off time from emergency medical services (EMS) arrival to epinephrine administration was applied. The majority received epinephrine > 10 min from EMS arrival (54.2%). The highest survival to discharge was noted when epinephrine was given before 4 min, which occurred in only 7% of patients. Moreover, each additional minute of time from EMS arrival to epinephrine was associated with 4% decrease in odds of survival to hospital discharge (OR 0.96; 95%CI 0.95–0.98). However, there are profound differences in patients' characteristics, underlying etiology, treatment and timing and outcomes between patients in and out of hospital.

Donnino et al.[12] conducted a post hoc analysis of prospectively collected data in a large multicenter registry of in-hospital cardiac arrests (Get With The Guidelines-Resuscitation). They included 25,095 patients from 570 hospitals with asystole (55%) or pulseless electrical activity (45%). The median time to epinephrine administration was three minutes (interquartile range 2–4). Survival to 24-h occurred in 6280 (27%) patients, but only 2603 (10%) survived to discharge. A stepwise decrease in survival to discharge with additional minute of first administration of epinephrine was also observed: 929 (12%) survived when epinephrine was given in the first minute, 392 (12%) in the second minute, 305 (11%) in the third minute, 208 (9%) in the fourth minute, 335 (10%) in the fifth minute, 124 (10%) in the sixth minute, and 310 (7%) in the seventh minute or later (P < 0.001). The results of our study were consistent with the stepwise decrease in ROSC with every minute delay in epinephrine administration however, our primary outcome with sustained ROSC for up to 24-h. We used a cutoff of 1-min for first epinephrine administration. This was used due to the time-sensitive interventions required during the low-flow state to maintain coronary and cerebral perfusion without interruption. Results of this study show that immediate epinephrine administration is associated with higher rates of ROSC (20-min – 24-h) (OR 1.93; 95%CI 1.58–2.36) when compared with early epinephrine (≥2-min). Additionally, Figure 2 demonstrates a sharp decrease in ROSC from 18.90% when epinephrine was administered between 0 and 1 min to 4.40% when epinephrine was administered between 2 and 3 min. Therefore, the number of patients who need to be treated with epinephrine within 1-min to achieve one patient with ROSC (20 min-24 h) is 7.

Interestingly, an initial rhythm of PEA and avoiding intubation during CPR independently carry a higher likelihood of sustained ROSC when compared with asystole and intubation during CPR. These findings are consistent with previous studies.[24–26] PEA generally carries better prognosis than asystole.[24,25] However, the insertion of an endotracheal tube during CPR may hinder from more critical actions such as chest compressions or the early administration of epinephrine. A retrospective study by Anderson et al. examined the GWTG-R registry and found that patients intubated in the first 15-min of cardiac arrest had lower survival compared to those intubated after the first 15-min (RR 0.75 95%CI [0.73–0.76]).[26]

While the American Heart Association (AHA) recommend immediate and uninterrupted chest compressions to maintain coronary and cerebral perfusion, there is no current strong recommendations on the timing of first epinephrine administration nor any recommendation on a maximum dose.[9] In fact, the latest AHA guidelines recommend that epinephrine should be administered as early as possible then every 3–5-min thereafter.[9] The physiologic rationale for early epinephrine administration is strong.[1–3] The combination of immediate high-quality chest compression and immediate epinephrine administration could potentially result in better outcomes. Although, the results of our study encourage immediate epinephrine administration, they question the benefit of epinephrine after a certain amount of time.


This was a retrospective analysis. This limitation may have been addressed by applying regression models. However, it is possible that unmeasured confounding factors still exist. Data represents experiences from three different sites which may have also affected the results. Moreover, we were unable to assess the quality of cardiopulmonary resuscitation in each case and investigate how it affected the results of our study. This may limit the generalizability of our results.