Study Question: Does the frequency of epinephrine administration during in-hospital cardiac arrest (IHCA) impact survival to hospital discharge?
Study Description: This was a retrospective review of data from a multicenter registry of patients from January 2000 through November 2009. Adult patients with an IHCA in a general hospital ward or ICU bed who received at least two IV or intraosseus epinephrine doses were included. Patients were stratified based on pre-specified epinephrine average dosing period (defined as time between first dose and the resuscitation endpoint divided by total number of doses subsequent to the first dose): 1 to < 3 min/dose, 3 to < 4 min/dose, 4 to < 5 min/dose, 5 to < 6 min/dose, 7 to < 8 min/dose, 8 to < 9 min/dose, and 9 to < 10 min/dose. The exact time of the first epinephrine dose is required by the registry, however, exact time(s) of subsequent doses is not required and therefore unknown. Patients for whom the dosing period or number of doses could not be determined were excluded.
Results: A total of 20,909 IHCA events were included for analysis. The most common presenting cardiac rhythm was asystole (46%) followed by PEA (39%) and a small portion with shockable rhythms (13%). Mean cardiac arrest time was 19 ± 10 min. Return of spontaneous circulation (ROSC) occurred in 36.2% while survival to hospital discharge occurred in 7%. Compared with a reference 4-5 min/dose interval, survival to hospital discharge was significantly higher in patients with a higher average epinephrine dosing period (adjusted OR [95% CI]: 2.17 [1.62-2.92] for 9-10 min/dose, 1.79 [1.38-2.32] for 8-9 min/dose, 1.3 [1.02-1.65] for 7-8 min/dose, 1.41 [1.12-1.78] for 6-7 min/dose, 0.96 [0.78-1.19] for 5-6 min/dose, 0.96 [0.76-1.21] for 3-4 min/dose, 0.78 [0.59-1.03] for 1-3 min/dose). Additionally, an average epinephrine dosing period of 1-3 min/dose was associated with increased mortality in non-shockable rhythms.
Conclusion(s): Less frequent epinephrine dosing than recommended by consensus guidelines was associated with improved survival, and findings were consistent for both shockable and non-shockable rhythms.
Perspective: Administration of epinephrine is routine during IHCA and is supported by consensus guidelines. While evidence supports its use to increase ROSC, it has not been shown to increase long-term survival. The current study questions the most appropriate epinephrine dosing interval with results that favor less frequent administration than currently recommended. Based on limitations of the study’s definition of dosing period, which used an average number of doses per time frame rather than exact time interval between each dose, and an unknown impact of consistency of dosing period, further study is needed to determine the optimal epinephrine administration frequency and resulting impact on outcomes.