Epinephrine and norepinephrine are the drugs of choice for continuous intravenous vasopressor therapy to manage post-resuscitation shock (PRS). However, in patients who sustain PRS after out-of-the hospital cardiac arrest (OHCA), it is unclear if one agent is preferred over the other. This is important, as survival after OHCA is only about 10%. Read more.

Epinephrine (EPI) and norepinephrine (NE) are the drugs of choice for continuous intravenous vasopressor therapy to manage post-resuscitation shock (PRS). However, in patients who sustain PRS after out-of-the hospital cardiac arrest (OHCA), it is unclear if one agent is preferred over the other. This is important, as survival after OHCA is only about 10%.

Investigators in France conducted an observational multicenter study of consecutive hospital admissions involving PRS to compare outcomes of EPI versus NE use in patients admitted live to the ICU with PRS after successful OHCA resuscitation.

All cases of OHCA admitted to five French university hospitals between May 15, 2011, and May 15, 2018, were included in the study. PRS was defined as a need for pressors for more than 6 hours despite adequate fluid loading. Patients were excluded from analysis if the cause of cardiac arrest was due to extra-cardiac causes (e.g., trauma, drowning, drug overdose, electrocution, or asphyxia), if there was refractory cardiac arrest without sustainable return of spontaneous circulation (ROSC) or refractory shock requiring extracorporeal membrane oxygenation, if continuous IV EPI or NE was not utilized, or if both EPI and NE were administered as continuous IV infusions simultaneously.

The primary outcome of this study was all-cause mortality during the hospital stay. Secondary endpoints included cardiovascular-specific mortality (i.e., recurrent cardiac arrest or refractory hemodynamic shock) or unfavorable neurologic status (i.e., a Cerebral Performance Category [CPC] score of 3-5).

CPC scores are used as an outcome measure for post-arrest neurologic function. CPC scores range from 1 (indicative of good recovery) to 5 (signifies death). A sensitivity analysis was performed on all deaths that occurred in the ICU. A Cardiac Arrest Hospital Prognosis (CAHP) score was determined. CAHP is a tool to determine prognosis following early stratification of ICU patients following OHCA.

Of the 1,421 patients admitted with OHCA following PRS, 766 patients were enrolled in the study. Mean age of the study population was 64 years, and almost three-quarters were male. Sixty-three percent of patients were treated with NE and 37% were managed with EPI. Since this study was not randomized, there were some important differences between the study populations; however, propensity analyses were conducted to mitigate these confounders.

Patients in the IV EPI group less often had an initial shockable rhythm; had longer time from CPR to ROSC; had lower blood pressure on admission; had higher serum lactate levels, lower arterial pH at admission, and higher prevalence of myocardial dysfunction; and had higher heart rates (HRs) (HR 95/min vs. 90/min, P = .02).

The median dose of EPI was 0.7 mcg/kg/min compared with a median NE dose of 0.6 mcg/kg/min in the first 48 hours. The duration of catecholamine use did not differ between the agents.

Overall, 31% of patients survived to hospital discharge. Of these, neurologic outcomes were favorable in 98%, as data were missing for 18 of the patients.

Of the 69% of patients (n = 531) who died during hospital stay, 34% died of cardiovascular causes (27% died due to refractory hemodynamic shock and 7% from recurrent cardiac arrest). Forty percent died after withdrawal of life-sustaining treatments due to neurologic impairments.

Early recurrent cardiac arrest (i.e., within the first 48 hours) was more frequent in patients treated with EPI (7%) versus NE (2%) (P <.001). Additionally, patients treated with EPI had a higher all-cause mortality during hospitalization (83% vs. 61%, respectively; P <.001). Further, there were more deaths due to refractory shock (35% vs. 9%, P <.001) and recurrent cardiac arrest (9% vs. 3%, P <.001) and a lower frequency of favorable neurologic outcomes (15% vs. 37%, P <.001) in patients treated with EPI compared with NE.

When comparing patients who were or were not discharged alive, IV EPI was independently associated with all-cause mortality (odds ratio [OR] = 2.6, 95% CI, 1.4-4.7, P = .002). These findings held up after controlling for moribund status, restricting analysis to patients with CAHP scores less than 150, limiting outcomes to patients with CAHP greater than 150, or excluding patients treated with EPI before ROSC.

This paper provides guidance for pharmacists when recommending vasopressors for the management of post-resuscitative resuscitation following cardiac arrest. Until more definitive data become available, this study offers pharmacists critical information on recommending EPI or NE for the management of PRS after OHCA.

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