Bougouin W, Slimani K, Renaudier M, Sudden Death Expertise Center Investigators, et al. Epinephrine versus norepinephrine in cardiac arrest patients with post-resuscitation shock. Intensive Care Med. 2022;48(3):300-310.
To determine if epinephrine or norepinephrine is a superior continuous vasopressor for patients with out of hospital cardiac arrest in post-resuscitation shock
Survival in out-of-hospital cardiac arrest is poor,1 and American and European guidelines underline the importance of optimizing hemodynamics in post-resuscitation shock after out of hospital cardiac arrest (OHCA).2,3 Several studies have compared epinephrine and norepinephrine as a continuous vasopressor in septic shock4 and cardiogenic shock,5 but studies have not looked at epinephrine versus norepinephrine in post-resuscitation shock.
Retrospective observational study looking at all cases of OHCA in Paris, France through the Sudden Death Expertise Center registry. Multivariate regression and propensity matching were used for analysis.
- Patients in the Sudden Death Expertise Center registry with post-resuscitation shock, which was defined as the need for continuous vasopressors for greater than 6 hours despite adequate fluid resuscitation after ROSC
- Patients with extra-cardiac cause of their cardiac arrest such as trauma, drowning, drug overdose, electrocution, asphyxia from an external cause, refractory cardiac arrest without ROSC, refractory shock requiring ECMO, and continuous intravenous infusions of both epinephrine and norepinephrinePowered to detect a 10% difference in Day 7 survival if 750 patients were enrolled. In total, 801 critically ill patients requiring emergency endotracheal intubation were enrolled with 396 in the etomidate arm and 395 in the ketamine arm (some patients were lost to post-enrollment withdrawals).
Primary outcome was all-cause mortality during hospital stay
Secondary outcomes included cardiovascular-specific mortality and unfavorable neurological status at hospital discharge (high cerebral performance category score including death)
- 1421 patients initially identified, and after excluding patients, 766 patients were included in the study
- 481 (63%) were treated with norepinephrine, and 285 (37%) were treated with epinephrine
- The kappa score, a statistic characterizing inter-rater reliability, was 0.87, indicating excellent agreement in data collection
- Baseline characteristic highlights, similarities between groups: median age 64, 650/766 (73%) were male, median time collapse to CPR was 5 minutes, CPR to ROSC was 22 minutes
- Baseline characteristic highlights, difference between groups: Statistically significant differences in time from CPR to ROSC in groups (20 minutes in norepinephrine group, 25 minutes in epinephrine group, P<0.0001) and initial shockable rhythm (276/481, 57%, in norepinephrine group, 124/285, 44%, in epinephrine group, P<0.001). Patients in epinephrine group also had statistically significant initial lower blood pressure, higher initial lactate, lower arterial pH, higher prevalence of myocardial dysfunction, were less likely to undergo coronary angiography, and were less likely to receive targeted temperature management
- Overall, 531/766 (69%) all-cause mortality during hospital stay in both groups. 235 patients survived to hospital discharge, 212 of those with a favorable neurologic outcome.
- Primary outcome: patients with epinephrine had a higher all cause mortality during hospital stay (83% vs 61%, P<0.001)
- Secondary outcomes: patients with epinephrine had more deaths from cardiovascular specific mortality (44% vs 11%, P<0.001) and lower frequency of favorable neurologic outcomes (15% vs 37%, P<0.001) compared to those treated with norepinephrine
- Authors performed a multivariable analysis, propensity matching, and sensitivity analyses to account for differences in patient baseline characteristics, and concluded epinephrine infusion was independently associated with all-cause mortality, cardiovascular specific mortality, and unfavorable neurological outcome in comparison with norepinephrine infusion
- This is an observational study looking retrospectively at associations between outcomes, and cannot prove causality.
- There were important differences in baseline characteristics between groups treated with norepinephrine versus epinephrine infusion. Authors used several different advanced statistical techniques to try to account for these differences, and in using several different strategies, their findings of epinephrine group having worse outcomes held true.
- Despite these statistical techniques, it is impossible to fully control for indication bias without a randomized control trial.
- Epinephrine prior to ROSC may have served as a confounding variable, though this is the situation we would expect to encounter in the real world as well.
Post-resuscitation shock occurs in 50-70% of patients after OHCA, and is a mixed model of shock where patients initially develop myocardial dysfunction (usually reversible) followed by vasoplegia. This study provides evidence that norepinephrine is likely a preferable vasopressor to epinephrine in post-resuscitation shock.
- Narayan SM, Wang PJ, Daubert JP. New Concepts in Sudden Cardiac Arrest to Address an Intractable Epidemic: JACC State-of-the-Art Review. J Am Coll Cardiol. 2019;73(1):70-88.
- Nolan JP, Sandroni C, Böttiger BW, et al. European Resuscitation Council and European Society of Intensive Care Medicine guidelines 2021: post-resuscitation care. Intensive Care Med. 2021;47(4):369-421.
- Soar J, Berg KM, Andersen LW, Adult Advanced Life Support Collaborators et al. Adult Advanced Life Support: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations. Resuscitation. 2020;156:A80-A119.
- Myburgh JA, Higgins A, Jovanovska A, Lipman J, Ramakrishnan N, Santamaria J; CAT Study investigators. A comparison of epinephrine and norepinephrine in critically ill patients. Intensive Care Med. 2008;34(12):2226-34.
- Levy B, Clere-Jehl R, Legras A, et al. Epinephrine Versus Norepinephrine for Cardiogenic Shock After Acute Myocardial Infarction. J Am Coll Cardiol. 2018;72(2):173-182.