Washington University Emergency Medicine Journal Club – July 14, 2026
Dr. Brian Cohn
Hello all,
For this academic year we will be holding journal club during normal Tuesday morning conference time. This month’s topic will be the use of continuous IV epinephrine infusion vs continuous norepinephrine infusion in the management of shock following return of spontaneous circulation from cardiac arrest.
The PGY-1, PGY-2, and PGY-3 articles will be appraised using the Therapy review form. The PGY-4 article will be appraised using the Meta-analysis review form.
Vignette
You’re working a busy overnight shift in the emergency department when EMS brings in a 58-year-old man who suffered a witnessed cardiac arrest at his nephew’s Bar Mitzvah. CPR was initiated immediately by the Rabbi and EMS was called. After two rounds of ACLS and one defibrillation for ventricular fibrillation, he achieved return of spontaneous circulation (ROSC) in the field.
He arrives to the ED intubated, unresponsive, and hypotensive. His blood pressure is 72/38 mm Hg, heart rate is 118 beats/min, and oxygen saturation is 98% on mechanical ventilation. He is cool, mottled, and has poor peripheral perfusion. Bedside ultrasound shows a grossly preserved left ventricular ejection fraction without obvious pericardial effusion or right heart strain. A liter of fluid has already been started, but his blood pressure remains critically low.
The nurse asks whether you would like to start an epinephrine drip to support his blood pressure. Your attending notes that post–cardiac arrest shock is common and it has been standard to use epinephrine to support both peripheral arterial tone and maintain cardiac output. You remember hearing about a recent meta-analysis demonstrating that norepinephrine was superior to epinephrine in managing post-arrest shock following ROSC. You settle on an epinephrine drip (which was already being prepped by nursing) but decide that after your shift you are going to do a deeper dive into the evidence.
PICO Question
Population: Adults with shock after return of spontaneous circulation following
cardiac arrest
Intervention: Intravenous norepinephrine infusion
Comparison: Intravenous epinephrine infusion
Outcome: Improved hemodynamic stability, mortality, neurologic outcome, rearrest,
need for renal replacement therapy
Search Strategy
PubMed was searched using the terms: (“cardiac arrest” OR “return of spontaneous
circulation” OR postresuscitation) AND (epinephrine AND norepinephrine) (https://
tinyurl.com/3zh66k74). This resulted in 190 citations, from which one metaanalysis
and three primary studies were selected.
Article 1: Bougouin W, Slimani K, Renaudier M, et al; Sudden Death Expertise Center
Investigators. Epinephrine versus norepinephrine in cardiac arrest patients with
post-resuscitation shock. Intensive Care Med. 2022 Mar;48(3):300-310. [Answer Key].
Article 2: Smida T, Crowe RP, Martin PS, Scheidler JF, Price BS, Bardes JM. A
retrospective, multi-agency ‘target trial emulation’ for the comparison of postresuscitation
epinephrine to norepinephrine. Resuscitation. 2024 May;198:110201.
doi: 10.1016/j.resuscitation.2024.110201. Epub 2024 Apr 4. [Answer Key].
Article 3: Weiss A, Dang C, Mabrey D, Stanton M, Feih J, Rein L, Feldman R.
Comparison of Clinical Outcomes with Initial Norepinephrine or Epinephrine for
Hemodynamic Support After Return of Spontaneous Circulation. Shock. 2021 Dec
1;56(6):988-993. [Answer Key].
Article 4: Williams CA, Pourmand A, Hintze T, et al. Norepinephrine versus
epinephrine after cardiac arrest: A systematic review and meta-analysis. Am J Emerg
Med. 2025 Sep;95:107-114. [Answer Key].
Bottom Line
Shock is common following successful resuscitation from cardiac arrest, occurring in 50 to 70% of cases. Multiple factors contribute to this condition, including myocardial dysfunction, vasoplegia, and hypovolemia. Vasopressor support is frequently necessary and most commonly includes epinephrine or norepinephrine. Norepinephrine primarily provides α₁-adrenergic receptor agonism, resulting in systemic vasoconstriction, with only moderate β₁ activity and modest inotropic support. Epinephrine, on the other hand, stimulates α₁, β₁, and β₂ receptors. While there is some theoretical benefit to increased inotropy in the setting of myocardial dysfunction following cardiac arrest via its strong β₁ stimulation, the downside is a resulting increased myocardial oxygen demand placing undue stress on the post-arrest heart. The 2025 AHA guidelines found insufficient evidence to recommend one agent over the other. We sought to review the evidence comparing these two agents to further our understandings of the literature on this topic.
Using a multicenter, observational cohort from the Paris Sudden Death Expertise Center registry that included 766 patients admitted alive to the ICU with postresuscitation shock, Bougouin et al found that epinephrine was associated with higher in-hospital all-cause mortality than norepinephrine (83% vs. 61%; OR 3.1, 95% CI 2.2–4.4) and lower rates favorable neurological outcomes (15% vs. 37%). Recurrent cardiac arrest within 48 hours was also more common with epinephrine (7% vs. 2%, P < 0.001). After adjustment by logistic regression, epinephrine remained associated with higher all-cause mortality (OR 2.6, 95% CI 1.4–4.7); similar results were seen using propensity score matching (OR 2.1, 95% CI 1.1–4). Despite the use of statistical methods to adjust for baseline differences in group, the retrospective nature of this study leaves it at high risk of selection bias and confounding. Additionally, only short-term clinical outcomes were considered.
Smida et al used retrospective date from the 2018–2022 ESO Data Collaborative dataset of EMS encounters and found similar unadjusted rates of rearrest (21.9% epinephrine vs. 18.3% norepinephrine, p=0.06) and mortality (83.0% vs. 80.6%, p=0.49) between agents, though shockable rearrest was more common with epinephrine (6.3% vs. 3.7%, p=0.01). In adjusted analysis, there was no significant association between vasopressor choice and rearrest (aOR 0.93, 95% CI 0.72–1.21), shockable rearrest, mortality, or time-to-rearrest (hazard ratio 1.0, p=0.95). Again, the retrospective nature of the included data results in a high risk of selection bias and confounding, although vasopressor choice in this study was dictated by protocol rather than paramedic choice for 80% of participating EMS agencies.
In Weiss et al, a small single-center retrospective study involving 87 patients treated at a tertiary academic level I trauma center ED in Milwaukee, Wisconsin, the composite outcome (refractory hypotension, rearrest, or death) occurred more often in the ED among patients receiving epinephrine than norepinephrine (50% vs. 22.2%; RR 2.25, 95% CI 1.20–4.20). This difference lost significance by 6 hours (RR 1.29, 95% CI 0.93–1.78) and narrowed further by full hospitalization (RR 1.19, 95% CI 1.01–1.40). Patients receiving epinephrine were also more likely to need an additional catecholamine agent (RR 1.61, 95% CI 1.05–2.45). After multivariable adjustment, epinephrine remained independently associated with the ED composite outcome (aOR 3.94, 95% CI 1.38–12.2, p=0.013); logistic regression was not reported for the primary outcome at 6-hours or by hospital discharge.
A systematic review and meta-analysis on this topic included 6 studies, of which were 5 retrospective observational studies comprising 3,458 patients while only one small study (n = 40) was a randomized controlled trial. Pooled results suggest that norepinephrine was associated with significantly lower odds of recurrent arrest compared to epinephrine (OR 0.47, 95% CI 0.24–0.92, p=0.03), though heterogeneity between studies was high (I²=89%). This benefit was significant only in OHCA-only studies (OR 0.32, 95% CI 0.13–0.72). For survival to discharge, norepinephrine showed a non-significant trend toward benefit (OR 2.04, 95% CI 0.93–4.47, p=0.07; 19% vs. 9% raw survival), and for unfavorable neurologic outcome there was also no significant difference (OR 1.72, 95% CI 0.92–3.22, p=0.09).
Across all four sources, norepinephrine demonstrated trends toward better short-term outcomes than epinephrine, though no significant difference was observed for more patient-centered outcomes such as survival to discharge or favorable neurologic outcomes. The EMS-based study is the notable exception, showing no adjusted difference at all. All studies except the single RCT are retrospective and observational, at high risk of selection bias and confounding, and there is no large RCT to provide more robust data. Given the apparent short-term benefit to norepinephrine over epinephrine, with some non-statistically significant trends toward better hospital survival, norepinephrine seems the better candidate for management of post-arrest shock, though the data is far from definitive.