Epinephrine versus norepinephrine in cardiogenic shock: a systematic review and meta-analysis of adjusted clinical outcomes

Background/Introduction Vasoactive therapy is central to the management of cardiogenic shock (CS). Although current guidelines recommend norepinephrine as the first-line vasopressor, epinephrine remains used in clinical practice, particularly in advanced shock states. Comparative evidence on clinical outcomes remains limited and predominantly observational. Purpose To evaluate the association between epinephrine versus norepinephrine use and clinical outcomes in patients with cardiogenic shock. Methods A systematic search of MEDLINE, Embase, and Cochrane databases was performed to identify studies comparing epinephrine and norepinephrine in adult patients with CS. Randomised and observational studies were eligible. Eight studies were included in the qualitative synthesis. Of these, four observational studies reported multivariable-adjusted mortality estimates suitable for quantitative pooling, and two studies reported outcomes related to continuous renal replacement therapy (CRRT). Adjusted odds ratios (aORs) for mortality were pooled using random-effects meta-analysis with Hartung–Knapp adjustment. Risk ratios (RRs) were pooled for CRRT outcomes using random-effects models. Statistical heterogeneity was assessed using the I² statistic. Risk of bias was evaluated using validated tools appropriate to study design. Analyses were performed using R (RStudio version 2026.01.0, Build 392). Results Eight studies were included in the qualitative synthesis. Across studies, epinephrine use was associated with greater metabolic derangement, higher vasoactive requirements, and increased markers of organ dysfunction. Four observational studies reporting adjusted mortality estimates were included in the quantitative analysis. Epinephrine use was associated with higher short-term mortality compared with norepinephrine (random-effects aOR 2.73; 95% CI 1.01–7.35; I² = 63.7%) (Figure 1). Two studies reported CRRT outcomes. Epinephrine use was associated with a higher risk of CRRT requirement (random-effects RR 3.22; 95% CI 1.78–5.82; I² = 0%) (Figure 2). Conclusion(s) In patients with cardiogenic shock, epinephrine use is associated with worse short-term clinical outcomes, including higher mortality and increased need for renal replacement therapy, compared with norepinephrine. These findings are consistent with current guideline recommendations favouring norepinephrine as the first-line vasopressor in CS. However, given the limited number of studies and the observational nature of the available evidence, residual confounding cannot be excluded, and adequately powered randomised trials are warranted.