Evidence Maps of Vasopressor Use in Adult Patients With Septic Shock: An Umbrella Review

Studies investigating different classes of vasopressors for septic shock are ongoing, and discrepancies persist among the increasing number of meta-analyses. This umbrella review and evidence map aim to provide a comprehensive overview of the current evidence and to evaluate the highest-quality evidence regarding the efficacy and safety of vasopressors in the treatment of septic shock.

We searched PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews from inception to August 2024. We included meta-analyses of randomized controlled trials that compared vasopressors for the treatment of adult patients with septic shock. The methodological quality of the included meta-analyses was assessed using A MeaSurement Tool to Assess Systematic Reviews 2 (AMSTAR 2). The quality of evidence for each outcome was evaluated using the modified Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The best available evidence was identified using the Jadad decision algorithm.

A total of thirty-one eligible meta-analyses were included. The comparison of norepinephrine with vasopressin was the most frequently studied, followed by comparisons of norepinephrine with dopamine. Norepinephrine was found to be superior to dopamine in reducing mortality, heart rate, and the incidence of arrhythmia. Methylene blue demonstrated a reduction in mortality, even though this finding was supported by low GRADE evidence. Meta-analyses comparing norepinephrine with phenylephrine, epinephrine, and angiotensin II showed no significant differences in mortality, also with low GRADE evidence. The addition of vasopressin to norepinephrine was associated with comparable mortality, a lower risk of arrhythmia, and a higher risk of digital ischemia, with moderate GRADE evidence. In contrast, the addition of terlipressin showed no significant differences.

Current evidence fails to demonstrate superior efficacy of alternative vasoactive agents compared to norepinephrine across all evaluated outcome indicators. Considering both the reduced risk of arrhythmias and the increased risk of digital ischemia associated with vasopressin, clinicians should individualize therapy based on patient-specific factors. In addition, our evidence maps identify gaps in the existing literature, highlighting areas for future research.