S01E64 | VASSPR Trial: Does Earlier Vasopressin Save Lives in Septic Shock?

When should we add vasopressin in septic shock? At a norepinephrine dose of 0.1 mcg/kg/min, or should we wait until 0.4? In this episode of PRISM Rounds, we examine the VASSPR trial, published in JAMA in October 2026. This pragmatic, cluster-randomized crossover trial enrolled 3,959 patients across 13 hospitals and compared earlier versus later vasopressin initiation strategies. Earlier initiation increased vasopressin use and reduced the norepinephrine dose at which it was started. However, 28-day mortality was similar between groups (31.8% vs 33.0%), with no significant improvement in kidney replacement therapy-free days. We explore the trial's strengths, imperfect adherence, implications for current sepsis guidelines, and why a fixed norepinephrine threshold may not capture the complexity of septic shock. The central question: Should vasopressor management be guided by a number, or by the patient's evolving physiology? A practical, evidence-based discussion for intensivists, emergency physicians, hospitalists, fellows, nurses, and ICU pharmacists. Primary article: Peltan ID, et al. Effect of Vasopressin Initiation Threshold on Septic Shock Mortality: The VASSPR Cluster Crossover Randomized Strategy Trial. JAMA. October 14, 2026. https://doi.org/10.1001/jama.2026.21333 Tags: Septic Shock, VASSPR Trial, Vasopressin, Norepinephrine, Critical Care, Intensive Care, Sepsis, Vasopressors, Hemodynamics, JAMA, Clinical Trials, Evidence-Based Medicine, PRISM Rounds At PRISM Rounds, we use AI-generated voices to bring you thoughtfully curated medical research in an engaging, conversational format. While we do our best to keep things accurate, occasional errors or mispronunciations may slip through. We hope these episodes spark curiosity and encourage you to explore the original research.