Effect of Vasopressin Initiation Threshold on Septic Shock Mortality: The VASSPR Cluster Crossover Randomized Strategy Trial
JAMA, 2026 · Pragmatic cluster-randomized monthly crossover strategy trial, 13 hospitals and 3959 patients
What the trial found
28-day mortality was 31.8% versus 33.0%; adjusted risk difference −0.4 percentage points (95% CI −2.7 to 1.3); P=.62.
Current guideline position
This trial must be interpreted alongside indication-specific guidance; its result alone does not establish a universal treatment policy.
Clinical interpretation
A universal lower initiation threshold did not improve survival. This does not overturn adjunctive vasopressin use or establish an obligatory threshold for every patient.
Limitations
The subset of sepsis with profound circulatory and cellular/metabolic abnormality — clinically identified by a vasopressor requirement to maintain MAP ≥ 65 mmHg plus lactate > 2 mmol/L despite adequate fluid resuscitation.
Cellular dysoxia, DO2/VO2 physiology, the 4 shock phenotypes, dynamic fluid responsiveness (PLR/PPV) vs fluid tolerance (VExUS), and vasoactive pharmacology.
Life-threatening organ dysfunction caused by a dysregulated host response to infection — recognized by an acute rise in SOFA score, not by infection plus fever alone.