This pragmatic cluster-crossover randomized trial enrolled 3959 adults with septic shock across 13 hospitals, comparing hospital strategies recommending vasopressin initiation at lower versus higher doses of other vasopressors. At 28 days, mortality was 31.8% versus 33.0%; the adjusted risk difference was −0.4 percentage points (95% CI, −2.7 to 1.3), without a statistically significant reduction. Median kidney replacement therapy-free days were identical between strategies, with an adjusted marginal odds ratio of 1.01 (95% CI, 0.91 to 1.14). The intervention tested hospital-level recommendations rather than individually assigned vasopressin initiation.
A lower-threshold hospital strategy did not demonstrate reduced 28-day mortality in septic shock. These results address implementation strategies, not equivalence between individual vasopressin initiation thresholds.
Study limitation: Hospital-level recommendations produced overlapping initiation doses, limiting interpretation as a direct comparison of strictly separated individual treatment thresholds.
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