ArticleIntensive care medicine2026
Ultra-early versus early adjunctive vasopressin initiation after norepinephrine escalation in septic shock: a target trial emulation.
Article in Intensive care medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
purposeThe optimal timing of adjunctive vasopressin after norepinephrine escalation in septic shock remains uncertain. We emulated a target trial comparing ultra-early vasopressin initiation within 0-3 h with early initiation within > 3-6 h after the norepinephrine infusion rate reached 0.25 μg/kg/min or higher.
methodsWe emulated a target trial using electronic health record databases (MIMIC-IV 2008-2022 and eICU-CRD 2014-2015). Adults with septic shock who reached the norepinephrine threshold before vasopressin use were eligible. We used the clone-censor-weight method to estimate cumulative incidence curves under the ultra-early and early initiation strategies and compared them via the weighted Cox model.
resultsAmong 3810 eligible patients, after cloning, 744 clones adhered to the ultra-early strategy and 293 clones adhered to the early strategy. The weighted 28-day mortality risk was 48.1% under the ultra-early strategy and 53.0% under the early strategy (risk difference, - 5.0 percentage points; 95% confidence interval [CI] - 6.8 to - 3.2), with a restricted mean survival time difference of 1.58 days (95% CI 1.21-1.92) and a hazard ratio (HR) of 0.82 (95% CI 0.78-0.85). Ultra-early initiation was associated with lower renal replacement therapy (HR, 0.68; 95% CI 0.63-0.74), continuous renal replacement therapy (HR, 0.61; 95% CI 0.55-0.68), and medically treated arrhythmia (HR, 0.91; 95% CI 0.83-0.99), but not with lower acute kidney injury.
conclusionsAmong adults with septic shock whose norepinephrine infusion reached 0.25 μg/kg/min or higher before vasopressin use, vasopressin initiation within 0-3 h was associated with lower 28-day mortality than initiation within > 3-6 h.
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