.png){kind=icon}
.png){kind=icon}
Return
Ultra-early versus early adjunctive vasopressin initiation after norepinephrine escalation in septic shock: a target trial emulation
.png){kind=icon}
PRE
AI
T
T
M
T
J
T
S
T
DOI：10.1007/s00134-026-08575-3.png)
.png){kind=icon}
Original request for help.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
The 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. We 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. Among 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. Among 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.
Keywords:
Septic shock
Vasopressin
Norepinephrine
Treatment timing
Target trial emulation
Clone-censor-weight
Journal
IF:
21.2
Papers:
1.2W
Citations:
3.0W
Organization
Cited Papers