Ultra-early versus early adjunctive vasopressin initiation after norepinephrine escalation in septic shock: a target trial emulation
Authors' conclusion
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.
Study context
- Population
- Adults with septic shock who reached norepinephrine 0.25 μg/kg/min or higher before vasopressin use (MIMIC-IV 2008–2022, eICU-CRD 2014–2015)eligible
- Participants
- 3,810 adults
- Exposure
- Ultra-early vs Early
- Ultra-earlyn = 744
- Earlyn = 293reference
- Outcome
- Mortality
- Follow-up
- 28 days
Methodological detailsobservational cohort study, clone-censor-weight method, weighted Cox model, electronic health record databases (MIMIC-IV, eICU-CRD)
- Observational cohort study
- Clone-censor-weight method
- Weighted Cox model
- Electronic health record databases (MIMIC-IV, eICU-CRD)
Main finding
As reported in the abstract
28-day mortality
Each group vs earlyRestricted mean survival time difference, days (95% CI)
Ultra-early
1.58(1.21–1.92)
Each group vs earlyHazard ratio (95% CI)
Ultra-early
0.82(0.78–0.85)
- Ultra-early
- risk difference - 5.0 percentage points (95% CI - 6.8 to - 3.2)
Observational data: associations, not effects.
Further findings
| Outcome | HR (95% CI) | |
|---|---|---|
| RRT | 0.68 (0.63–0.74) | |
| CRRT | 0.61 (0.55–0.68) | |
| 0.512Hazard ratio (log scale) |
AKI
- Ultra-early initiation not associated with lower AKI
Safety
| Outcome | HR (95% CI) | |
|---|---|---|
| Medically treated arrhythmia | 0.91 (0.83–0.99) | |
| 0.512Hazard ratio (log scale) |
Original publication
Ultra-early versus early adjunctive vasopressin initiation after norepinephrine escalation in septic shock: a target trial emulation. Intensive Care Med. Published 11 August 2026. doi:10.
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