Association Between Vasopressor Discontinuation Sequence and Clinical Outcomes in Septic Shock: Norepinephrine Versus Vasopressin in the MIMIC-IV Database

Background/Objectives: The optimal order in which to withdraw norepinephrine (NE) and vasopressin (VP) when weaning vasopressor support in septic shock is uncertain. We compared clinical outcomes between NE-first and VP-first discontinuation. Methods: This retrospective cohort study used MIMIC-IV version 3.1 (2008–2022). We included adults with septic shock receiving concurrent NE and VP who underwent sequential discontinuation, with the remaining agent continued for at least 60 min. The primary outcome was 28-day all-cause mortality. Firth-penalized logistic regression was adjusted for age, sex, first-day Sequential Organ Failure Assessment (SOFA) score, and peri-overlap lactate. Additional models incorporated pre-discontinuation measurements. Results: Of 187 patients, 87 were NE-first and 100 VP-first. Twenty-eight-day mortality was 31.0% versus 35.0% (VP-first versus NE-first adjusted odds ratio 1.15, 95% confidence interval 0.62–2.13; p = 0.66). Additional adjustment for pre-discontinuation mean arterial pressure (MAP) and heart rate, followed by both drug doses, yielded odds ratios of 1.05 (0.56–1.97; n = 184) and 0.90 (0.40–2.04; n = 183), respectively. At least one recorded MAP below 65 mmHg occurred in 73.3% and 81.0% of assessable patients. Conclusions: No statistically significant association between discontinuation order and 28-day mortality was observed in this small, selected cohort. The wide confidence intervals remain compatible with clinically important differences.