Introduction: Vasopressors, a cornerstone in the management of shock, are critical for maintaining adequate tissue perfusion. According to Surviving Sepsis Campaign guidelines, norepinephrine is recommended first-line vasopressor. Vasopressin is suggested as a second-line agent rather than further increasing norepinephrine doses. However, guidelines do not specify the exact dose or optimal timing for vasopressin initiation.Several studies have explored this, especially since higher norepinephrine doses have been associated with increased mortality. To address this, we conducted a meta-analysis of randomized controlled trials and observational studies evaluating the timing of vasopressin initiation in patients with septic shock receiving norepinephrine.
Methods: A comprehensive literature search was conducted using PubMed, Scopus, and Cochrane Library, covering studies published up to February 2025. We included studies comparing early versus late administration of vasopressin as an adjunct to norepinephrine in patients with septic shock. After applying exclusion criteria, eight studies were included in the final analysis—one clinical trial and seven observational studies. The primary outcome was mortality. Secondary outcomes included ICU length of stay (LOS), incidence of arrhythmias, and need for renal replacement therapy (RRT).
Results: The overall mortality in early vasopressin group was 38% compared to 48% in late vasopressin initiation group. There was a statistically significant difference between two groups with an odds ratio (OR) of 0.72 and a 95% Confidence Interval (CI) of 0.59-0.87. ICU stay was shorter in the early group (6.8 vs. 7.76 days; 95% CI: –0.03 to –0.24; p = 0.02). CRRT was needed less often in the early group (68% vs. 88%), though not statistically significant (95% CI: 0.55–0.98; p = 0.366). Arrhythmias were comparable (14% vs. 11%; 95% CI: 0.55–1.78; p = 0.974).
Conclusions: Our meta-analysis, the most recent to date, shows that early vasopressin initiation is associated with significantly reduced mortality, shorter ICU stays, and lower rates of RRT use. In critically ill patients with septic shock, early addition of vasopressin to norepinephrine may offer a mortality benefit. However, larger randomized trials are warranted to confirm these findings and better define optimal timing.
.jpeg.jpg "Ayesha Anwar, MD (she/her/hers) photo")
