Vasopressin versus norepinephrine infusion in patients with septic shock

The VASST (Vasopressin and Septic Shock Trial) was one of the most important clinical trials in intensive care, conducted by James A. Russell and colleagues at Canadian, Australian, and American centers. The multicenter, double-blind, randomized study evaluated whether adding low-dose vasopressin to vasopressor therapy would reduce mortality in septic shock patients already receiving catecholamines.

The 778 patients with septic shock refractory to fluids and on norepinephrine (≥ 5 µg/min) were randomized to receive vasopressin 0.01-0.03 U/min or additional norepinephrine 5-15 µg/min, maintaining MAP between 65-75 mmHg. The primary endpoint was 28-day all-cause mortality.

Results were clinically important although statistically neutral on the primary outcome: 28-day mortality was 35.4% in the vasopressin group vs 39.3% in the norepinephrine group (p = 0.26), with no significant difference. Similar results were observed at 90 days (43.9% vs 49.6%, p = 0.11). However, subgroup analysis revealed that in patients with less severe septic shock (receiving baseline norepinephrine of 5-15 µg/min), vasopressin was associated with significantly lower mortality (26.5% vs 35.7%, p = 0.05).

This trial established vasopressin as a safe adjunct to norepinephrine in septic shock, with no evidence of additional toxicity. Although it did not demonstrate overall benefit, the finding in less severe patients influenced the Surviving Sepsis Campaign guidelines, which began recommending vasopressin as a second-line vasopressor — particularly to reduce norepinephrine doses and in patients who fail to reach target MAP with catecholamines alone.