Timing of adjunctive vasopressin initiation for septic shock patients and hospital mortality: A multicentre observational study.

Objective: The optimal timing of vasopressin initiation as an adjunctive vasopressor remains unclear. We aimed to study the association between the timing of vasopressin commencement, pre-specified physiological parameters, and hospital mortality. Design: We conducted a multicentre, retrospective, observational study. Setting: Twelve ICUs in Queensland, Australia between January 2015 and December 2021. Participants: Adult patients with septic shock who received vasopressin as an adjunctive vasopressor within 72 hours of ICU admission. Main Outcome: Hospital mortality. Results: Overall, 2747 patients fulfilled the inclusion criteria. Of these, 1850 (67%) started vasopressin within six hours of vasopressor therapy start, while 897 (33%) started vasopressin between six hours and 72 hours. APACHE III score, peak lactate, and creatinine were higher in the early start group. Early vasopressin start was independently associated with decreased hospital mortality (aOR = 0.69, 95% CI = 0.57-0.83). Vasopressin infusion start was also associated with an immediate decrease in the noradrenaline-equivalent dose regardless of timing. There was a statistically significant favourable breakpoint at vasopressin start for the course of arterial pH, lactate, heart rate and crystalloid infusion rate (p<0.001). Conclusions: In patients with septic shock, early adjunctive vasopressin initiation was independently associated with lower hospital mortality. Vasopressin starting at any time was also associated with reduced tachycardia, acidosis, and hyperlactatemia.