Vasopressin versus noradrenaline as initial therapy in septic shock. Is vasopressin-related renal protection doomed to “vanish” in the haze?

Gordon et al. recently reported the results of the multicenter Vasopressin vs. Norepinephrine as Initial Therapy in Septic Shock (VANISH) trial comparing the effect of these two potent vasopressors on kidney failure in adult patients with septic shock (1). Rationale for this study was the landmark Vasopressin and Septic Shock Trial (VASST) which found an association between low-dose (0.01 to 0.03 U per minute) vasopressin and decreased mortality in less severe septic shock but no difference between vasopressin and noradrenaline on global mortality or organ dysfunction rates (2). Post-hoc analysis of the VASST study suggested that vasopressin treatment was associated with a trend to reduced progression to renal failure or loss, less need for renal replacement therapy, and reduced mortality in septic shock patients at risk of kidney injury (3). This concurred with earlier small clinical studies demonstrating an improvement in creatinine clearance in vasopressin-treated patients (4,5). Unfortunately, the VANISH study did not find a difference in the number of kidney failure-free days in surviving patients receiving vasopressin or noradrenaline. The observation that, in the vasopressin group, fewer renal replacement therapy was required and that those who did not survive and/or experienced renal failure had less kidney failure-free days procured only some meagre scientific solace (1)