Two Pressors, both Alike in Dignity? Vasopressin versus Norepinephrine and Renal Failure in Sepsis

If you’re in the Acute Kidney Injury business, you get used to disappointment. Acute Kidney Injury, or AKI to the cognoscenti, is common in hospitalized patients with sepsis and raises the mortality risk by about a factor of 7.

Yet study after study of potential treatments for AKI have failed. This is important to me because, as a nephrologist I not only care for patients with Acute Kidney Injury, I am an author of a study that failed to improve their outcomes.



And at first, a study appearing in the Journal of the American Medical Association seemed to be just another failed effort. Upon closer inspection, though, it might offer a ray of hope.

Researchers in the UK conducted a randomized trial to determine if the vasoconstrictor vasopressin was superior to the vasoconstrictor norepinephrine in patients with sepsis – an only modestly tortured acronym makes this the VANISH trial. If you remember your physiology, much of the disastrous consequences of sepsis are due to hypotension. To date, norepinephrine has served well as our first line agent to raise blood pressure in septic patients once IV fluids have failed.

But emerging evidence has suggested that vasopressin, which operates on a different receptor than norepinephrine might be particularly beneficial in septic patients, and might even increase perfusion to the poor kidneys.  In short, could vasopressin be the silver bullet to prevent AKI in this population?

The researchers randomized 421 patients with sepsis who needed a pressor agent to either norepinephrine or vasopressin. The primary outcome was the number of days in the next month they would be free of renal failure.  And the results?  Bupkis. Like all the AKI studies before it, this one showed no difference between the groups.

But let’s grasp at some straws. If you look at the number of patients who required dialysis, there was a significant difference: 25% in the vasopressin group, 35% in the norepinephrine group. And dialysis is a real outcome, not just some biochemical measure – this is something that would actually matter to patients.

Yes, of course, this was one of many secondary analyses, and the statistics weren’t adjusted for multiple comparisons. But when you’re on a life raft, even a light drizzle can be refreshing.

I’d be remiss not to point out a significant problem with the study: by the time the researchers got to the patients, more than 80% were already receiving a pressor – mostly norepinephrine.  We were supposed to be testing what pressor is the best to start first when a patient crashes – but issues with getting randomized study drug to the patient in a timely fashion across multiple centers precluded this possibility. There may be some room for improvement if we want to invest in another VANISH trial, perhaps focusing on the dialysis outcome.

Final analysis? This study shouldn’t change practice.  I mean, it’s a negative study. But hope is alive, folks. And hope, thy name just might be vasopressin.