Which Vasopressor Is Best in Septic Shock?

Greg Martin, MD


November 28, 2016

Treating Septic Shock: The VANISH Trial

Septic shock occurs in approximately 200,000 people each year in the United States, with roughly 50,000 deaths annually.[1] In addition to treating the underlying infection, the mainstay of cardiovascular resuscitation in septic shock is the administration of intravenous fluids and vasopressor agents. Norepinephrine is the recommended first-line vasopressor.[2] Relative vasopressin deficiency in septic shock has been theorized, however. Some data suggest that arginine vasopressin (AVP) may be renoprotective and, in combination with corticosteroids, may improve survival.[3]

With this in mind, the recent VANISH trial[4] sought to determine whether AVP in higher than previously used doses (up to 0.06 U/min) would improve renal outcomes compared with norepinephrine. Patients (N = 409) were randomly assigned to one of four groups:

  • AVP plus hydrocortisone;

  • AVP plus placebo;

  • Norepinephrine plus hydrocortisone; or

  • Norepinephrine plus placebo.

No difference was observed in mortality, whether or not corticosteroids were administered. Kidney failure in survivors occurred equally (57.0% for AVP vs 59.2% for norepinephrine) whether or not corticosteroids were given. The number of kidney failure–free days in nonsurvivors was similar (9 days for AVP vs 13 days for norepinephrine), with less use of renal replacement therapy in the AVP group than in the norepinephrine group (25.4% vs 35.3%). The researchers concluded that early use of vasopressin compared with norepinephrine in patients with septic shock does not benefit kidney function, although larger trials may be necessary.


Until the publication of the Vasopressin and Septic Shock Trial (VASST),[5] which showed no improvement in mortality with AVP, there had been a great deal of interest in the use of AVP because it theoretically reverses a relative hormone deficiency and works through a different mechanism from the catecholamine-driven vasopressors (eg, norepinephrine). The use of AVP in septic shock declined after that time and the drug was relegated to a lower rung in the most recent Surviving Sepsis Campaign guidelines.[2] Still, AVP has a role as an adjunctive agent in the most severe forms of septic shock, a role that might have expanded if AVP had been shown to avert organ dysfunction, which was once thought to be the case.[6] Unfortunately, the VANISH trial found that neither of the two tested doses of AVP reliably produced a clinically important improvement when administered with the aim of preventing kidney failure in patients with septic shock.


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