February 28, 2008
Vasopressin versus Norepinephrine Infusion in Patients with Septic Shock.
What was the research question?
Does low-dose vasopressin decrease mortality in septic shock patients on conventional (catecholamine) vasopressors as compared with norepinephrine?
How did they do it?
Multicenter, randomized, double-blind trial in twenty-seven centers in Canada, Australia, and the United State.
778 patients with septic shock who were on a minimum of 5 μg/min of norepinephrine, were randomized to receive either low-dose vasopressin (396 patients) at 0.01 to 0.03 U/min, or norepinephrine at 5 to 15 μg/min (382 patients) in addition to open-label vasopressors.
All vasopressors were titrated as per protocol to maintain a mean blood pressure target of 65 to 75 mmHg.
The primary end point was the mortality rate 28 days.
What did they find?
28-day mortality was not significantly different between the vasopressin and norepinephrine groups (35.4% vs 39.3%; P=0.26), same for 90-day mortality (43.9% vs 49.6%; P=0.11).
Serious adverse events were not significantly different (10.3% vs 10.5%; P=1.00).
Patients with less severe septic shock, the 28-day mortality rate was lower in the vasopressin group than in the norepinephrine group (26.5% vs. 35.7%; P=0.05); however, in patients with more severe septic shock, there was no significant difference in 28-day mortality (44.0% vs 42.5%; P=0.76).
No significant no significant difference in days alive and free of organ dysfunction, need for renal replacement therapy, need for corticosteroids, and Length of stay (ICU and hospital).
Are there any limitations?
Potential type II error as observed mortality rates were lower than expected of 60%.
The mean arterial pressure at baseline was 72 to 73 mm Hg, therefore, the study was not testing patients with refractory shock, but it is a test of low-dose vasopressin as a “catecholamine-sparing agent”.
Earlier initiation of vasopressin may have been associated with better outcome as it was started after a mean time of 12 hours.
What does it mean?
Low-dose vasopressin as compared to norepinephrine did not reduce mortality rates in septic shock patients who were treated with catecholamine vasopressors.
Vasopressin is added to norepinephrine in practice as a “catecholamine-sparing agent” when norepinephrine dose reaches 0.3-0.5 μg/kg/min.