N Engl J Med. 2008 Feb 28;358(9):877-87.
Russell JA, Walley KR, Singer J, Gordon AC, Hébert PC, Cooper DJ, Holmes CL,
Mehta S, Granton JT, Storms MM, Cook DJ, Presneill JJ, Ayers D; VASST
Investigators.
iCAPTURE Centre, Vancouver, BC, Canada. jrussell@mrl.ubc.ca
BACKGROUND: Vasopressin is commonly used as an adjunct to catecholamines to
support blood pressure in refractory septic shock, but its effect on mortality is
unknown. We hypothesized that low-dose vasopressin as compared with
norepinephrine would decrease mortality among patients with septic shock who were
being treated with conventional (catecholamine) vasopressors. METHODS: In this
multicenter, randomized, double-blind trial, we assigned patients who had septic
shock and were receiving a minimum of 5 microg of norepinephrine per minute to
receive either low-dose vasopressin (0.01 to 0.03 U per minute) or norepinephrine
(5 to 15 microg per minute) in addition to open-label vasopressors. All
vasopressor infusions were titrated and tapered according to protocols to
maintain a target blood pressure. The primary end point was the mortality rate 28
days after the start of infusions. RESULTS: A total of 778 patients underwent
randomization, were infused with the study drug (396 patients received
vasopressin, and 382 norepinephrine), and were included in the analysis. There
was no significant difference between the vasopressin and norepinephrine groups
in the 28-day mortality rate (35.4% and 39.3%, respectively; P=0.26) or in 90-day
mortality (43.9% and 49.6%, respectively; P=0.11). There were no significant
differences in the overall rates of serious adverse events (10.3% and 10.5%,
respectively; P=1.00). In the prospectively defined stratum of less severe septic
shock, the mortality rate was lower in the vasopressin group than in the
norepinephrine group at 28 days (26.5% vs. 35.7%, P=0.05); in the stratum of more
severe septic shock, there was no significant difference in 28-day mortality
(44.0% and 42.5%, respectively; P=0.76). A test for heterogeneity between these
two study strata was not significant (P=0.10). CONCLUSIONS: Low-dose vasopressin
did not reduce mortality rates as compared with norepinephrine among patients
with septic shock who were treated with catecholamine vasopressors. (Current
Controlled Trials number, ISRCTN94845869 [controlled-trials.com].). Copyright
2008 Massachusetts Medical Society.