Vasopressin versus norepinephrine infusion in patients with septic shock.
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].).
Russell
James A
JA
iCAPTURE Centre, Vancouver, BC, Canada. jrussell@mrl.ubc.ca
Walley
Keith R
KR
Singer
Joel
J
Gordon
Anthony C
AC
Hébert
Paul C
PC
Cooper
D James
DJ
Holmes
Cheryl L
CL
Mehta
Sangeeta
S
Granton
John T
JT
Storms
Michelle M
MM
Cook
Deborah J
DJ
Presneill
Jeffrey J
JJ
Ayers
Dieter
D
D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects*; D002395:Catecholamines / Q000008:administration & dosage / Q000009:adverse effects; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000008:administration & dosage* / Q000009:adverse effects; D012720:Severity of Illness Index; D012772:Shock, Septic / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D017211:Treatment Failure; D014662:Vasoconstrictor Agents / Q000008:administration & dosage* / Q000009:adverse effects; D014667:Vasopressins / Q000008:administration & dosage* / Q000009:adverse effects
D002395:Catecholamines; D014662:Vasoconstrictor Agents; D014667:Vasopressins; D009638:Norepinephrine