Vasopressin versus Norepinephrine Infusion in Patients with Septic Shock
James A. Russell, M.D., Keith R. Walley, M.D., Joel Singer, Ph.D., Anthony C. Gordon, M.B., B.S., M.D., Paul C. Hébert, M.D., D. James Cooper, B.M., B.S., M.D., Cheryl L. Holmes, M.D., Sangeeta Mehta, M.D., John T. Granton, M.D., Michelle M. Storms, B.Sc.N., Deborah J. Cook, M.D., Jeffrey J. Presneill, M.B., B.S., Ph.D., Dieter Ayers, M.Sc., for the VASST Investigators
Background Vasopressin is commonly used as an adjunct to catecholaminesto support blood pressure in refractory septic shock, but itseffect on mortality is unknown. We hypothesized that low-dosevasopressin as compared with norepinephrine would decrease mortalityamong patients with septic shock who were being treated withconventional (catecholamine) vasopressors.
Methods In this multicenter, randomized, double-blind trial,we assigned patients who had septic shock and were receivinga minimum of 5 µg of norepinephrine per minute to receiveeither low-dose vasopressin (0.01 to 0.03 U per minute) or norepinephrine(5 to 15 µg per minute) in addition to open-label vasopressors.All vasopressor infusions were titrated and tapered accordingto protocols to maintain a target blood pressure. The primaryend point was the mortality rate 28 days after the start ofinfusions.
Results A total of 778 patients underwent randomization, wereinfused with the study drug (396 patients received vasopressin,and 382 norepinephrine), and were included in the analysis.There was no significant difference between the vasopressinand 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 significantdifferences in the overall rates of serious adverse events (10.3%and 10.5%, respectively; P=1.00). In the prospectively definedstratum of less severe septic shock, the mortality rate waslower in the vasopressin group than in the norepinephrine groupat 28 days (26.5% vs. 35.7%, P=0.05); in the stratum of moresevere septic shock, there was no significant difference in28-day mortality (44.0% and 42.5%, respectively; P=0.76). Atest for heterogeneity between these two study strata was notsignificant (P=0.10).
Conclusions Low-dose vasopressin did not reduce mortality ratesas compared with norepinephrine among patients with septic shockwho were treated with catecholamine vasopressors. (Current ControlledTrials number, ISRCTN94845869
[controlled-trials.com]
.)
Source Information
From the iCAPTURE Centre, Vancouver, BC (J.A.R., K.R.W., A.C.G., M.M.S.); St. Paul's Hospital, Vancouver, BC (J.A.R., K.R.W., J.S., A.C.G., M.M.S., D.A.); Ottawa Hospital, University of Ottawa, Ottawa (P.C.H.); Kelowna General Hospital, Kelowna, BC, and University of British Columbia, Vancouver (C.L.H.); Mount Sinai Hospital, Toronto (S.M.); Toronto General Hospital, Toronto Western Hospital, and University of Toronto, Toronto (J.T.G.); and St. Joseph's Hospital and McMaster University, Hamilton, ON (D.J. Cook) — all in Canada; and Alfred Hospital and Monash University, Melbourne (D.J. Cooper); and Royal Melbourne Hospital and University of Melbourne (J.J.P.) — all in Melbourne, Australia.
Address reprint requests to Dr. Russell at Critical Care Medicine, St. Paul's Hospital, 1081 Burrard St., Vancouver, BC V6Z 1Y6, Canada, or at jrussell{at}mrl.ubc.ca.
Vasopressin in Septic Shock
Boyle W. A., Leone M., Dünser M. W., Hasibeder W. R., Wenzel V., Landry D. W., Oliver J. A., Mogyorosi A., Russell J. A., Walley K. R.
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N Engl J Med 2008;
358:2736-2738, Jun 19, 2008.
Correspondence
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