Abstract
Objective
To compare the effects of vasopressin versus norepinephrine infusion on the outcome of kidney injury in septic shock.
Design and setting
Post-hoc analysis of the multi-center double-blind randomized controlled trial of vasopressin versus norepinephrine in adult patients who had septic shock (VASST).
Patients and intervention
Seven hundred seventy-eight patients were randomized to receive a blinded infusion of either low-dose vasopressin (0.01–0.03 U/min) or norepinephrine infusion (5–15 μg/min) in addition to open-label vasopressors and were included in the outcome analysis. All vasopressors were titrated and weaned to maintain a target blood pressure.
Measurement and results
RIFLE criteria for acute kidney injury were used to compare the effects of vasopressin versus norepinephrine. In view of multiple simultaneous comparisons, a p value of 0.01 was considered statistically significant. Kidney injury was present in 464 patients (59.6%) at study entry. In patients in the RIFLE “Risk” category (n = 106), vasopressin as compared with norepinephrine was associated with a trend to a lower rate of progression to renal “Failure” or “Loss” categories (20.8 vs. 39.6%, respectively, p = 0.03), and a lower rate of use of renal replacement therapy (17.0 vs. 37.7%, p = 0.02). Mortality rates in the “Risk” category patients treated with vasopressin compared to norepinephrine were 30.8 versus 54.7%, p = 0.01, but this did not reach significance in a multiple logistic regression analysis (OR = 0.33, 99% CI 0.10–1.09, p = 0.02). The interaction of treatment group and RIFLE category was significant in predicting mortality.
Conclusions
Vasopressin may reduce progression to renal failure and mortality in patients at risk of kidney injury who have septic shock.
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Acknowledgments
Support: Canadian Institutes of Health Research, grant number: MCT 44152. Registration: ISRCTN94845869, http://www.controlled-trials.com. Anthony C. Gordon is grateful for support from the NIHR Biomedical Research Centre funding scheme. Keith R. Walley is a Michael Smith Foundation for Health Research Distinguished Scholar. Deborah J. Cook is a Chair of the Canadian Institutes of Health Research.
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For the Vasopressin and Septic Shock Trial (VASST) Investigators.
Appendix
Appendix
In addition to the authors, the following persons and institutions participated in the VASST trial: Writing Committee: A.C. Gordon, J.A. Russell (chair), K.R. Walley, C.L. Holmes, J.T. Granton, P.C. Hebert, D.J. Cooper, S. Mehta, J. Singer, D.J. Cook, J.J. Presneill, M.M. Storms; Executive Committee: J.A. Russell (chair), K.R. Walley, C.L. Holmes, J.T. Granton, P.C. Hebert, D.J. Cooper, S. Mehta, J. Singer, A.C. Gordon, M.M. Storms (project coordinator), S. Jones (administrative assistant); Management Committee: J.A. Russell (chair), M.M. Storms (project coordinator), K.R. Walley, C.L. Holmes, J. Singer, A.C. Gordon, S. Jones (administrative assistant); DSMB: G.R. Bernard (chair), A.S. Slutsky, G.A Wells; CIHR: A. Gasparini; Data Management: J. Singer, B. Savage, D. Ayers, R. Woods, K. Wu, M. Maralit. Dr Gordon had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. VASST Clinical Centers: Canada. British Columbia; St. Paul’s Hospital; Vancouver General; Kelowna General Hospital; Richmond General Hospital; Royal Columbian. Manitoba; St. Boniface; Winnipeg Health Science Centre. Ontario; Ottawa Hospital, General Campus; UHN—Toronto General & Toronto Western Hospitals; St. Joseph’s Hospital; Mount Sinai Hospital; Ottawa Hospital, Civic Campus; St. Michael’s; Sunnybrook and Women’s College Health Science Centre; Hamilton Health Sciences Centre; London Health Sciences Centre; Sudbury Regional Hospital; Charles LeMoyne Hospital; Windsor—Hotel Dieu Hospital. Australia. Victoria; Alfred Hospital; Royal Melbourne; Monash Medical Center. Western Australia; Royal Perth Hospital. South Australia; Flinders Medical Center. USA. Mayo Hospital.
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Gordon, A.C., Russell, J.A., Walley, K.R. et al. The effects of vasopressin on acute kidney injury in septic shock. Intensive Care Med 36, 83–91 (2010). https://doi.org/10.1007/s00134-009-1687-x
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DOI: https://doi.org/10.1007/s00134-009-1687-x