Skip to main content
Log in

The effects of vasopressin on acute kidney injury in septic shock

  • Original
  • Published:
Intensive Care Medicine Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Schrier RW, Wang W (2004) Acute renal failure and sepsis. N Engl J Med 351:159–169

    Article  CAS  PubMed  Google Scholar 

  2. Hoste EA, Lameire NH, Vanholder RC, Benoit DD, Decruyenaere JM, Colardyn FA (2003) Acute renal failure in patients with sepsis in a surgical ICU: predictive factors, incidence, comorbidity, and outcome. J Am Soc Nephrol 14:1022–1030

    Article  PubMed  Google Scholar 

  3. Lopes JA, Jorge S, Resina C, Santos C, Pereira A, Neves J, Antunes F, Prata MM (2007) Prognostic utility of RIFLE for acute renal failure in patients with sepsis. Crit Care 11:408

    Article  PubMed  Google Scholar 

  4. Rangel-Frausto MS, Pittet D, Costigan M, Hwang T, Davis CS, Wenzel RP (1995) The natural history of the systemic inflammatory response syndrome (SIRS). A prospective study. Jama 273:117–123

    Article  CAS  PubMed  Google Scholar 

  5. Neveu H, Kleinknecht D, Brivet F, Loirat P, Landais P (1996) Prognostic factors in acute renal failure due to sepsis. Results of a prospective multicentre study. The French Study Group on Acute Renal Failure. Nephrol Dial Transplant 11:293–299

    CAS  PubMed  Google Scholar 

  6. Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P (2004) Acute renal failure—definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 8:R204–R212

    Article  PubMed  Google Scholar 

  7. Bellomo R, Chapman M, Finfer S, Hickling K, Myburgh J (2000) Low-dose dopamine in patients with early renal dysfunction: a placebo-controlled randomised trial. Australian and New Zealand Intensive Care Society (ANZICS) Clinical Trials Group. Lancet 356:2139–2143

    Article  CAS  PubMed  Google Scholar 

  8. Barrett LK, Singer M, Clapp LH (2007) Vasopressin: mechanisms of action on the vasculature in health and in septic shock. Crit Care Med 35:33–40

    Article  CAS  PubMed  Google Scholar 

  9. Landry DW, Levin HR, Gallant EM, Seo S, D’Alessandro D, Oz MC, Oliver JA (1997) Vasopressin pressor hypersensitivity in vasodilatory septic shock. Crit Care Med 25:1279–1282

    Article  CAS  PubMed  Google Scholar 

  10. Holmes CL, Walley KR, Chittock DR, Lehman T, Russell JA (2001) The effects of vasopressin on hemodynamics and renal function in severe septic shock: a case series. Intensive Care Med 27:1416–1421

    Article  CAS  PubMed  Google Scholar 

  11. Patel BM, Chittock DR, Russell JA, Walley KR (2002) Beneficial effects of short-term vasopressin infusion during severe septic shock. Anesthesiology 96:576–582

    Article  CAS  PubMed  Google Scholar 

  12. Lauzier F, Levy B, Lamarre P, Lesur O (2006) Vasopressin or norepinephrine in early hyperdynamic septic shock: a randomized clinical trial. Intensive Care Med 32:1782–1789

    Article  CAS  PubMed  Google Scholar 

  13. Gordon AC, Russell JA, Holmes Boulton CL, Singer J, Storms MM, Walley KR (2007) The effect of vasopressin on renal function in septic shock. Am J Respir Crit Care Med 175:A596

    Google Scholar 

  14. Russell JA, Walley KR, Singer J, Gordon AC, Hebert PC, Cooper DJ, Holmes CL, Mehta S, Granton JT, Storms MM, Cook DJ, Presneill JJ, Ayers D (2008) Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med 358:877–887

    Article  CAS  PubMed  Google Scholar 

  15. (1992) American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 20:864–874

    Google Scholar 

  16. Ahlstrom A, Kuitunen A, Peltonen S, Hynninen M, Tallgren M, Aaltonen J, Pettila V (2006) Comparison of 2 acute renal failure severity scores to general scoring systems in the critically ill. Am J Kidney Dis 48:262–268

    Article  PubMed  Google Scholar 

  17. Bernard G (1997) The Brussels Score. Sepsis 1:43–44

    Article  Google Scholar 

  18. Hoste EA, Clermont G, Kersten A, Venkataraman R, Angus DC, De Bacquer D, Kellum JA (2006) RIFLE criteria for acute kidney injury are associated with hospital mortality in critically ill patients: a cohort analysis. Crit Care 10:R73

    Article  PubMed  Google Scholar 

  19. Uchino S, Bellomo R, Goldsmith D, Bates S, Ronco C (2006) An assessment of the RIFLE criteria for acute renal failure in hospitalized patients. Crit Care Med 34:1913–1917

    Article  PubMed  Google Scholar 

  20. Ostermann M, Chang RW (2007) Acute kidney injury in the intensive care unit according to RIFLE. Crit Care Med 35:1837–1843

    Article  PubMed  Google Scholar 

  21. Bagshaw SM, George C, Dinu I, Bellomo R (2008) A multi-centre evaluation of the rifle criteria for early acute kidney injury in critically ill patients. Nephrol Dial Transplant 23:1203–1210

    Article  PubMed  Google Scholar 

  22. Cruz DN, Bolgan I, Perazella MA, Bonello M, de Cal M, Corradi V, Polanco N, Ocampo C, Nalesso F, Piccinni P, Ronco C (2007) North East Italian Prospective Hospital Renal Outcome Survey on Acute Kidney Injury (NEiPHROS-AKI): targeting the problem with the RIFLE Criteria. Clin J Am Soc Nephrol 2:418–425

    Article  PubMed  Google Scholar 

  23. Lopes JA, Jorge S, Silva S, de Almeida E, Abreu F, Martins C, do Carmo JA, Lacerda JF, Prata MM (2006) An assessment of the RIFLE criteria for acute renal failure following myeloablative autologous and allogeneic haematopoietic cell transplantation. Bone Marrow Transpl 38:395

    Article  CAS  Google Scholar 

  24. Lopes JA, Jorge S, Neves FC, Caneira M, da Costa AG, Ferreira AC, Prata MM (2007) An assessment of the RIFLE criteria for acute renal failure in severely burned patients. Nephrol Dial Transplant 22:285

    Article  PubMed  Google Scholar 

  25. Lopes JA, Fernandes J, Jorge S, Neves J, Antunes F, Prata MM (2007) An assessment of the RIFLE criteria for acute renal failure in critically ill HIV-infected patients. Crit Care 11:401

    Article  PubMed  Google Scholar 

  26. Kuitunen A, Vento A, Suojaranta-Ylinen R, Pettila V (2006) Acute renal failure after cardiac surgery: evaluation of the RIFLE classification. Ann Thorac Surg 81:542–546

    Article  PubMed  Google Scholar 

  27. Ricci Z, Cruz D, Ronco C (2008) The RIFLE criteria and mortality in acute kidney injury: a systematic review. Kidney Int 73:538–546

    Article  CAS  PubMed  Google Scholar 

  28. Joannidis M, Metnitz B, Bauer P, Schusterschitz N, Moreno R, Druml W, Metnitz PG (2009) Acute kidney injury in critically ill patients classified by AKIN versus RIFLE using the SAPS 3 database. Intensive Care Med. doi: 10.1007/s00134-00009-01530-00134

  29. Edwards RM, Trizna W, Kinter LB (1989) Renal microvascular effects of vasopressin and vasopressin antagonists. Am J Physiol 256:F274–F278

    CAS  PubMed  Google Scholar 

  30. Lenz K, Hortnagl H, Druml W, Reither H, Schmid R, Schneeweiss B, Laggner A, Grimm G, Gerbes AL (1991) Ornipressin in the treatment of functional renal failure in decompensated liver cirrhosis. Effects on renal hemodynamics and atrial natriuretic factor. Gastroenterology 101:1060–1067

    CAS  PubMed  Google Scholar 

  31. Bomzon L, Rosendorff C (1975) Renovascular resistance and noradrenaline. Am J Physiol 229:1649–1653

    CAS  PubMed  Google Scholar 

  32. Bellomo R, Kellum JA, Wisniewski SR, Pinsky MR (1999) Effects of norepinephrine on the renal vasculature in normal and endotoxemic dogs. Am J Respir Crit Care Med 159:1186–1192

    CAS  PubMed  Google Scholar 

  33. Assmann SF, Pocock SJ, Enos LE, Kasten LE (2000) Subgroup analysis and other (mis)uses of baseline data in clinical trials. Lancet 355:1064–1069

    Article  CAS  PubMed  Google Scholar 

  34. Palevsky PM, Zhang JH, O’Connor TZ, Chertow GM, Crowley ST, Choudhury D, Finkel K, Kellum JA, Paganini E, Schein RM, Smith MW, Swanson KM, Thompson BT, Vijayan A, Watnick S, Star RA, Peduzzi P (2008) Intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med 359:7–20

    Article  CAS  PubMed  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Anthony C. Gordon.

Additional information

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.

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00134-009-1687-x

Keywords

Navigation