Indian Journal of Critical Care Medicine

Register      Login

SEARCH WITHIN CONTENT

FIND ARTICLE

Volume / Issue

Online First

Archive
Related articles

VOLUME 20 , ISSUE 9 ( 2016 ) > List of Articles

SYSTEMATIC REVIEW

Systematic review of statins in sepsis: There is no evidence of dose response

Sandeep Gudibande, Tony Whitehouse, Catherine Snelson, Tonny Veenith, Morgan Quinn, Claire Moody, Bill Tunnicliffe, Zahid Khan, Mav Manji, Nick Murphy

Keywords : low dose, mortality, sepsis, statin,High dose

Citation Information : Gudibande S, Whitehouse T, Snelson C, Veenith T, Quinn M, Moody C, Tunnicliffe B, Khan Z, Manji M, Murphy N. Systematic review of statins in sepsis: There is no evidence of dose response. Indian J Crit Care Med 2016; 20 (9):534-541.

DOI: 10.4103/0972-5229.190366

License: CC BY-ND 3.0

Published Online: 00-09-2016

Copyright Statement:  Copyright © 2016; Jaypee Brothers Medical Publishers (P) Ltd.


Abstract

Objectives: Sepsis is a common cause of morbidity and mortality and is associated with significant costs to the healthcare organizations. We performed a systematic review and meta-analysis to assess whether high or low-dose statin therapy improved mortality in patients with sepsis. Methods: The trials analyzed in this study were multicenter or single center randomized control studies using statins for sepsis in a hospital setting. The patients included were adults with suspected or confirmed infection. Interventions: This study found eight randomized controlled trials where participants were given either a statin or placebo daily for 14–28 days, the duration of their illness, or until their death or discharge, which ever occurred first. Primary and Secondary Outcomes Measured: This meta-analysis measured the effect of statin therapy on in hospital and 28 days mortality. Results: In unselected patients, there was no demonstrable difference in the 28 days mortality (relative risk [RR] 0.88 95% confidence interval [CI], 0.70–1.12 and P = 0.16). There was also no significant difference between statin versus placebo for in-hospital mortality (RR 0.98 95% CI, 0.85–1.14 P = 0.36). When the studies where divided into low-dose and high-dose groups, there were no statistically significant differences for in-hospital mortality between low-dose statin versus placebo for (RR 0.81 CI 0.44–1.49 P = 0.27) or high-dose statin versus placebo (RR 0.99 95% CI 0.85–1.16, P = 0.28). There was no significant difference in adverse effects between the high- and low-dose groups. Conclusions: In this meta-analysis, we found that the use of statins did not significantly improve either in-hospital mortality or 28-day mortality in patients with sepsis. In the low-dose group, there were fewer quality multicenter studies; hence, conclusions based on the results of this subgroup are limited.


PDF Share
  1. Vincent JL, Sakr Y, Sprung CL, Ranieri VM, Reinhart K, Gerlach H, et al. Sepsis in European intensive care units: Results of the SOAP study. Crit Care Med 2006;34:344-53.
  2. Hall MJ, Williams SN, DeFrances CJ, Golosinskiy A. Inpatient care for septicemia or sepsis: A challenge for patients and hospitals. NCHS Data Brief 2011;62:1-8.
  3. Torio CM, Andrews RM. National Inpatient Hospital Costs: The Most Expensive Conditions by Payer, 2011: Statistical Brief #160. Healthcare Cost and Utilization Project (HCUP) Statistical Briefs; 2006. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24199255. [Last cited on 2016 Jul 24].
  4. Terblanche M, Almog Y, Rosenson RS, Smith TS, Hackam DG. Statins: Panacea for sepsis? Lancet Infect Dis 2006;6:242-8.
  5. Liao JK, Laufs U. Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol 2005;45:89-118.
  6. Merx MW, Liehn EA, Graf J, van de Sandt A, Schaltenbrand M, Schrader J, et al. Statin treatment after onset of sepsis in a murine model improves survival. Circulation 2005;112:117-24.
  7. Kruger P, Fitzsimmons K, Cook D, Jones M, Nimmo G. Statin therapy is associated with fewer deaths in patients with bacteraemia. Intensive Care Med 2006;32:75-9.
  8. Terblanche M, Almog Y, Rosenson RS, Smith TS, Hackam DG. Statins and sepsis: Multiple modifications at multiple levels. Lancet Infect Dis 2007;7:358-68.
  9. Drage SM, Barber VS, Young JD. Statins and sepsis: Panacea or pandora's box? Lancet Infect Dis 2007;7:80.
  10. De Loecker I, Preiser JC. Statins in the critically ill. Ann Intensive Care 2012;2:19.
  11. Greenwood J, Mason JC. Statins and the vascular endothelial inflammatory response. Trends Immunol 2007;28:88-98.
  12. Papazian L, Roch A, Charles PE, Penot-Ragon C, Perrin G, Roulier P, et al. Effect of statin therapy on mortality in patients with ventilator-associated pneumonia: A randomized clinical trial. JAMA 2013;310:1692-700.
  13. Heart TN. Rosuvastatin for sepsis-associated acute respiratory distress syndrome. N Engl J Med 2014;370:2191-200.
  14. The Cochrane Collaboration. Review Manager (RevMan) [Computer Program]. Copenhagen: The Nordic Cochrane Centre; 2014.
  15. Higgins JPT, Green S, editors. Cochrane handbook for systematic reviews of interventions version 5.1.0 [updated March 2011]. The Cochrane Collaboration; 2011. Available from http://handbook.cochrane.org. [Last accessed on 2016 Sep 07].
  16. Hsu I, Spinler SA, Johnson NE. Comparative evaluation of the safety and efficacy of HMG-CoA reductase inhibitor monotherapy in the treatment of primary hypercholesterolemia. Ann Pharmacother 1995;29:743-59.
  17. Jones PH, Davidson MH, Stein EA, Bays HE, McKenney JM, Miller E, et al. Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR* Trial). Am J Cardiol 2003;92:152-60.
  18. Novack V, Eisinger M, Frenkel A, Terblanche M, Adhikari NK, Douvdevani A, et al. The effects of statin therapy on inflammatory cytokines in patients with bacterial infections: A randomized double-blind placebo controlled clinical trial. Intensive Care Med 2009;35:1255-60.
  19. Patel JM, Snaith C, Thickett DR, Linhartova L, Melody T, Hawkey P, et al. Randomized double-blind placebo-controlled trial of 40 mg/day of atorvastatin in reducing the severity of sepsis in ward patients (ASEPSIS Trial). Crit Care 2012;16:R231.
  20. Bradford RH, Shear CL, Chremos AN, Dujovne C, Downton M, Franklin FA, et al. Expanded clinical evaluation of lovastatin (EXCEL) study results. I. Efficacy in modifying plasma lipoproteins and adverse event profile in 8245 patients with moderate hypercholesterolemia. Arch Intern Med 1991;151:43-9.
  21. Angulo P. Nonalcoholic fatty liver disease. N Engl J Med 2002;346:1221-31.
  22. Farmer JA. Learning from the cerivastatin experience. Lancet 2001;358:1383-5.
  23. McAuley DF, Laffey JG, O'Kane CM, Perkins GD, Mullan B, Trinder TJ, et al. Simvastatin in the acute respiratory distress syndrome. N Engl J Med 2014;371:1695-703.
  24. Deshpande A, Pasupuleti V, Rothberg MB. Statin therapy and mortality from sepsis: A meta-analysis of randomized trials. Am J Med 2015;128:410-7.e1.
  25. Almog Y, Shefer A, Novack V, Maimon N, Barski L, Eizinger M, et al. Prior statin therapy is associated with a decreased rate of severe sepsis. Circulation 2004;110:880-5.
  26. Dhas BB, Ashmi H, Bhat BV. Sepsis genomics: Stepping forward toward sepsis prevention?. Int J Adv Med Health Res 2014;1:8-15.
  27. Kruger PS, Harward ML, Jones MA, Joyce CJ, Kostner KM, Roberts MS, et al. Continuation of statin therapy in patients with presumed infection: A randomized controlled trial. Am J Respir Crit Care Med 2011;183:774-81.
  28. Kruger P, Bailey M, Bellomo R, Cooper DJ, Harward M, Higgins A, et al. A multicenter randomized trial of atorvastatin therapy in intensive care patients with severe sepsis. Am J Respir Crit Care Med 2013;187:743-50.
  29. Craig TR, Duffy MJ, Shyamsundar M, McDowell C, O'Kane CM, Elborn JS, et al. A randomized clinical trial of hydroxymethylglutaryl- coenzyme a reductase inhibition for acute lung injury (The HARP Study). Am J Respir Crit Care Med 2011;183:620-6.
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.