Indian Journal of Critical Care Medicine

Register      Login

SEARCH WITHIN CONTENT

FIND ARTICLE

Volume / Issue

Online First

Archive
Related articles

VOLUME 21 , ISSUE 10 ( 2017 ) > List of Articles

RESEARCH ARTICLE

The effects of atorvastatin on inflammatory responses and mortality in septic shock: A single-center, randomized controlled trial

Sudeep Kumar, Arvind Kumar Baronia, Ratender Singh

Keywords : Inflammatory biomarkers, mortality, septic shock, statins

Citation Information : Kumar S, Baronia A K, Singh R. The effects of atorvastatin on inflammatory responses and mortality in septic shock: A single-center, randomized controlled trial. Indian J Crit Care Med 2017; 21 (10):646-654.

DOI: 10.4103/ijccm.IJCCM_474_16

License: CC BY-ND 3.0

Published Online: 01-12-2016

Copyright Statement:  Copyright © 2017; The Author(s).


Abstract

Aim of the Study: Pleiotropic effect of statins can modulate inflammation in septic shock. We tested the hypothesis whether statins can reduce mortality in septic shock. Patients and Methods: We conducted a randomized double-blinded trial with treatment (40 mg dose of atorvastatin for 7 days) and control (placebo) arm in adult septic shock patients admitted to the Intensive Care Unit. Primary (28-day mortality) and secondary (vasopressor-, ventilation-, and renal replacement therapy-free days) outcomes, with lipid profile and adverse effects, were documented. Inflammatory biomarkers (interleukin [IL]-1, IL-6, tumor-necrosis-factor [TNF]-α, interferon [IFN], and C-reactive protein [CRP]), were also measured before (day 1 [D1]) and after start of trial drug (D4 and D7). Results: Seventy-three septic shock patients with 36 and 37 included in the atorvastatin and placebo group, respectively. Both groups were equally matched. Twenty-eight-day mortality, event-free days, lipid profile, and adverse effects were also not significantly different between groups. Reduced levels of IL-1, IL-6, TNF-α, IFN, and CRP were observed in the atorvastatin group. Also observed were significant day-wise changes in inflammatory biomarkers. Conclusions: Atorvastatin-induced changes in inflammatory biomarkers did not confer mortality benefit in septic shock (ClinicalTrials.govNCT02681653).


PDF Share
  1. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 2016;315:801-10.
  2. Blanco-Colio LM, Tuñón J, Martín-Ventura JL, Egido J. Anti-inflammatory and immunomodulatory effects of statins. Kidney Int 2003;63:12-23.
  3. Terblanche M, Almog Y, Rosenson RS, Smith TS, Hackam DG. Statins: Panacea for sepsis? Lancet Infect Dis 2006;6:242-8.
  4. Mekontso-Dessap A, Brun-Buisson C. Statins: The next step in adjuvant therapy for sepsis? Intensive Care Med 2006;32:11-4.
  5. Wan YD, Sun TW, Kan QC, Guan FX, Zhang SG. Effect of statin therapy on mortality from infection and sepsis: A meta-analysis of randomized and observational studies. Crit Care 2014;18:R71.
  6. Deshpande A, Pasupuleti V, Rothberg MB. Statin therapy and mortality from sepsis: A meta-analysis of randomized trials. Am J Med 2015;128:410-70.
  7. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving sepsis campaign: International guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 2013;41:580-637.
  8. Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et al. 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 1992;20:864-74.
  9. Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS international sepsis definitions conference. Intensive Care Med 2003;29:530-8.
  10. 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.
  11. 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.
  12. 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.
  13. Kruger P, Bailey M, Bellomo R, Cooper DJ, Harward M, Higgins A, et al. Amulticenter randomized trial of atorvastatin therapy in intensive care patients with severe sepsis. Am J Respir Crit Care Med 2013;187:743-50.
  14. 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.
  15. El Gendy HA, Elsharnouby NM. Safety and vasopressor effect of rosuvastatin in septic patients. Egypt J Anaesth 2014;30:311-7.
  16. National Heart, Lung, and Blood Institute ARDS Clinical Trials Network, Truwit JD, Bernard GR, Steingrub J, Matthay MA, Liu KD, et al. Rosuvastatin for sepsis-associated acute respiratory distress syndrome. N Engl J Med 2014;370:2191-200.
  17. Zheng Z, Jayaram R, Jiang L, Emberson J, Zhao Y, Li Q, et al. Perioperative rosuvastatin in cardiac surgery. N Engl J Med 2016;374:1744-53.
  18. Prinz V, Laufs U, Gertz K, Kronenberg G, Balkaya M, Leithner C, et al. Intravenous rosuvastatin for acute stroke treatment: An animal study. Stroke 2008;39:433-8.
  19. Laufs U, Adam O. Acute effects of statins. J Am Coll Cardiol 2012;59:71-3.
PDF Share
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.