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2007, Number 6

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Gac Med Mex 2007; 143 (6)

Estatinas, ¿alternativa terapéutica en sepsis?

Carrillo-Esper R, Rivera-Buendía S, Carrillo-Córdova JR, Carrillo-Córdova LD

Language: Spanish
References: 35
Page: 499-503
PDF size: 54.82 Kb.


ABSTRACT

Sepsis continues to be a major cause of morbidity and mortality. Evidence is emerging from observational studies and basic science research that statins might be associated with reduced mortality in sepsis. Statins have diverse immunomodulatory and antiinflammatory properties independent of their lipid-lowering ability. The protective association between statins and sepsis persisted in high-risk subgroups including patients with diabetes mellitus, those with malignancy, and those receiving steroids. This review discusses the basis of these observations and the current place of statin therapy in patients with sepsis. This is a rapidly growing field of fascinating experimental biology. It suggests an urgent need to investigate the pharmacology of these drugs and reappraise their therapeutic indications in critically ill patients. If this finding is supported by prospective controlled trials, statins may play an important role in sepsis related mortality. By the other hand statins are significantly cheaper than other therapies that have been shown to improve outcome in sepsis, and the demonstration of mortality benefit would have enormous cost-benefit implication.


REFERENCES

  1. Levy MM, Fink MP, Marshall JC. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 2003;31:1250-1256.

  2. Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 2003;348:1546-1554.

  3. Dellinger PR, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 2004;32:858-873.

  4. Heart Protection Study Investigators. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002;360:7-22.

  5. Ross R. Atherosclerosis an inflammatory disease. N Engl J Med 1999;340:115-126.

  6. Terblanche M, Almog Y, Rosenson RS, Smith TS, Hackman DG. Statins: panacea for sepsis? Lancet Infect Dis 2006;6:242-248.

  7. Weber C, Erl W, Weber KS. HMG-CoA reductase inhibitors decrease CD11b expression and CD11b-dependent adhesion of monocytes to endothelium and reduce increased adhesiveness of monocytes isolated from patients with hypercholesterolemia. J Am Coll Cardiol 1997;30:1212-1217.

  8. Wagner AH, Schwabe O, Hecker M. Atorvastatin inhibition of cytokineinducible nitric oxide synthase expression in native endothelial cells in situ. Br J Pharmacol 2002;136:143-149.

  9. Almog Y. Statins, inflammation, and sepsis: Hypothesis. Chest 2003;124:740-743.

  10. Laufs U, La Fata V, Plutzky J. Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation 1998;97:1129-1135.

  11. Weitz-Schmidt G, Welzenbach K, Brinkmann V. Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site. Nat Med 2001;7:687-692.

  12. Frenette PS. Locking a leukocyte integrin with statins. N Engl J Med 2001;345:1419-1421.

  13. Jialal I, Stein D, Balis D. Effect of hydroxymethyl glutaryl coenzyme a reductase inhibitor therapy on high sensitive C-reactive protein levels. Circulation 2001;103:1933-1935.

  14. Rice JB, Stoll LL, Li WG. Low level endotoxin induces potent inflammatory activation of human blood vessels: inhibition by statins. Arterioscler Thromb Vasc Biol 2003;23:1576-1582.

  15. Pruefer D, Makowski J, Schnell M. Simvastatin inhibits inflammatory properties of Staphylococcus aureus alpha-toxin. Circulation 2002;106:2104 -2110.

  16. Mason JC, Ahmed Z , Mankoff R. Statin-induced expression of decayaccelerating factor protects vascular endothelium against complement-mediated injury. Circ Res 2002;91:696-703.

  17. Kwak B, Mulhaupt F, Myit S, Mach F. Statins as a newly recognized type of immunomodulator. Nat Med 2000;6:1399-402.

  18. Giusti-Paiva A, Martínez MR, Félix JV, da Rocha MJ, Carnio EC, Elías LL, et al. Simvastatin decreases nitric oxide overproduction and reverts the impaired vascular responsiveness induced by endotoxic shock in rats. Shock 2004;21:271-275.

  19. Warnholtz A, Genth-Zotz S, Münzel T. Should treatment of sepsis include statins? Circulation 2005;111;1735-1737.

  20. Merx MW, Liehn EA, Janssens U. HMG-CoA reductase inhibitor simvastatin profoundly improves survival in a murine model of sepsis. Circulation 2004;109:2560-2565.

  21. Ando H, Takamura T, Ota T, Nagai Y, Kobayashi K. Cerivastatin improves survival of mice with lipopolysacharide-induced sepsis. J Pharmacol Exp Ther 2000;294:1043-1046.

  22. Merx MW, Liehn EA, Graf J. Statin treatment after onset of sepsis in a murine model improves survival. Circulation 2005;112:117-124.

  23. 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;880-885.

  24. Mortensen EM, Restrepo MI, Anzueto A, Pugh J. The effect of prior statin use on 30-day mortality for patients hospitalized with community-acquired pneumonia. Respir Res 2005;6:82.

  25. Steiner S, Speidl WS, Pleiner J, Seidinger D, Zorn G, Kaun C, et al. Simvastatin blunts endotoxin induced tissue factor in vivo. Circulation 2005;111:1841-1846.

  26. Liappis AP, Kan VL, Rochester CG, Simon GL. The effect of statins on mortality in patients with bacteremia. Clin Infect Dis 2001;33:1352-1357.

  27. Hackam DG, Mamdani M, Li P, Redelmeier DA. Statins and sepsis in patients with cardiovascular disease: a population-based cohort analysis. Lancet 2006;367:413-418.

  28. 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;32:75-79.

  29. Schrier RW, Wang W. Acute renal failure and sepsis. N Engl J Med 2004;351:159-169.

  30. Yasuda H, Yuen PS, Hu X, Zhou H, Star RA. Simvastatin improves sepsisinduced mortality and acute kidney injury via renal vascular effects. Kidney Int 2006;69:1535-1542.

  31. Motoyama T, Okamoto K, Kukita I, Hamaguchi M, Kinoshita Y, Ogawa H. Possible role of increased oxidant stress in multiple organ failure after systemic inflammatory response syndrome. Crit Care Med 2003;31:1048-1052.

  32. Baigent C, Keech A, Kearney PM. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90 056 participants in 14 randomised trials of statins. Lancet 2005;366:1267-1278.

  33. Tolman K. The liver and lovastatin. Am J Cardiol 2002;89:1374-1380.

  34. Baker SK, Tarnopolsky MA. Statin-associated neuromyotoxicity. Drugs Today 2005;41:267-293.

  35. Knopp RH. Drug treatment of lipid disorders. N Engl J Med 1999;341:498- 511.




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