>Year 2009, Issue 3
Montoya GC, Hernández LA, Poblano MM, Olvera GC, Aguirre SJ, Granillo JF
Antiinflammatory effect of the cystatins in sepsis
Rev Asoc Mex Med Crit y Ter Int 2009; 23 (3)
PDF: 173.76 Kb.
Statins has a well known pleiotrophic effect as antiinflammatory, immunomodulators. It has been proposed as a therapeutic tool in septical patients.
Purpose:To investigate posible statins therapeutic uses in the induced sepsis inflammatory process.
Methods: This was a prospective, long term and experimental design study.
Results: Prospective analysis of 40 patients was due, they were divided in two randomized groups.
The control group was under 80 mg of simvastatin medication along 14 days. Measures of inflammatory markers:
globular sedimentation velocity (GSV), C-reactive protein (C-RP), Anti thrombin III) were performed at
beginning of trial and 5, 10 and 14 day. We observed decreased levels of GSV 19 (14-23), 36 (27-50)
(p ‹ 0.01). C-RP 6 (4-9), 13 (9-18), (p ‹ 0.01) and increased levels of antithrombin III 57 (49-65),
36 (29-49) (p ‹ 0.01) since fifth day. Mechanical ventilation days rated on 10 (2-12), 16 (4-18)
(p ‹ 0.04). Long stay on Critical Care Unit 15 (14-16), 22 (18-26), (p ‹ 0.01).
Conclusion: This study demonstrate that statins are eable to decrease the systemic inflammatory
response and also showns reduce the mechanical ventilation time rates and so on with the patient long stay.
Martin GS, Maninno DM, Eaton S et al. The epidemiology of Sepsis in the United States from 1979 through 2000. N Engl J Med 2003;348:1546-1554.
Bone RC, Balk RA, Cerra FB. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest 1992;101:1644.
Levy MM, Fink MP, Marshall JC et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 2003;31:1250-1256.
Hotchkiss R, Karl I. The Pathophysiology and Treatment of Sepsis. N Engl J Med 2003;348:138-50.
Russell J. Management of Sepsis. N Engl J Med 206;355:1699-713.
Ferreira FL, Bota DP, Bross A et al. Serial Evaluation of the SOFA score to predict Outcome in Critically Ill Patients. JAMA 2001;286:1754-1758.
De Leon Rosales SP. Prevalence of Infections in Intensive Care Units in Mexico: A Multicenter Study. Critical Care Med 2000;28:1316-1321.
Calabrò P, Yeh E. The Pleiotropic Effects: of Statins. Curr Opin Cardiol 2005;20:541-546.
Takemoto M, Liao JK. Pleiotropic effects of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors. Arterioscl Thromb Vasc Biol 2001;21:1712-1719.
Majumdar S, McAlister FA, Eurich DT, Padwa RS, Marrie TTJ. Statins and outcomes in patients admitted to hospital with community acquired pneumoniae: population based prospective cohort study. BMJ 2006;333:999-1003.
Almong Y. Statins, inflammation, and sepsis, hypothesis. Chest 2003;124:740-743.
Chua D, Tsang Rs, Kuo IF. The role of statins therapy in sepsis. Ann Pharmacother 2007;41:647-52.
Almog Y, Shefer A, Novack V et al. Prior statin therapy is associated with a decreased rate of severe sepsis. Circulation 2004;110:880-885.
Schönbeck U, Lobby P. Inflammation. Immunity and HMG-CoA reductase inhibitors statins as anti-inflammatory agents? Circulation 2004;109:18-26.
Liappis AP, Kan VL, Rochester CG, Simon GL. The effect of statin on mortality in patients with bacteremia. Clin Infect Dis 2001;33:1352-1357.
Schmidt H, Hennen R, Keller A et al. Association of statins therapy and increased survival in patients with multiple organ dysfunction syndrome. Intensive Care Med 2006;32:1248-51.
Kruger P FK, Cook D, Jones M, Nimmo G. Statins therapy is associated with fewer deaths in patients with bacteremia. Intensive Care Med 2006;32:75-79.
Hackman DG MM, Li P, Redelmeir DA. Statins and sepsis in patients with cardiovascular disease: a population based cohort analysis. Lancet 2006;367:413-418.
Thomsen RW, Hundborg HH, Johnsen SP et al. Statins use and mortality with 180 days after bacteremia: a population-based cohort study. Crit Care Med 2006;34: 1080-06.
Whtite B, Perry D. Acquired antithrombin deficiency in sepsis. british journal of haematology 2001;112:26-31.
Pettilä V, Pentt J, Pettilä M et al. Predictive value of antithrombin III and serum C-reactive protein concentration in critically ill patients with suspected sepsis. Crit Care Med 2002;30:271-275.
Lobo SM, Lobo FR, Bota DP et al. C-reactive protein levels correlate with mortality and organ failure in critically ill patients. Chest 2003;123:2043-49.
Chan KY, Bouchers ES, Gandhi PJ, Silva MA. HMG-CoA reductase inhibitors for lowering elevated levels of C-reactive protein. Am J Health Sys Pharm 2004;61:1676-81.
Undas A, Brummel-Ziendins K, Mann K. Statins and blood coagulation. Arterioscler Thromb Vasc Biol 2005; 25:287-294.
Mach F. Statins as immunomodulatory agents. Circulation 2004;109:15-17.
Reinhart K, Bayer O, Brunkhorst F, Meisner M. Markers of endothelial damage in organ dysfunction and sepsis. Crit Care Med 2002;30:302-312.
Vincent JL. Microvascular endothelial dysfunction a renewed appreciation of sepsis pathophysiology. Crit Care 2001;5(suppl 2):S1-S5.
Greenwood J, Mason JC. Statins and the vascular endothelial inflammatory response. Trends Immunol 2007;28:88-98.
Terbalanche M, Almong Y et al. Statins and sepsis: multiple modifications at multiple levels. Lancet Infect Dis 2007;7:358-68.
Pleiner J, Schaller G, Mittermayer F et al. Simvastatin prevents vascular hyporeactivity during inflammation. Circulation 2004;110:3349-54.
Giusti-Paiva A, Martinez MR, Felix JV et al. Simvastatin decreased nitric oxide overproduction and reverts the impaired vascular responsiveness induced by endotoxic shock in rats. Shock 2004;21:271-75.
Landmesser U, Bahlmann F, Muller M et al. Simvastatin versus ezetimibe: pleiotropic and lipid lowering effects on endothelial function in humans. Circulation 2005;111:2356-2363.
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.
Marshall JC. Sepsis: current status, future aspects. Curr Opin Crit Care 2004;10:250-264.
Terblanche M, Almong Y, Rosenson RS, Smith TS, Hackam DG. Statins: panacea for sepsis? Lancet Infect Dis 2006;6:242-248.
Niessner A, Steiner S, Speidl WS et al. Simvastatin suppresses endotoxin-induced upregulation of toll-like receptors 4 and 2 in vivo. Atherosclerosis 2006;189:408-13.
Steiner S, Speidl WS, Pleiner J et al. Simvastatin blunts endotoxin-induced tissue factor in vivo. Circulation 2005;111:1841-46.
Veillard NR, Braunersreuther V, Arnaud C et al. Simvastatin modulates chemokine receptor expression by geranylgeranyl isoprenoid pathway in human endothelial cells and macrophages. Atherosclerosis 2006;188:51-58.
Membreño JP. Marcadores de activación endotelial y coagulación en pacientes con síndrome de respuesta inflamatoria sistémica por sepsis. The ABC Medical Center 2008:1-50.
Rivers E, Nguyen B, Havstad S. Early goal direct therapy in the treatment of severe sepsis and septic shcock. N Engl J Med 2001;344:699-709.
Gao F, Linhartova L, Johnoson McD. Statins and sepsis. Br J Anaesth 2008;100:288-98.
>Year 2009, Issue 3