Pilot Trial of Statin Use in Burn Patients

Summary

This is a 90 day study, with patients receiving either oral Rosuvastatin or placebo for up to 28 days. The study will assess the affect of statins administered soon after burn injury on C-reactive protein (CRP) levels, patient mortality and the incidence of septic shock. The investigators also seek to describe the correlation between exposure to statins and development of delirium and de-novo long-term cognitive impairment. Hypothesis: 1. Statin administration within 96 hours of burn is safe, will decrease CRP, and will decrease septic shock and mortality in burn patients. 2. The investigators hypothesize that burn patients will have a de-novo long term cognitive impairment at 3 months after burn. 3. The investigators hypothesize the use of statins in burn patients will reduce the development and the degree of cognitive impairment at 3 months post burn.

Timeline

Start

2010-03

Primary completion

2011-02

Completion

2011-05

Publications

• Background Bloemsma GC, Dokter J, Boxma H, Oen IM. Mortality and causes of death in a burn centre. Burns. 2008 Dec;34(8):1103-7. doi: 10.1016/j.burns.2008.02.010. Epub 2008 Jun 6.
• Background Woodward B, Cartwright M. Safety of drotrecogin alfa (activated) in severe sepsis: data from adult clinical trials and observational studies. J Crit Care. 2009 Dec;24(4):595-602. doi: 10.1016/j.jcrc.2008.11.011. Epub 2009 Feb 12.
• Background Almog Y, Shefer A, Novack V, Maimon N, Barski L, Eizinger M, Friger M, Zeller L, Danon A. Prior statin therapy is associated with a decreased rate of severe sepsis. Circulation. 2004 Aug 17;110(7):880-5. doi: 10.1161/01.CIR.0000138932.17956.F1. Epub 2004 Aug 2.
• Background Chua D, Tsang RS, Kuo IF. The role of statin therapy in sepsis. Ann Pharmacother. 2007 Apr;41(4):647-52. doi: 10.1345/aph.1H550. Epub 2007 Mar 27.
• Background Merx MW, Weber C. Statins in the intensive care unit. Curr Opin Crit Care. 2006 Aug;12(4):309-14. doi: 10.1097/01.ccx.0000235207.00322.96.
• Background Efron DT, Sorock G, Haut ER, Chang D, Schneider E, Mackenzie E, Cornwell EE 3rd, Jurkovich GJ. Preinjury statin use is associated with improved in-hospital survival in elderly trauma patients. J Trauma. 2008 Jan;64(1):66-73; discussion 73-4. doi: 10.1097/TA.0b013e31815b842a.
• Background Fogerty MD, Efron D, Morandi A, Guy JS, Abumrad NN, Barbul A. Effect of preinjury statin use on mortality and septic shock in elderly burn patients. J Trauma. 2010 Jul;69(1):99-103. doi: 10.1097/TA.0b013e3181df61b1.
• Background Merx MW, Liehn EA, Graf J, van de Sandt A, Schaltenbrand M, Schrader J, Hanrath P, Weber C. Statin treatment after onset of sepsis in a murine model improves survival. Circulation. 2005 Jul 5;112(1):117-24. doi: 10.1161/CIRCULATIONAHA.104.502195.
• Background Merx MW, Liehn EA, Janssens U, Lutticken R, Schrader J, Hanrath P, Weber C. HMG-CoA reductase inhibitor simvastatin profoundly improves survival in a murine model of sepsis. Circulation. 2004 Jun 1;109(21):2560-5. doi: 10.1161/01.CIR.0000129774.09737.5B. Epub 2004 May 3.
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• Background Istvan ES, Deisenhofer J. Structural mechanism for statin inhibition of HMG-CoA reductase. Science. 2001 May 11;292(5519):1160-4. doi: 10.1126/science.1059344.
• Background Terblanche M, Almog Y, Rosenson RS, Smith TS, Hackam DG. Statins and sepsis: multiple modifications at multiple levels. Lancet Infect Dis. 2007 May;7(5):358-68. doi: 10.1016/S1473-3099(07)70111-1.
• Background Gao F, Linhartova L, Johnston AM, Thickett DR. Statins and sepsis. Br J Anaesth. 2008 Mar;100(3):288-98. doi: 10.1093/bja/aem406.
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• Background McGown CC, Brookes ZL. Beneficial effects of statins on the microcirculation during sepsis: the role of nitric oxide. Br J Anaesth. 2007 Feb;98(2):163-75. doi: 10.1093/bja/ael358.
• Background Hopkins RO, Weaver LK, Chan KJ, Orme JF Jr. Quality of life, emotional, and cognitive function following acute respiratory distress syndrome. J Int Neuropsychol Soc. 2004 Nov;10(7):1005-17. doi: 10.1017/s135561770410711x.
• Background Jackson JC, Gordon SM, Hart RP, Hopkins RO, Ely EW. The association between delirium and cognitive decline: a review of the empirical literature. Neuropsychol Rev. 2004 Jun;14(2):87-98. doi: 10.1023/b:nerv.0000028080.39602.17.
• Background Varney NR, Ju D, Shepherd JS, Kealey GP. Long-term neuropsychological sequelae of severe burns. Arch Clin Neuropsychol. 1998 Nov;13(8):737-49.
• Background McNicoll L, Pisani MA, Zhang Y, Ely EW, Siegel MD, Inouye SK. Delirium in the intensive care unit: occurrence and clinical course in older patients. J Am Geriatr Soc. 2003 May;51(5):591-8. doi: 10.1034/j.1600-0579.2003.00201.x.
• Background Ely EW, Inouye SK, Bernard GR, Gordon S, Francis J, May L, Truman B, Speroff T, Gautam S, Margolin R, Hart RP, Dittus R. Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU). JAMA. 2001 Dec 5;286(21):2703-10. doi: 10.1001/jama.286.21.2703.
• Background Bergeron N, Dubois MJ, Dumont M, Dial S, Skrobik Y. Intensive Care Delirium Screening Checklist: evaluation of a new screening tool. Intensive Care Med. 2001 May;27(5):859-64. doi: 10.1007/s001340100909.
• Background Thomason JW, Shintani A, Peterson JF, Pun BT, Jackson JC, Ely EW. Intensive care unit delirium is an independent predictor of longer hospital stay: a prospective analysis of 261 non-ventilated patients. Crit Care. 2005 Aug;9(4):R375-81. doi: 10.1186/cc3729. Epub 2005 Jun 1.
• Background Peterson JF, Pun BT, Dittus RS, Thomason JW, Jackson JC, Shintani AK, Ely EW. Delirium and its motoric subtypes: a study of 614 critically ill patients. J Am Geriatr Soc. 2006 Mar;54(3):479-84. doi: 10.1111/j.1532-5415.2005.00621.x.
• Background Pandharipande P, Cotton BA, Shintani A, Thompson J, Costabile S, Truman Pun B, Dittus R, Ely EW. Motoric subtypes of delirium in mechanically ventilated surgical and trauma intensive care unit patients. Intensive Care Med. 2007 Oct;33(10):1726-31. doi: 10.1007/s00134-007-0687-y. Epub 2007 Jun 5.
• Background Ely EW, Margolin R, Francis J, May L, Truman B, Dittus R, Speroff T, Gautam S, Bernard GR, Inouye SK. Evaluation of delirium in critically ill patients: validation of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Crit Care Med. 2001 Jul;29(7):1370-9. doi: 10.1097/00003246-200107000-00012.
• Background Ely EW, Shintani A, Truman B, Speroff T, Gordon SM, Harrell FE Jr, Inouye SK, Bernard GR, Dittus RS. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA. 2004 Apr 14;291(14):1753-62. doi: 10.1001/jama.291.14.1753.
• Background Dubois MJ, Bergeron N, Dumont M, Dial S, Skrobik Y. Delirium in an intensive care unit: a study of risk factors. Intensive Care Med. 2001 Aug;27(8):1297-304. doi: 10.1007/s001340101017.
• Background Pandharipande P, Shintani A, Peterson J, Pun BT, Wilkinson GR, Dittus RS, Bernard GR, Ely EW. Lorazepam is an independent risk factor for transitioning to delirium in intensive care unit patients. Anesthesiology. 2006 Jan;104(1):21-6. doi: 10.1097/00000542-200601000-00005.
• Background Pandharipande P, Cotton BA, Shintani A, Thompson J, Pun BT, Morris JA Jr, Dittus R, Ely EW. Prevalence and risk factors for development of delirium in surgical and trauma intensive care unit patients. J Trauma. 2008 Jul;65(1):34-41. doi: 10.1097/TA.0b013e31814b2c4d.
• Background Brown C, Albrecht R, Pettit H, McFadden T, Schermer C. Opioid and benzodiazepine withdrawal syndrome in adult burn patients. Am Surg. 2000 Apr;66(4):367-70; discussion 370-1.
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• Background Dehne MG, Sablotzki A, Hoffmann A, Muhling J, Dietrich FE, Hempelmann G. Alterations of acute phase reaction and cytokine production in patients following severe burn injury. Burns. 2002 Sep;28(6):535-42. doi: 10.1016/s0305-4179(02)00050-5.
• Background Ulrich D, Noah EM, Pallua N. [Plasma endotoxin, procalcitonin, C-reactive protein, and organ functions in patients with major burns]. Handchir Mikrochir Plast Chir. 2001 Jul;33(4):262-6. doi: 10.1055/s-2001-16595. German.
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• Background Armitage J. The safety of statins in clinical practice. Lancet. 2007 Nov 24;370(9601):1781-90. doi: 10.1016/S0140-6736(07)60716-8.
• Background Sachse C, Machens HG, Felmerer G, Berger A, Henkel E. Procalcitonin as a marker for the early diagnosis of severe infection after thermal injury. J Burn Care Rehabil. 1999 Sep-Oct;20(5):354-60. doi: 10.1097/00004630-199909000-00004.
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Drugs

Indications

No indication recorded.