Early dexamethasone treatment for septic shock patients
a prospective randomized clinical trial
Keywords:
Infection, Septic shock, Sepsis, Glucocorticoids, DexamethasoneAbstract
CONTEXT AND OBJECTIVE: Sepsis and septic shock are very common conditions among critically ill patients that lead to multiple organ dysfunction syndrome (MODS) and death. Our purpose was to investigate the effi cacy of early administration of dexamethasone for patients with septic shock, with the aim of halting the progression towards MODS and death. DESIGN AND SETTING: Prospective, randomized, double-blind, single-center study, developed in a surgical intensive care unit at Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo. METHODS: The study involved 29 patients with septic shock. All eligible patients were prospectively randomized to receive either a dose of 0.2 mg/kg of dexamethasone (group D) or placebo (group P), given three times at intervals of 36 hours. The patients were monitored over a seven-day period by means of the sequential organ failure assessment score. RESULTS: Patients treated with dexamethasone did not require vasopressor therapy for as much time over the seven-day period as did the placebo group (p = 0.043). Seven-day mortality was 67% in group P (10 out of 15) and 21% in group D (3 out of 14) (relative risk = 0.31, 95% confi - dence interval 0.11 to 0.88). Dexamethasone enhanced the effects of vasopressor drugs. CONCLUSIONS: Early treatment with dexamethasone reduced the seven-day mortality among septic shock patients and showed a trend towards reduction of 28-day mortality.
Downloads
References
Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med. 2003;348(2):138-50.
Christman JW, Lancaster LH, Blackwell TS. Nuclear factor kappa B: a pivotal role in the systemic inflammatory response syndrome and new target for therapy. Intensive Care Med. 1998;24(11):1131-8.
Scheinman RI, Cogswell PC, Lofquist AK, Baldwin AS Jr. Role of transcriptional activation of I kappa B alpha in mediation of immuno- suppression by glucocorticoids. Science. 1995;270(5234):283-6.
Briegel J, Forst H, Haller M, et al. Stress doses of hydrocortisone reverse hyperdynamic septic shock: a prospective, randomized, dou- ble-blind, single-center study. Crit Care Med. 1999;27(4):723-32.
Meduri GU, Headley AS, Golden E, et al. Effect of prolonged methylprednisolone therapy in unresolving acute respira- tory distress syndrome: a randomized controlled trial. JAMA. 1998;280(2):159-65.
Carlet J; International Sepsis Forum. Immunological therapy in sepsis: currently available. Intensive Care Med. 2001;27 (Suppl 1):S93-103.
Cicarelli DD, Benseñor FE, Vieira JE. Effects of single dose of dexamethasone on patients with systemic inflammatory response. Sao Paulo Med J. 2006;124(2):90-5.
Schimmer BP, Parker KL. Adrenocorticotropic hormone; adreno- cortical steroids and their synthetic analogs; inhibitors of the synthesis and actions of adrenocortical hormones. In: Hardman JG, Limbird LE, Molinoff PB, Ruddon RW, Gilman AG, editors. Goodman and Gilman’s the pharmacological basis of therapeutics. 9th ed. New York: McGraw-Hill; 1996. p. 1459-85.
Reade MC, Young JD. Consent for observational studies in critical care: time to open Pandora’s Box. Anaesthesia. 2003;58(1):1-3.
Cook R, Cook D, Tilley J, Lee K, Marshall J; Canadian Critical Care Trials Group. Multiple organ dysfunction: baseline and se- rial component scores. Crit Care Med. 2001;29(11):2046-50.
Vincent JL, Moreno R, Takala J, et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunc- tion/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996;22(7):707-10.
Vincent JL, de Mendonça A, Cantraine F, et al. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on “sepsis-related problems” of the European Society of Intensive Care Medicine. Crit Care Med. 1998;26(11):1793-800.
Pettilä V, Pettilä M, Sarna S, Voutilainen P, Takkunen O. Comparison of multiple organ dysfunction scores in the predic- tion of hospital mortality in the critically ill. Crit Care Med. 2002;30(8):1705-11.
Póvoa P, Almeida E, Moreira P, et al. C-reactive protein as an indicator of sepsis. Intensive Care Med. 1998;24(10):1052-6.
Hollenberg SM, Ahrens TS, Annane D, et al. Practice parameters for hemodynamic support of sepsis in adult patients: 2004 update. Crit Care Med. 2004;32(9):1928-48.
Greenberg RS, Daniels SR, Flanders WD, Eley JW, Boring JR. Medical epidemiology. 3rd ed. New York: McGraw-Hill; 2001.
MacLaren R, Jung R. Stress-dose corticosteroids therapy for sepsis and acute lung injury or acute respiratory distress syndrome in critically ill adults. Pharmacotherapy. 2002;22(9):1140-56.
Manglik S, Flores E, Lubarsky L, Fernandez F, Chhibber VL, Tayek JA. Glucocorticoid insufficiency in patients who present to the hospital with severe sepsis: a prospective clinical trial. Crit Care Med. 2003;31(6):1668-75.
Abraham E, Evans T. Corticosteroids and septic shock. JAMA. 2002;288(7):886-7.
Annane D, Sébille V, Charpentier C, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA. 2002;288(7):862-71.
Matot I, Sprung CL. Corticosteroids in septic shock: resurrection of the last rites? Crit Care Med. 1998;26(4):627-30.
Meduri GU, Kanangat S. Glucocorticoid treatment of sepsis and acute respiratory distress syndrome: time for a critical reappraisal. Crit Care Med. 1998;26(4):630-3.
Thompson BT. Glucocorticoids and acute lung injury. Crit Care Med. 2003;31(4 Suppl):S253-7.
Martin GS, Bernard GR; International Sepsis Forum. Airway and lung in sepsis. Intensive Care Med. 2001;27(Suppl 1):S63-79.
