Corticosteroids Influence the Mortality and Morbidity of Acute Critical Illness

Mohamed Y Rady; Daniel J Johnson; Bhavesh Patel; Joel Larson; Richard Helmers


Crit Care. 2006;10(3) 

In This Article

Abstract and Introduction

Introduction: Use of corticosteroids for adrenal supplementation and attenuation of the inflammatory and immune response is widespread in acute critical illness. The study hypothesis was that exposure to corticosteroids influences the mortality and morbidity in acute critical illness.
Methods: This case-control retrospective study was performed in a single multidisciplinary intensive care unit at a tertiary care institution and consisted of 10,285 critically ill patients admitted between 1 January 1999 and 31 December 2004. Demographics, comorbidities, acute illness characteristics including severity measured by Sequential Organ Failure Assessment, concurrent medications, therapeutic interventions and incidence of infections were obtained from electronic medical records, were examined with multiple regression analysis and were adjusted for propensity of corticosteroid exposure. The primary outcome was hospital death, and the secondary outcome was transfer to a care facility at hospital discharge.
Results: Corticosteroid exposure in 2,632 (26%) patients was characterized by younger age, more females, higher Charlson comorbidity and maximal daily Sequential Organ Failure Assessment scores compared with control patients. Corticosteroids potentiated metabolic and neuromuscular sequels of critical illness with increased requirements for diuretics, insulin, protracted weaning from mechanical ventilation, need for tracheostomy and discharge to a care facility. Early exposure to corticosteroids predisposed to recurrent and late onset of polymicrobial and fungal hospital-acquired infections. Corticosteroids increased the risk for death or disability after adjustments for comorbidities and acute illness characteristics.
Conclusion: Corticosteroids increased the risk for death or disability in critical illness. Hospital-acquired infections and metabolic and neuromuscular sequels of critical illness were exacerbated by corticosteroids. Careful appraisal of the indications for use of corticosteroids is necessary to balance the benefits and risks from exposure in acute critical illness.

Administration of corticosteroids in a variety of settings in acute critical illness has become widespread. Corticosteroids are used therapeutically for relative adrenal insufficiency as well as for the attenuation of the inflammatory and immune response in the critically ill.[1] Early use of corticosteroids has been recommended in sepsis, acute lung injury, acute respiratory distress syndrome and refractory vasodilatory shock.[2,3,4,5] The Corticosteroid Randomization after Significant Head Injury study, a large, international, randomized placebo-controlled trial, was terminated after enrolment of 10,000 patients because of an unexpected rise in the death rate after early administration of corticosteroids.[6] That study report raised concerns with regard to the safety of corticosteroids since, up to that time, they had been liberally administered in a variety of life-threatening illnesses with the intent to improve survival. These concerns were substantiated when we observed, in a previous study, that administration of corticosteroids increased the mortality in vasopressor-dependent critical illness.[7] A similar observation of an unexpected increase in mortality from corticosteroids use was also reported from a randomized controlled trial of corticosteroids in late acute respiratory distress syndrome.[8]

The morbidity related to metabolic, immune and musculoskeletal side-effects of corticosteroids in noncritical illness has been recognized and has created great interest in developing alternative treatments to avoid these complications. In transplantation practice, the therapeutic use of corticosteroids for immunosuppression has decreased because of the introduction of other therapies targeted against specific cytokines including tumour necrosis factor and interleukins or selective lymphocytes calcineurin inhibition.[9,10] New immunosuppression regimes produced superior allograft survival and yet had fewer side effects than traditional high-dose corticosteroids.[11,12] For autoimmune inflammatory disorders and rheumatologic diseases, the use of corticosteroids has also declined because of better treatment options targeting inflammatory cytokines known to influence the progression of these conditions.[13,14,15,16]

The use of corticosteroids in noncritical illness has gradually diminished, yet their use in acute critical illness appears to be expanding in relative adrenal insufficiency, sepsis and systemic inflammatory organ injury. This study was designed to address the following questions: What are the frequency and patient characteristics associated with corticosteroid use in acute critical illness? Does the exposure to corticosteroids influence death or disability? What were the mechanisms for the observed effects of corticosteroids in acute critical illness? This study was a retrospective case-control analysis of all admissions to an adult intensive care unit (ICU) with exposure to corticosteroids defining the case group.


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