Chapter 68: Controversies: Corticosteroids for ARDS: Friend or Foe?

INTRODUCTION

The acute respiratory distress syndrome (ARDS) is a common and vexing problem faced by critical care providers worldwide. Despite extensive investigation over the last three decades, the impact of ARDS in terms of morbidity, mortality, and health care costs remains very high. In the United States alone, ARDS affects as many as 200,000 people per year with a mortality rate from 30% to 50% and costs in excess of $60,000 per hospitalization.^1,2 The management of patients with ARDS is essentially supportive using a lung protective ventilatory strategy and treatment of the precipitating cause.³ The use of corticosteroids in patients with ARDS is controversial with widely dissenting opinions on this topic.⁴ At least 6 meta-analyses have been performed with conflicting conclusions.^5,6,7,8,9,10 However, a summation of this data would suggest that glucocorticoids (GCs) improve oxygenation, increase the number of ventilator-free days, decrease intensive care unit (ICU) and hospital length of stay with a possible mortality benefit with no clear evidence of an increase in complications. Despite the potential benefit of GCs in patients with ARDS, survey data suggest that most clinicians do not prescribe these agents to their patients with ARDS.¹¹ The purpose of this review is to outline the rationale for GC treatment in ARDS, discuss the factors affecting response to treatment, review the results of clinical trials and the myths concerning GC-related side effects and outline a protocol for GC treatment based on the best available data.

BRIEF REVIEW OF PATHOGENESIS

ARDS develops rapidly, in most patients within 12 to 48 hours of developing an illness associated with severe systemic inflammation. Injury to the alveolar-capillary membrane (ACM) causes exudative neutrophilic inflammatory edema, resulting in severe gas exchange impairment and lung compliance abnormalities. The lung-injury score (LIS) quantifies the impaired respiratory physiology in ARDS by using a 4-point score based on the level of positive end-expiratory pressure (PEEP), ratio of partial arterial oxygen tension (PaO₂) to fraction of inspired oxygen (FiO₂) (PaO₂:FiO₂), the quasistatic lung compliance, and the degree of infiltration on chest radiograph.¹² Using these criteria, the evolution of ARDS can be divided into resolving and unresolving ARDS based on achieving a 1-point reduction in LIS by day 7.¹³

Experimental and clinical evidence has demonstrated a strong cause and effect relationship between persistence in systemic inflammation and progression (unresolving) of ARDS. At the cellular level, patients with unresolving ARDS have inadequate GC-GC receptor (GR)-mediated downregulation of inflammatory transcription factor nuclear factor-κB (NF-κB) despite elevated levels of circulating cortisol, a condition recently defined as critical-illness-related corticosteroid insufficiency (CIRCI).^14,15 Patients with unresolving ARDS have persistent elevation in both systemic and bronchoalveolar lavage (BAL) levels of inflammatory mediators, markers of fibrogenesis, and ACM permeability. At the tissue level, uninhibited increased NF-κB activation leads to ongoing ...