Q UARTERLY E VIDENCE - BASED R EVIEWS ON C URRENT T OPICS IN C RITICAL C ARE M EDICINE BY LEADING C ANADIAN C ONTENT E XPERTS Volume 8, Issue 3 2011 Acknowledgements: Canadian Institutes of Health Research Public Health Agency of Canada John Granton, MD Chair, Canadian Critical Care Society John Marshall, MD Chair, Canadian Critical Care Trials Group Margaret Herridge, MD Editor, Critical Care Rounds Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are highly lethal syndromes of pulmonary inflammation. These disorders commonly compli- cate a variety of critical illnesses, including pneumonia (present in 46% of patients with ALI/ARDS), nonpulmonary sepsis (33%), aspiration (11%), severe trauma (7%), blood transfusions (3%), and pancreatitis (3%). 1 Together, they affect up to 20% of critically ill, mechanically ventilated patients. 2,3 Corticosteroids have been a mainstay of therapy in these conditions for decades, and the effectiveness and safety of these agents has been studied extensively. This issue of Critical Care Rounds reviews the existing literature on corticosteroid use in ALI/ARDS and highlights what remains unknown. In a recent multicentre prospective cohort study, the incidence of ALI was 79 per 100 000 person-years, 1 yielding more than 26 000 cases per year when applied to the Canadian 2009 population. Mortality estimates for ALI and ARDS range from 30%– 50%. 1 However, the societal burden of this illness is not solely attributable to the asso- ciated death rate. In a Canadian multicentre prospective observational study of severe ARDS patients, Herridge et al 4 described median durations of mechanical ventilation (21 days), stay in an intensive care unit (ICU; 25 days), and hospitalization (48 days). In a 2-year follow-up of Canadian ARDS survivors, one-third received inpatient rehabilita- tion (median length of stay 36 days), and 51% of those who were discharged received home care support services (median 28 visits). Hospital readmission was frequent (39%) and constituted the largest portion of healthcare expenditures following the initial hos- pitalization (mean post-hospital discharge costs $28 350). 5 A Strong Biologic Rationale for Systemic Corticosteroid Therapy Current evidence suggests that excessive production of proinflammatory cytokines (tumour necrosis factor, interleukin [IL]-1, IL-6, and IL-8) and neutrophil recruitment to the lungs together mediate the lung pathology of ALI and ARDS. 6 The duration of inflammatory cytokine production can be prolonged, which is associated with a worse outcome for patients with ARDS. 7 Meduri et al 8 hypothesized that systemic inflammation induces a state of peripheral glucocorticoid resistance. They observed that peripheral blood leucocytes exposed to plasma from ARDS patients produce inflammatory cytokines, and that administration of methylprednisolone to the same patients reduced inflammatory cytokine production. In animal models of ALI, Rocco et al 9 showed that corticosteroids reduce lung elastance and the deposition of collagen fibres in the extracellular matrix of the lung. In human patients, Meduri et al 10 found that procollagen aminoterminal propep- tides (types I and III) in plasma and bronchoalveolar lavage increased in nonresolving ARDS and that corticosteroid administration was associated with reductions in these markers. They also reported a significant correlation between biomarker reductions and Corticosteroids in Acute Lung Injury and Acute Respiratory Distress Syndrome B Y F RANÇOIS L AMONTAGNE , MD, MS C , AND M AUREEN M EADE , MD, MS C ® The editorial content of Critical Care Rounds is determined solely by the Canadian Critical Care Society. Dr. Lamontagne is Assistant Professor, Centre de Recherche Clinique Étienne-Le Bel and Department of Internal Medicine, University of Sherbrooke, Sherbrooke, Quebec. Dr. Meade is Associate Professor, Department of Medicine, and Joint Member, Department of Clinical Epidemiology and Biostatistics, McMaster University, and Attending Staff, Intensive Care Unit, Hamilton Health Sciences, Hamilton, Ontario. Disclosure: The authors have no disclosures with regard to the contents of this issue.