Accepted: 7 April 1999 T. Marras ´ S. Mehta ( ) ) Critical Care Unit, Mount Sinai Hospital and University of Toronto, 600 University Avenue, Suite 1818, Toronto, Ontario, Canada M5G 1X5 e-mail: geeta.mehta@utoronto.ca Tel.: + 1±416±5864679, Fax: + 1±416±5868558 M. Herridge Toronto Hospital and University of Toronto, Eaton Wing North 10, Room 212, 200 Elizabeth Street, Toronto General Division, Toronto, Ontario, Canada M5G 2C4 Introduction The acute respiratory distress syndrome (ARDS) is an important problem in critical care medicine due to its relatively high incidence and substantial mortality. The complex series of inflammatory events leading to the development of ARDS occur as a result of direct (pneu- monia, aspiration, toxic inhalation, pulmonary contu- sion) or indirect (sepsis, non-thoracic trauma, hyper- transfusion) pulmonary insults [Bernard GR et al. (1994) Am J Respir Crit Care Med 149: 818±824]. The early phase of ARDS is characterized by an interstitial neutrophilic infiltrate, an airspace exudate composed of fluid, fibrin, erythrocytes and hyaline membranes and a proliferation of type II alveolar cells. During the later fibroproliferative phase, lymphocyte and fibro- blast recruitment can lead to collagen deposition and fi- brosis. Although the chest radiograph suggests diffuse infiltrates, CT scanning reveals a much more heteroge- neous pattern, with predominantly dependent lung in- volvement. General treatment principles include rever- sal of the underlying cause, ventilatory strategies to maintain oxygenation and avoid further lung injury, pa- tient positioning and careful fluid management. ARDS mortality is approximately 40 %, with sepsis and multi- organ failure responsible for the majority of deaths [Kollef MH et al. (1995) New Engl J Med 332: 27±37]. Despite extensive research, there is insufficient evi- dence to support the use of any specific modality to re- duce morbidity or mortality in ARDS [Luce JM (1998) Crit Care Med 26:369±376]. Since the original descrip- tion of the ARDS, there has been great interest in the use of corticosteroids in these patients [Ashbaugh DG et al. (1967) Lancet 2: 319±323]. This issue has been studied by several groups, with most data derived from case series. The following discussion reviews the three most recent randomized-controlled studies evaluating the role of corticosteroids in the treatment of ARDS. Meduri GU, Headley AS, Golden E, Carson SJ, Um- berger RA, Kelso T, Tolley EA (1998) Effect of pro- longed methylprednisolone therapy in unresolving acute respiratory distress syndrome: a randomized con- trolled trial. JAMA 280: 159±165 To determine the effects of prolonged steroid therapy on lung function and mortality in non-resolving ARDS, Meduri and coworkers conducted a randomized, place- bo-controlled trial in four medical intensive care units (ICUs). Adults who fulfilled the American-European Consensus Conference (AECC) criteria for the diagno- sis of ARDS [Bernard GR et al. (1994) Am J Respir Crit Care Med 149: 818±824], had been mechanically ventilated for 7 days and had no evidence of untreated infection were included. Additional enrollment criteria included a Lung Injury Score (LIS) [Murray JF et al. (1988) Am Rev Respir Dis 138: 720±723] of 2.5 or great- er, with a reduction of less than 1 point from day 1 of ARDS. Exclusion criteria included a diagnosis of ARDS for 3 weeks or more, a history of extensive burns, a life expectancy of less than 3 months, pregnan- cy, recent major gastrointestinal bleeding or the pres- ence of a disease requiring systemic steroids. Patients were randomized in blocks of three (2:1 steroid to place- bo) and stratified by study site to either methylpredniso- lone (MP, 2 mg/kg perday, in four divided doses for 2 weeks, followed by a 2-week taper) or placebo. Venti- lator management was designed to limit plateau pres- sure to 35 cmH 2 O, and fiberoptic bronchoscopy with bi- lateral bronchoalveolar lavage (BAL) was performed in all patients as part of sepsis surveillance. Patients in ei- ther group were blindly crossed over if they failed to T. Marras M. Herridge S. Mehta Corticosteroid therapy in acute respiratory distress syndrome Intensive Care Med (1999) 25: 1191±1193 Ó Springer-Verlag 1999 CURRENT TOPICS