N Adhikari1, K E A Burns, M O Meade. 1. Critical Care Medicine and Medicine, Sunnybrook and Women's College Health Centre, 2075 Bayview Avenue, B7.04a, Toronto, M4N 3M5, Ontario, Canada. neill.adhikari@sw.ca
Abstract
BACKGROUND: Multiple pharmacologic treatments have been studied for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). OBJECTIVES: Our objective was to determine the effects of pharmacologic treatments on clinical outcomes in adults with ALI or ARDS. SEARCH STRATEGY: We searched OVID versions of CENTRAL (The Cochrane Library Issue 3, 2003), MEDLINE (1966 to week 2, January 2004), EMBASE (1980 to week 4, 2004), CINAHL (1982 to week 2, January 2004), and HEALTHSTAR (1995 to December 2003); proceedings from four conferences (1994 to 2003); and bibliographies of review articles and included studies. SELECTION CRITERIA: Randomized controlled trials of pharmacologic treatments compared to no therapy or placebo for established ALI or ARDS in adults admitted to an intensive care unit, with measurement of early mortality (primary outcome), late mortality, duration of mechanical ventilation, ventilator-free days to day 28, or adverse events. We excluded trials of nitric oxide, partial liquid ventilation, fluid and nutritional interventions, oxygen, and trials in other populations reporting outcomes in subgroups of patients with ALI or ARDS. DATA COLLECTION AND ANALYSIS: Two reviewers independently screened titles and abstracts, rated studies for inclusion, extracted data and assessed methodologic quality of included studies. Disagreements were resolved by consensus in consultation with a third reviewer. For each pharmacologic therapy, we quantitatively pooled the results of studies using random effects models where permitted by the available data. We contacted study authors when clarification of the primary outcome was required. MAIN RESULTS: Thirty three trials randomizing 3272 patients met our inclusion criteria. Pooling of results showed no effect on early mortality of prostaglandin E1 (seven trials randomizing 697 patients; relative risk [RR] 0.95, 95% confidence interval [CI] 0.77 to 1.17), N-acetylcysteine (five trials randomizing 239 patients; RR 0.89, 95% CI 0.65 to 1.21), early high-dose corticosteroids (two trials randomizing 187 patients; RR 1.12, 95% CI 0.72 to 1.74), or surfactant (nine trials randomizing 1441 patients; RR 0.93, 95% CI 0.77 to 1.12). Two interventions were beneficial in single small trials; corticosteroids given for late phase ARDS reduced hospital mortality (24 patients; RR 0.20, 95% CI 0.05 to 0.81), and pentoxifylline reduced one-month mortality (RR 0.67, 95% CI 0.47 to 0.95) in 30 patients with metastatic cancer and ARDS. Individual trials of nine additional interventions failed to show a beneficial effect on prespecified outcomes. REVIEWERS' CONCLUSIONS: Effective pharmacotherapy for ALI and ARDS is extremely limited, with insufficient evidence to support any specific intervention.
BACKGROUND: Multiple pharmacologic treatments have been studied for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). OBJECTIVES: Our objective was to determine the effects of pharmacologic treatments on clinical outcomes in adults with ALI or ARDS. SEARCH STRATEGY: We searched OVID versions of CENTRAL (The Cochrane Library Issue 3, 2003), MEDLINE (1966 to week 2, January 2004), EMBASE (1980 to week 4, 2004), CINAHL (1982 to week 2, January 2004), and HEALTHSTAR (1995 to December 2003); proceedings from four conferences (1994 to 2003); and bibliographies of review articles and included studies. SELECTION CRITERIA: Randomized controlled trials of pharmacologic treatments compared to no therapy or placebo for established ALI or ARDS in adults admitted to an intensive care unit, with measurement of early mortality (primary outcome), late mortality, duration of mechanical ventilation, ventilator-free days to day 28, or adverse events. We excluded trials of nitric oxide, partial liquid ventilation, fluid and nutritional interventions, oxygen, and trials in other populations reporting outcomes in subgroups of patients with ALI or ARDS. DATA COLLECTION AND ANALYSIS: Two reviewers independently screened titles and abstracts, rated studies for inclusion, extracted data and assessed methodologic quality of included studies. Disagreements were resolved by consensus in consultation with a third reviewer. For each pharmacologic therapy, we quantitatively pooled the results of studies using random effects models where permitted by the available data. We contacted study authors when clarification of the primary outcome was required. MAIN RESULTS: Thirty three trials randomizing 3272 patients met our inclusion criteria. Pooling of results showed no effect on early mortality of prostaglandin E1 (seven trials randomizing 697 patients; relative risk [RR] 0.95, 95% confidence interval [CI] 0.77 to 1.17), N-acetylcysteine (five trials randomizing 239 patients; RR 0.89, 95% CI 0.65 to 1.21), early high-dose corticosteroids (two trials randomizing 187 patients; RR 1.12, 95% CI 0.72 to 1.74), or surfactant (nine trials randomizing 1441 patients; RR 0.93, 95% CI 0.77 to 1.12). Two interventions were beneficial in single small trials; corticosteroids given for late phase ARDS reduced hospital mortality (24 patients; RR 0.20, 95% CI 0.05 to 0.81), and pentoxifylline reduced one-month mortality (RR 0.67, 95% CI 0.47 to 0.95) in 30 patients with metastatic cancer and ARDS. Individual trials of nine additional interventions failed to show a beneficial effect on prespecified outcomes. REVIEWERS' CONCLUSIONS: Effective pharmacotherapy for ALI and ARDS is extremely limited, with insufficient evidence to support any specific intervention.
Authors: Bruce A Davidson; R Robert Vethanayagam; Melissa J Grimm; Barbara A Mullan; Krishnan Raghavendran; Timothy S Blackwell; Michael L Freeman; Vanniarajan Ayyasamy; Keshav K Singh; Michael B Sporn; Kiyoshi Itagaki; Carl J Hauser; Paul R Knight; Brahm H Segal Journal: J Immunol Date: 2013-01-07 Impact factor: 5.422