High levels of PEEP may improve survival in acute respiratory distress syndrome: A meta-analysis.

OBJECTIVE: Positive end-expiratory pressure (PEEP) has been viewed as an essential component of mechanical ventilation in acute respiratory distress syndrome (ARDS) and acute lung injury (ALI). However, clinical trials have not yet convincingly demonstrated that high PEEP levels improve survival. The object of this study was to test a priori hypotheses that a small but clinically important mortality benefit of high PEEP did exist, especially in patients with greater overall severity of illness and differences in PEEP protocols might have affected the study results. METHODS: Meta-analysis of randomized controlled trials comparing high versus low PEEP in ARDS/ALI. Studies were identified by search of MEDLINE (1950-2008) and other sources. MEASUREMENTS AND MAIN RESULTS: Five studies including 2447 patients were identified. A pooled analysis showed a significant reduction in hospital mortality in favor of high PEEP (RR=0.89; 95% CI, 0.80-0.99; p=0.03). However, significant statistical and clinical heterogeneities such as differences in disease severity and ventilator protocols were found. The differences in PEEP protocols were not associated with differences in mortality rates. A logistic analysis suggested that the beneficial effect of high PEEP was greater in patients with higher ICU severity scores. CONCLUSIONS: The statistical and clinical heterogeneities make proper interpretation of the results difficult. However, a small, but significant mortality benefit of high PEEP may exist. In addition, our analysis suggests the effects of high PEEP are greater in patients with higher ICU severity scores.

Safety, tolerability and risk benefit analysis of tiotropium in COPD.

COPD is a chronic disease and, like many other chronic diseases, there is no treatment to reverse the severity of the disease except for lung transplant. To date, no inhaled medications have been shown to improve survival. Tiotropium bromide is a long-acting inhaled anticholinergic drug for the treatment of COPD that can improve lung function, reduce symptoms and exacerbations, and improve quality of life with once-daily dosing. It was initially approved and marketed in several countries in Europe in 2002 and then approved in the US in 2004. Tiotropium is generally well tolerated with dry mouth being the main adverse effect. Other adverse effects include constipation, tachycardia, blurred vision, urinary retention and increased intraocular pressure. Despite the recently raised concerns about an excess risk of cardiovascular adverse events with inhaled anticholinergic agents, the risk/benefit ratio of tiotropium appears still favorable given the favorable safety profile demonstrated in the UPLIFT study. However, caution should be advised in patients at high risk for cardiovascular disease given the paucity of data in such patients.