Stress ulcer prophylaxis in adult neurocritical care patients--no firm evidence for benefit or harm.

In volume 19 (2015) of Critical Care, Liu et al. [1] present a systematic review of risks and benefits of stress ulcer prophylaxis (SUP) in adult neurocritical care patients. A total of eight randomised controlled trials (RCTs) on SUP with proton pump inhibitors or histamine-2 receptor antagonists versus placebo or no prophylaxis in neurocritical care patients was assessed. The authors conclude that SUP is superior to placebo/no prophylaxis in reducing gastrointestinal (GI) bleeding and all-cause mortality, while not increasing the risk of nosocomial pneumonia [1]. We would like to thank the authors for highlighting an important topic with significant clinical equipoise; however, we are worried that biased results and conclusions are presented. First, the review holds methodological limitations, including the fact that no predefined sensitivity analysis with continuity correction in the zero-event trials was planned or performed, and importantly the risk of random errors using trial sequential analysis (TSA) was not assessed. Applying TSA to the three trials with lowest risk of bias [1] suggests that an estimated required information size of 2005 patients and 1790 patients are needed to