title: Risks and benefits of stress ulcer prophylaxis in adult neurocritical care patients: a systematic review and meta-analysis of randomized controlled trials.
abstract: BACKGROUND
  Neurocritical care patients are at high risk for stress-related upper gastrointestinal (UGI) bleeding. The aim of this meta-analysis was to evaluate the risks and benefits of stress ulcer prophylaxis (SUP) in this patient group.
  
  
  METHODS
  A systematic search of major electronic literature databases was conducted. Eligible studies were randomized controlled trials (RCTs) in which researchers compared the effects of SUP (with proton pump inhibitors or histamine 2 receptor antagonists) with placebo or no prophylaxis in neurocritical care patients. The primary outcome was UGI bleeding, and secondary outcomes were all-cause mortality and nosocomial pneumonia. Study heterogeneity was sought and quantified. The results were reported as risk ratios/relative risks (RRs) with 95 % confidence intervals (CIs).
  
  
  RESULTS
  We included 8 RCTs comprising an aggregate of 829 neurocritical care patients. Among these trials, one study conducted in a non-intensive care unit setting that did not meet our inclusion criteria was ultimately included based on further evaluation. All studies were judged as having a high or unclear risk of bias. SUP was more effective than placebo or no prophylaxis at reducing UGI bleeding (random effects: RR 0.31; 95 % CI 0.20-0.47; P < 0.00001; I (2) = 45 %) and all-cause mortality (fixed effects: RR 0.70; 95 % CI 0.50-0.98; P = 0.04; I (2) = 0 %). There was no difference between SUP and placebo or no prophylaxis regarding nosocomial pneumonia (random effects: RR 1.14; 95 % CI 0.67-1.94; P = 0.62; I (2) = 42 %). The slight asymmetry of the funnel plots raised the concern of small trial bias, and apparent heterogeneity existed in participants, interventions, control treatments, and outcome measures.
  
  
  CONCLUSIONS
  In neurocritical care patients, SUP seems to be more effective than placebo or no prophylaxis in preventing UGI bleeding and reducing all-cause mortality while not increasing the risk of nosocomial pneumonia. The robustness of this conclusion is limited by a lack of trials with a low risk of bias, sparse data, heterogeneity among trials, and a concern regarding small trial bias.
  
  
  BACKGROUND
  International Prospective Register of Systematic Reviews (PROSPERO) identifier: CRD42015015802 . Date of registration: 6 Jan 2015.
authors.affiliation: Division of Neurosurgery, Arrowhead Regional Medical Center, 400 North Pepper Avenue, Colton, CA, 92324, USA. akingi@sina.com.
authors.forename: Bolin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, Xijing Hospital, Fourth Military Medical University, Xi'an, People's Republic of China. hanliu@fmmu.edu.cn.
authors.forename: Shujuan
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, Fourth Military Medical University, Xi'an, People's Republic of China. yinanan@aliyun.com.
authors.forename: Anan
authors.initials: A
authors.lastname: Yin
authors.affiliation: Division of Neurosurgery, Arrowhead Regional Medical Center, 400 North Pepper Avenue, Colton, CA, 92324, USA. siddiqij@armc.sbcounty.gov.
authors.forename: Javed
authors.initials: J
authors.lastname: Siddiqi
mesh_terms: D000328:Adult; D001930:Brain Injuries / Q000150:complications*; D006635:Histamine H2 Antagonists / Q000627:therapeutic use; D006801:Humans; D054328:Proton Pump Inhibitors / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D013276:Stomach Ulcer / Q000209:etiology / Q000517:prevention & control*; D013315:Stress, Psychological / Q000150:complications*
chemical_list: D006635:Histamine H2 Antagonists; D054328:Proton Pump Inhibitors