title: Efficacy and safety of proton pump inhibitors for stress ulcer prophylaxis in critically ill patients: a systematic review and meta-analysis of randomized trials.
abstract: BACKGROUND
  The relative efficacy and safety of proton pump inhibitors (PPIs) compared to histamine-2-receptor antagonists (H2RAs) should guide their use in reducing bleeding risk in the critically ill.
  
  
  METHODS
  We searched the Cochrane library, MEDLINE, EMBASE, ACPJC, clinical trials registries, and conference proceedings through November 2015 without language or publication date restrictions. Only randomized controlled trials (RCTs) of PPIs vs H2RAs for stress ulcer prophylaxis in critically ill adults for clinically important bleeding, overt gastrointestinal (GI) bleeding, nosocomial pneumonia, mortality, ICU length of stay and Clostridium difficile infection were included. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess our confidence in the evidence for each outcome.
  
  
  RESULTS
  In 19 trials enrolling 2117 patients, PPIs were more effective than H2RAs in reducing the risk of clinically important GI bleeding (RR 0.39; 95 % CI 0.21, 0.71; P = 0.002; I (2) = 0 %, moderate confidence) and overt GI bleeding (RR 0.48; 95 % CI 0.34, 0.66; P < 0.0001; I (2) = 3 %, moderate confidence). PPI use did not significantly affect risk of pneumonia (RR 1.12; 95 % CI 0.86, 1.46; P = 0.39; I (2) = 2 %, low confidence), mortality (RR 1.05; 95 % CI 0.87, 1.27; P = 0.61; I (2) = 0 %, moderate confidence), or ICU length of stay (mean difference (MD), -0.38 days; 95 % CI -1.49, 0.74; P = 0.51; I (2) = 30 %, low confidence). No RCT reported Clostridium difficile infection.
  
  
  CONCLUSIONS
  PPIs were superior to H2RAs in preventing clinically important and overt GI bleeding, without significantly increasing the risk of pneumonia or mortality. Their impact on Clostridium difficile infection is yet to be determined.
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Canada.|Department of Internal Medicine, United Arab Emirates University, Alain, United Arab Emirates.
authors.forename: Fayez
authors.initials: F
authors.lastname: Alshamsi
authors.affiliation: Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, Canada.
authors.forename: Emilie
authors.initials: E
authors.lastname: Belley-Cote
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Canada.|Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, Canada.
authors.forename: Deborah
authors.initials: D
authors.lastname: Cook
authors.affiliation: Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, Canada.|Department of Surgery, Division of Neurosurgery, McMaster University, Hamilton, Canada.
authors.forename: Saleh A
authors.initials: SA
authors.lastname: Almenawer
authors.affiliation: Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, Canada.
authors.forename: Zuhoor
authors.initials: Z
authors.lastname: Alqahtani
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Canada.
authors.forename: Dan
authors.initials: D
authors.lastname: Perri
authors.affiliation: Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, Canada.
authors.forename: Lehana
authors.initials: L
authors.lastname: Thabane
authors.affiliation: Department of Critical Care, Security Forces Hospital, Riyadh, Saudi Arabia.|Department of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
authors.forename: Awad
authors.initials: A
authors.lastname: Al-Omari
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Canada.
authors.forename: Kim
authors.initials: K
authors.lastname: Lewis
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Canada.|Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, Canada.
authors.forename: Gordon
authors.initials: G
authors.lastname: Guyatt
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Canada. alhazzaw@mcmaster.ca.|Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, Canada. alhazzaw@mcmaster.ca.|Department of Medicine, Division of Critical Care, St Joseph's Healthcare, 50 Charlton Avenue East, Hamilton, ON, L8N 4A6, Canada. alhazzaw@mcmaster.ca.
authors.forename: Waleed
authors.initials: W
authors.lastname: Alhazzani
mesh_terms: D004381:Duodenal Ulcer / Q000150:complications / Q000188:drug therapy; D006471:Gastrointestinal Hemorrhage / Q000517:prevention & control; D006635:Histamine H2 Antagonists / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D010437:Peptic Ulcer / Q000150:complications / Q000188:drug therapy; D054328:Proton Pump Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D013276:Stomach Ulcer / Q000150:complications / Q000188:drug therapy
chemical_list: D006635:Histamine H2 Antagonists; D054328:Proton Pump Inhibitors