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Table 1 Characteristics of the included studies

From: Risks and benefits of stress ulcer prophylaxis in adult neurocritical care patients: a systematic review and meta-analysis of randomized controlled trials

Study Patients, n Lost to follow-up, n (%)a Setting/country Trial duration (mo) Diagnosis EN Inclusion criteria (population) Exclusion criteria Intervention Comparator Outcomes UGI bleeding definition
Control: no prophylaxis
Reusser et al., 1990 [11] 40 57/97 (59 %) Single center/Switzerland 26 TBI, ICH No Severe acute traumatic or spontaneous hemorrhage intracranial lesion and neurosurgery and MV >48 h Age <15 yr, GI surgery, PUD, SUP, UGI bleeding Ranitidine 50 mg IV every 8/6 h titrated to maintain gastric pH ≥4 No prophylaxis Overt UGI bleeding, mortality Bright red bleeding via NG tube, melena, or decrease of blood hemoglobin level >2 g/dl within 24 h associated with a positive stool guaiac test or with gastric drainage of >100 ml of coffee-ground material
Control: placebo
Burgess et al., 1995 [12] 34 0 (0 %) Single center/United States 9 TBI No Severe head injury and GCS ≤10 PUD, GI injury, SUP, oral intake Ranitidine 6.25 mg/h continuous IV for up to 72 h Placebo Overt UGI bleeding, mortality Hematemesis, hematochezia, bright red blood per NG tube or coffee-ground NG tube aspirates, and a 5 % decrease from baseline in hematocrit occurring at least 8 h after study drug initiation
Chan et al., 1995 [22] 101 0 (0 %) Single center/China 17 CVD, brain tumor, CNS infection, hydrocephalus Yes Nontraumatic cerebral disease and at least two risk factors for UGI bleedingb UGI bleeding; chronic GI disease; PUD; concurrent heart, lung, kidney, hematological, and liver diseases Ranitidine 50 mg IV every 6 h or 150 mg PO every 12 h when starting EN Placebo Clinically important UGI bleeding, nosocomial pneumonia Gastroduodenal bleeding requiring blood transfusions and/or surgery for acute perforated ulcers, lesions confirmed either endoscopically or during abdominal surgery
Halloran et al., 1980 [13] 50 0 (0 %) Single center/United States 20 TBI Yes Severe head injury and neurological deficits Apnea and fixed dilated pupils and no motor response, PUD, pregnancy, GI injury, severe hepatic or renal disease Cimetidine 300 mg IV every 4 h for up to 3 wk Placebo Overt UGI bleeding, mortality Bright red blood or a 4+ positive stool guaiac test in the gastric aspirate for three consecutive 8-h periods (exclusive of first day after injury), excluding oropharyngeal source of bleeding
Liu et al., 2013 [16] 165 19/184 (10 %) Single center/China 32 ICH No CT-proven ICH within 72 h of ictus and neurosurgery, NG tube in place, baseline gastric pH <4, negative GOBT, age >18 yr AVM, PUD, facial trauma, anticoagulants, AKI, thrombocytopenia, died within 72 h after ictus Omeprazole 40 mg IV every 12 h for up to 7 days, cimetidine 300 mg IV every 6 h for up to 7 days Placebo Overt UGI bleeding, mortality, nosocomial pneumonia Hematemesis, aspiration of coffee-ground material from NG tube, or melena, proven by positive GOBT or FOBT, with or without hemodynamic instability resulting from gross bleeding that needed transfusion
Metz et al., 1993 [14] 167 0 (0 %) Multicenter/United States 20 TBI No Severe head injury with 24 h of injury and GCS ≤10, NG tube in place, age >18 yr, expected ICU stay ≥72 h GI bleeding, severe burns >20 %, AKI, PUD, thrombocytopenia, SUP Ranitidine 6.25 mg/h continuous IV for up to 5 days Placebo Overt UGI bleeding, nosocomial pneumonia • Gastroccult positive NG tube drainage and coffee-ground material for the previous 8 h
• Minimum of 50 ml bright red blood per NG tube
• Hematemesis in the last 8 h
• Hemoccult positive stool
• Melena
• Hematochezia;
with or without endoscopic or surgical confirmation of UGI source of bleeding
Misra et al., 2005 [15] 141 35/176 (20 %) Single center/India 24 ICH Yes CT-proven ICH within 7 days of ictus AVM, coagulopathy, hepatic or renal disease, PUD, anticoagulants Ranitidine 50 mg IV every 8 h Placebo Overt UGI bleeding, mortality, nosocomial pneumonia Gross blood, coffee-ground aspirate from NG tube, hematemesis or melena
Zhang et al., 2014 [28] 180 0 (0 %) Single center/China NA ICH Yes CT-proven ICH within 72 h of ictus, age 30–75 yr Traumatic or brain tumor-related hemorrhage, coagulopathy, PUD, mental disorder or dementia, concurrently included in other clinical trials Esomeprazole 40 mg/day (n = 36) or lansoprazole 40 mg/day (n = 36) PO, ranitidine 150 mg/day (n = 36) or famotidine 40 mg/day (n = 36) PO Placebo Overt UGI bleeding Clinical evidence of GI bleeding reported, but definition not specified (endoscopy used in all patients at approximately day 21 since SUP)
  1. AKI acute kidney injury, AVM arteriovenous malformation, CNS central nervous system, CT computed tomography, CVD cerebrovascular disease, EN enteral nutrition, FOBT fecal occult blood test, GCS Glasgow Coma Scale, GI gastrointestinal, GOBT gastric occult blood test, ICH intracerebral hemorrhage, IV intravenous, MV mechanical ventilation, NA not available, NG nasogastric, PO per os, PUD peptic ulcer disease, SUP stress ulcer prophylaxis, TBI traumatic brain injury, UGI upper gastrointestinal
  2. aNumber and percentage of patients lost to follow-up and due to other reasons not included in the analysis for the primary outcome among all eligible patients
  3. bRisk factors included preoperative coma (GCS <9), inappropriate secretion of antidiuretic hormone, major postoperative complications requiring reoperation, age ≥60 yr, and pyogenic CNS infection