Chan 1995.

Methods	Parallel‐group randomised controlled trial
Participants	Baseline characteristics Number randomised: ‐ Number analysed: 101 participants Ranitidine Age (years; mean (range)): 61 (17‐84) Number of participants (n): 49 Gender (male/female; n): 26/23 Placebo Age (years; mean (range)): 61 (32‐89) Number of participants (n): 52 Gender (male/female; n): 28/24 Inclusion criteria Suffering from nontraumatic neurological lesions with ≥ 2 of the following risk factors Preoperative coma Inappropriate secretion of ADH Major PO complications requiring reoperation Age ≥ 60 years Pyogenic CNS infection Exclusion criteria Failure to obtain consent (4 patients) Presence of GD bleeding before neurosurgery (10 patients) Past history of chronic GD disease or chronic ulcer, identified at endoscopy (9 patients) Concomitant major medical illnesses such as heart, lung, kidney, haematological, and liver problems (7 patients) Baseline imbalances: The nature and location of diseases, types of operations, number of preoperative risk factors, and demographic data were comparable in the 2 groups
Interventions	Ranitidine Dose (total/d): 200 or 300 mg Duration of treatment (days): ‐ Route: IV or PO Intervention: 200 mg IV, or 300 mg PO when enteric feeding started Concomitant medications: artificial ventilation with muscle paralysis using pancuronium and sedation with midazolam. Additional bolus doses of sedative and analgesic medications were given during endoscopy. Concomitant medications included dexamethasone, 4 mg every 6 hours, and a single dose of ceftriaxone (1 g), which was given intravenously as prophylaxis with the first dose of ranitidine or placebo. Subsequent antibiotic medications were administered only for treatment of culture proven infections. Those patients who required anticonvulsant therapy or prophylaxis received phenytoin (00 mg every 8 hours) Placebo Dose (total/d): ‐ Duration of treatment (days): ‐ Route: IV, PO Intervention: normal saline Concomitant medications: artificial ventilation with muscle paralysis using pancuronium and sedation with midazolam, additional bolus doses of sedative and analgesic medications were given during endoscopy. Concomitant medications included dexamethasone, 4 mg every 6 hours, and a single dose of ceftriaxone (1 g), which was given intravenously as prophylaxis with the first dose of ranitidine or placebo. Subsequent antibiotic medications were administered only for treatment of culture proven infections. Participants who required anticonvulsant therapy or prophylaxis received phenytoin (00 mg every 8 hours) Adherence to regimen: ‐ Duration of trial: July 1988 to December 1989 Duration of follow‐up: ‐
Outcomes	Outcomes reported in trial and used in review Gastroduodenal bleeding defined as Normal (without GD lesions), Asymptomatic (presence of endoscopically documented acute GD lesions but no evidence of bleeding), and Symptomatic from GD lesions (presence of endoscopic stigmata of recent haemorrhage, requiring blood transfusion and/or surgery to stop bleeding, or treatment of peritonitis as a result of perforation of acute GD tract ulcers) All‐cause mortality Adverse events of interventions Outcomes sought but not reported in trial VAP Duration of ICU stay Duration of intubation Number of blood transfusions Outcomes reported, but not used in review Chest infection Risk factors for development of symptomatic GD lesions Neurological recovery
Notes	Setting: Neurological Intensive Care Unit, Department of Surgery, Queen Mary Hospital, University of Hong Kong Source of funding: University of Hong Kong Research Grant and Lee Wing Tat Research Grant Conflicts of interest: ‐ Ethics approval: The protocol used in our trial was approved by the Ethics Committee of the Faculty of Medicine, at the University of Hong Kong Informed consent: Written consent was obtained from patients or their next of kin Clinical trials registration: ‐ Sample calculation: 49 patients would be required in each arm of the trial with a power of 0.8 and a 0.95 significance level by 2‐tailed test Comments: The endpoint of the trial was the development of symptomatic GD lesions defined as GD bleeding requiring blood transfusions and/or surgery for acute perforated ulcers
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "randomised in a standard double blind manner" Comment: not enough information on sequence generation reported
Allocation concealment (selection bias)	Unclear risk	Comment: no information on allocation concealment reported
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "All patients were randomised in a standard double‐blind manner to receive either ranitidine (50 mg) or placebo medication (normal saline) identical in appearance and volume"
Blinding (detection bias) Clinically important upper GI bleeding	Low risk	Quote: "Final outcomes were also assessed by an independent observer to ascertain whether they were a direct result of the GD lesions" "Endoscopic examination of the GD tract up to the second part of the duodenum was performed in all patients within 12 hours of surgery. Additional bolus doses of sedative and analgesic medications we re given during endoscopy. A nasogastric tube was passed into the stomach after endoscopy; its position was confirmed by radiological means, and it was connected to a bag for free drainage. Aspiration from the tube was performed at 6‐hour intervals and a pH paper was used to measure the pH of the gastric content. The total volume of daily gastric output was recorded"
Blinding (detection bias) Nosocomial pneumonia	Unclear risk	Comment: Trial did not address this outcome
Blinding of outcome assessment (detection bias) Adverse reactions of interventions	Unclear risk	Comment: no details on criteria for diagnosis of other outcomes reported
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: no missing outcome data. All participants randomised at baseline are also included in analyses of outcomes
Selective reporting (reporting bias)	High risk	Comment: Outcome data for blood transfusions were not reported by treatment group, but as totals. Other outcomes were reported completely. More outcomes were reported in the Results section than in the Methods section
Other bias	Low risk	Comment: no other sources of bias suspected