Weigelt 1981.

Methods	Quasi‐randomised trial
Participants	Baseline characteristics Number randomised: 77 participants Number analysed: 77 participants Antacid Age (years; mean (range)): overall. 40.5 (16 to 88) Number of participants (n): 16 Gender (male/female; n): ‐ Cimetidine (300 mg every 4 hours) Age (years; mean (SD)): ‐ Number of participants (n): 19 Gender (male/female; n): ‐ Cimetidine (300 mg every 6 hours) Age (years; mean (SD)): ‐ Number of participants (n): 19 Gender (male/female; n): ‐ Cimetidine (400 mg every 4 hours) Age (years; mean (SD)): ‐ Number of participants (n): 23 Gender (male/female; n): ‐ Inclusion criteria Admission to the surgical intensive care unit Presence of nasogastric or gastrostomy tube Definition of illness severity by a therapeutic intervention scoring system (TISS) (classification of II or greater) Exclusion criteria Active peptic ulcer diseases Previous operative procedure designed to alter gastric acid secretion Compromised renal function Institution of stress ulcer prophylaxis prior to notification of investigators Baseline imbalances: Quote: "A modification of Theraputic intervention scoring system (TISS) was used to grade severity of illness for patient selection and group comparison" Comment: Average TISS score was 3 for antacids and 3.16 for combined cimetidine groups
Interventions	Antacids Dose (total/d): 30 mL Duration of treatment (days, mean (range)): 8.5 (1 to 28) Route: ‐ Intervention: antacid, a combination of aluminium hydroxide and magnesium hydroxide (Maalox) to maintain gastric pH of 6. The initial dose of antacid was 30 mL. This dose was increased in 30‐mL increments if gastric pH was not controlled Concomitant medications: ‐ Cimetidine Dose (total/d): 50 mg Duration of treatment (days, mean (range)): 2.6 (1 to 11) Route: IV Intervention: cimetidine (300 mg) intravenously every 6 hours or cimetidine (300 mg) intravenously every 4 hours or cimetidine (400 mg) intravenously every 4 hours Concomitant medications: ‐ Adherence to regimen: Quote: "The pH control in the antacid group was achieved with an average dose of 30 mL of antacid every two hours (range 15 to 120 mL/hour). Only one patient required more than 60 mL/hour for pH control. The duration of cimetidine treatment was similar in the three groups regardless of the efficacy of pH control" Comment: According to the study report, pH was controlled in 14 cimetidine participants. The rest might have switched over to antacids according to the study protocol (but this is not clearly mentioned in the study report) Duration of trial: February 1979 to August 1979 Duration of follow up: Quote: "All patients were followed up until death, discharge from ICU or institution of enteral feedings"
Outcomes	Outcomes sought in review and reported in trial Primary outcomes Incidence of upper GI bleeding defined as blood per nasogastric tube (guaiac–positive nasogastric aspirate, unaccompanied by a fall in haematocrit value or obvious GI tract bleeding not considered to be clinically important) Secondary outcomes All‐cause mortality in ICU Adverse events of interventions Outcomes sought but not reported in trial Incidence of ventilator‐associated pneumonia All‐cause mortality in hospital Duration of ICU stay Duration of intubation Units of blood transfused Outcomes reported but not used in review Intragastric pH status Participants (with GI bleeding) requiring blood transfusion
Notes	Setting: Departments of Surgery, South‐Western Medical School, University of Texas Health Science Centre, Dallas Source of funding: ‐ Conflicts of interest: ‐ Ethics approval: ‐ Informed consent: ‐ Clinical trials registration: ‐ Sample size calculation: ‐ Additional notes: Cimetidine groups were combined to form a common interventional arm vs antacids, as the review did not aim to investigate efficacy among different routes of administration of the same intervention
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	Quote: "Patients entering the study were randomised by hospital unit number into one of the four groups…" Comment: This was a quasi–randomised trial, and sequence was not generated
Allocation concealment (selection bias)	High risk	Quote: "Patients entering the study were randomised by hospital unit number into one of the four groups…" Comment: This was a quasi–randomised trial, and allocation was not concealed
Blinding of participants and personnel (performance bias) All outcomes	High risk	Comment: Tthis was not a placebo‐controlled trial, and the different modes of administering study interventions would not have made it possible to blind study personnel and participants. Therefore, high risk of performance bias
Blinding (detection bias) Clinically important upper GI bleeding	Low risk	Comment: unclear on the blinding of outcome assessors. However, GI bleeding was an objective outcome that was detected as per the study definition, so the likelihood of performance or detection bias is low
Blinding (detection bias) Nosocomial pneumonia	Unclear risk	Comment: Study did not address this outcome
Blinding of outcome assessment (detection bias) Adverse reactions of interventions	Low risk	Comment: Outcomes of interest were objective in nature, so the likelihood of performance or detection bias is low
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: All quasi‐randomised participants were part of the final analysis, so there is no attrition bias
Selective reporting (reporting bias)	Low risk	Comment: All intended outcomes were analysed and reported
Other bias	Low risk	Comment: unclear on source of funding. No other form of bias detected