Kingsley 1985.

Methods	Randomised controlled trial
Participants	Baseline characteristics Number randomised: 263 participants Number analysed: 249 participants Antacids Age (years; mean (range)): ‐ Number of participants (n): 61+64 Gender (male/female; n): ‐ Cimetidine Age (years; mean (range)): ‐ Number of participants (n): 64+59 Gender (male/female; n): ‐ Inclusion criteria Suffering from a variety of illnesses classified II or greater by therapeutic intervention scoring system (TISS) Exclusion criteria Patients receiving oral intake History of peptic ulcer or coagulopathy or gastrointestinal bleeding Having undergone oesophageal or gastric operation before admission to the study Baseline imbalances: Quote: "The patients were randomised to the four different groups were fairly homogenous and were exposed to essentially the same risk factors" Comment: no clear mention of gender, age, and type of risk factor distribution in the study report. In all participants, a variety of illness classified II or greater by therapeutic intervention scoring system (TISS) were diagnosed
Interventions	Antacids bolus Dose (total/d): 7200 mL Duration of treatment (days): until enteric feeding was begun, or patient was discharged from the critical care unit or died Route: NG tube Intervention: antacid bolus at a rate of 90 mL every 3 hours. Nasogastric tube was clamped until the subsequent instillation; if regurgitation occurred around the nasogastric tube, it was unclamped and connected to low suction Concomitant medications: Gastric pH was measured and recorded hourly. Gastric contents were tested for frank or occult bleeding every 3 hours by guaiac tests Antacids continuous Dose (total/d): 1440 mL Duration of treatment (days): until enteric feeding was begun, or until patient was discharged from the critical care unit or died Route: IV Intervention: continuous antacid drip (AA‐D) at the rate of 60 mL per hour Concomitant medications: Gastric pH was measured and recorded hourly. Gastric contents were tested for frank or occult bleeding every 3 hours by guaiac tests Cimetidine bolus Dose (total/d): 1200 mg Duration of treatment (days): until enteric feeding was begun, or patient was discharged from the critical care unit or died Route: IV Intervention: IV cimetidine bolus 300 mg every 6 hours Concomitant medications: Gastric pH was measured and recorded hourly. Gastric contents were tested for frank or occult bleeding every 3 hours by guaiac tests Cimetidine continuous Dose (total/d): 1200 mg Duration of treatment (days): until enteric feeding was begun, or patient was discharged from the critical care unit or died Route: IV Intervention: continuous cimetidine drip at a dose of 50 mg per hour Concomitant medications: Gastric pH was measured and recorded hourly. Gastric contents were tested for frank or occult bleeding every 3 hours by guaiac tests Adherence to regimen: Quote: "...14 patients initially admitted to the study were excluded for failure to follow protocol", "Any patient who developed severe diarrhoea was given alternagel instead of Mylanta" Comments: not sure which groups the 14 participants belonged to. Nine participants needed to be switched to alternagel Duration of trial: ‐ Duration of follow‐up: not clearly mentioned in the study report. Probably until death or discharge
Outcomes	Outcomes sought in review and reported in trial Incidence of clinically important upper GI bleeding defined as presence of bright blood in the nasogastric tube, which would not clear with iced saline lavage or if melena occurred. Guaiac‐positive aspirate, not accompanied by a fall in haematocrit or obvious bleeding; was not considered significant All‐cause mortality in ICU Number of participants requiring blood transfusion (does not appear entirely due to GI bleeding) Units of blood transfused (total units of blood transfused provided; no mean and SD) Adverse events of interventions Outcomes sought but not reported in trial VAP All‐cause mortality in the hospital Duration of intubation Outcomes reported in trial but not used in review Gastric pH values Superior mode of delivery for both the interventions Endoscopic evaluation of gastric mucosa
Notes	Setting: Hurley Medical Centre, Michigan, USA Source of funding: ‐ Conflicts of interest: ‐ Ethics approval: ‐ Informed consent: ‐ Clinical trials registration: ‐ Sample size calculation: ‐ Additional notes: Mean blood transfusion due to gastrointestinal haemorrhage was 1335 mL (range: 0 to 4500 mL). This is not mentioned separately for both groups. Irreversible haemorrhagic shock was the cause of death in 2 cimetidine participants
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Comment: not clearly mentioned in the study report
Allocation concealment (selection bias)	Unclear risk	Comment: not clearly mentioned in the study report
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Comment: Given the mode of administration and dosing regimens, it would not have been possible to blind study personnel. Therefore unclear whether this would have caused any performance bias
Blinding (detection bias) Clinically important upper GI bleeding	Low risk	Comment: unclear whether the outcome assessor was blinded. GI bleeding was an objective outcome that was detected as per the definition in the study protocol
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: All other outcomes of interest were objective in nature
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "...14 patients initially admitted to the study were excluded for failure to follow protocol" Comment: unclear on which groups the 14 participants were initially randomised to. But this accounts to be around 5% of total participants and is uniformly distributed across groups
Selective reporting (reporting bias)	Low risk	Comment: All intended outcomes were analysed and reported
Other bias	Low risk	Comment: unclear on the source of funding. No additional biases suspected