Lopez‐Herce 1992.

Methods	Open‐label randomised controlled trial
Participants	Baseline characteristics Number randomised: 165 participants Number analysed: 140 participants Overall Age (years; mean (range)): 4.6 years (0 days ‐ 20 years) Number of participants (n): 140 (no prophylaxis n = 35, Almagate n = 35, Ranitidine n = 35, Sucralfate n= 35) Gender (male/female; n): 85/55 Inclusion criteria Admitted in the paediatric ICU One of the following criteria: shock, acute cardiac failure, acute respiratory failure, acute liver failure, acute renal failure, sepsis or serious focal infection, coagulopathy, acute nephrologic dysfunction, multiple trauma, severe metabolic acidosis following major surgery Exclusion criteria Nasal or pharyngeal bleeding (difficulty in distinguishing from upper GI bleed) Baseline imbalances: Groups were similar when compared using indexes (Theraputic Interventiobn Scoring System, Physiological Stability Index, Multi Organ System Failure Scoring System, Zinner and Tryba). Detailed baseline characteristics for each group are not provided in the study report
Interventions	No prophylaxis Dose (total/d): ‐ Duration of treatment (days): ‐ Route: ‐ Intervention: no prophylaxis Concomitant medications: All patients had a nasogastric tube in place and gastric fluid drained by gravity. The position of the stomach was confirmed by radiograph. Patients were not fed during the study. Pressor drugs, dopamine, dobutamine, isoproterenol and epinephrine sedatives, barbiturates, diazepoxides, opiates, and muscle relaxants Almagate Dose (total/d): varies Duration of treatment (days): ‐ Route: NG tube Intervention: 0.25 mL/kg every 2 hours via NG tube. If this dose did not increase the gastric pH to ≥ 4, then dosage was increased by 0.25 mL/kg up to a maximum dose of 1 mL/kg Concomitant medications: All patients had a nasogastric tube in place and gastric fluid drained by gravity. The position of the stomach was confirmed by radiograph. Patients were not fed during the study. Pressor drugs, dopamine, dobutamine, isoproterenol and epinephrine sedatives, barbiturates, diazepoxides, opiates, and muscle relaxants Ranitidine Dose (total/d): varies Duration of treatment (days): ‐ Route: IV Intervention: 1.5 mg/kg of ranitidine every 6 hours via IV Concomitant medications: All patients had a nasogastric tube in place and gastric fluid drained by gravity. The position of the stomach was confirmed by radiograph. Patients were not fed during the study. Pressor drugs, dopamine, dobutamine, isoproterenol and epinephrine sedatives, barbiturates, diazepoxides, opiates, and muscle relaxants Sucralfate Dose (total/d): varies Duration of treatment (days): ‐ Route: NG tube Intervention: Children < 10 kg received 0.5 g sucralfate via nasogastric tube. Children > 10 kg received 1 g every 6 hours via nasogastric tube (tablets were dissolved in 5 to 10 mL of water, and drug was administered by nasogastric tube; the tube was subsequently flushed with 2 to 3 mL of water to prevent tube obstruction) Concomitant medications: All patients had a nasogastric tube in place and gastric fluid drained by gravity. The position of the stomach was confirmed by radiograph. Patients were not fed during the study. Pressor drugs, dopamine, dobutamine, isoproterenol and epinephrine sedatives, barbiturates, diazepoxides, opiates, and muscle relaxants. Adherence to regimen: 165 randomised, 25 "excluded because of protocol reasons"; 1 patient in the Amalgamate group had watery diarrhoea and treatment was switched to ranitidine. In 6 patients from the control group (no prophylaxis) who developed GI bleed, 2 were given Amalgamate, 2 were given sucralfate, and 2 were given amalgamate Duration of trial: June 1986 to June 1988 Duration of follow‐up: ‐
Outcomes	Outcomes sought in review and reported in trial Primary outcome GI haemorrhage microscopic or macroscopic: non‐haemorraghic, slight ('coffee grounds' or small amounts of red blood) and important (with haematological and/or haemodynamic repercussion (e.g. a decrease in haematocrit > 15% or need for transfusion, hypotension, or need for volume and/or pressors)) Secondary outcomes Adverse events of interventions Outcomes sought in review but not reported in trial All‐cause mortality in the hospital Duration of ICU stay Duration of intubation Number of participants requiring blood transfusions Units of blood transfused Outcomes reported in trial but not used in review Incidence of nosocomial pneumonia (data unclear) Intragastric pH All‐cause mortality in ICU (data unclear for each interventional arm)
Notes	Setting: Pediatric ICU, LaPaz Children’s Hospital, Madrid, Spain Source of funding: ‐ Conflicts of interest: ‐ Ethics approval: Quote: "The study was approved by the institutional review board" Clinical trials registration: ‐ Sample size calculation: ‐ Additional notes: One of the 7 participants in the control group with GI bleeding did not receive any treatment; the others were given the following: amalgamate to 2 participants, ranitidine to 2 participants, and sucralfate to 2 participants. The last participant needed ranitidine too to decrease the intensity of bleeding. In the antacid group, 1 child died of haemorrhage, and the other was given ranitidine and sucralfate to contain the bleeding. In the ranitidine group, 1 participant improved within the first 24 hours, without receiving any other drug. In the second participant, the intensity of bleeding decreased when amalgamate was added, and the third participant died. In the sucralfate group, the statue of the lone participant with haemorrhage improved without any addition of another drug It is mentioned that there was no incidence of nosocomial pneumonia, but under "side effects", the study reports 5 incidences of the same and goes on to say that there was a difference between groups with respect to this outcome. The incidence in each group remains unclear
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	High risk	Comment: This 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: no blinding of outcome assessors reported, but GI bleeding was detected as per the definition in the study protocol
Blinding (detection bias) Nosocomial pneumonia	High risk	Comment: no blinding of outcome assessors reported, and definition for detecting pneumonia was not clearly mentioned in the study protocol. Moreover the outcome was not clearly reported in the study
Blinding of outcome assessment (detection bias) Adverse reactions of interventions	Low risk	Comment: The outcome of interest was objective in nature, so the likelihood of performance and detection bias is low
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: Although it mentions that 165 children were randomised and 25 were excluded because of various protocol violations, it is not clear to which of the 4 study groups these 25 children belonged. A per‐protocol analysis was done, and there appears to be no imbalance between groups with respect to the number of participants available for analysis. Therefore, the likelihood of bias due to attrition is low
Selective reporting (reporting bias)	High risk	Comment: A high mortality rate of 38.4% is found in patients with important (major) upper GI bleeding, but counts for each intervention are not given separately. Data on macroscopic upper GI bleeding, slight (microscopic) upper GI bleeding, and mortality are not reported for each intervention separately but are reported for the entire study. Data for pneumonia are not clear
Other bias	Low risk	Comment: Study is unclear on source of funding. No other known source of bias