Interventions for preventing upper gastrointestinal bleeding in people admitted to intensive care units

Ingrid Toews; Aneesh Thomas George; John V Peter; Richard Kirubakaran; Luís Eduardo S Fontes; Jabez Paul Barnabas Ezekiel; Joerg J Meerpohl

doi:10.1002/14651858.CD008687.pub2

Intervenciones para la prevención de la hemorragia digestiva alta en pacientes ingresados a la unidad de cuidados intensivos

Appendices

Appendix 1. Glossary of medical terms

Antimicrobial – active against microbes.

Aspiration – action or process of drawing breath.

Bicarbonate ions ‐ bicarbonate serves a crucial biochemical role in the physiological pH buffering system.

Bronchial ‐ related to the bronchi or bronchioles.

Creatinine – compound that is produced by metabolism of creatine and is excreted in the urine.

Cytoprotective – providing protection to cells against harmful agents.

Enteral nutrition – nutrition passing through the intestine, either naturally via the mouth and oesophagus, or through an artificial opening.

Flora ‐ population of microbes inhabiting the outside or inside surfaces of the body.

Gastric – concerning the stomach.

Gram stain – method used to distinguish different types of bacteria by staining them.

Haemoglobin ‐ red protein responsible for transporting oxygen into the blood of vertebrates.

Hyperaemia ‐ excess of blood in the vessels supplying an organ or another part of the body.

Hypermagnesaemia ‐ high level of magnesium in the blood.

Hypomagnesaemia ‐ low level of magnesium in the blood.

Hypoperfusion ‐ decreased flow of blood through an organ.

Hypophosphataemia ‐ abnormally low level of phosphate in the blood.

Infiltrate ‐ substance denser than air such as pus, blood, or protein that lingers within the parenchyma of the lungs.

Interstitial nephritis – type of bacterial infection of the kidneys.

Ischaemia ‐ inadequate blood supply to an organ or part of the body.

Lesion ‐ region in an organ or tissue that has suffered damage through injury or disease.

Leucocytosis ‐ increase in the number of white cells in the blood.

Leucopaenia ‐ reduction in the number of white cells in the blood.

Luminal ‐ concerning the interior of the gastrointestinal tract.

Microcirculation ‐ circulation of the blood in the smallest blood vessels.

Morbidity ‐ the condition of being diseased.

Mortality ‐ the number of deaths in a given area or period, or from a particular cause.

Mucosal ‐ concerning the mucosa.

Neutropaenia ‐ presence of abnormally few neutrophils in the blood.

Nosocomial – originating in a hospital.

Occult bleeding – bleeding that is detectable only chemically or microscopically.

Cytochrome P‐450 mediated drug interaction ‐ a drug interaction mediated via the cytochrome P‐450, a family of isozymes responsible for biotransformation of many drugs via oxidation.

Pathogenic – causing disease.

Pathophysiology ‐ disordered physiological processes associated with disease or injury.

Pancreatitis ‐ inflammation of the pancreas.

Peptic ‐ related to digestion.

pH ‐ figure expressing the acidity or alkalinity of a solution.

Pharmacological ‐ concerned with uses, effects, and modes of action of drugs.

Pleural – concerning the serous membranes lining the thorax and enveloping the lungs.

Pneumonia ‐ lung inflammation caused by bacterial or viral infection.

Postural – concerning the position in which someone holds his or her body when standing or sitting.

Prophylaxis ‐ preventive treatment.

Prostaglandin ‐ group of compounds with varying hormone‐like effects.

Pulmonary – related to the lungs.

Purulent ‐ consisting of, containing, or discharging pus.

Pyaemia ‐ blood poisoning caused by spread in the bloodstream of pus‐forming bacteria.

Quinolones ‐ antibiotic derived from quinoline.

Rales ‐ abnormal rattling sounds heard when unhealthy lungs are examined with a stethoscope.

Renal – related to the kidneys.

Reperfusion ‐ action of restoring the flow of blood to an organ or tissue.

Sepsis ‐ presence in tissues of harmful bacteria and their toxins.

Splanchnic ‐ related to the viscera or internal organs.

Tetracyclines ‐ any of a large group of antibiotics with a molecular structure containing four rings.

Thrombocytopaenia ‐ condition characterised by abnormally low levels of thrombocytes in the blood.

Tracheo‐bronchial colonisation ‐ colonisation of the lower airways by bacteria.

Ulceration – development of or affected by an ulcer.

Ventilator ‐ appliance for artificial respiration.

Appendix 2. CENTRAL search strategy

(stomach or antrum or antral or pyloric or pylorus or gastri$ or epigastr$ or duodenal or duodenum or gastro‐duodenal or gastroduodenal or oeso*ag* or esp*ag* or "upper GI" or UGI).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
(h*emorrhag$ or bleed$ or re‐bleed$ or rebleed$).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
1 and 2
exp Gastrointestinal Hemorrhage/
(gastr$ adj3 mucosal adj3 injur$).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
exp injury/ and exp gastric mucosa/
or/3‐6
(stress adj3 ulcer$).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
(h*emorrhag$ or bleed$ or re‐bleed$ or rebleed$).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
(ulcer$ or lesion$).mp.
exp Peptic Ulcer/
9 and (10 or 11)
8 or 12
h*ematemesis.mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
(melena or melaena).mp.
(coffee adj1 ground).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
or/14‐16
7 or 13 or 17
exp Intensive Care/ or exp Critical Illness/ or exp Critical care/ or exp Intensive care units/ or exp Monitoring, Physiologic/
exp Enteral nutrition/
(Nasogastric adj2 (intubat* or tube*)).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
exp Intubation, Gastrointestinal/
exp Feeding Apparatus/ or exp Nutritional Support/ or exp Enteric Feeding/ or exp Tube Feeding/
nasoduodenal tube*.mp.
force feeding$.mp.
or/19‐25
exp Histamine H2 Antagonists/
H2 receptor Antagonist*.mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
H2 blocker*.mp.
(ranitidine or azanplus or biotidin or pylorid or raciran or raniberl or ranisen or ranitidin or rantec or sostril or taladine or tritec or wal‐zan or zantac).mp.
(cimetidine or acitak or altramet or biomet or dyspamet or eureceptor or galenamet or histodil or peptimax or phimetin or tagamet or ultec or zita).mp.
(famotidine or fluxid or leader acid reducer or mylanta or pepcid).mp.
(roxatidine or Roxit).mp.
(Nizatidine or axid or zinga).mp.
exp proton pump inhibitors/
(omeprazole or losec or nexium or prilosec or rapinex or zegerid).mp.
(Esomeprazole or Sompraz or Zoleri or Nexium or Lucen or Esopral or Axagon or Nexiam).mp.
(Rabeprazole or aciphex or dexrabeprazole or pariet or rablet).mp.
(pantoprazole or protium or protonix).mp.
(lansoprazole or agopton or bamalite or lanzoprazole or lanzor or monolitum or ogast or ogastro or opiren or prevacid or prezal or pro ulco or promeco or takepron or ulpax or zoton).mp.
prostaglandins e, synthetic/
(misoprostol or cytotec or glefos).mp.
enprostil.mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
rioprostil.mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
Cholinergic Antagonists/
(Pirenzepine or Gastrozepin or Bisvanil or Gasteril or Leblon or Pirenzepin or Pirenzepina or Pirenzepine Gastrozepin or Pirenzepinum or Tabe or Ulcosan).mp.
(Propantheline or Pro‐Banthine).mp.
(Oxyphenonium or Antrenyl or Argicillin or Methacin or Methocidin or Methocidine or Methocidinum or Metocidina or Hydroxymethylgramicidin or Oxiphenonum).mp.
(Doxepin or adapin or apodoxepin or aponal or deptran or desidox or doneurin or doxepia or doxepinbiomo or espadox or mareen or prudoxin or quitaxon or silenor or sinequan or xepin or zonalon).mp.
(Trimipramine or rhotrimine or stangyl or surmontil).mp.
exp antacids/
(sodium bicarbonate or baking soda or bicarb or bicarbonate of soda or carbonic acid monosodium salt or citrocarbonate or monosodium carbonate or neut or neutra caine or soda bic or sodium acid carbonate or sodium hydrogen carbonate).mp.
(sodium citrate or 2‐hydroxypropanetricarboxylic acid or albright's solution or bicitra or citra or citrate or citric acid or cystemme or cystoleve or cytra‐2 or liqui‐dualcitra or oracit or shohl's solution or uralyt).mp.
(magnesium hydroxide or antacids magnesium oh or brucite or magnesium hydrate or mil‐par or milk of magnesia).mp.
(aluminium hydroxide gel or aldrox or algeldrate or alhydrogel or aloh‐gel or alternagel or alu‐cap or alu‐tab or alugel or aluminium hydroxide mixture bp or aluminium hydroxide oral suspension bp or aluminum hydroxide or aluminum hydroxide gel or amphojel or andursil or basalgel or brasivil or brimos or dialume or hydrated alumina or pepsamer or rocgel).mp.
(magnesium trisilicate or sepiolite or Alenic Alka or Gaviscon or Genaton).mp.
(Magaldrate or Gadral or Magaltop or Magralibi or Riopan).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
(calcium carbonate or alka‐mints or alkets or alkums or amilac or amitone or antacid extra strength or aragonite or cacit or caco or cal oys or cal‐gest or calcarb or calceos or calci mix or calcichew or calcidrink or calcitab or calcite or calcium antacid or calcium concentrate or calcium liquid softgel or calcium milk or calcium oyster or calcium‐based antacid or calmicid or caltrate or caltro or chalk or chewable calcium or chooz or dicarbosil or equilet or extra strength mylanta calci tabs or limestone or maalox antacid barrier or maalox children or maalox quick dissolve or marble or milk of calcium or mor‐cal or mylanta child or nephro calci or o‐calcium or os‐cal or oscal or oysco or oyst cal or oyster calcium or oyster shell or pepto‐bismol children or rolaids calcium rich or rolaids sodium free or rolaids softchews or super calcium or surpass or titralac or tums or ultra mylanta calci tabs or uni‐cal or uni‐mint or vaterite).mp.
(sucralfate or aluminum sucrose sulfate or antepsin or carafate or ulcerban or ulcogant or ulsanic or xactdose).mp.
(colloidal bismuth subcitrate or bi‐citrate or biselic or bismofarma or bismuth citrate or bismuth subcitrate or bismuth tripotassium dicitrate or bissubcit or de‐nol or de‐noltab or gastrodenol or sucrato or tripotassium dicitratobismuthate or ventrisol‐polfa).mp.
(carbenoxolone sodium or bioplex or bioral or carbenoxalone or carbosan or disodium enoxolone or duogastrone or pharmaxolon or sanodin).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
Deglycyrrhizinised Liquorice.mp.
or/27‐62
18 and 26 and 63

Update search on 15 June 2016 and 22 August 2017:

exp Upper Gastrointestinal Tract/
(stomach or antrum or antral or pyloric or pylorus or gastri* or gastro* or duoden* or epigastr* or gastritis or duodenitis).tw,kw.
(esophag* or oesophag* or gastroduoden* or gastrointestinal).tw,kw.
exp Peptic Ulcer/
(peptic or ulcer* or upper GI or UGI or PUD).tw,kw.
or/1‐5
(hemorrhag* or haemorrhag* or bleed* or rebleed* or re‐bleed* or bled or rebled).tw,kw.
(mucosa* adj2 (injur* or damage* or lesion*)).tw,kw.
exp Hemorrhage/
or/7‐9
6 and 10
exp Gastrointestinal Hemorrhage/
exp melena/
(melena or melaena).tw,kw.
exp hematemesis/
(haematemesis or hematemesis).tw,kw.
((coffee adj ground) or "UGIB").tw,kw.
or/11‐17
exp Intensive Care Units/
exp Critical Illness/
exp Critical care/
(intensive care or critical care or respiratory care or recovery room or close attention unit* or special care unit* or coronary care or burn unit* or ICU or RCU or CCU).tw,kw.
((critical or critically or severe or serious*) adj2 (ill or illness)).tw,kw.
((head or brain or severe or multiple) adj2 (injur* or trauma*)).tw,kw.
exp Respiration, Artificial/
(((mechanical* or artificial or controlled) adj2 (ventilat* or respiration)) or on ventilator or ventilated patients).tw,kw.
((prophylaxis or prophylactic or prevent*) and (((after or post) adj2 (surgery or operat*)) or postoperat* or sepsis or hepatic failure* or respiratory failure* or renal failure* or burns or transplantation or stroke or incubated or acute pancreatitis or intracerebral h*morrhag* or intracerebral bleed*)).ti,ab.
or/19‐27
18 and 28
(stress adj2 (ulcer* or gastritis or bleed* or hemorrhage* or haemorrhage*)).tw,kw.
29 or 30
limit 31 to yr="2012 ‐Current"
remove duplicates from 32

Appendix 3. MEDLINE search strategy

randomized controlled trial.pt.
controlled clinical trial.pt.
randomized.ab.
placebo.ab.
drug therapy.fs.
randomly.ab.
trial.ab.
groups.ab.
or/1‐8
exp animals/ not humans.sh.
9 not 10
(stomach or antrum or antral or pyloric or pylorus or gastri$ or epigastr$ or duodenal or duodenum or gastro‐duodenal or gastroduodenal or oeso*ag* or esp*ag* or "upper GI" or UGI).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
(h*emorrhag$ or bleed$ or re‐bleed$ or rebleed$).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
12 and 13
exp Gastrointestinal Hemorrhage/
(gastr$ adj3 mucosal adj3 injur$).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
exp injury/ and exp gastric mucosa/
or/14‐17
(stress adj3 ulcer$).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
(h*emorrhag$ or bleed$ or re‐bleed$ or rebleed$).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
(ulcer$ or lesion$).mp.
exp Peptic Ulcer/
20 and (21 or 22)
19 or 23
h*ematemesis.mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
(melena or melaena).mp.
(coffee adj1 ground).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
or/25‐27
18 or 24 or 28
exp Intensive Care/ or exp Critical Illness/ or exp Critical care/ or exp Intensive care units/ or exp Monitoring, Physiologic/
exp Enteral nutrition/
(Nasogastric adj2 (intubat* or tube*)).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
exp Intubation, Gastrointestinal/
exp Feeding Apparatus/ or exp Nutritional Support/ or exp Enteric Feeding/ or exp Tube Feeding/
nasoduodenal tube*.mp.
force feeding$.mp.
or/30‐36
exp Histamine H2 Antagonists/
H2 receptor Antagonist*.mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
H2 blocker*.mp.
(ranitidine or azanplus or biotidin or pylorid or raciran or raniberl or ranisen or ranitidin or rantec or sostril or taladine or tritec or wal‐zan or zantac).mp.
(cimetidine or acitak or altramet or biomet or dyspamet or eureceptor or galenamet or histodil or peptimax or phimetin or tagamet or ultec or zita).mp.
(famotidine or fluxid or leader acid reducer or mylanta or pepcid).mp.
(roxatidine or Roxit).mp.
(Nizatidine or axid or zinga).mp.
exp proton pump inhibitors/
(omeprazole or losec or nexium or prilosec or rapinex or zegerid).mp.
(Esomeprazole or Sompraz or Zoleri or Nexium or Lucen or Esopral or Axagon or Nexiam).mp.
(Rabeprazole or aciphex or dexrabeprazole or pariet or rablet).mp.
(pantoprazole or protium or protonix).mp.
(lansoprazole or agopton or bamalite or lanzoprazole or lanzor or monolitum or ogast or ogastro or opiren or prevacid or prezal or pro ulco or promeco or takepron or ulpax or zoton).mp.
prostaglandins e, synthetic/
(misoprostol or cytotec or glefos).mp.
enprostil.mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
rioprostil.mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
Cholinergic Antagonists/
(Pirenzepine or Gastrozepin or Bisvanil or Gasteril or Leblon or Pirenzepin or Pirenzepina or Pirenzepine Gastrozepin or Pirenzepinum or Tabe or Ulcosan).mp.
(Propantheline or Pro‐Banthine).mp.
(Oxyphenonium or Antrenyl or Argicillin or Methacin or Methocidin or Methocidine or Methocidinum or Metocidina or Hydroxymethylgramicidin or Oxiphenonum).mp.
(Doxepin or adapin or apodoxepin or aponal or deptran or desidox or doneurin or doxepia or doxepinbiomo or espadox or mareen or prudoxin or quitaxon or silenor or sinequan or xepin or zonalon).mp.
(Trimipramine or rhotrimine or stangyl or surmontil).mp.
exp antacids/
(sodium bicarbonate or baking soda or bicarb or bicarbonate of soda or carbonic acid monosodium salt or citrocarbonate or monosodium carbonate or neut or neutra caine or soda bic or sodium acid carbonate or sodium hydrogen carbonate).mp.
(sodium citrate or 2‐hydroxypropanetricarboxylic acid or albright's solution or bicitra or citra or citrate or citric acid or cystemme or cystoleve or cytra‐2 or liqui‐dualcitra or oracit or shohl's solution or uralyt).mp.
(magnesium hydroxide or antacids magnesium oh or brucite or magnesium hydrate or mil‐par or milk of magnesia).mp.
(aluminium hydroxide gel or aldrox or algeldrate or alhydrogel or aloh‐gel or alternagel or alu‐cap or alu‐tab or alugel or aluminium hydroxide mixture bp or aluminium hydroxide oral suspension bp or aluminum hydroxide or aluminum hydroxide gel or amphojel or andursil or basalgel or brasivil or brimos or dialume or hydrated alumina or pepsamer or rocgel).mp.
(magnesium trisilicate or sepiolite or Alenic Alka or Gaviscon or Genaton).mp.
(Magaldrate or Gadral or Magaltop or Magralibi or Riopan).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
(calcium carbonate or alka‐mints or alkets or alkums or amilac or amitone or antacid extra strength or aragonite or cacit or caco or cal oys or cal‐gest or calcarb or calceos or calci mix or calcichew or calcidrink or calcitab or calcite or calcium antacid or calcium concentrate or calcium liquid softgel or calcium milk or calcium oyster or calcium‐based antacid or calmicid or caltrate or caltro or chalk or chewable calcium or chooz or dicarbosil or equilet or extra strength mylanta calci tabs or limestone or maalox antacid barrier or maalox children or maalox quick dissolve or marble or milk of calcium or mor‐cal or mylanta child or nephro calci or o‐calcium or os‐cal or oscal or oysco or oyst cal or oyster calcium or oyster shell or pepto‐bismol children or rolaids calcium rich or rolaids sodium free or rolaids softchews or super calcium or surpass or titralac or tums or ultra mylanta calci tabs or uni‐cal or uni‐mint or vaterite).mp.
(sucralfate or aluminum sucrose sulfate or antepsin or carafate or ulcerban or ulcogant or ulsanic or xactdose).mp.
(colloidal bismuth subcitrate or bi‐citrate or biselic or bismofarma or bismuth citrate or bismuth subcitrate or bismuth tripotassium dicitrate or bissubcit or de‐nol or de‐noltab or gastrodenol or sucrato or tripotassium dicitratobismuthate or ventrisol‐polfa).mp.
(carbenoxolone sodium or bioplex or bioral or carbenoxalone or carbosan or disodium enoxolone or duogastrone or pharmaxolon or sanodin).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
Deglycyrrhizinised Liquorice.mp.
or/38‐73
29 and 37 and 74
11 and 75

Update search on 15 June 2016 and 22 August 2017:

exp Upper Gastrointestinal Tract/
(stomach or antrum or antral or pyloric or pylorus or gastri* or gastro* or duoden* or epigastr* or gastritis or duodenitis).tw,kw.
(esophag* or oesophag* or gastroduoden* or gastrointestinal).tw,kw.
exp Peptic Ulcer/
(peptic or ulcer* or upper GI or UGI or PUD).tw,kw.
or/1‐5
(hemorrhag* or haemorrhag* or bleed* or rebleed* or re‐bleed* or bled or rebled).tw,kw.
(mucosa* adj2 (injur* or damage* or lesion*)).tw,kw.
exp Hemorrhage/
or/7‐9
6 and 10
exp Gastrointestinal Hemorrhage/
exp melena/
(melena or melaena).tw,kw.
exp hematemesis/
(haematemesis or hematemesis).tw,kw.
((coffee adj ground) or "UGIB").tw,kw.
or/11‐17
exp Intensive Care Units/
exp Critical Illness/
exp Critical care/
(intensive care or critical care or respiratory care or recovery room or close attention unit* or special care unit* or coronary care or burn unit* or ICU or RCU or CCU).tw,kw.
((critical or critically or severe or serious*) adj2 (ill or illness)).tw,kw.
((head or brain or severe or multiple) adj2 (injur* or trauma*)).tw,kw.
exp Respiration, Artificial/
(((mechanical* or artificial or controlled) adj2 (ventilat* or respiration)) or on ventilator or ventilated patients).tw,kw.
((prophylaxis or prophylactic or prevent*) and (((after or post) adj2 (surgery or operat*)) or postoperat* or sepsis or hepatic failure* or respiratory failure* or renal failure* or burns or transplantation or stroke or incubated or acute pancreatitis or intracerebral h*morrhag* or intracerebral bleed*)).ti,ab.
or/19‐27
18 and 28
(stress adj2 (ulcer* or gastritis or bleed* or hemorrhage* or haemorrhage*)).tw,kw.
29 or 30
randomized controlled trial.pt.
controlled clinical trial.pt.
random*.ab.
placebo.ab.
drug therapy.fs.
trial.ab.
groups.ab.
or/32‐38
exp animals/ not humans.sh.
39 not 40
31 and 41
limit 42 to yr="2012 ‐Current"

Appendix 4. Embase search strategy

Clinical trial/
Randomized controlled trial/
Randomization/
Single‐Blind Method/
Double‐Blind Method/
Cross‐Over Studies/
Random Allocation/
Placebo/
Randomi?ed controlled trial$.tw.
Rct.tw.
Random allocation.tw.
Randomly allocated.tw.
Allocated randomly.tw.
(allocated adj2 random).tw.
Single blind$.tw.
Double blind$.tw.
((treble or triple) adj blind$).tw.
Placebo$.tw.
Prospective study/
or/1‐19
Case study/
Case report.tw.
Abstract report/ or letter/
or/21‐23
20 not 24
(stomach or antrum or antral or pyloric or pylorus or gastri$ or epigastr$ or duodenal or duodenum or gastro‐duodenal or gastroduodenal or oeso*ag* or esp*ag* or "upper GI" or UGI).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
(h*emorrhag$ or bleed$ or re‐bleed$ or rebleed$).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
26 and 27
gastrointestinal hemorrhage/ or duodenum bleeding/ or peptic ulcer bleeding/ or stomach hemorrhage/ or upper gastrointestinal bleeding/
(gastr$ adj3 mucosal adj3 injur$).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
or/28‐30
(stress adj3 ulcer$).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
(h*emorrhag$ or bleed$ or re‐bleed$ or rebleed$).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
(ulcer$ or lesion$).mp.
exp Peptic Ulcer/
33 and (34 or 35)
32 or 36
h*ematemesis.mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
(melena or melaena).mp.
(coffee adj1 ground).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
or/38‐40
31 or 37 or 41
intensive care/ or exp artificial feeding/ or artificial ventilation/ or exp Critical Illness/ or exp Intensive care units/ or patient monitoring/
(Nasogastric adj2 (intubat* or tube*)).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
exp digestive tract intubation/
exp Feeding Apparatus/ or exp Nutritional Support/
nasoduodenal tube*.mp.
force feeding$.mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
or/43‐48
exp histamine H2 receptor antagonist/
H2 receptor Antagonist*.mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
H2 blocker*.mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
(ranitidine or azanplus or biotidin or pylorid or raciran or raniberl or ranisen or ranitidin or rantec or sostril or taladine or tritec or wal‐zan or zantac).mp.
(cimetidine or acitak or altramet or biomet or dyspamet or eureceptor or galenamet or histodil or peptimax or phimetin or tagamet or ultec or zita).mp.
(famotidine or fluxid or leader acid reducer or mylanta or pepcid).mp.
(roxatidine or Roxit).mp.
(Nizatidine or axid or zinga).mp.
exp proton pump inhibitors/
(omeprazole or losec or nexium or prilosec or rapinex or zegerid).mp.
(Esomeprazole or Sompraz or Zoleri or Nexium or Lucen or Esopral or Axagon or Nexiam).mp.
(Rabeprazole or aciphex or dexrabeprazole or pariet or rablet).mp.
(pantoprazole or protium or protonix).mp.
(lansoprazole or agopton or bamalite or lanzoprazole or lanzor or monolitum or ogast or ogastro or opiren or prevacid or prezal or pro ulco or promeco or takepron or ulpax or zoton).mp.
prostaglandin E/
(misoprostol or cytotec or glefos).mp.
enprostil.mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
rioprostil.mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
cholinergic receptor blocking agent/
(Pirenzepine or Gastrozepin or Bisvanil or Gasteril or Leblon or Pirenzepin or Pirenzepina or Pirenzepine Gastrozepin or Pirenzepinum or Tabe or Ulcosan).mp.
(Propantheline or Pro‐Banthine).mp.
(Oxyphenonium or Antrenyl or Argicillin or Methacin or Methocidin or Methocidine or Methocidinum or Metocidina or Hydroxymethylgramicidin or Oxiphenonum).mp.
(Doxepin or adapin or apodoxepin or aponal or deptran or desidox or doneurin or doxepia or doxepinbiomo or espadox or mareen or prudoxin or quitaxon or silenor or sinequan or xepin or zonalon).mp.
(Trimipramine or rhotrimine or stangyl or surmontil).mp.
antacid agent/
(sodium bicarbonate or baking soda or bicarb or bicarbonate of soda or carbonic acid monosodium salt or citrocarbonate or monosodium carbonate or neut or neutra caine or soda bic or sodium acid carbonate or sodium hydrogen carbonate).mp.
(sodium citrate or 2‐hydroxypropanetricarboxylic acid or albright's solution or bicitra or citra or citrate or citric acid or cystemme or cystoleve or cytra‐2 or liqui‐dualcitra or oracit or shohl's solution or uralyt).mp.
(magnesium hydroxide or antacids magnesium oh or brucite or magnesium hydrate or mil‐par or milk of magnesia).mp.
(aluminium hydroxide gel or aldrox or algeldrate or alhydrogel or aloh‐gel or alternagel or alu‐cap or alu‐tab or alugel or aluminium hydroxide mixture bp or aluminium hydroxide oral suspension bp or aluminum hydroxide or aluminum hydroxide gel or amphojel or andursil or basalgel or brasivil or brimos or dialume or hydrated alumina or pepsamer or rocgel).mp.
(magnesium trisilicate or sepiolite or Alenic Alka or Gaviscon or Genaton).mp.
(Magaldrate or Gadral or Magaltop or Magralibi or Riopan).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
(calcium carbonate or alka‐mints or alkets or alkums or amilac or amitone or antacid extra strength or aragonite or cacit or caco or cal oys or cal‐gest or calcarb or calceos or calci mix or calcichew or calcidrink or calcitab or calcite or calcium antacid or calcium concentrate or calcium liquid softgel or calcium milk or calcium oyster or calcium‐based antacid or calmicid or caltrate or caltro or chalk or chewable calcium or chooz or dicarbosil or equilet or extra strength mylanta calci tabs or limestone or maalox antacid barrier or maalox children or maalox quick dissolve or marble or milk of calcium or mor‐cal or mylanta child or nephro calci or o‐calcium or os‐cal or oscal or oysco or oyst cal or oyster calcium or oyster shell or pepto‐bismol children or rolaids calcium rich or rolaids sodium free or rolaids softchews or super calcium or surpass or titralac or tums or ultra mylanta calci tabs or uni‐cal or uni‐mint or vaterite).mp.
(sucralfate or aluminum sucrose sulfate or antepsin or carafate or ulcerban or ulcogant or ulsanic or xactdose).mp.
(colloidal bismuth subcitrate or bi‐citrate or biselic or bismofarma or bismuth citrate or bismuth subcitrate or bismuth tripotassium dicitrate or bissubcit or de‐nol or de‐noltab or gastrodenol or sucrato or tripotassium dicitratobismuthate or ventrisol‐polfa).mp.
(carbenoxolone sodium or bioplex or bioral or carbenoxalone or carbosan or disodium enoxolone or duogastrone or pharmaxolon or sanodin).mp. [mp=title, abstract, subject headings, heading word, drug trade name, original title, device manufacturer, drug manufacturer name]
Deglycyrrhizinised Liquorice.mp.
or/50‐85
42 and 49 and 86
25 and 87

Update search on 15 June 2016 and 22 August 2017:

exp upper gastrointestinal tract/
(stomach or antrum or antral or pyloric or pylorus or gastri* or gastro* or duoden* or epigastr* or gastritis or duodenitis).tw,kw.
(esophag* or oesophag* or gastroduoden* or gastrointestinal).tw,kw.
exp peptic ulcer/
(peptic or ulcer* or upper GI or UGI or PUD).tw,kw.
or/1‐5
(hemorrhag* or haemorrhag* or bleed* or rebleed* or re‐bleed* or bled or rebled).tw,kw.
(mucosa* adj2 (injur* or damage* or lesion*)).tw,kw.
exp bleeding/
or/7‐9
6 and 10
exp gastrointestinal hemorrhage/
exp melena/
(melena or melaena).tw,kw.
exp hematemesis/
(haematemesis or hematemesis).tw,kw.
((coffee adj ground) or "UGIB").tw,kw.
or/11‐17
exp intensive care unit/
exp critical illness/
exp intensive care/
(intensive care or critical care or respiratory care or recovery room or close attention unit* or special care unit* or coronary care or burn unit* or ICU or RCU or CCU).tw,kw.
((critical or critically or severe or serious*) adj2 (ill or illness)).tw,kw.
((head or brain or severe or multiple) adj2 (injur* or trauma*)).tw,kw.
exp artificial ventilation/
(((mechanical* or artificial or controlled) adj2 (ventilat* or respiration)) or on ventilator or ventilated patients).tw,kw.
((prophylaxis or prophylactic or prevent*) and (((after or post) adj2 (surgery or operat*)) or postoperat* or sepsis or hepatic failure* or respiratory failure* or renal failure* or burns or transplantation or stroke or incubated or acute pancreatitis or intracerebral h*morrhag* or intracerebral bleed*)).ti,ab.
or/19‐27
18 and 28
(stress adj2 (ulcer* or gastritis or bleed* or hemorrhage* or haemorrhage*)).tw,kw.
29 or 30
random:.tw.
placebo:.mp.
double‐blind:.tw.
32 or 33 or 34
31 and 35
limit 36 to yr="2012 ‐Current"

Appendix 5. LILACS search strategy

Descriptors in Health Sciences (DeCS) were used to account for Portuguese, Spanish and English terms in LILACS.

(E02.760.190.400 or N02.278.388.493 or E02.760.190) [DeCS Category] and (C06.405.227 or C06.405.227.400 or A12.459.764 or C06.405.227.700) [DeCS Category]

Update search on 15 June 2016 and 22 August 2017:

(((tw:(ulcer OR stomach OR antrum OR antral OR gastri* OR gastro* OR duoden* OR epigastr* OR gastritis OR duodenitis OR esophageal* OR oesophageal*)) AND (tw:(hemorrhag* OR haemorrhag* OR bleed* OR rebleed* OR re‐bleed* OR bled OR rebled))) OR (tw: (stress ulcer*)) OR (mh: (c06.405.227)) ) AND ( (mh: (e02.760.190)) OR (tw: (intensive care OR critical care OR critically ill OR mechanical* ventilat*))) AND (instance:"regional") AND ( db:("LILACS") AND type_of_study:("clinical_trials"))

Figure 1

PRISMA flow chart of included studies.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 4

Funnel plot of comparison: 1 Interventions versus placebo or no prophylaxis, outcome: 1.1 Clinically important upper GI bleeding.

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Figure 5

Funnel plot of comparison: 2 H2 receptor antagonists versus placebo or no prophylaxis, outcome: 2.1 Clinically important upper GI bleeding.

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Figure 6

Funnel plot of comparison: 9 H2 receptor antagonists versus proton pump inhibitors, outcome: 9.1 Clinically important upper GI bleeding.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 7

Funnel plot of comparison: 10 H2 receptor antagonists versus antacids, outcome: 10.1 Clinically important upper GI bleeding.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 8

Funnel plot of comparison: 11 H2 receptor antagonists versus sucralfate, outcome: 11.1 Clinically important upper GI bleeding.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 9

Funnel plot of comparison: 19 Antacids versus sucralfate, outcome: 19.1 Clinically important upper GI bleeding.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.1

Comparison 1 Interventions versus placebo or no prophylaxis, Outcome 1 Clinically important upper GI bleeding.

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Analysis 1.2

Comparison 1 Interventions versus placebo or no prophylaxis, Outcome 2 Nosocomial pneumonia.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.3

Comparison 1 Interventions versus placebo or no prophylaxis, Outcome 3 All‐cause mortality in ICU.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.4

Comparison 1 Interventions versus placebo or no prophylaxis, Outcome 4 All‐cause mortality in hospital.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.5

Comparison 1 Interventions versus placebo or no prophylaxis, Outcome 5 Duration of ICU stay.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.6

Comparison 1 Interventions versus placebo or no prophylaxis, Outcome 6 Duration of intubation.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.7

Comparison 1 Interventions versus placebo or no prophylaxis, Outcome 7 Number of participants requiring blood transfusions.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.8

Comparison 1 Interventions versus placebo or no prophylaxis, Outcome 8 Units of blood transfused.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.1

Comparison 2 H2 receptor antagonists versus placebo or no prophylaxis, Outcome 1 Clinically important upper GI bleeding.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.2

Comparison 2 H2 receptor antagonists versus placebo or no prophylaxis, Outcome 2 Nosocomial pneumonia.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.3

Comparison 2 H2 receptor antagonists versus placebo or no prophylaxis, Outcome 3 All‐cause mortality in ICU.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.4

Comparison 2 H2 receptor antagonists versus placebo or no prophylaxis, Outcome 4 All‐cause mortality in hospital.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.5

Comparison 2 H2 receptor antagonists versus placebo or no prophylaxis, Outcome 5 Duration of ICU stay.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.6

Comparison 2 H2 receptor antagonists versus placebo or no prophylaxis, Outcome 6 Duration of intubation.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.7

Comparison 2 H2 receptor antagonists versus placebo or no prophylaxis, Outcome 7 Number of participants requiring blood transfusions.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.8

Comparison 2 H2 receptor antagonists versus placebo or no prophylaxis, Outcome 8 Units of blood transfused.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.9

Comparison 2 H2 receptor antagonists versus placebo or no prophylaxis, Outcome 9 Adverse events of interventions.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 3.1

Comparison 3 Proton pump inhibitors versus placebo or no prophylaxis, Outcome 1 Clinically important upper GI bleeding.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 3.2

Comparison 3 Proton pump inhibitors versus placebo or no prophylaxis, Outcome 2 Nosocomial pneumonia.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 3.3

Comparison 3 Proton pump inhibitors versus placebo or no prophylaxis, Outcome 3 All‐cause mortality in ICU.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 3.4

Comparison 3 Proton pump inhibitors versus placebo or no prophylaxis, Outcome 4 All‐cause mortality in hospital.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 3.5

Comparison 3 Proton pump inhibitors versus placebo or no prophylaxis, Outcome 5 Duration of ICU stay.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 3.6

Comparison 3 Proton pump inhibitors versus placebo or no prophylaxis, Outcome 6 Duration of intubation.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 4.1

Comparison 4 Proton pump inhibitors + sucralfate versus no prophylaxis, Outcome 1 Clinically important upper GI bleeding.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 5.1

Comparison 5 Prostaglandin analogues versus placebo or no prophylaxis, Outcome 1 Clinically important upper GI bleeding.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 5.2

Comparison 5 Prostaglandin analogues versus placebo or no prophylaxis, Outcome 2 All‐cause mortality in ICU.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 6.1

Comparison 6 Anticholinergics versus placebo or no prophylaxis, Outcome 1 Clinically important upper GI bleeding.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 6.2

Comparison 6 Anticholinergics versus placebo or no prophylaxis, Outcome 2 Nosocomial pneumonia.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 6.3

Comparison 6 Anticholinergics versus placebo or no prophylaxis, Outcome 3 All‐cause mortality in ICU.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 7.1

Comparison 7 Antacids versus placebo or no prophylaxis, Outcome 1 Clinically important upper GI bleeding.

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Analysis 7.2

Comparison 7 Antacids versus placebo or no prophylaxis, Outcome 2 All‐cause mortality in ICU.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 7.3

Comparison 7 Antacids versus placebo or no prophylaxis, Outcome 3 All‐cause mortality in hospital.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 7.4

Comparison 7 Antacids versus placebo or no prophylaxis, Outcome 4 Number of participants requiring blood transfusions.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 7.5

Comparison 7 Antacids versus placebo or no prophylaxis, Outcome 5 Adverse events of interventions.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 8.1

Comparison 8 Sucralfate versus placebo or no prophylaxis, Outcome 1 Clinically important upper GI bleeding.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 8.2

Comparison 8 Sucralfate versus placebo or no prophylaxis, Outcome 2 Nosocomial pneumonia.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 8.3

Comparison 8 Sucralfate versus placebo or no prophylaxis, Outcome 3 All‐cause mortality in ICU.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 8.4

Comparison 8 Sucralfate versus placebo or no prophylaxis, Outcome 4 All‐cause mortality in hospital.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 8.5

Comparison 8 Sucralfate versus placebo or no prophylaxis, Outcome 5 Duration of ICU stay.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 8.6

Comparison 8 Sucralfate versus placebo or no prophylaxis, Outcome 6 Duration of intubation.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 8.7

Comparison 8 Sucralfate versus placebo or no prophylaxis, Outcome 7 Number of participants requiring blood transfusions.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 8.8

Comparison 8 Sucralfate versus placebo or no prophylaxis, Outcome 8 Units of blood transfused.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 8.9

Comparison 8 Sucralfate versus placebo or no prophylaxis, Outcome 9 Adverse events of interventions.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 9.1

Comparison 9 H2 receptor antagonists versus proton pump inhibitors, Outcome 1 Clinically important upper GI bleeding.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 9.2

Comparison 9 H2 receptor antagonists versus proton pump inhibitors, Outcome 2 Nosocomial pneumonia.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 9.3

Comparison 9 H2 receptor antagonists versus proton pump inhibitors, Outcome 3 All‐cause mortality in ICU.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 9.4

Comparison 9 H2 receptor antagonists versus proton pump inhibitors, Outcome 4 All‐cause mortality in hospital.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 9.5

Comparison 9 H2 receptor antagonists versus proton pump inhibitors, Outcome 5 Duration of ICU stay.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 9.6

Comparison 9 H2 receptor antagonists versus proton pump inhibitors, Outcome 6 Duration of intubation.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 9.7

Comparison 9 H2 receptor antagonists versus proton pump inhibitors, Outcome 7 Number of participants requiring blood transfusions.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 9.8

Comparison 9 H2 receptor antagonists versus proton pump inhibitors, Outcome 8 Adverse events of interventions.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 10.1

Comparison 10 H2 receptor antagonists versus antacids, Outcome 1 Clinically important upper GI bleeding.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 10.2

Comparison 10 H2 receptor antagonists versus antacids, Outcome 2 Nosocomial pneumonia.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 10.3

Comparison 10 H2 receptor antagonists versus antacids, Outcome 3 All‐cause mortality in ICU.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 10.4

Comparison 10 H2 receptor antagonists versus antacids, Outcome 4 All‐cause mortality in hospital.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 10.5

Comparison 10 H2 receptor antagonists versus antacids, Outcome 5 Duration of intubation.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 10.6

Comparison 10 H2 receptor antagonists versus antacids, Outcome 6 Number of participants requiring blood transfusions.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 10.7

Comparison 10 H2 receptor antagonists versus antacids, Outcome 7 Adverse events of interventions.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 11.1

Comparison 11 H2 receptor antagonists versus sucralfate, Outcome 1 Clinically important upper GI bleeding.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 11.2

Comparison 11 H2 receptor antagonists versus sucralfate, Outcome 2 Nosocomial pneumonia.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 11.3

Comparison 11 H2 receptor antagonists versus sucralfate, Outcome 3 All‐cause mortality in ICU.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 11.4

Comparison 11 H2 receptor antagonists versus sucralfate, Outcome 4 All‐cause mortality in hospital.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 11.5

Comparison 11 H2 receptor antagonists versus sucralfate, Outcome 5 Duration of intubation.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 11.6

Comparison 11 H2 receptor antagonists versus sucralfate, Outcome 6 Duration of ICU stay.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 11.7

Comparison 11 H2 receptor antagonists versus sucralfate, Outcome 7 Number of participants requiring blood transfusion.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 11.8

Comparison 11 H2 receptor antagonists versus sucralfate, Outcome 8 Units of blood transfused.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 11.9

Comparison 11 H2 receptor antagonists versus sucralfate, Outcome 9 Adverse events of interventions.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 12.1

Comparison 12 H2 receptor antagonists versus anticholinergics, Outcome 1 Clinically important upper GI bleeding.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 12.2

Comparison 12 H2 receptor antagonists versus anticholinergics, Outcome 2 Nosocomial pneumonia.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 12.3

Comparison 12 H2 receptor antagonists versus anticholinergics, Outcome 3 All‐cause mortality in ICU.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 12.4

Comparison 12 H2 receptor antagonists versus anticholinergics, Outcome 4 Number of participants requiring blood transfusion.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 12.5

Comparison 12 H2 receptor antagonists versus anticholinergics, Outcome 5 Adverse events of interventions.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 13.1

Comparison 13 H2 receptor antagonists versus prostaglandin analogues, Outcome 1 Clinically important upper GI bleeding.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 13.2

Comparison 13 H2 receptor antagonists versus prostaglandin analogues, Outcome 2 All‐cause mortality in ICU.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 14.1

Comparison 14 H2 receptor antagonists versus teprenone, Outcome 1 Clinically important upper GI bleeding.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 14.2

Comparison 14 H2 receptor antagonists versus teprenone, Outcome 2 All‐cause mortality in ICU.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 14.3

Comparison 14 H2 receptor antagonists versus teprenone, Outcome 3 Number of participants requiring blood transfusion.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 15.1

Comparison 15 H2 receptor antagonist + antacids versus sucralfate, Outcome 1 Clinically important upper GI bleeding.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 15.2

Comparison 15 H2 receptor antagonist + antacids versus sucralfate, Outcome 2 Nosocomial pneumonia.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 15.3

Comparison 15 H2 receptor antagonist + antacids versus sucralfate, Outcome 3 All‐cause mortality in ICU.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 15.4

Comparison 15 H2 receptor antagonist + antacids versus sucralfate, Outcome 4 Duration of ICU stay.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 15.5

Comparison 15 H2 receptor antagonist + antacids versus sucralfate, Outcome 5 Duration of intubation.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 15.6

Comparison 15 H2 receptor antagonist + antacids versus sucralfate, Outcome 6 Number of participants requiring blood transfusion.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 16.1

Comparison 16 Proton pump inhibitors versus teprenone, Outcome 1 Clinically important upper GI bleeding.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 16.2

Comparison 16 Proton pump inhibitors versus teprenone, Outcome 2 All‐cause mortality in ICU.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 16.3

Comparison 16 Proton pump inhibitors versus teprenone, Outcome 3 Number of participants requiring blood transfusion.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 17.1

Comparison 17 Proton pump inhibitor plus naloxone versus naloxone, Outcome 1 Clinically important upper GI bleeding.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 17.2

Comparison 17 Proton pump inhibitor plus naloxone versus naloxone, Outcome 2 All‐cause mortality in hospital.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 17.3

Comparison 17 Proton pump inhibitor plus naloxone versus naloxone, Outcome 3 Adverse events ‐ gastrointestinal discomfort.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 18.1

Comparison 18 Proton pump inhibitors versus other medication (not defined), Outcome 1 Clinically important upper GI bleeding.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 18.2

Comparison 18 Proton pump inhibitors versus other medication (not defined), Outcome 2 Nosocomial pneumonia.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 18.3

Comparison 18 Proton pump inhibitors versus other medication (not defined), Outcome 3 All‐cause mortality in hospital.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 19.1

Comparison 19 Antacids versus sucralfate, Outcome 1 Clinically important upper GI bleeding.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 19.2

Comparison 19 Antacids versus sucralfate, Outcome 2 Nosocomial pneumonia.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 19.3

Comparison 19 Antacids versus sucralfate, Outcome 3 All‐cause mortality in ICU.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 19.4

Comparison 19 Antacids versus sucralfate, Outcome 4 All‐cause mortality in hospital.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 19.5

Comparison 19 Antacids versus sucralfate, Outcome 5 Duration of ICU stay.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 19.6

Comparison 19 Antacids versus sucralfate, Outcome 6 Duration of intubation.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 19.7

Comparison 19 Antacids versus sucralfate, Outcome 7 Number of participants requiring blood transfusion.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 19.8

Comparison 19 Antacids versus sucralfate, Outcome 8 Adverse events of interventions.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 20.1

Comparison 20 Antacids versus prostaglandin analogues, Outcome 1 Clinically important upper GI bleeding.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 20.2

Comparison 20 Antacids versus prostaglandin analogues, Outcome 2 All‐cause mortality in ICU.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 20.3

Comparison 20 Antacids versus prostaglandin analogues, Outcome 3 Adverse events of interventions.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 21.1

Comparison 21 Antacids versus bioflavonoids, Outcome 1 Clinically important upper GI bleeding.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 21.2

Comparison 21 Antacids versus bioflavonoids, Outcome 2 Number of participants requiring blood transfusion.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 22.1

Comparison 22 Sucralfate versus proton pump inhibitors, Outcome 1 Clinically important upper GI bleeding.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 22.2

Comparison 22 Sucralfate versus proton pump inhibitors, Outcome 2 Nosocomial pneumonia.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 22.3

Comparison 22 Sucralfate versus proton pump inhibitors, Outcome 3 All‐cause mortality in ICU.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 22.4

Comparison 22 Sucralfate versus proton pump inhibitors, Outcome 4 All‐cause mortality in hospital.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 22.5

Comparison 22 Sucralfate versus proton pump inhibitors, Outcome 5 Duration of ICU stay.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 22.6

Comparison 22 Sucralfate versus proton pump inhibitors, Outcome 6 Duration of intubation.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 22.7

Comparison 22 Sucralfate versus proton pump inhibitors, Outcome 7 Number of participants requiring blood transfusion.

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Analysis 22.8

Comparison 22 Sucralfate versus proton pump inhibitors, Outcome 8 Adverse events of interventions.

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Analysis 23.1

Comparison 23 Sucralfate versus bioflavonoids, Outcome 1 Clinically important upper GI bleeding.

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Analysis 23.2

Comparison 23 Sucralfate versus bioflavonoids, Outcome 2 Number of participants requiring blood transfusion.

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Analysis 24.1

Comparison 24 Total parenteral nutrition (TPN) versus any other intervention + TPN, Outcome 1 Clinically important upper GI bleeding.

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Analysis 24.2

Comparison 24 Total parenteral nutrition (TPN) versus any other intervention + TPN, Outcome 2 All‐cause mortality in ICU.

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Analysis 24.3

Comparison 24 Total parenteral nutrition (TPN) versus any other intervention + TPN, Outcome 3 Duration of intubation.

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Analysis 25.1

Comparison 25 Bowel stimulation versus no prophylaxis, Outcome 1 Clinically important upper GI bleeding.

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Analysis 26.1

Comparison 26 Nasojejunal nutrition versus nasogastric nutrition, Outcome 1 Clinically important upper GI bleeding.

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Analysis 26.2

Comparison 26 Nasojejunal nutrition versus nasogastric nutrition, Outcome 2 Nosocomial pneumonia.

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Analysis 26.3

Comparison 26 Nasojejunal nutrition versus nasogastric nutrition, Outcome 3 All‐cause mortality in hospital.

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Analysis 26.4

Comparison 26 Nasojejunal nutrition versus nasogastric nutrition, Outcome 4 Adverse events of interventions.

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Analysis 27.1

Comparison 27 Enteral plus parenteral nutrition versus other nutrition regimens, Outcome 1 Nosocomial pneumonia.

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Analysis 27.2

Comparison 27 Enteral plus parenteral nutrition versus other nutrition regimens, Outcome 2 All‐cause mortality in hospital.

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Analysis 27.3

Comparison 27 Enteral plus parenteral nutrition versus other nutrition regimens, Outcome 3 Duration of ICU stay.

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Analysis 27.4

Comparison 27 Enteral plus parenteral nutrition versus other nutrition regimens, Outcome 4 Duration of intubation.

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Analysis 27.5

Comparison 27 Enteral plus parenteral nutrition versus other nutrition regimens, Outcome 5 Adverse events ‐ stress ulcer.

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Analysis 27.6

Comparison 27 Enteral plus parenteral nutrition versus other nutrition regimens, Outcome 6 Adverse events ‐ diarrhoea.

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Analysis 27.7

Comparison 27 Enteral plus parenteral nutrition versus other nutrition regimens, Outcome 7 Adverse events ‐ pyaemia.

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Analysis 27.8

Comparison 27 Enteral plus parenteral nutrition versus other nutrition regimens, Outcome 8 Adverse events ‐ intracranial infection.

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Analysis 27.9

Comparison 27 Enteral plus parenteral nutrition versus other nutrition regimens, Outcome 9 Adverse events ‐ hypoproteinaemia.

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Summary of findings for the main comparison. Interventions compared with placebo or no prophylaxis for preventing upper gastrointestinal bleeding in people admitted to intensive care units

Any intervention compared with placebo or no prophylaxis for preventing upper gastrointestinal bleeding in people admitted to intensive care units
Patient or population: people admitted to intensive care units Setting: ICU Intervention: any intervention Comparison: placebo or no prophylaxis
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with placebo or no prophylaxis	Risk with Interventions
Clinically important upper GI bleeding Follow‐up: 15 days^†	Study population		RR 0.47 (0.39 to 0.57)	3207 (30 RCTs)	⊕⊕⊕⊝ MODERATE^a
	188 per 1000	88 per 1000 (73 to 107)
Nosocomial pneumonia Follow‐up: 48 hours after extubation^‡	Study population		RR 1.15 (0.90 to 1.48)	1331 (9 RCTs)	⊕⊕⊝⊝ LOW^b,c
	143 per 1000	164 per 1000 (129 to 211)
All‐cause mortality in ICU Follow‐up: 4 weeks^§	Study population		RR 1.10 (0.90 to 1.34)	2159 (19 RCTs)	⊕⊕⊝⊝ LOW^b,d
	152 per 1000	168 per 1000 (137 to 204)
Duration of ICU stay Follow‐up: not reported	Mean duration of ICU stay ranged from 8.6 to 11.1 days	MD 0.24 days higher (1.13 days lower to 1.61 higher days)	‐	447 (2 RCTs)	⊕⊕⊝⊝ LOW^b,e
Number of participants requiring blood transfusion Follow‐up: 48 hours after discharge^‡	Study population		RR 0.63 (0.41 to 0.97)	981 (9 RCTs)	⊕⊕⊕⊝ MODERATE^f
	96 per 1000	60 per 1000 (39 to 93)
Serious adverse events	Not reported
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). ^‡Duration of follow‐up reported in one study. ^†Duration of follow‐up reported in four studies. ^§Duration of follow‐up reported in five studies. CI: confidence interval; GI: gastrointestinal; ICU: intensive care unit; MD: mean difference; RCT: randomised controlled trial; RR: risk ratio.
GRADE Working Group grades of evidence. High certainty: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect. Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.
^aDowngraded by one level for risk of bias because of high risk of selection bias in one study, high risk of performance bias in nine studies, high risk of detection bias in five studies, high risk of attrition bias in four studies, high risk of reporting bias in five studies, and high risk of other biases in four studies. ^bDowngraded by one level for imprecision because effect estimate and 95% CI were compatible with benefit and harm. ^cDowngraded by one level for risk of bias because of high risk of performance bias in three studies, high risk of detection bias in one study, and high risk of attrition bias in two studies. ^dDowngraded by one level for risk of bias because of high risk of performance bias in seven studies and high risk of attrition bias in two studies. ^eDowngraded by one level for risk of bias because of high risk of performance bias in one study. ^fDowngraded by one level for risk of bias because of high risk of selection bias in one study, high risk of performance bias in two studies, high risk of attrition bias in one study, high risk of reporting bias in one study, and high risk of other biases in one study.

Summary of findings for the main comparison. Interventions compared with placebo or no prophylaxis for preventing upper gastrointestinal bleeding in people admitted to intensive care units

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Summary of findings 2. H2 receptor antagonists compared with placebo or no prophylaxis for preventing upper gastrointestinal bleeding in people admitted to intensive care units

H2 receptor antagonists compared with placebo or no prophylaxis for preventing upper gastrointestinal bleeding in people admitted to intensive care units
Patient or population: people admitted to intensive care units Setting: ICU Intervention: H2 receptor antagonists Comparison: placebo or no prophylaxis
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with placebo or no prophylaxis	Risk with H2 receptor antagonists
Clinically important upper GI bleeding Follow‐up: 15 days/weeks^†	Study population		RR 0.50 (0.36 to 0.70)	2149 (24 RCTs)	⊕⊕⊕⊝ MODERATE^a
	182 per 1000	91 per 1000 (65 to 127)
Nosocomial pneumonia Follow‐up: 48 hours after extubation^‡	Study population		RR 1.12 (0.85 to 1.48)	945 (8 RCTs)	⊕⊕⊝⊝ LOW^b,c
	146 per 1000	164 per 1000 (124 to 216)
All‐cause mortality in ICU Follow‐up: 4 weeks^§	Study population		RR 1.12 (0.88 to 1.42)	1428 (14 RCTs)	⊕⊕⊝⊝ LOW^b,d
	145 per 1000	162 per 1000 (127 to 205)
Duration of ICU stay Follow‐up: not reported	Mean duration of ICU stay ranged from 8.6 to 11.1 days	MD 0.73 days higher (0.92 days lower to 2.38 days higher)	‐	230 (2 RCTs)	⊕⊕⊝⊝ LOW^b,e
Number of participants requiring blood transfusions Follow‐up: 48 hours after extubation^ǁ	Study population		RR 0.58 (0.36 to 0.95)	655 (7 RCTs)	⊕⊕⊕⊝ MODERATE^f
	112 per 1000	65 per 1000 (40 to 107)
Serious adverse events	Not reported
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). ^†Duration of follow‐up reported in four studies. ^‡Duration of follow‐up reported in two studies. ^§Duration of follow‐up reported in five studies. ^ǁDuration of follow‐up reported in one study. CI: confidence interval; GI: gastrointestinal; ICU: intensive care unit; MD: mean difference; RCT: randomised controlled trial; RR: risk ratio.
GRADE Working Group grades of evidence. High certainty: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect. Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.
^aDowngraded by one level for risk of bias because of high risk of selection bias in one study, high risk of performance bias in eight studies, high risk of attrition bias in two studies, high risk of reporting bias in four studies, and high risk of other biases in three studies. ^bDowngraded by one level for imprecision because 95% CI was compatible with benefit and harm. ^cDowngraded by one level for risk of bias because of high risk performance bias in three studies and high risk of attrition bias in one study. ^dDowngraded by one level for risk of bias because of high risk of performance bias in three studies and high risk of attrition bias in one study. ^eDowngraded by one level for risk of bias because of high risk of performance bias in one study. ^fDowngraded by one level for risk of bias because of high risk of selection bias in one study, high risk of performance bias in two studies, high risk of attrition bias in one study, and high risk of other biases in one study.

Summary of findings 2. H2 receptor antagonists compared with placebo or no prophylaxis for preventing upper gastrointestinal bleeding in people admitted to intensive care units

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Summary of findings 3. Proton pump inhibitors compared with placebo or no prophylaxis for preventing upper gastrointestinal bleeding in people admitted to intensive care units

Proton pump inhibitors compared with placebo or no prophylaxis for preventing upper gastrointestinal bleeding in people admitted to intensive care units
Patient or population: people admitted to intensive care units Setting: ICU Intervention: proton pump inhibitors Comparison: placebo or no prophylaxis
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with placebo or no prophylaxis	Risk with proton pump inhibitors
Clinically important upper GI bleeding Follow‐up: not reported	Study population		RR 0.63 (0.18 to 2.22)	237 (3 RCTs)	⊕⊕⊝⊝ LOW^a,b
	49 per 1000	31 per 1000 (9 to 108)
Nosocomial pneumonia Follow‐up: not reported	Study population		RR 1.24 (0.77 to 1.98)	227 (2 RCTs)	⊕⊕⊝⊝ LOW^a,c
	188 per 1000	233 per 1000 (145 to 372)
All‐cause mortality in ICU Follow‐up: not reported	Study population		RR 1.09 (0.60 to 1.99)	258 (3 RCTs)	⊕⊕⊝⊝ LOW^a,c
	134 per 1000	146 per 1000 (80 to 266)
Duration of ICU stay Follow‐up: not reported	Mean duration of ICU stay ranged from 8.6 to 11.1 days	MD 0.03 days lower (1.63 days lower to 1.58 days higher)	‐	227 (2 RCTs)	⊕⊕⊝⊝ LOW^a,c
Number of participants requiring blood transfusion	Not reported
Serious adverse events	Not reported
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; GI: gastrointestinal; ICU: intensive care unit; MD: mean difference; RCT: randomised controlled trial; RR: risk ratio.
GRADE Working Group grades of evidence. High certainty: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect. Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.
^aDowngraded by one level for imprecision because 95% CI was compatible with benefit and harm. ^bDowngraded by one level for risk of bias because of high risk of performance bias in one study and high risk of attrition bias in one study. ^cDowngraded by one level for risk of bias because of high risk of performance bias in one study.

Summary of findings 3. Proton pump inhibitors compared with placebo or no prophylaxis for preventing upper gastrointestinal bleeding in people admitted to intensive care units

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Summary of findings 4. Antacids compared with placebo or no prophylaxis for preventing upper gastrointestinal bleeding in people admitted to intensive care units

Antacids compared with placebo or no prophylaxis for preventing upper gastrointestinal bleeding in people admitted to intensive care units
Patient or population: people admitted to intensive care units Setting: ICU Intervention: antacids Comparison: placebo or no prophylaxis
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with placebo or no prophylaxis	Risk with antacids
Clinically important upper GI bleeding Follow‐up: not reported	Study population		RR 0.49 (0.25 to 0.99)	774 (8 RCTs)	⊕⊕⊝⊝ LOW^a,b
	170 per 1000	83 per 1000 (43 to 168)
Nosocomial pneumonia	Not reported
All‐cause mortality in ICU Follow‐up: not reported	Study population		RR 1.01 (0.53 to 1.96)	300 (2 RCTs)	⊕⊕⊝⊝ LOW^c,d
	161 per 1000	163 per 1000 (85 to 316)
Duration of ICU stay	Not reported
Number of participants requiring blood transfusions Follow‐up: not reported	Study population		RR 0.94 (0.30 to 2.96)	226 (2 RCTs)	⊕⊕⊝⊝ LOW^c,e
	45 per 1000	43 per 1000 (14 to 135)
Serious adverse events	Not reported
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; GI: gastrointestinal; ICU: intensive care unit; RCT: randomised controlled trial; RR: risk ratio.
GRADE Working Group grades of evidence. High certainty: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect. Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.
^aDowngraded by one level for inconsistency because of moderate heterogeneity; I² = 56%. ^bDowngraded by one level for risk of bias because of high risk of performance bias in five studies, high risk of detection bias in one study, high risk of reporting bias in two studies, and high risk of other biases in one study. ^cDowngraded by one level for imprecision because 95% CI was compatible with benefit and harm. ^dDowngraded by one level for risk of bias because of high risk of performance bias in two studies. ^eDowngraded by one level for risk of bias because of high risk of performance bias in one study.

Summary of findings 4. Antacids compared with placebo or no prophylaxis for preventing upper gastrointestinal bleeding in people admitted to intensive care units

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Summary of findings 5. Sucralfate compared with placebo or no prophylaxis for preventing upper gastrointestinal bleeding in people admitted to intensive care units

Sucralfate compared with placebo or no prophylaxis for preventing upper gastrointestinal bleeding in people admitted to intensive care units
Patient or population: people admitted to intensive care units Setting: ICU Intervention: sucralfate Comparison: placebo or no prophylaxis
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with placebo or no prophylaxis	Risk with sucralfate
Clinically important upper GI bleeding Follow‐up: 15 days^†	Study population		RR 0.53 (0.32 to 0.88)	598 (7 RCTs)	⊕⊕⊕⊝ MODERATE^a
	108 per 1000	57 per 1000 (35 to 95)
Nosocomial pneumonia Follow‐up: not reported	Study population		RR 1.33 (0.86 to 2.04)	450 (4 RCTs)	⊕⊕⊝⊝ LOW^b,c
	122 per 1000	163 per 1000 (105 to 249)
All‐cause mortality in ICU Follow‐up: 15 days^†	Study population		RR 0.97 (0.66 to 1.43)	500 (5 RCTs)	⊕⊕⊝⊝ LOW^b,d
	165 per 1000	160 per 1000 (109 to 236)
Duration of ICU stay Follow‐up: not reported	Mean duration of ICU stay ranged from 8.6 to 11.1 days	MD 0.02 days lower (1.70 days lower to 1.65 days higher)	‐	224 (2 RCTs)	⊕⊕⊝⊝ LOW^b,e
Number of participants requiring blood transfusion Follow‐up: not reported	Study population		RR 0.60 (0.15 to 2.44)	200 (1 RCT)	⊕⊕⊝⊝ LOW^b,e
	50 per 1000	30 per 1000 (8 to 122)
Serious adverse events	Not reported
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). ^†Duration of follow‐up reported in only one study. CI: confidence interval; GI: gastrointestinal; ICU: intensive care unit; MD: mean difference; RCT: randomised controlled trial; RR: risk ratio.
GRADE Working Group grades of evidence. High certainty: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect. Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.
^aDowngraded by one level for risk of bias because of high risk of performance bias in five studies, high risk of reporting bias in one study, and high risk of other biases in one study. ^bDowngraded by one level for imprecision because 95% CI was compatible with benefit and harm. ^cDowngraded by one level for risk of bias because of high risk of performance bias in two studies. ^dDowngraded by one level for risk of bias because of high risk of performance bias in three studies. ^eDowngraded by one level for risk of bias because of high risk of performance bias in one study.

Summary of findings 5. Sucralfate compared with placebo or no prophylaxis for preventing upper gastrointestinal bleeding in people admitted to intensive care units

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Summary of findings 6. H2 receptor antagonists compared with proton pump inhibitors for preventing upper gastrointestinal bleeding in people admitted to intensive care units

H2 receptor antagonists compared with proton pump inhibitors for preventing upper gastrointestinal bleeding in people admitted to intensive care units
Patient or population: people admitted to intensive care units Setting: ICU Intervention: H2 receptor antagonists Comparison: proton pump inhibitors
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with proton pump inhibitors	Risk with H2 receptor antagonists
Clinically important upper GI bleeding Follow‐up: not reported	Study population		RR 2.90 (1.83 to 4.58)	1636 (13 RCTs)	⊕⊕⊝⊝ LOW^a,b
	25 per 1000	73 per 1000 (46 to 115)
Nosocomial pneumonia Follow‐up: 30 days^†	Study population		RR 1.02 (0.77 to 1.35)	1256 (10 RCTs)	⊕⊕⊝⊝ LOW^c,d
	123 per 1000	126 per 1000 (95 to 166)
All‐cause mortality in ICU Follow‐up: 30 days^†	Study population		RR 0.96 (0.78 to 1.19)	1564 (12 RCTs)	⊕⊕⊝⊝ LOW^c,e
	158 per 1000	152 per 1000 (124 to 189)
Duration of ICU stay Follow‐up: not reported	Mean duration of ICU stay ranged from 7.7 to 23.6 days	MD 0.14 days higher (1.14 days lower to 1.41 days higher)	‐	482 (5 RCTs)	⊕⊕⊝⊝ LOW^c,f
Number of participants requiring blood transfusion Follow‐up: not reported	Study population		RR 1.98 (0.75 to 5.21)	575 (3 RCTs)	⊕⊕⊕⊝ MODERATE^c
	17 per 1000	35 per 1000 (13 to 91)
Serious adverse events	Not reported
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). ^†Duration of follow‐up reported in only one study. CI: confidence interval; GI: gastrointestinal; ICU: intensive care unit; MD: mean difference; RCT: randomised controlled trial; RR: risk ratio.
GRADE Working Group grades of evidence. High certainty: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect. Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.
^aDowngraded by one level for inconsistency because of substantial heterogeneity; I² = 59%. ^bDowngraded by one level for risk of bias because of high risk of selection bias in one study, high risk of performance bias in five studies, high risk of detection bias in two studies, and high risk of other biases in one study. ^cDowngraded by one level for imprecision because 95% CI was compatible with benefit and harm. ^dDowngraded by one level for risk of bias because of high risk of performance bias in four studies, high risk of detection bias in two studies, and high risk of other biases in one study. ^eDowngraded by one level for risk of bias because of high risk of performance bias in five studies, high risk of attrition bias in one study, and high risk of other biases in one study. ^fDowngraded by one level for risk of bias because of high risk of performance bias in three studies, high risk of attrition bias in one study, and high risk of other biases in one study.

Summary of findings 6. H2 receptor antagonists compared with proton pump inhibitors for preventing upper gastrointestinal bleeding in people admitted to intensive care units

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Summary of findings 7. H2 receptor antagonists compared with antacids for preventing upper gastrointestinal bleeding in people admitted to intensive care units

H2 receptor antagonists compared with antacids for preventing upper gastrointestinal bleeding in people admitted to intensive care units
Patient or population: people admitted to intensive care units Setting: ICU Intervention: H2 receptor antagonists Comparison: antacids
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with antacids	Risk with H2 receptor antagonists
Clinically important upper GI bleeding Follow‐up: 25 days^†	Study population		RR 0.96 (0.67 to 1.36)	1700 (16 RCTs)	⊕⊕⊝⊝ LOW^a,b
	86 per 1000	82 per 1000 (57 to 117)
Nosocomial pneumonia Follow‐up: 25 days^‡	Study population		RR 1.05 (0.81 to 1.36)	581 (4 RCTs)	⊕⊕⊝⊝ LOW^a,c
	280 per 1000	294 per 1000 (227 to 381)
All‐cause mortality in ICU Follow‐up: 25 days^§	Study population		RR 1.01 (0.66 to 1.55)	1321 (11 RCTs)	⊕⊝⊝⊝ VERY LOW^a,d,e
	163 per 1000	165 per 1000 (108 to 253)
Duration of ICU stay	Not reported
Number of participants requiring blood transfusion Follow‐up: not reported	Study population		RR 2.49 (1.35 to 4.62)	744 (6 RCTs)	⊕⊕⊕⊝ MODERATE^f
	30 per 1000	75 per 1000 (41 to 139)
Serious adverse events	Not reported
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). ^†Duration of follow‐up reported in two studies. ^‡Duration of follow‐up reported in one study. ^§Duration of follow‐up reported in three studies. CI: confidence interval; GI: gastrointestinal; ICU: intensive care unit; RCT: randomised controlled trial; RR: risk ratio.
GRADE Working Group grades of evidence. High certainty: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect. Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.
^aDowngraded by one level for imprecision because 95% CI was compatible with benefit and harm. ^bDowngraded by one level for risk of bias because of high risk of selection bias in two studies, high risk of performance bias in 12 studies, high risk of detection bias in two studies, and high risk of reporting bias in two studies. ^cDowngraded by one level for risk of bias because of high risk of selection bias in one study, high risk of performance bias in four studies, high risk of detection bias in one study, and high risk of reporting bias in one study. ^dDowngraded by one level for inconsistency because of moderate heterogeneity; I² = 53%. ^eDowngraded by one level for risk of bias because of high risk of selection bias in two studies, high risk of performance bias in nine studies, and high risk of reporting bias in one study. ^fDowngraded by one level for risk of bias because of high risk of selection bias in one study and high risk of performance bias in four studies.

Summary of findings 7. H2 receptor antagonists compared with antacids for preventing upper gastrointestinal bleeding in people admitted to intensive care units

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Summary of findings 8. H2 receptor antagonists compared with sucralfate for preventing upper gastrointestinal bleeding in people admitted to intensive care units

H2 receptor antagonists compared with sucralfate for preventing upper gastrointestinal bleeding in people admitted to intensive care units
Patient or population: people admitted to intensive care units Setting: ICU Intervention: H2 receptor antagonists Comparison: sucralfate
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with sucralfate	Risk with H2 receptor antagonists
Clinically important upper GI bleeding Follow‐up: 15 days^†	Study population		RR 1.10 (0.87 to 1.41)	3316 (24 RCTs)	⊕⊕⊝⊝ LOW^a,b
	66 per 1000	73 per 1000 (58 to 93)
Nosocomial pneumonia Follow‐up: 25 days^‡	Study population		RR 1.22 (1.07 to 1.40)	3041 (17 RCTs)	⊕⊕⊕⊝ MODERATE^c
	189 per 1000	230 per 1000 (202 to 264)
All‐cause mortality in ICU Follow‐up: 25 days^§	Study population		RR 1.09 (0.95 to 1.24)	3178 (21 RCTs)	⊕⊕⊝⊝ LOW^a,d
	204 per 1000	222 per 1000 (194 to 253)
Duration of ICU stay Follow‐up: 2 weeks	Mean duration of ICU stay ranged from 7.9 to 13.7 days	MD 0.01 days higher (1.92 days lower to 1.95 days higher)	‐	1791 (6 RCTs)	⊕⊝⊝⊝ VERY LOW^a,e,f
Number of participants requiring blood transfusion Follow‐up: until death or discharge^ǁ	Study population		RR 1.25 (0.70 to 2.23)	1095 (9 RCTs)	⊕⊕⊝⊝ LOW^a,g
	35 per 1000	43 per 1000 (24 to 77)
Serious adverse events	Not reported
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). ^†Duration of follow‐up reported in five studies. ^‡Duration of follow‐up reported in three studies. ^§Duration of follow‐up reported in six studies. ^ǁDuration of follow‐up reported in one study. CI: confidence interval; GI: gastrointestinal; ICU: intensive care unit; MD: mean difference; RCT: randomised controlled trial; RR: risk ratio.
GRADE Working Group grades of evidence. High certainty: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect. Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.
^aDowngraded by one level for imprecision because 95% CI was compatible with benefit and harm. ^bDowngraded by one level for risk of bias because of high risk of selection bias in one study, high risk of performance bias in 20 studies, high risk of detection bias in two studies, high risk of attrition bias in two studies, high risk of reporting bias in four studies, and high risk of other biases in two studies. ^cDowngraded by one level for risk of bias because of high risk of selection bias in two studies, high risk of performance bias in 12 studies, high risk of detection bias in one study, high risk of attrition bias in one study, and high risk of reporting bias in two studies. ^dDowngraded by one level for risk of bias because of high risk of selection bias in two studies, high risk of performance bias in 16 studies, high risk of detection bias in one study, high risk of attrition bias in two studies, high risk of reporting bias in three studies, and high risk of other biases in one study. ^eDowngraded by one level for inconsistency because of considerable heterogeneity; I² = 82%. ^fDowngraded by one level for risk of bias because of high risk of performance bias in four studies and high risk of attrition bias in one study. ^gDowngraded by one level for risk of bias because of high risk of performance bias in eight studies, high risk of attrition bias in one study, high risk of reporting bias in one study, and high risk of other biases in one study.

Summary of findings 8. H2 receptor antagonists compared with sucralfate for preventing upper gastrointestinal bleeding in people admitted to intensive care units

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Summary of findings 9. Antacids compared with sucralfate for preventing upper gastrointestinal bleeding in people admitted to intensive care units

Antacids compared with sucralfate for preventing upper gastrointestinal bleeding in people admitted to intensive care units
Patient or population: people admitted to intensive care units Setting: ICU Intervention: antacids Comparison: sucralfate
Outcomes	*Anticipated absolute effects (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with sucralfate	Risk with antacids
Clinically important upper GI bleeding Follow‐up: 21 days^†	Study population		RR 1.00 (0.72 to 1.39)	1772 (16 RCTs)	⊕⊕⊝⊝ LOW^a,b
	66 per 1000	66 per 1000 (47 to 91)
Nosocomial pneumonia Follow‐up: 25 days^‡	Study population		RR 1.04 (0.84 to 1.30)	996 (7 RCTs)	⊕⊕⊝⊝ LOW^a,c
	232 per 1000	242 per 1000 (195 to 302)
All‐cause mortality in ICU Follow‐up: 25 days^†	Study population		RR 1.15 (0.93 to 1.40)	1249 (11 RCTs)	⊕⊕⊝⊝ LOW^a,d
	206 per 1000	237 per 1000 (192 to 289)
Duration of ICU stay Follow‐up: not reported	Mean duration of ICU stay ranged from 10.4 to 16.8 days	MD 2.5 days lower (6.61 days lower to 1.61 days higher)	‐	227 (2 RCTs)	⊕⊕⊝⊝ LOW^a,e
Number of participants requiring blood transfusion Follow‐up: until discharge or onset of GI bleeding^§	Study population		RR 0.73 (0.40 to 1.34)	667 (6 RCTs)	⊕⊕⊝⊝ LOW^a,f
	52 per 1000	38 per 1000 (21 to 69)
Serious adverse events	Not reported
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). ^†Duration of follow‐up reported in four studies. ^‡Duration of follow‐up reported in two studies. ^§Duration of follow‐up reported in one study. CI: confidence interval; GI: gastrointestinal; ICU: intensive care unit; MD: mean difference; RCT: randomised controlled trial; RR: risk ratio.
GRADE Working Group grades of evidence. High certainty: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect. Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.
^aDowngraded by one level for imprecision because 95% CI was compatible with benefit and harm. ^bDowngraded by one level for risk of bias because of high risk of selection bias in three studies, high risk of performance bias in 12 studies, high risk of detection bias in one study, high risk of attrition bias in one study, high risk of reporting bias in two studies, and high risk of other biases in two studies. ^cDowngraded by one level for risk of bias because of high risk of performance bias in four studies, high risk of detection bias in one study, high risk of reporting bias in one study, and high risk of other biases in one study. ^dDowngraded by one level for risk of bias because of high risk of selection bias in three studies, high risk of performance bias in eight studies, high risk of attrition bias in one study, high risk of reporting bias in one study, and high risk of other biases in one study. ^eDowngraded by one level for risk of bias because of high risk of attrition bias in one study. ^fDowngraded by one level for risk of bias because of high risk of selection bias in one study, high risk of performance bias in six studies, and high risk of other biases in one study.

Summary of findings 9. Antacids compared with sucralfate for preventing upper gastrointestinal bleeding in people admitted to intensive care units

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Comparison 1. Interventions versus placebo or no prophylaxis

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinically important upper GI bleeding Show forest plot	30	3132	Risk Ratio (M‐H, Fixed, 95% CI)	0.47 [0.39, 0.57]

1.1 H2 receptor antagonists vs placebo or no prophylaxis	24	1844	Risk Ratio (M‐H, Fixed, 95% CI)	0.46 [0.37, 0.59]
1.2 Proton pump inhibitors vs placebo or no prophylaxis	3	159	Risk Ratio (M‐H, Fixed, 95% CI)	0.57 [0.13, 2.59]
1.3 Prostagladin analogues vs placebo or no prophylaxis	1	58	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.22, 4.55]
1.4 Anticholinergics vs placebo or no prophylaxis	2	103	Risk Ratio (M‐H, Fixed, 95% CI)	0.87 [0.30, 2.49]
1.5 Antacids vs placebo or no prophylaxis	7	515	Risk Ratio (M‐H, Fixed, 95% CI)	0.39 [0.23, 0.63]
1.6 Sucralfate vs placebo or no prophylaxis	7	453	Risk Ratio (M‐H, Fixed, 95% CI)	0.47 [0.25, 0.87]
2 Nosocomial pneumonia Show forest plot	9	1331	Risk Ratio (M‐H, Fixed, 95% CI)	1.15 [0.90, 1.48]

2.1 H2 receptor antagonists vs placebo or no prophylaxis	8	788	Risk Ratio (M‐H, Fixed, 95% CI)	1.06 [0.77, 1.46]
2.2 Proton pump inhibitors vs placebo or no prophylaxis	2	149	Risk Ratio (M‐H, Fixed, 95% CI)	1.13 [0.59, 2.17]
2.3 Anticholinergics vs placebo or no prophylaxis	1	72	Risk Ratio (M‐H, Fixed, 95% CI)	1.06 [0.43, 2.59]
2.4 Sucralfate vs placebo or no prophylaxis	4	322	Risk Ratio (M‐H, Fixed, 95% CI)	1.59 [0.84, 3.01]
3 All‐cause mortality in ICU Show forest plot	19	2159	Risk Ratio (M‐H, Fixed, 95% CI)	1.10 [0.90, 1.34]

3.1 H2 receptor antagonists vs placebo or no prophylaxis	14	1209	Risk Ratio (M‐H, Fixed, 95% CI)	1.16 [0.89, 1.53]
3.2 Proton pump inhibitors vs placebo or no prophylaxis	3	180	Risk Ratio (M‐H, Fixed, 95% CI)	1.05 [0.46, 2.38]
3.3 Prostagladin analogues vs placebo or no prophylaxis	1	58	Risk Ratio (M‐H, Fixed, 95% CI)	1.14 [0.48, 2.74]
3.4 Anticholinergics vs placebo or no prophylaxis	2	103	Risk Ratio (M‐H, Fixed, 95% CI)	1.22 [0.59, 2.56]
3.5 Antacids vs placebo or no prophylaxis	2	250	Risk Ratio (M‐H, Fixed, 95% CI)	1.02 [0.58, 1.79]
3.6 Sucralfate vs placebo or no prophylaxis	5	359	Risk Ratio (M‐H, Fixed, 95% CI)	0.93 [0.58, 1.51]
4 All‐cause mortality in hospital Show forest plot	5	857	Risk Ratio (M‐H, Fixed, 95% CI)	1.15 [0.85, 1.55]

4.1 H2 receptor antagonists vs placebo or no prophylaxis	4	387	Risk Ratio (M‐H, Fixed, 95% CI)	1.14 [0.71, 1.83]
4.2 Proton pump inhibitors vs placebo or no prophylaxis	1	100	Risk Ratio (M‐H, Fixed, 95% CI)	1.17 [0.42, 3.22]
4.3 Antacids vs placebo or no prophylaxis	1	126	Risk Ratio (M‐H, Fixed, 95% CI)	1.44 [0.79, 2.64]
4.4 Sucralfate vs placebo or no prophylaxis	2	244	Risk Ratio (M‐H, Fixed, 95% CI)	0.94 [0.53, 1.68]
5 Duration of ICU stay Show forest plot	2	447	Mean Difference (IV, Fixed, 95% CI)	0.24 [‐1.13, 1.61]

5.1 H2 receptor antagonists vs placebo or no prophylaxis	2	152	Mean Difference (IV, Fixed, 95% CI)	0.73 [‐1.64, 3.09]
5.2 Proton pump inhibitors vs placebo or no prophylaxis	2	149	Mean Difference (IV, Fixed, 95% CI)	0.01 [‐2.33, 2.35]
5.3 Sucralfate vs placebo or no prophylaxis	2	146	Mean Difference (IV, Fixed, 95% CI)	‐0.01 [‐2.40, 2.38]
6 Duration of intubation Show forest plot	2	447	Mean Difference (IV, Fixed, 95% CI)	0.87 [‐0.58, 2.31]

6.1 H2 receptor antagonists vs placebo or no prophylaxis	2	152	Mean Difference (IV, Fixed, 95% CI)	0.78 [‐1.72, 3.29]
6.2 Proton pump inhibitors vs placebo or no prophylaxis	2	149	Mean Difference (IV, Fixed, 95% CI)	0.36 [‐2.18, 2.90]
6.3 Sucralfate vs placebo or no prophylaxis	2	146	Mean Difference (IV, Fixed, 95% CI)	1.43 [‐1.04, 3.89]
7 Number of participants requiring blood transfusions Show forest plot	9	981	Risk Ratio (M‐H, Fixed, 95% CI)	0.63 [0.41, 0.97]

7.1 H2 receptor antagonists vs placebo or no prophylaxis	7	605	Risk Ratio (M‐H, Fixed, 95% CI)	0.57 [0.35, 0.94]
7.2 Antacids vs placebo or no prophylaxis	2	226	Risk Ratio (M‐H, Fixed, 95% CI)	0.94 [0.30, 2.96]
7.3 Sucralfate vs placebo or no prophylaxis	1	150	Risk Ratio (M‐H, Fixed, 95% CI)	0.75 [0.13, 4.34]
8 Units of blood transfused Show forest plot	2	309	Mean Difference (IV, Random, 95% CI)	0.09 [‐0.99, 1.17]

8.1 H2 receptor antagonists vs placebo or no prophylaxis	2	159	Mean Difference (IV, Random, 95% CI)	‐1.73 [‐6.37, 2.90]
8.2 Sucralfate vs placebo or no prophylaxis	1	150	Mean Difference (IV, Random, 95% CI)	0.80 [0.25, 1.35]

Comparison 1. Interventions versus placebo or no prophylaxis

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Comparison 2. H2 receptor antagonists versus placebo or no prophylaxis

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinically important upper GI bleeding Show forest plot	24	2149	Risk Ratio (M‐H, Random, 95% CI)	0.50 [0.36, 0.70]

1.1 Cimetidine vs placebo	10	772	Risk Ratio (M‐H, Random, 95% CI)	0.53 [0.28, 1.02]
1.2 Famotidine vs placebo	1	146	Risk Ratio (M‐H, Random, 95% CI)	2.11 [0.20, 22.79]
1.3 Ranitidine vs placebo	5	446	Risk Ratio (M‐H, Random, 95% CI)	0.36 [0.17, 0.77]
1.4 Cimetidine vs no prophylaxis	3	516	Risk Ratio (M‐H, Random, 95% CI)	0.59 [0.23, 1.48]
1.5 Famotidine vs no prophylaxis	1	50	Risk Ratio (M‐H, Random, 95% CI)	0.3 [0.09, 0.96]
1.6 Ranitidine vs no prophylaxis	4	219	Risk Ratio (M‐H, Random, 95% CI)	0.51 [0.26, 1.00]
2 Nosocomial pneumonia Show forest plot	8	945	Risk Ratio (M‐H, Fixed, 95% CI)	1.12 [0.85, 1.48]

2.1 Cimetidine vs placebo	2	204	Risk Ratio (M‐H, Fixed, 95% CI)	0.34 [0.06, 2.00]
2.2 Famotidine vs placebo	1	146	Risk Ratio (M‐H, Fixed, 95% CI)	1.48 [0.49, 4.45]
2.3 Ranitidine vs placebo	2	277	Risk Ratio (M‐H, Fixed, 95% CI)	0.79 [0.47, 1.31]
2.4 Cimetidine vs no prophylaxis	1	200	Risk Ratio (M‐H, Fixed, 95% CI)	2.17 [0.86, 5.47]
2.5 Ranitidine vs no prophylaxis	2	118	Risk Ratio (M‐H, Fixed, 95% CI)	1.33 [0.93, 1.90]
3 All‐cause mortality in ICU Show forest plot	14	1428	Risk Ratio (M‐H, Fixed, 95% CI)	1.12 [0.88, 1.42]

3.1 Cimetidine vs placebo	4	478	Risk Ratio (M‐H, Fixed, 95% CI)	1.05 [0.66, 1.68]
3.2 Famotidine vs placebo	1	146	Risk Ratio (M‐H, Fixed, 95% CI)	1.32 [0.55, 3.16]
3.3 Ranitidine vs placebo	2	148	Risk Ratio (M‐H, Fixed, 95% CI)	0.69 [0.31, 1.54]
3.4 Cimetidine vs no prophylaxis	2	400	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.61, 1.63]
3.5 Famotidine vs no prophylaxis	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	1.25 [0.59, 2.64]
3.6 Ranitidine vs no prophylaxis	4	206	Risk Ratio (M‐H, Fixed, 95% CI)	1.58 [0.97, 2.58]
4 All‐cause mortality in hospital Show forest plot	4	487	Risk Ratio (M‐H, Fixed, 95% CI)	1.16 [0.79, 1.70]

4.1 Famotidine vs placebo	1	146	Risk Ratio (M‐H, Fixed, 95% CI)	0.89 [0.43, 1.86]
4.2 Ranitidine vs placebo	1	101	Risk Ratio (M‐H, Fixed, 95% CI)	0.35 [0.01, 8.47]
4.3 Cimetidine vs no prophylaxis	1	200	Risk Ratio (M‐H, Fixed, 95% CI)	1.47 [0.88, 2.46]
4.4 Ranitidine vs no prophylaxis	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	0.92 [0.33, 2.53]
5 Duration of ICU stay Show forest plot	2	230	Mean Difference (IV, Fixed, 95% CI)	0.73 [‐0.92, 2.38]

5.1 Famotidine vs placebo	1	146	Mean Difference (IV, Fixed, 95% CI)	1.5 [‐1.93, 4.93]
5.2 Ranitidine vs no prophylaxis	1	84	Mean Difference (IV, Fixed, 95% CI)	0.5 [‐1.38, 2.38]
6 Duration of intubation Show forest plot	2	230	Mean Difference (IV, Fixed, 95% CI)	0.79 [‐0.95, 2.54]

6.1 Famotidine vs placebo	1	146	Mean Difference (IV, Fixed, 95% CI)	1.20 [‐1.86, 4.26]
6.2 Ranitidine vs no prophylaxis	1	84	Mean Difference (IV, Fixed, 95% CI)	0.60 [‐1.52, 2.72]
7 Number of participants requiring blood transfusions Show forest plot	7	655	Risk Ratio (M‐H, Fixed, 95% CI)	0.58 [0.36, 0.95]

7.1 Cimetidine vs placebo	3	107	Risk Ratio (M‐H, Fixed, 95% CI)	0.39 [0.19, 0.79]
7.2 Ranitidine vs placebo	2	148	Risk Ratio (M‐H, Fixed, 95% CI)	1.05 [0.24, 4.60]
7.3 Cimetidine vs no prophylaxis	2	400	Risk Ratio (M‐H, Fixed, 95% CI)	0.77 [0.35, 1.71]
8 Units of blood transfused Show forest plot	2	209	Mean Difference (IV, Fixed, 95% CI)	0.33 [‐0.04, 0.70]

8.1 Cimetidine vs placebo	1	9	Mean Difference (IV, Fixed, 95% CI)	‐4.35 [‐7.35, ‐1.35]
8.2 Cimetidine vs no prophylaxis	1	200	Mean Difference (IV, Fixed, 95% CI)	0.40 [0.03, 0.77]
9 Adverse events of interventions Show forest plot	8		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

9.1 Diarrhoea	2	225	Risk Ratio (M‐H, Fixed, 95% CI)	1.30 [0.57, 2.96]
9.2 Thrombocytopenia	1	200	Risk Ratio (M‐H, Fixed, 95% CI)	3.0 [0.12, 72.77]
9.3 Hypophosphatemia	1	25	Risk Ratio (M‐H, Fixed, 95% CI)	3.75 [0.17, 84.02]
9.4 Mental confusion	5	657	Risk Ratio (M‐H, Fixed, 95% CI)	2.01 [1.10, 3.65]
9.5 Nausea and vomiting	2	287	Risk Ratio (M‐H, Fixed, 95% CI)	0.46 [0.09, 2.35]
9.6 Increased creatinine levels	1	200	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.64, 1.69]
9.7 Erythema	1	70	Risk Ratio (M‐H, Fixed, 95% CI)	3.0 [0.13, 71.22]
9.8 Pancreatitis	1	39	Risk Ratio (M‐H, Fixed, 95% CI)	0.29 [0.01, 6.66]
9.9 Chest infection	1	101	Risk Ratio (M‐H, Fixed, 95% CI)	1.74 [0.92, 3.30]
9.10 Delirium	1	39	Risk Ratio (M‐H, Fixed, 95% CI)	2.59 [0.11, 59.93]
9.11 Hallucinations	1	39	Risk Ratio (M‐H, Fixed, 95% CI)	2.59 [0.11, 59.93]
9.12 Severe bleeding	1	101	Risk Ratio (M‐H, Fixed, 95% CI)	0.35 [0.01, 8.47]

Comparison 2. H2 receptor antagonists versus placebo or no prophylaxis

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Comparison 3. Proton pump inhibitors versus placebo or no prophylaxis

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinically important upper GI bleeding Show forest plot	3	237	Risk Ratio (M‐H, Fixed, 95% CI)	0.63 [0.18, 2.22]

1.1 Omeprazole vs placebo	1	147	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.07, 16.34]
1.2 Omeprazole vs no prophylaxis	1	80	Risk Ratio (M‐H, Fixed, 95% CI)	0.74 [0.13, 4.18]
1.3 Pantoprazole vs placebo	1	10	Risk Ratio (M‐H, Fixed, 95% CI)	0.28 [0.02, 4.66]
2 Nosocomial pneumonia Show forest plot	2	227	Risk Ratio (M‐H, Fixed, 95% CI)	1.24 [0.77, 1.98]

2.1 Omeprazole vs placebo	1	147	Risk Ratio (M‐H, Fixed, 95% CI)	1.67 [0.57, 4.86]
2.2 Omeprazole vs no prophylaxis	1	80	Risk Ratio (M‐H, Fixed, 95% CI)	1.11 [0.66, 1.84]
3 All‐cause mortality in ICU Show forest plot	3	258	Risk Ratio (M‐H, Fixed, 95% CI)	1.09 [0.60, 1.99]

3.1 Omeprazole vs placebo	2	178	Risk Ratio (M‐H, Fixed, 95% CI)	1.20 [0.51, 2.83]
3.2 Omeprazole vs no prophylaxis	1	80	Risk Ratio (M‐H, Fixed, 95% CI)	0.98 [0.42, 2.29]
4 All‐cause mortality in hospital Show forest plot	1	150	Risk Ratio (M‐H, Fixed, 95% CI)	1.08 [0.54, 2.13]

4.1 Omeprazole vs placebo	1	150	Risk Ratio (M‐H, Fixed, 95% CI)	1.08 [0.54, 2.13]
5 Duration of ICU stay Show forest plot	2	227	Mean Difference (IV, Fixed, 95% CI)	‐0.03 [‐1.63, 1.58]

5.1 Omeprazole vs placebo	1	147	Mean Difference (IV, Fixed, 95% CI)	‐0.90 [‐3.96, 2.16]
5.2 Omeprazole vs no prophylaxis	1	80	Mean Difference (IV, Fixed, 95% CI)	0.30 [‐1.58, 2.18]
6 Duration of intubation Show forest plot	2	227	Mean Difference (IV, Fixed, 95% CI)	0.36 [‐1.43, 2.15]

6.1 Omeprazole vs placebo	1	147	Mean Difference (IV, Fixed, 95% CI)	0.5 [‐2.72, 3.72]
6.2 Omeprazole vs no prophylaxis	1	80	Mean Difference (IV, Fixed, 95% CI)	0.30 [‐1.85, 2.45]

Comparison 3. Proton pump inhibitors versus placebo or no prophylaxis

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Comparison 4. Proton pump inhibitors + sucralfate versus no prophylaxis

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinically important upper GI bleeding Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 4. Proton pump inhibitors + sucralfate versus no prophylaxis

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Comparison 5. Prostaglandin analogues versus placebo or no prophylaxis

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinically important upper GI bleeding Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

1.1 Prostaglandin analogues vs placebo	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2 All‐cause mortality in ICU Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 5. Prostaglandin analogues versus placebo or no prophylaxis

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Comparison 6. Anticholinergics versus placebo or no prophylaxis

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinically important upper GI bleeding Show forest plot	2	131	Risk Ratio (M‐H, Fixed, 95% CI)	0.95 [0.36, 2.51]

1.1 Pirenzepine vs placebo	1	101	Risk Ratio (M‐H, Fixed, 95% CI)	1.94 [0.34, 11.13]
1.2 Pirenzepin + ranitidine vs placebo + ranitidine	1	30	Risk Ratio (M‐H, Fixed, 95% CI)	0.6 [0.17, 2.07]
2 Nosocomial pneumonia Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2.1 Pirenzepine vs placebo	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3 All‐cause mortality in ICU Show forest plot	2	131	Risk Ratio (M‐H, Fixed, 95% CI)	1.23 [0.66, 2.30]

3.1 Pirenzepine vs placebo	1	101	Risk Ratio (M‐H, Fixed, 95% CI)	1.30 [0.65, 2.60]
3.2 Pirenzepine + ranitidine vs placebo + ranitidine	1	30	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.24, 4.18]

Comparison 6. Anticholinergics versus placebo or no prophylaxis

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Comparison 7. Antacids versus placebo or no prophylaxis

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinically important upper GI bleeding Show forest plot	8	774	Risk Ratio (M‐H, Random, 95% CI)	0.49 [0.25, 0.99]

1.1 Antacids vs placebo	2	145	Risk Ratio (M‐H, Random, 95% CI)	2.04 [0.72, 5.79]
1.2 Antacids vs no prophylaxis	6	629	Risk Ratio (M‐H, Random, 95% CI)	0.35 [0.20, 0.60]
2 All‐cause mortality in ICU Show forest plot	2	300	Risk Ratio (M‐H, Random, 95% CI)	1.01 [0.53, 1.96]

2.1 Antacids vs no prophylaxis	2	300	Risk Ratio (M‐H, Random, 95% CI)	1.01 [0.53, 1.96]
3 All‐cause mortality in hospital Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3.1 Antacids vs no prophylaxis	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4 Number of participants requiring blood transfusions Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

4.1 Antacids vs no prophylaxis	2	226	Risk Ratio (M‐H, Fixed, 95% CI)	0.94 [0.30, 2.96]
5 Adverse events of interventions Show forest plot	4		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

5.1 Diarrhoea	4	395	Risk Ratio (M‐H, Fixed, 95% CI)	3.56 [1.83, 6.94]
5.2 Hypomagnesaemia	1	25	Risk Ratio (M‐H, Fixed, 95% CI)	3.75 [0.17, 84.02]
5.3 Hypophosphataemia	2	225	Risk Ratio (M‐H, Fixed, 95% CI)	5.48 [1.81, 16.61]
5.4 Hypermagnesaemia	1	100	Risk Ratio (M‐H, Fixed, 95% CI)	6.73 [0.36, 127.02]
5.5 Nausea and vomiting	3	370	Risk Ratio (M‐H, Fixed, 95% CI)	2.39 [0.86, 6.64]
5.6 Mental confusion	1	200	Risk Ratio (M‐H, Fixed, 95% CI)	1.27 [0.61, 2.67]
5.7 Creatinine increase	1	200	Risk Ratio (M‐H, Fixed, 95% CI)	1.17 [0.73, 1.87]

Comparison 7. Antacids versus placebo or no prophylaxis

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Comparison 8. Sucralfate versus placebo or no prophylaxis

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinically important upper GI bleeding Show forest plot	7	598	Risk Ratio (M‐H, Fixed, 95% CI)	0.53 [0.32, 0.88]

1.1 Sucralfate vs placebo	2	170	Risk Ratio (M‐H, Fixed, 95% CI)	1.40 [0.30, 6.62]
1.2 Sucralfate vs no prophylaxis	5	428	Risk Ratio (M‐H, Fixed, 95% CI)	0.46 [0.26, 0.80]
2 Nosocomial pneumonia Show forest plot	4	450	Risk Ratio (M‐H, Fixed, 95% CI)	1.33 [0.86, 2.04]

2.1 Sucralfate vs placebo	2	170	Risk Ratio (M‐H, Fixed, 95% CI)	1.43 [0.49, 4.16]
2.2 Sucralfate vs no prophylaxis	2	280	Risk Ratio (M‐H, Fixed, 95% CI)	1.30 [0.82, 2.07]
3 All‐cause mortality in ICU Show forest plot	5	500	Risk Ratio (M‐H, Fixed, 95% CI)	0.97 [0.66, 1.43]

3.1 Sucralfate vs placebo	2	170	Risk Ratio (M‐H, Fixed, 95% CI)	0.92 [0.48, 1.80]
3.2 Sucralfate vs no prophylaxis	3	330	Risk Ratio (M‐H, Fixed, 95% CI)	0.99 [0.62, 1.60]
4 All‐cause mortality in hospital Show forest plot	2	344	Risk Ratio (M‐H, Fixed, 95% CI)	0.97 [0.62, 1.52]

4.1 Sucralfate vs placebo	1	144	Risk Ratio (M‐H, Fixed, 95% CI)	1.09 [0.54, 2.18]
4.2 Sucralfate vs no prophylaxis	1	200	Risk Ratio (M‐H, Fixed, 95% CI)	0.89 [0.49, 1.62]
5 Duration of ICU stay Show forest plot	2	224	Mean Difference (IV, Fixed, 95% CI)	‐0.02 [‐1.70, 1.65]

5.1 Sucralfate vs placebo	1	144	Mean Difference (IV, Fixed, 95% CI)	‐0.70 [‐4.07, 2.67]
5.2 Sucralfate vs no prophylaxis	1	80	Mean Difference (IV, Fixed, 95% CI)	0.20 [‐1.73, 2.13]
6 Duration of intubation Show forest plot	2	224	Mean Difference (IV, Fixed, 95% CI)	1.42 [‐0.27, 3.10]

6.1 Sucralfate vs placebo	1	144	Mean Difference (IV, Fixed, 95% CI)	0.80 [‐2.20, 3.80]
6.2 Sucralfate vs no prophylaxis	1	80	Mean Difference (IV, Fixed, 95% CI)	1.70 [‐0.34, 3.74]
7 Number of participants requiring blood transfusions Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

7.1 Sucralfate vs no prophylaxis	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
8 Units of blood transfused Show forest plot	1	200	Mean Difference (IV, Fixed, 95% CI)	0.8 [0.32, 1.28]

8.1 Sucralfate vs no prophylaxis	1	200	Mean Difference (IV, Fixed, 95% CI)	0.8 [0.32, 1.28]
9 Adverse events of interventions Show forest plot	1	70	Risk Ratio (M‐H, Fixed, 95% CI)	9.0 [0.50, 161.13]

9.1 Nausea / Vomiting	1	70	Risk Ratio (M‐H, Fixed, 95% CI)	9.0 [0.50, 161.13]

Comparison 8. Sucralfate versus placebo or no prophylaxis

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Comparison 9. H2 receptor antagonists versus proton pump inhibitors

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinically important upper GI bleeding Show forest plot	13	1636	Risk Ratio (M‐H, Fixed, 95% CI)	2.90 [1.83, 4.58]

1.1 Cimetidine vs omeprazole	1	359	Risk Ratio (M‐H, Fixed, 95% CI)	1.40 [0.55, 3.61]
1.2 Famotidine vs lansoprazole	1	51	Risk Ratio (M‐H, Fixed, 95% CI)	3.63 [0.15, 84.98]
1.3 Famotidine vs omeprazole	1	143	Risk Ratio (M‐H, Fixed, 95% CI)	2.03 [0.19, 21.87]
1.4 Famotidine vs pantoprazole	2	159	Risk Ratio (M‐H, Fixed, 95% CI)	0.73 [0.18, 3.04]
1.5 Famotidine vs esomeprazole	2	371	Risk Ratio (M‐H, Fixed, 95% CI)	7.53 [1.39, 40.85]
1.6 Ranitidine vs omeprazole	5	413	Risk Ratio (M‐H, Fixed, 95% CI)	4.08 [1.99, 8.36]
1.7 Ranitidine vs rabeprazole	1	140	Risk Ratio (M‐H, Fixed, 95% CI)	9.0 [0.49, 164.09]
2 Nosocomial pneumonia Show forest plot	10	1256	Risk Ratio (M‐H, Fixed, 95% CI)	1.02 [0.77, 1.35]

2.1 Cimetidine vs omeprazole	1	359	Risk Ratio (M‐H, Fixed, 95% CI)	0.84 [0.45, 1.54]
2.2 Cimetidine vs pantoprazole	1	202	Risk Ratio (M‐H, Fixed, 95% CI)	0.89 [0.28, 2.91]
2.3 Famotidine vs esomeprazole	1	60	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.07, 15.26]
2.4 Famotidine vs omeprazole	1	143	Risk Ratio (M‐H, Fixed, 95% CI)	0.89 [0.34, 2.32]
2.5 Ranitidine vs omeprazole	5	413	Risk Ratio (M‐H, Fixed, 95% CI)	1.19 [0.80, 1.75]
2.6 H2 receptor antagonists (not defined) vs proton pump inhibitors (not defined)	1	79	Risk Ratio (M‐H, Fixed, 95% CI)	1.03 [0.47, 2.26]
3 All‐cause mortality in ICU Show forest plot	12	1564	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.78, 1.19]

3.1 Cimetidine vs omeprazole	1	359	Risk Ratio (M‐H, Fixed, 95% CI)	0.76 [0.45, 1.30]
3.2 Cimetidine vs pantoprazole	1	202	Risk Ratio (M‐H, Fixed, 95% CI)	0.80 [0.25, 2.55]
3.3 Famotidine vs omeprazole	1	143	Risk Ratio (M‐H, Fixed, 95% CI)	1.13 [0.49, 2.61]
3.4 Ranitidine vs omeprazole	5	387	Risk Ratio (M‐H, Fixed, 95% CI)	1.10 [0.86, 1.40]
3.5 Ranitidine vs pantoprazole	3	333	Risk Ratio (M‐H, Fixed, 95% CI)	0.66 [0.31, 1.43]
3.6 Ranitidine vs rabeprazole	1	140	Risk Ratio (M‐H, Fixed, 95% CI)	3.0 [0.12, 72.40]
4 All‐cause mortality in hospital Show forest plot	2	454	Risk Ratio (M‐H, Fixed, 95% CI)	0.72 [0.37, 1.43]

4.1 Famotidine vs esomeprazole	1	311	Risk Ratio (M‐H, Fixed, 95% CI)	0.37 [0.04, 3.49]
4.2 Famotidine vs omeprazole	1	143	Risk Ratio (M‐H, Fixed, 95% CI)	0.80 [0.39, 1.63]
5 Duration of ICU stay Show forest plot	5	482	Mean Difference (IV, Fixed, 95% CI)	0.14 [‐1.14, 1.41]

5.1 Famotidine vs esomeprazole	1	60	Mean Difference (IV, Fixed, 95% CI)	‐0.30 [‐6.51, 5.91]
5.2 Famotidine vs omeprazole	1	143	Mean Difference (IV, Fixed, 95% CI)	2.40 [‐0.44, 5.24]
5.3 Ranitidine vs omeprazole	3	279	Mean Difference (IV, Fixed, 95% CI)	‐0.44 [‐1.90, 1.02]
6 Duration of intubation Show forest plot	5	542	Mean Difference (IV, Fixed, 95% CI)	‐0.35 [‐1.48, 0.78]

6.1 Famotidine vs omeprazole	1	143	Mean Difference (IV, Fixed, 95% CI)	0.70 [‐2.24, 3.64]
6.2 Ranitidine vs omeprazole	3	279	Mean Difference (IV, Fixed, 95% CI)	‐0.78 [‐2.24, 0.67]
6.3 Ranitidine vs pantoprazole	1	120	Mean Difference (IV, Fixed, 95% CI)	0.07 [‐2.18, 2.32]
7 Number of participants requiring blood transfusions Show forest plot	3	575	Risk Ratio (M‐H, Fixed, 95% CI)	1.98 [0.75, 5.21]

7.1 Cimetidine vs omeprazole	1	359	Risk Ratio (M‐H, Fixed, 95% CI)	0.98 [0.29, 3.34]
7.2 Ranitidine vs omeprazole	1	76	Risk Ratio (M‐H, Fixed, 95% CI)	5.0 [0.25, 100.80]
7.3 Ranitidine vs rabeprazole	1	140	Risk Ratio (M‐H, Fixed, 95% CI)	9.0 [0.49, 164.09]
8 Adverse events of interventions Show forest plot	5		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

8.1 Pyrexia	1	202	Risk Ratio (M‐H, Fixed, 95% CI)	0.93 [0.05, 19.03]
8.2 Thrombocytopaenia	2	253	Risk Ratio (M‐H, Fixed, 95% CI)	3.64 [0.65, 20.46]
8.3 Neuroleptic malignant syndrome	1	202	Risk Ratio (M‐H, Fixed, 95% CI)	1.56 [0.06, 37.42]
8.4 Cholestatic jaundice	1	202	Risk Ratio (M‐H, Fixed, 95% CI)	1.56 [0.06, 37.42]
8.5 Abnormal liver function test	1	202	Risk Ratio (M‐H, Fixed, 95% CI)	1.56 [0.06, 37.42]
8.6 Pruritus	1	202	Risk Ratio (M‐H, Fixed, 95% CI)	1.56 [0.06, 37.42]
8.7 Phlebitis	1	202	Risk Ratio (M‐H, Fixed, 95% CI)	1.56 [0.06, 37.42]
8.8 Major CV events	1	311	Risk Ratio (M‐H, Fixed, 95% CI)	0.79 [0.26, 2.43]
8.9 Abdominal distension and vomiting	1	90	Risk Ratio (M‐H, Fixed, 95% CI)	1.15 [0.62, 2.14]
8.10 Hypomagnesaemia	1	129	Risk Ratio (M‐H, Fixed, 95% CI)	0.43 [0.16, 1.13]
8.11 Nausea and vomiting	1	129	Risk Ratio (M‐H, Fixed, 95% CI)	0.48 [0.13, 1.77]
8.12 Diarrhoea	1	129	Risk Ratio (M‐H, Fixed, 95% CI)	1.11 [0.16, 7.67]

Comparison 9. H2 receptor antagonists versus proton pump inhibitors

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Comparison 10. H2 receptor antagonists versus antacids

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinically important upper GI bleeding Show forest plot	16	1700	Risk Ratio (M‐H, Random, 95% CI)	0.96 [0.67, 1.36]

1.1 Cimetidine vs antacids	11	1155	Risk Ratio (M‐H, Random, 95% CI)	1.07 [0.65, 1.78]
1.2 Cimetidine + pirenzepine vs antacid + pirenzepine	1	66	Risk Ratio (M‐H, Random, 95% CI)	1.0 [0.15, 6.68]
1.3 Ranitidine vs antacids	4	479	Risk Ratio (M‐H, Random, 95% CI)	0.72 [0.42, 1.23]
2 Nosocomial pneumonia Show forest plot	4	581	Risk Ratio (M‐H, Fixed, 95% CI)	1.05 [0.81, 1.36]

2.1 Cimetidine vs antacids	2	136	Risk Ratio (M‐H, Fixed, 95% CI)	1.24 [0.70, 2.19]
2.2 Ranitidine vs antacids	2	445	Risk Ratio (M‐H, Fixed, 95% CI)	1.00 [0.75, 1.34]
3 All‐cause mortality in ICU Show forest plot	11	1321	Risk Ratio (M‐H, Random, 95% CI)	1.01 [0.66, 1.55]

3.1 Cimetidine vs antacids	8	885	Risk Ratio (M‐H, Random, 95% CI)	1.05 [0.69, 1.59]
3.2 Cimetidine + pirenzepine vs antacid + pirenzepine	1	66	Risk Ratio (M‐H, Random, 95% CI)	1.25 [0.37, 4.25]
3.3 Ranitidine vs antacids	2	370	Risk Ratio (M‐H, Random, 95% CI)	1.13 [0.14, 8.97]
4 All‐cause mortality in hospital Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

4.1 Ranitidine vs antacids	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
5 Duration of intubation Show forest plot	3	121	Mean Difference (IV, Random, 95% CI)	‐0.81 [‐3.85, 2.23]

5.1 Cimetidine vs antacids	3	121	Mean Difference (IV, Random, 95% CI)	‐0.81 [‐3.85, 2.23]
6 Number of participants requiring blood transfusions Show forest plot	6	744	Risk Ratio (M‐H, Fixed, 95% CI)	2.49 [1.35, 4.62]

6.1 Cimetidine vs antacids	5	583	Risk Ratio (M‐H, Fixed, 95% CI)	2.47 [1.32, 4.63]
6.2 Ranitidine vs antacids	1	161	Risk Ratio (M‐H, Fixed, 95% CI)	3.04 [0.13, 73.46]
7 Adverse events of interventions Show forest plot	12		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

7.1 Diarrhoea	6	777	Risk Ratio (M‐H, Fixed, 95% CI)	0.23 [0.13, 0.43]
7.2 Thrombocytopaenia	4	452	Risk Ratio (M‐H, Fixed, 95% CI)	1.40 [0.93, 2.09]
7.3 Nausea and vomiting	4	380	Risk Ratio (M‐H, Fixed, 95% CI)	0.46 [0.19, 1.10]
7.4 Hypophosphataemia	2	108	Risk Ratio (M‐H, Fixed, 95% CI)	0.24 [0.04, 1.30]
7.5 Hypomagnesaemia	1	22	Risk Ratio (M‐H, Fixed, 95% CI)	0.33 [0.02, 7.39]
7.6 Increase in creatinine	2	286	Risk Ratio (M‐H, Fixed, 95% CI)	0.85 [0.56, 1.28]
7.7 Mental confusion	4	476	Risk Ratio (M‐H, Fixed, 95% CI)	1.26 [0.77, 2.07]
7.8 Hypermagnesaemia	2	115	Risk Ratio (M‐H, Fixed, 95% CI)	0.58 [0.17, 2.03]
7.9 Rash/Erythema	2	231	Risk Ratio (M‐H, Fixed, 95% CI)	3.02 [0.32, 28.53]
7.10 Alkalosis	1	75	Risk Ratio (M‐H, Fixed, 95% CI)	0.32 [0.01, 7.73]
7.11 Dryness of mouth	1	67	Risk Ratio (M‐H, Fixed, 95% CI)	5.15 [0.26, 103.33]
7.12 Leucopaenia	1	161	Risk Ratio (M‐H, Fixed, 95% CI)	3.04 [0.13, 73.46]

Comparison 10. H2 receptor antagonists versus antacids

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Comparison 11. H2 receptor antagonists versus sucralfate

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinically important upper GI bleeding Show forest plot	24	3316	Risk Ratio (M‐H, Fixed, 95% CI)	1.10 [0.87, 1.41]

1.1 Cimetidine vs sucralfate	7	873	Risk Ratio (M‐H, Fixed, 95% CI)	1.37 [0.87, 2.14]
1.2 Famotidine vs sucralfate	2	190	Risk Ratio (M‐H, Fixed, 95% CI)	0.62 [0.21, 1.78]
1.3 Ranitidine vs sucralfate	14	2186	Risk Ratio (M‐H, Fixed, 95% CI)	1.03 [0.76, 1.39]
1.4 Cimetidine + pirenzepine vs sucralfate + pirenzepine	1	67	Risk Ratio (M‐H, Fixed, 95% CI)	5.15 [0.26, 103.33]
2 Nosocomial pneumonia Show forest plot	17	3041	Risk Ratio (M‐H, Fixed, 95% CI)	1.22 [1.07, 1.40]

2.1 Cimetidine vs sucralfate	5	758	Risk Ratio (M‐H, Fixed, 95% CI)	1.13 [0.87, 1.47]
2.2 Famotidine vs sucralfate	1	140	Risk Ratio (M‐H, Fixed, 95% CI)	1.13 [0.40, 3.20]
2.3 Ranitidine vs sucralfate	11	2143	Risk Ratio (M‐H, Fixed, 95% CI)	1.26 [1.07, 1.48]
3 All‐cause mortality in ICU Show forest plot	21	3178	Risk Ratio (M‐H, Fixed, 95% CI)	1.09 [0.95, 1.24]

3.1 Cimetidine vs sucralfate	6	814	Risk Ratio (M‐H, Fixed, 95% CI)	1.18 [0.91, 1.54]
3.2 Famotidine vs sucralfate	2	190	Risk Ratio (M‐H, Fixed, 95% CI)	1.23 [0.69, 2.19]
3.3 Ranitidine vs sucralfate	12	2107	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.88, 1.22]
3.4 Cimetidine + pirenzepine vs sucralfate + pirenzepine	1	67	Risk Ratio (M‐H, Fixed, 95% CI)	1.29 [0.38, 4.38]
4 All‐cause mortality in hospital Show forest plot	4	717	Risk Ratio (M‐H, Fixed, 95% CI)	1.14 [0.86, 1.50]

4.1 Cimetidine vs sucralfate	2	413	Risk Ratio (M‐H, Fixed, 95% CI)	1.28 [0.86, 1.92]
4.2 Ranitidine vs sucralfate	1	164	Risk Ratio (M‐H, Fixed, 95% CI)	1.11 [0.71, 1.74]
4.3 Famotidine vs sucralfate	1	140	Risk Ratio (M‐H, Fixed, 95% CI)	0.82 [0.40, 1.71]
5 Duration of intubation Show forest plot	10	1751	Mean Difference (IV, Random, 95% CI)	0.22 [‐1.55, 2.00]

5.1 Cimetidine vs sucralfate	2	97	Mean Difference (IV, Random, 95% CI)	0.58 [‐1.71, 2.87]
5.2 Famotidine vs sucralfate	1	140	Mean Difference (IV, Random, 95% CI)	0.40 [‐2.30, 3.10]
5.3 Ranitidine vs sucralfate	7	1514	Mean Difference (IV, Random, 95% CI)	0.15 [‐2.12, 2.43]
6 Duration of ICU stay Show forest plot	6	1791	Mean Difference (IV, Random, 95% CI)	0.01 [‐1.92, 1.95]

6.1 Cimetidine vs sucralfate	1	213	Mean Difference (IV, Random, 95% CI)	0.0 [‐3.05, 3.05]
6.2 Famotidine vs sucralfate	1	140	Mean Difference (IV, Random, 95% CI)	2.20 [‐0.96, 5.36]
6.3 Ranitidine vs sucralfate	4	1438	Mean Difference (IV, Random, 95% CI)	‐0.43 [‐2.70, 1.84]
7 Number of participants requiring blood transfusion Show forest plot	9	1095	Risk Ratio (M‐H, Fixed, 95% CI)	1.25 [0.70, 2.23]

7.1 Cimetidine vs sucralfate	5	732	Risk Ratio (M‐H, Fixed, 95% CI)	1.00 [0.47, 2.16]
7.2 Ranitidine vs sucralfate	4	363	Risk Ratio (M‐H, Fixed, 95% CI)	1.77 [0.71, 4.39]
8 Units of blood transfused Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

8.1 Cimetidine vs sucralfate	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
9 Adverse events of interventions Show forest plot	6		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

9.1 Thrombocytopaenia	2	240	Risk Ratio (M‐H, Fixed, 95% CI)	4.72 [0.56, 39.47]
9.2 Nausea and vomiting	2	137	Risk Ratio (M‐H, Fixed, 95% CI)	0.07 [0.01, 0.54]
9.3 Hypermagnesaemia	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	2.71 [0.31, 23.93]
9.4 Rash/Erythema	2	233	Risk Ratio (M‐H, Fixed, 95% CI)	3.06 [0.32, 28.87]
9.5 Confusion	3	382	Risk Ratio (M‐H, Fixed, 95% CI)	4.48 [0.77, 26.00]
9.6 Neutropaenia	1	114	Risk Ratio (M‐H, Fixed, 95% CI)	5.18 [0.25, 105.47]
9.7 Dryness of mouth	1	67	Risk Ratio (M‐H, Fixed, 95% CI)	5.15 [0.26, 103.33]
9.8 Leucopaenia	1	163	Risk Ratio (M‐H, Fixed, 95% CI)	3.11 [0.13, 75.26]

Comparison 11. H2 receptor antagonists versus sucralfate

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Comparison 12. H2 receptor antagonists versus anticholinergics

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinically important upper GI bleeding Show forest plot	3	556	Risk Ratio (M‐H, Fixed, 95% CI)	1.37 [0.58, 3.26]

1.1 Cimetidine vs pirenzepine	1	55	Risk Ratio (M‐H, Fixed, 95% CI)	1.45 [0.26, 7.99]
1.2 Ranitidine vs pirenzepine	2	501	Risk Ratio (M‐H, Fixed, 95% CI)	1.35 [0.50, 3.67]
2 Nosocomial pneumonia Show forest plot	3	544	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.50, 1.84]

2.1 Famotidine vs pirenzepine	1	43	Risk Ratio (M‐H, Fixed, 95% CI)	0.32 [0.01, 7.42]
2.2 Ranitidine vs pirenzepine	2	501	Risk Ratio (M‐H, Fixed, 95% CI)	1.03 [0.53, 2.01]
3 All‐cause mortality in ICU Show forest plot	2	501	Risk Ratio (M‐H, Random, 95% CI)	0.89 [0.21, 3.87]

3.1 Ranitidine vs pirenzepine	2	501	Risk Ratio (M‐H, Random, 95% CI)	0.89 [0.21, 3.87]
4 Number of participants requiring blood transfusion Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

4.1 Ranitidine vs pirenzepine	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
5 Adverse events of interventions Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

5.1 Tachycardia	1	55	Risk Ratio (M‐H, Fixed, 95% CI)	0.11 [0.01, 1.90]
5.2 High temperature	1	43	Risk Ratio (M‐H, Fixed, 95% CI)	0.53 [0.21, 1.32]

Comparison 12. H2 receptor antagonists versus anticholinergics

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Comparison 13. H2 receptor antagonists versus prostaglandin analogues

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinically important upper GI bleeding Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

1.1 Cimetidine vs misoprostol	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2 All‐cause mortality in ICU Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2.1 Cimetidine vs misoprostol	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 13. H2 receptor antagonists versus prostaglandin analogues

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Comparison 14. H2 receptor antagonists versus teprenone

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinically important upper GI bleeding Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

1.1 Ranitidine vs teprenone	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2 All‐cause mortality in ICU Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2.1 Ranitidine vs teprenone	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3 Number of participants requiring blood transfusion Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3.1 Ranitidine vs teprenone	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 14. H2 receptor antagonists versus teprenone

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Comparison 15. H2 receptor antagonist + antacids versus sucralfate

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinically important upper GI bleeding Show forest plot	2	230	Risk Ratio (M‐H, Fixed, 95% CI)	0.24 [0.06, 0.95]

1.1 Cimetidine + antacids vs sucralfate	1	100	Risk Ratio (M‐H, Fixed, 95% CI)	0.14 [0.01, 2.70]
1.2 Cimetidine or ranitidine + antacids vs sucralfate	1	130	Risk Ratio (M‐H, Fixed, 95% CI)	0.29 [0.06, 1.41]
2 Nosocomial pneumonia Show forest plot	3	281	Risk Ratio (M‐H, Random, 95% CI)	1.09 [0.51, 2.32]

2.1 Cimetidine + antacids vs sucralfate	1	100	Risk Ratio (M‐H, Random, 95% CI)	0.53 [0.26, 1.07]
2.2 Ranitidine + antacids vs sucralfate	1	51	Risk Ratio (M‐H, Random, 95% CI)	1.27 [0.64, 2.53]
2.3 Cimetidine or ranitidine + antacids vs sucralfate	1	130	Risk Ratio (M‐H, Random, 95% CI)	2.02 [0.89, 4.58]
3 All‐cause mortality in ICU Show forest plot	2	230	Risk Ratio (M‐H, Fixed, 95% CI)	1.38 [0.92, 2.05]

3.1 Cimetidine + antacids vs sucralfate	1	100	Risk Ratio (M‐H, Fixed, 95% CI)	1.0 [0.46, 2.19]
3.2 Cimetidine or ranitidine + antacids vs sucralfate	1	130	Risk Ratio (M‐H, Fixed, 95% CI)	1.57 [0.99, 2.50]
4 Duration of ICU stay Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

5 Duration of intubation Show forest plot	2	230	Mean Difference (IV, Random, 95% CI)	‐1.24 [‐13.82, 11.33]

5.1 Cimetidine + antacids vs sucralfate	1	100	Mean Difference (IV, Random, 95% CI)	‐8.8 [‐20.11, 2.51]
5.2 Cimetidine or ranitidine + antacids vs sucralfate	1	130	Mean Difference (IV, Random, 95% CI)	4.20 [‐0.54, 8.94]
6 Number of participants requiring blood transfusion Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 15. H2 receptor antagonist + antacids versus sucralfate

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Comparison 16. Proton pump inhibitors versus teprenone

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinically important upper GI bleeding Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

1.1 Proton pump inhibitors vs teprenone	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2 All‐cause mortality in ICU Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2.1 Proton pump inhibitors vs teprenone	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3 Number of participants requiring blood transfusion Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3.1 Proton pump inhibitors vs teprenone	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 16. Proton pump inhibitors versus teprenone

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Comparison 17. Proton pump inhibitor plus naloxone versus naloxone

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinically important upper GI bleeding Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2 All‐cause mortality in hospital Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3 Adverse events ‐ gastrointestinal discomfort Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 17. Proton pump inhibitor plus naloxone versus naloxone

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Comparison 18. Proton pump inhibitors versus other medication (not defined)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinically important upper GI bleeding Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2 Nosocomial pneumonia Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3 All‐cause mortality in hospital Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 18. Proton pump inhibitors versus other medication (not defined)

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Comparison 19. Antacids versus sucralfate

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinically important upper GI bleeding Show forest plot	16	1772	Risk Ratio (M‐H, Fixed, 95% CI)	1.00 [0.72, 1.39]

1.1 Antacids vs sucralfate	15	1705	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.69, 1.35]
1.2 Antacid + pirenzepine vs sucralfate + pirenzepine	1	67	Risk Ratio (M‐H, Fixed, 95% CI)	5.15 [0.26, 103.33]
2 Nosocomial pneumonia Show forest plot	7		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

2.1 Antacids vs sucralfate	7	996	Risk Ratio (M‐H, Fixed, 95% CI)	1.04 [0.84, 1.30]
3 All‐cause mortality in ICU Show forest plot	11	1249	Risk Ratio (M‐H, Fixed, 95% CI)	1.15 [0.93, 1.40]

3.1 Antacid vs sucralfate	10	1182	Risk Ratio (M‐H, Fixed, 95% CI)	1.15 [0.94, 1.41]
3.2 Antacid + pirenzepine vs sucralfate + pirenzepine	1	67	Risk Ratio (M‐H, Fixed, 95% CI)	1.03 [0.28, 3.78]
4 All‐cause mortality in hospital Show forest plot	3	450	Risk Ratio (M‐H, Random, 95% CI)	0.98 [0.69, 1.39]

5 Duration of ICU stay Show forest plot	2		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

5.1 Antacids vs sucralfate	2	227	Mean Difference (IV, Fixed, 95% CI)	‐2.50 [‐6.61, 1.61]
6 Duration of intubation Show forest plot	4		Std. Mean Difference (IV, Fixed, 95% CI)	Subtotals only

6.1 Antacids vs sucralfate	4	281	Std. Mean Difference (IV, Fixed, 95% CI)	‐0.18 [‐0.41, 0.06]
7 Number of participants requiring blood transfusion Show forest plot	6	667	Risk Ratio (M‐H, Fixed, 95% CI)	0.73 [0.40, 1.34]

8 Adverse events of interventions Show forest plot	9		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

8.1 Diarrhoea	6	599	Risk Ratio (M‐H, Fixed, 95% CI)	12.40 [3.88, 39.64]
8.2 Hypermagnesaemia	4	317	Risk Ratio (M‐H, Fixed, 95% CI)	4.72 [1.24, 17.95]
8.3 Nausea and vomiting	3	223	Risk Ratio (M‐H, Fixed, 95% CI)	0.63 [0.28, 1.41]
8.4 Thrombocytopaenia	1	38	Risk Ratio (M‐H, Fixed, 95% CI)	5.0 [0.26, 97.70]
8.5 Severe alkalosis	1	100	Risk Ratio (M‐H, Fixed, 95% CI)	3.0 [0.13, 71.92]
8.6 Allergic reactions	1	100	Risk Ratio (M‐H, Fixed, 95% CI)	0.2 [0.01, 4.06]

Comparison 19. Antacids versus sucralfate

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Comparison 20. Antacids versus prostaglandin analogues

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinically important upper GI bleeding Show forest plot	2	329	Risk Ratio (M‐H, Fixed, 95% CI)	0.33 [0.12, 0.91]

2 All‐cause mortality in ICU Show forest plot	2	417	Risk Ratio (M‐H, Fixed, 95% CI)	0.84 [0.42, 1.67]

3 Adverse events of interventions Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

3.1 Diarrhoea	1	368	Risk Ratio (M‐H, Fixed, 95% CI)	0.92 [0.64, 1.33]
3.2 Elevated serum bicarbonate	1	338	Risk Ratio (M‐H, Fixed, 95% CI)	2.21 [1.27, 3.87]
3.3 Phospate levels < 2.5 mg/dL	1	276	Risk Ratio (M‐H, Fixed, 95% CI)	1.66 [1.01, 2.73]

Comparison 20. Antacids versus prostaglandin analogues

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Comparison 21. Antacids versus bioflavonoids

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinically important upper GI bleeding Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2 Number of participants requiring blood transfusion Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 21. Antacids versus bioflavonoids

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Comparison 22. Sucralfate versus proton pump inhibitors

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinically important upper GI bleeding Show forest plot	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.1 Sucralfate vs omeprazole	3	287	Risk Ratio (M‐H, Fixed, 95% CI)	2.58 [0.77, 8.63]
2 Nosocomial pneumonia Show forest plot	4	424	Risk Ratio (M‐H, Random, 95% CI)	0.67 [0.41, 1.09]

2.1 Sucralfate vs omeprazole	3	287	Risk Ratio (M‐H, Random, 95% CI)	0.88 [0.57, 1.36]
2.2 Sucralfate vs pantoprazole	1	137	Risk Ratio (M‐H, Random, 95% CI)	0.39 [0.20, 0.75]
3 All‐cause mortality in ICU Show forest plot	4	424	Risk Ratio (M‐H, Fixed, 95% CI)	1.07 [0.68, 1.68]

3.1 Sucralfate vs omeprazole	3	287	Risk Ratio (M‐H, Fixed, 95% CI)	1.26 [0.75, 2.11]
3.2 Sucralfate vs pantoprazole	1	137	Risk Ratio (M‐H, Fixed, 95% CI)	0.65 [0.25, 1.68]
4 All‐cause mortality in hospital Show forest plot	2	278	Risk Ratio (M‐H, Fixed, 95% CI)	0.79 [0.46, 1.37]

4.1 Sucralfate vs omeprazole	1	141	Risk Ratio (M‐H, Fixed, 95% CI)	0.97 [0.49, 1.91]
4.2 Sucralfate vs pantoprazole	1	137	Risk Ratio (M‐H, Fixed, 95% CI)	0.56 [0.21, 1.45]
5 Duration of ICU stay Show forest plot	2		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

5.1 Sucralfate vs omeprazole	2	217	Mean Difference (IV, Fixed, 95% CI)	0.01 [‐1.68, 1.70]
6 Duration of intubation Show forest plot	3	354	Mean Difference (IV, Fixed, 95% CI)	‐0.16 [‐1.61, 1.28]

6.1 Sucralfate vs omeprazole	2	217	Mean Difference (IV, Fixed, 95% CI)	0.02 [‐1.56, 1.60]
6.2 Sucralfate vs pantoprazole	1	137	Mean Difference (IV, Fixed, 95% CI)	‐1.10 [‐4.69, 2.49]
7 Number of participants requiring blood transfusion Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

7.1 Sucralfate vs omeprazole	1	70	Risk Ratio (M‐H, Fixed, 95% CI)	5.91 [0.29, 118.78]
8 Adverse events of interventions Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

8.1 Fever	1	137	Risk Ratio (M‐H, Random, 95% CI)	0.81 [0.70, 0.94]
8.2 Leucocytosis	1	137	Risk Ratio (M‐H, Random, 95% CI)	0.66 [0.55, 0.80]
8.3 Sudden purulent sputum	1	137	Risk Ratio (M‐H, Random, 95% CI)	0.85 [0.38, 1.86]
8.4 Sudden cough or aggravation of coughing	1	137	Risk Ratio (M‐H, Random, 95% CI)	0.23 [0.07, 0.79]
8.5 Dyspnoea	1	137	Risk Ratio (M‐H, Random, 95% CI)	0.68 [0.54, 0.87]
8.6 Rales or bronchial sounds	1	137	Risk Ratio (M‐H, Random, 95% CI)	0.31 [0.19, 0.51]
8.7 Aggravation of blood gas exchange	1	137	Risk Ratio (M‐H, Random, 95% CI)	0.76 [0.49, 1.18]
8.8 Change in sputum quality	1	137	Risk Ratio (M‐H, Random, 95% CI)	0.23 [0.13, 0.40]

Comparison 22. Sucralfate versus proton pump inhibitors

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Comparison 23. Sucralfate versus bioflavonoids

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinically important upper GI bleeding Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2 Number of participants requiring blood transfusion Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 23. Sucralfate versus bioflavonoids

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Comparison 24. Total parenteral nutrition (TPN) versus any other intervention + TPN

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinically important upper GI bleeding Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.1 TPN vs ranitidine + TPN	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	0.8 [0.05, 12.14]
1.2 TPN vs sucralfate + TPN	1	49	Risk Ratio (M‐H, Fixed, 95% CI)	0.32 [0.03, 3.26]
2 All‐cause mortality in ICU Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

2.1 TPN vs ranitidine + TPN	1	54	Risk Ratio (M‐H, Fixed, 95% CI)	1.12 [0.41, 3.09]
2.2 TPN vs sucralfate + TPN	1	49	Risk Ratio (M‐H, Fixed, 95% CI)	0.63 [0.26, 1.52]
3 Duration of intubation Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

3.1 TPN vs ranitidine + TPN	1	54	Mean Difference (IV, Fixed, 95% CI)	‐2.0 [‐9.53, 5.53]
3.2 TPN vs sucralfate + TPN	1	49	Mean Difference (IV, Fixed, 95% CI)	3.0 [‐1.50, 7.50]

Comparison 24. Total parenteral nutrition (TPN) versus any other intervention + TPN

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Comparison 25. Bowel stimulation versus no prophylaxis

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinically important upper GI bleeding Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 25. Bowel stimulation versus no prophylaxis

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Comparison 26. Nasojejunal nutrition versus nasogastric nutrition

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Clinically important upper GI bleeding Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2 Nosocomial pneumonia Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3 All‐cause mortality in hospital Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

4 Adverse events of interventions Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 26. Nasojejunal nutrition versus nasogastric nutrition

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Comparison 27. Enteral plus parenteral nutrition versus other nutrition regimens

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Nosocomial pneumonia Show forest plot	1	120	Risk Ratio (M‐H, Fixed, 95% CI)	0.79 [0.44, 1.40]

1.1 Enteral plus parenteral nutrition vs enteral nutrition	1	60	Risk Ratio (M‐H, Fixed, 95% CI)	0.6 [0.29, 1.25]
1.2 Enteral plus parenteral nutrition vs parenteral nutrition	1	60	Risk Ratio (M‐H, Fixed, 95% CI)	1.25 [0.47, 3.33]
2 All‐cause mortality in hospital Show forest plot	1	120	Odds Ratio (M‐H, Fixed, 95% CI)	0.20 [0.06, 0.60]

2.1 Enteral plus parenteral nutrition vs enteral nutrition	1	60	Odds Ratio (M‐H, Fixed, 95% CI)	0.26 [0.05, 1.30]
2.2 Enteral plus parenteral nutrition vs parenteral nutrition	1	60	Odds Ratio (M‐H, Fixed, 95% CI)	0.15 [0.03, 0.74]
3 Duration of ICU stay Show forest plot	1	120	Mean Difference (IV, Fixed, 95% CI)	‐5.98 [‐8.81, ‐3.16]

3.1 Enteral plus parenteral nutrition vs enteral nutrition	1	60	Mean Difference (IV, Fixed, 95% CI)	‐3.81 [‐7.59, ‐0.03]
3.2 Enteral plus parenteral nutrition vs parenteral nutrition	1	60	Mean Difference (IV, Fixed, 95% CI)	‐8.72 [‐12.97, ‐4.47]
4 Duration of intubation Show forest plot	1	120	Mean Difference (IV, Fixed, 95% CI)	‐7.37 [‐9.29, ‐5.45]

4.1 Enteral plus parenteral nutrition vs enteral nutrition	1	60	Mean Difference (IV, Fixed, 95% CI)	‐4.17 [‐6.96, ‐1.38]
4.2 Enteral plus parenteral nutrition vs parenteral nutrition	1	60	Mean Difference (IV, Fixed, 95% CI)	‐10.24 [‐12.88, ‐7.60]
5 Adverse events ‐ stress ulcer Show forest plot	1	120	Risk Ratio (M‐H, Fixed, 95% CI)	0.69 [0.36, 1.33]

5.1 Enteral plus parenteral nutrition vs enteral nutrition	1	60	Risk Ratio (M‐H, Fixed, 95% CI)	1.14 [0.38, 3.45]
5.2 Enteral plus parenteral nutrition vs parenteral nutrition	1	60	Risk Ratio (M‐H, Fixed, 95% CI)	0.53 [0.23, 1.20]
6 Adverse events ‐ diarrhoea Show forest plot	1	120	Odds Ratio (M‐H, Fixed, 95% CI)	0.42 [0.17, 1.02]

6.1 Enteral plus parenteral nutrition vs enteral nutrition	1	60	Odds Ratio (M‐H, Fixed, 95% CI)	0.17 [0.05, 0.59]
6.2 Enteral plus parenteral nutrition vs parenteral nutrition	1	60	Odds Ratio (M‐H, Fixed, 95% CI)	1.42 [0.35, 5.73]
7 Adverse events ‐ pyaemia Show forest plot	1	120	Odds Ratio (M‐H, Fixed, 95% CI)	0.88 [0.37, 2.09]

7.1 Enteral plus parenteral nutrition vs enteral nutrition	1	60	Odds Ratio (M‐H, Fixed, 95% CI)	4.11 [0.87, 19.41]
7.2 Enteral plus parenteral nutrition vs parenteral nutrition	1	60	Odds Ratio (M‐H, Fixed, 95% CI)	0.37 [0.11, 1.21]
8 Adverse events ‐ intracranial infection Show forest plot	1	120	Odds Ratio (M‐H, Fixed, 95% CI)	0.43 [0.15, 1.25]

8.1 Enteral plus parenteral nutrition vs enteral nutrition	1	60	Odds Ratio (M‐H, Fixed, 95% CI)	0.83 [0.19, 3.63]
8.2 Enteral plus parenteral nutrition vs parenteral nutrition	1	60	Odds Ratio (M‐H, Fixed, 95% CI)	0.23 [0.05, 1.15]
9 Adverse events ‐ hypoproteinaemia Show forest plot	1	120	Odds Ratio (M‐H, Fixed, 95% CI)	0.11 [0.04, 0.27]

9.1 Enteral plus parenteral nutrition vs enteral nutrition	1	60	Odds Ratio (M‐H, Fixed, 95% CI)	0.20 [0.06, 0.72]
9.2 Enteral plus parenteral nutrition vs parenteral nutrition	1	60	Odds Ratio (M‐H, Fixed, 95% CI)	0.04 [0.01, 0.19]

Comparison 27. Enteral plus parenteral nutrition versus other nutrition regimens

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Intervenciones para la prevención de la hemorragia digestiva alta en pacientes ingresados a la unidad de cuidados intensivos

Appendices

Appendix 1. Glossary of medical terms

Appendix 2. CENTRAL search strategy

Appendix 3. MEDLINE search strategy

Appendix 4. Embase search strategy

Appendix 5. LILACS search strategy

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Appendices

Appendix 1. Glossary of medical terms

Appendix 2. CENTRAL search strategy

Appendix 3. MEDLINE search strategy

Appendix 4. Embase search strategy

Appendix 5. LILACS search strategy

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