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Meta-Analysis
. 2018 Jun 4;6(6):CD008687.
doi: 10.1002/14651858.CD008687.pub2.

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

Ingrid Toews  1 , Aneesh Thomas George, John V Peter, Richard Kirubakaran, Luís Eduardo S Fontes, Jabez Paul Barnabas Ezekiel, Joerg J Meerpohl
Affiliations
Meta-Analysis

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

Ingrid Toews et al. Cochrane Database Syst Rev. .

Abstract

Background: Upper gastrointestinal (GI) bleeding due to stress ulcers contributes to increased morbidity and mortality in people admitted to intensive care units (ICUs). Stress ulceration refers to GI mucosal injury related to the stress of being critically ill. ICU patients with major bleeding as a result of stress ulceration might have mortality rates approaching 48.5% to 65%. However, the incidence of stress-induced GI bleeding in ICUs has decreased, and not all critically ill patients need prophylaxis. Stress ulcer prophylaxis can result in adverse events such as ventilator-associated pneumonia; therefore, it is necessary to evaluate strategies that safely decrease the incidence of GI bleeding.

Objectives: To assess the effect and risk-benefit profile of interventions for preventing upper GI bleeding in people admitted to ICUs.

Search methods: We searched the following databases up to 23 August 2017, using relevant search terms: MEDLINE; Embase; the Cochrane Central Register of Controlled Trials; Latin American Caribbean Health Sciences Literature; and the Cochrane Upper Gastrointestinal and Pancreatic Disease Group Specialised Register, as published in the Cochrane Library (2017, Issue 8). We searched the reference lists of all included studies and those from relevant systematic reviews and meta-analyses to identify additional studies. We also searched the World Health Organization International Clinical Trials Registry Platform search portal and contacted individual researchers working in this field, as well as organisations and pharmaceutical companies, to identify unpublished and ongoing studies.

Selection criteria: We included randomised controlled trials (RCTs) and quasi-RCTs with participants of any age and gender admitted to ICUs for longer than 48 hours. We excluded studies in which participants were admitted to ICUs primarily for the management of GI bleeding and studies that compared different doses, routes, and regimens of one drug in the same class because we were not interested in intraclass effects of drugs.

Data collection and analysis: We used standard methodological procedures as recommended by Cochrane.

Main results: We identified 2292 unique records.We included 129 records reporting on 121 studies, including 12 ongoing studies and two studies awaiting classification.We judged the overall risk of bias of two studies as low. Selection bias was the most relevant risk of bias domain across the included studies, with 78 studies not clearly reporting the method used for random sequence generation. Reporting bias was the domain with least risk of bias, with 12 studies not reporting all outcomes that researchers intended to investigate.Any intervention versus placebo or no prophylaxisIn comparison with placebo, any intervention seems to have a beneficial effect on the occurrence of upper GI bleeding (risk ratio (RR) 0.47, 95% confidence interval (CI) 0.39 to 0.57; moderate certainty of evidence). The use of any intervention reduced the risk of upper GI bleeding by 10% (95% CI -12.0% to -7%). The effect estimate of any intervention versus placebo or no prophylaxis with respect to the occurrence of nosocomial pneumonia, all-cause mortality in the ICU, duration of ICU stay, duration of intubation (all with low certainty of evidence), the number of participants requiring blood transfusions (moderate certainty of evidence), and the units of blood transfused was consistent with benefits and harms. None of the included studies explicitly reported on serious adverse events.Individual interventions versus placebo or no prophylaxisIn comparison with placebo or no prophylaxis, antacids, H2 receptor antagonists, and sucralfate were effective in preventing upper GI bleeding in ICU patients. Researchers found that with H2 receptor antagonists compared with placebo or no prophylaxis, 11% less developed upper GI bleeding (95% CI -0.16 to -0.06; RR 0.50, 95% CI 0.36 to 0.70; 24 studies; 2149 participants; moderate certainty of evidence). Of ICU patients taking antacids versus placebo or no prophylaxis, 9% less developed upper GI bleeding (95% CI -0.17 to -0.00; RR 0.49, 95% CI 0.25 to 0.99; eight studies; 774 participants; low certainty of evidence). Among ICU patients taking sucralfate versus placebo or no prophylaxis, 5% less had upper GI bleeding (95% CI -0.10 to -0.01; RR 0.53, 95% CI 0.32 to 0.88; seven studies; 598 participants; moderate certainty of evidence). The remaining interventions including proton pump inhibitors did not show a significant effect in preventing upper GI bleeding in ICU patients when compared with placebo or no prophylaxis.Regarding the occurrence of nosocomial pneumonia, the effects of H2 receptor antagonists (RR 1.12, 95% CI 0.85 to 1.48; eight studies; 945 participants; low certainty of evidence) and of sucralfate (RR 1.33, 95% CI 0.86 to 2.04; four studies; 450 participants; low certainty of evidence) were consistent with benefits and harms when compared with placebo or no prophylaxis. None of the studies comparing antacids versus placebo or no prophylaxis provided data regarding nosocomial pneumonia.H2 receptor antagonists versus proton pump inhibitorsH2 receptor antagonists and proton pump inhibitors are most commonly used in practice to prevent upper GI bleeding in ICU patients. Proton pump inhibitors significantly more often prevented upper GI bleeding in ICU patients compared with H2 receptor antagonists (RR 2.90, 95% CI 1.83 to 4.58; 18 studies; 1636 participants; low certainty of evidence). When taking H2 receptor antagonists, 4.8% more patients might experience upper GI bleeding (95% CI 2.1% to 9%). Nosocomial pneumonia occurred in similar proportions of participants taking H2 receptor antagonists and participants taking proton pump inhibitors (RR 1.02, 95% CI 0.77 to 1.35; 10 studies; 1256 participants; low certainty of evidence).

Authors' conclusions: This review shows that antacids, sucralfate, and H2 receptor antagonists might be more effective in preventing upper GI bleeding in ICU patients compared with placebo or no prophylaxis. The effect estimates of any treatment versus no prophylaxis on nosocomial pneumonia were consistent with benefits and harms. Evidence of low certainty suggests that proton pump inhibitors might be more effective than H2 receptor antagonists. Therefore, patient-relevant benefits and especially harms of H2 receptor antagonists compared with proton pump inhibitors need to be assessed by larger, high-quality RCTs to confirm the results of previously conducted, smaller, and older studies.

PubMed Disclaimer

Conflict of interest statement

All review authors declare no conflict academic or financial interests that will influence the conduct, interpretation, or reporting of this review.

Figures

1
1
PRISMA flow chart of included studies.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
4
4
Funnel plot of comparison: 1 Interventions versus placebo or no prophylaxis, outcome: 1.1 Clinically important upper GI bleeding.
5
5
Funnel plot of comparison: 2 H2 receptor antagonists versus placebo or no prophylaxis, outcome: 2.1 Clinically important upper GI bleeding.
6
6
Funnel plot of comparison: 9 H2 receptor antagonists versus proton pump inhibitors, outcome: 9.1 Clinically important upper GI bleeding.
7
7
Funnel plot of comparison: 10 H2 receptor antagonists versus antacids, outcome: 10.1 Clinically important upper GI bleeding.
8
8
Funnel plot of comparison: 11 H2 receptor antagonists versus sucralfate, outcome: 11.1 Clinically important upper GI bleeding.
9
9
Funnel plot of comparison: 19 Antacids versus sucralfate, outcome: 19.1 Clinically important upper GI bleeding.
1.1
1.1. Analysis
Comparison 1 Interventions versus placebo or no prophylaxis, Outcome 1 Clinically important upper GI bleeding.
1.2
1.2. Analysis
Comparison 1 Interventions versus placebo or no prophylaxis, Outcome 2 Nosocomial pneumonia.
1.3
1.3. Analysis
Comparison 1 Interventions versus placebo or no prophylaxis, Outcome 3 All‐cause mortality in ICU.
1.4
1.4. Analysis
Comparison 1 Interventions versus placebo or no prophylaxis, Outcome 4 All‐cause mortality in hospital.
1.5
1.5. Analysis
Comparison 1 Interventions versus placebo or no prophylaxis, Outcome 5 Duration of ICU stay.
1.6
1.6. Analysis
Comparison 1 Interventions versus placebo or no prophylaxis, Outcome 6 Duration of intubation.
1.7
1.7. Analysis
Comparison 1 Interventions versus placebo or no prophylaxis, Outcome 7 Number of participants requiring blood transfusions.
1.8
1.8. Analysis
Comparison 1 Interventions versus placebo or no prophylaxis, Outcome 8 Units of blood transfused.
2.1
2.1. Analysis
Comparison 2 H2 receptor antagonists versus placebo or no prophylaxis, Outcome 1 Clinically important upper GI bleeding.
2.2
2.2. Analysis
Comparison 2 H2 receptor antagonists versus placebo or no prophylaxis, Outcome 2 Nosocomial pneumonia.
2.3
2.3. Analysis
Comparison 2 H2 receptor antagonists versus placebo or no prophylaxis, Outcome 3 All‐cause mortality in ICU.
2.4
2.4. Analysis
Comparison 2 H2 receptor antagonists versus placebo or no prophylaxis, Outcome 4 All‐cause mortality in hospital.
2.5
2.5. Analysis
Comparison 2 H2 receptor antagonists versus placebo or no prophylaxis, Outcome 5 Duration of ICU stay.
2.6
2.6. Analysis
Comparison 2 H2 receptor antagonists versus placebo or no prophylaxis, Outcome 6 Duration of intubation.
2.7
2.7. Analysis
Comparison 2 H2 receptor antagonists versus placebo or no prophylaxis, Outcome 7 Number of participants requiring blood transfusions.
2.8
2.8. Analysis
Comparison 2 H2 receptor antagonists versus placebo or no prophylaxis, Outcome 8 Units of blood transfused.
2.9
2.9. Analysis
Comparison 2 H2 receptor antagonists versus placebo or no prophylaxis, Outcome 9 Adverse events of interventions.
3.1
3.1. Analysis
Comparison 3 Proton pump inhibitors versus placebo or no prophylaxis, Outcome 1 Clinically important upper GI bleeding.
3.2
3.2. Analysis
Comparison 3 Proton pump inhibitors versus placebo or no prophylaxis, Outcome 2 Nosocomial pneumonia.
3.3
3.3. Analysis
Comparison 3 Proton pump inhibitors versus placebo or no prophylaxis, Outcome 3 All‐cause mortality in ICU.
3.4
3.4. Analysis
Comparison 3 Proton pump inhibitors versus placebo or no prophylaxis, Outcome 4 All‐cause mortality in hospital.
3.5
3.5. Analysis
Comparison 3 Proton pump inhibitors versus placebo or no prophylaxis, Outcome 5 Duration of ICU stay.
3.6
3.6. Analysis
Comparison 3 Proton pump inhibitors versus placebo or no prophylaxis, Outcome 6 Duration of intubation.
4.1
4.1. Analysis
Comparison 4 Proton pump inhibitors + sucralfate versus no prophylaxis, Outcome 1 Clinically important upper GI bleeding.
5.1
5.1. Analysis
Comparison 5 Prostaglandin analogues versus placebo or no prophylaxis, Outcome 1 Clinically important upper GI bleeding.
5.2
5.2. Analysis
Comparison 5 Prostaglandin analogues versus placebo or no prophylaxis, Outcome 2 All‐cause mortality in ICU.
6.1
6.1. Analysis
Comparison 6 Anticholinergics versus placebo or no prophylaxis, Outcome 1 Clinically important upper GI bleeding.
6.2
6.2. Analysis
Comparison 6 Anticholinergics versus placebo or no prophylaxis, Outcome 2 Nosocomial pneumonia.
6.3
6.3. Analysis
Comparison 6 Anticholinergics versus placebo or no prophylaxis, Outcome 3 All‐cause mortality in ICU.
7.1
7.1. Analysis
Comparison 7 Antacids versus placebo or no prophylaxis, Outcome 1 Clinically important upper GI bleeding.
7.2
7.2. Analysis
Comparison 7 Antacids versus placebo or no prophylaxis, Outcome 2 All‐cause mortality in ICU.
7.3
7.3. Analysis
Comparison 7 Antacids versus placebo or no prophylaxis, Outcome 3 All‐cause mortality in hospital.
7.4
7.4. Analysis
Comparison 7 Antacids versus placebo or no prophylaxis, Outcome 4 Number of participants requiring blood transfusions.
7.5
7.5. Analysis
Comparison 7 Antacids versus placebo or no prophylaxis, Outcome 5 Adverse events of interventions.
8.1
8.1. Analysis
Comparison 8 Sucralfate versus placebo or no prophylaxis, Outcome 1 Clinically important upper GI bleeding.
8.2
8.2. Analysis
Comparison 8 Sucralfate versus placebo or no prophylaxis, Outcome 2 Nosocomial pneumonia.
8.3
8.3. Analysis
Comparison 8 Sucralfate versus placebo or no prophylaxis, Outcome 3 All‐cause mortality in ICU.
8.4
8.4. Analysis
Comparison 8 Sucralfate versus placebo or no prophylaxis, Outcome 4 All‐cause mortality in hospital.
8.5
8.5. Analysis
Comparison 8 Sucralfate versus placebo or no prophylaxis, Outcome 5 Duration of ICU stay.
8.6
8.6. Analysis
Comparison 8 Sucralfate versus placebo or no prophylaxis, Outcome 6 Duration of intubation.
8.7
8.7. Analysis
Comparison 8 Sucralfate versus placebo or no prophylaxis, Outcome 7 Number of participants requiring blood transfusions.
8.8
8.8. Analysis
Comparison 8 Sucralfate versus placebo or no prophylaxis, Outcome 8 Units of blood transfused.
8.9
8.9. Analysis
Comparison 8 Sucralfate versus placebo or no prophylaxis, Outcome 9 Adverse events of interventions.
9.1
9.1. Analysis
Comparison 9 H2 receptor antagonists versus proton pump inhibitors, Outcome 1 Clinically important upper GI bleeding.
9.2
9.2. Analysis
Comparison 9 H2 receptor antagonists versus proton pump inhibitors, Outcome 2 Nosocomial pneumonia.
9.3
9.3. Analysis
Comparison 9 H2 receptor antagonists versus proton pump inhibitors, Outcome 3 All‐cause mortality in ICU.
9.4
9.4. Analysis
Comparison 9 H2 receptor antagonists versus proton pump inhibitors, Outcome 4 All‐cause mortality in hospital.
9.5
9.5. Analysis
Comparison 9 H2 receptor antagonists versus proton pump inhibitors, Outcome 5 Duration of ICU stay.
9.6
9.6. Analysis
Comparison 9 H2 receptor antagonists versus proton pump inhibitors, Outcome 6 Duration of intubation.
9.7
9.7. Analysis
Comparison 9 H2 receptor antagonists versus proton pump inhibitors, Outcome 7 Number of participants requiring blood transfusions.
9.8
9.8. Analysis
Comparison 9 H2 receptor antagonists versus proton pump inhibitors, Outcome 8 Adverse events of interventions.
10.1
10.1. Analysis
Comparison 10 H2 receptor antagonists versus antacids, Outcome 1 Clinically important upper GI bleeding.
10.2
10.2. Analysis
Comparison 10 H2 receptor antagonists versus antacids, Outcome 2 Nosocomial pneumonia.
10.3
10.3. Analysis
Comparison 10 H2 receptor antagonists versus antacids, Outcome 3 All‐cause mortality in ICU.
10.4
10.4. Analysis
Comparison 10 H2 receptor antagonists versus antacids, Outcome 4 All‐cause mortality in hospital.
10.5
10.5. Analysis
Comparison 10 H2 receptor antagonists versus antacids, Outcome 5 Duration of intubation.
10.6
10.6. Analysis
Comparison 10 H2 receptor antagonists versus antacids, Outcome 6 Number of participants requiring blood transfusions.
10.7
10.7. Analysis
Comparison 10 H2 receptor antagonists versus antacids, Outcome 7 Adverse events of interventions.
11.1
11.1. Analysis
Comparison 11 H2 receptor antagonists versus sucralfate, Outcome 1 Clinically important upper GI bleeding.
11.2
11.2. Analysis
Comparison 11 H2 receptor antagonists versus sucralfate, Outcome 2 Nosocomial pneumonia.
11.3
11.3. Analysis
Comparison 11 H2 receptor antagonists versus sucralfate, Outcome 3 All‐cause mortality in ICU.
11.4
11.4. Analysis
Comparison 11 H2 receptor antagonists versus sucralfate, Outcome 4 All‐cause mortality in hospital.
11.5
11.5. Analysis
Comparison 11 H2 receptor antagonists versus sucralfate, Outcome 5 Duration of intubation.
11.6
11.6. Analysis
Comparison 11 H2 receptor antagonists versus sucralfate, Outcome 6 Duration of ICU stay.
11.7
11.7. Analysis
Comparison 11 H2 receptor antagonists versus sucralfate, Outcome 7 Number of participants requiring blood transfusion.
11.8
11.8. Analysis
Comparison 11 H2 receptor antagonists versus sucralfate, Outcome 8 Units of blood transfused.
11.9
11.9. Analysis
Comparison 11 H2 receptor antagonists versus sucralfate, Outcome 9 Adverse events of interventions.
12.1
12.1. Analysis
Comparison 12 H2 receptor antagonists versus anticholinergics, Outcome 1 Clinically important upper GI bleeding.
12.2
12.2. Analysis
Comparison 12 H2 receptor antagonists versus anticholinergics, Outcome 2 Nosocomial pneumonia.
12.3
12.3. Analysis
Comparison 12 H2 receptor antagonists versus anticholinergics, Outcome 3 All‐cause mortality in ICU.
12.4
12.4. Analysis
Comparison 12 H2 receptor antagonists versus anticholinergics, Outcome 4 Number of participants requiring blood transfusion.
12.5
12.5. Analysis
Comparison 12 H2 receptor antagonists versus anticholinergics, Outcome 5 Adverse events of interventions.
13.1
13.1. Analysis
Comparison 13 H2 receptor antagonists versus prostaglandin analogues, Outcome 1 Clinically important upper GI bleeding.
13.2
13.2. Analysis
Comparison 13 H2 receptor antagonists versus prostaglandin analogues, Outcome 2 All‐cause mortality in ICU.
14.1
14.1. Analysis
Comparison 14 H2 receptor antagonists versus teprenone, Outcome 1 Clinically important upper GI bleeding.
14.2
14.2. Analysis
Comparison 14 H2 receptor antagonists versus teprenone, Outcome 2 All‐cause mortality in ICU.
14.3
14.3. Analysis
Comparison 14 H2 receptor antagonists versus teprenone, Outcome 3 Number of participants requiring blood transfusion.
15.1
15.1. Analysis
Comparison 15 H2 receptor antagonist + antacids versus sucralfate, Outcome 1 Clinically important upper GI bleeding.
15.2
15.2. Analysis
Comparison 15 H2 receptor antagonist + antacids versus sucralfate, Outcome 2 Nosocomial pneumonia.
15.3
15.3. Analysis
Comparison 15 H2 receptor antagonist + antacids versus sucralfate, Outcome 3 All‐cause mortality in ICU.
15.4
15.4. Analysis
Comparison 15 H2 receptor antagonist + antacids versus sucralfate, Outcome 4 Duration of ICU stay.
15.5
15.5. Analysis
Comparison 15 H2 receptor antagonist + antacids versus sucralfate, Outcome 5 Duration of intubation.
15.6
15.6. Analysis
Comparison 15 H2 receptor antagonist + antacids versus sucralfate, Outcome 6 Number of participants requiring blood transfusion.
16.1
16.1. Analysis
Comparison 16 Proton pump inhibitors versus teprenone, Outcome 1 Clinically important upper GI bleeding.
16.2
16.2. Analysis
Comparison 16 Proton pump inhibitors versus teprenone, Outcome 2 All‐cause mortality in ICU.
16.3
16.3. Analysis
Comparison 16 Proton pump inhibitors versus teprenone, Outcome 3 Number of participants requiring blood transfusion.
17.1
17.1. Analysis
Comparison 17 Proton pump inhibitor plus naloxone versus naloxone, Outcome 1 Clinically important upper GI bleeding.
17.2
17.2. Analysis
Comparison 17 Proton pump inhibitor plus naloxone versus naloxone, Outcome 2 All‐cause mortality in hospital.
17.3
17.3. Analysis
Comparison 17 Proton pump inhibitor plus naloxone versus naloxone, Outcome 3 Adverse events ‐ gastrointestinal discomfort.
18.1
18.1. Analysis
Comparison 18 Proton pump inhibitors versus other medication (not defined), Outcome 1 Clinically important upper GI bleeding.
18.2
18.2. Analysis
Comparison 18 Proton pump inhibitors versus other medication (not defined), Outcome 2 Nosocomial pneumonia.
18.3
18.3. Analysis
Comparison 18 Proton pump inhibitors versus other medication (not defined), Outcome 3 All‐cause mortality in hospital.
19.1
19.1. Analysis
Comparison 19 Antacids versus sucralfate, Outcome 1 Clinically important upper GI bleeding.
19.2
19.2. Analysis
Comparison 19 Antacids versus sucralfate, Outcome 2 Nosocomial pneumonia.
19.3
19.3. Analysis
Comparison 19 Antacids versus sucralfate, Outcome 3 All‐cause mortality in ICU.
19.4
19.4. Analysis
Comparison 19 Antacids versus sucralfate, Outcome 4 All‐cause mortality in hospital.
19.5
19.5. Analysis
Comparison 19 Antacids versus sucralfate, Outcome 5 Duration of ICU stay.
19.6
19.6. Analysis
Comparison 19 Antacids versus sucralfate, Outcome 6 Duration of intubation.
19.7
19.7. Analysis
Comparison 19 Antacids versus sucralfate, Outcome 7 Number of participants requiring blood transfusion.
19.8
19.8. Analysis
Comparison 19 Antacids versus sucralfate, Outcome 8 Adverse events of interventions.
20.1
20.1. Analysis
Comparison 20 Antacids versus prostaglandin analogues, Outcome 1 Clinically important upper GI bleeding.
20.2
20.2. Analysis
Comparison 20 Antacids versus prostaglandin analogues, Outcome 2 All‐cause mortality in ICU.
20.3
20.3. Analysis
Comparison 20 Antacids versus prostaglandin analogues, Outcome 3 Adverse events of interventions.
21.1
21.1. Analysis
Comparison 21 Antacids versus bioflavonoids, Outcome 1 Clinically important upper GI bleeding.
21.2
21.2. Analysis
Comparison 21 Antacids versus bioflavonoids, Outcome 2 Number of participants requiring blood transfusion.
22.1
22.1. Analysis
Comparison 22 Sucralfate versus proton pump inhibitors, Outcome 1 Clinically important upper GI bleeding.
22.2
22.2. Analysis
Comparison 22 Sucralfate versus proton pump inhibitors, Outcome 2 Nosocomial pneumonia.
22.3
22.3. Analysis
Comparison 22 Sucralfate versus proton pump inhibitors, Outcome 3 All‐cause mortality in ICU.
22.4
22.4. Analysis
Comparison 22 Sucralfate versus proton pump inhibitors, Outcome 4 All‐cause mortality in hospital.
22.5
22.5. Analysis
Comparison 22 Sucralfate versus proton pump inhibitors, Outcome 5 Duration of ICU stay.
22.6
22.6. Analysis
Comparison 22 Sucralfate versus proton pump inhibitors, Outcome 6 Duration of intubation.
22.7
22.7. Analysis
Comparison 22 Sucralfate versus proton pump inhibitors, Outcome 7 Number of participants requiring blood transfusion.
22.8
22.8. Analysis
Comparison 22 Sucralfate versus proton pump inhibitors, Outcome 8 Adverse events of interventions.
23.1
23.1. Analysis
Comparison 23 Sucralfate versus bioflavonoids, Outcome 1 Clinically important upper GI bleeding.
23.2
23.2. Analysis
Comparison 23 Sucralfate versus bioflavonoids, Outcome 2 Number of participants requiring blood transfusion.
24.1
24.1. Analysis
Comparison 24 Total parenteral nutrition (TPN) versus any other intervention + TPN, Outcome 1 Clinically important upper GI bleeding.
24.2
24.2. Analysis
Comparison 24 Total parenteral nutrition (TPN) versus any other intervention + TPN, Outcome 2 All‐cause mortality in ICU.
24.3
24.3. Analysis
Comparison 24 Total parenteral nutrition (TPN) versus any other intervention + TPN, Outcome 3 Duration of intubation.
25.1
25.1. Analysis
Comparison 25 Bowel stimulation versus no prophylaxis, Outcome 1 Clinically important upper GI bleeding.
26.1
26.1. Analysis
Comparison 26 Nasojejunal nutrition versus nasogastric nutrition, Outcome 1 Clinically important upper GI bleeding.
26.2
26.2. Analysis
Comparison 26 Nasojejunal nutrition versus nasogastric nutrition, Outcome 2 Nosocomial pneumonia.
26.3
26.3. Analysis
Comparison 26 Nasojejunal nutrition versus nasogastric nutrition, Outcome 3 All‐cause mortality in hospital.
26.4
26.4. Analysis
Comparison 26 Nasojejunal nutrition versus nasogastric nutrition, Outcome 4 Adverse events of interventions.
27.1
27.1. Analysis
Comparison 27 Enteral plus parenteral nutrition versus other nutrition regimens, Outcome 1 Nosocomial pneumonia.
27.2
27.2. Analysis
Comparison 27 Enteral plus parenteral nutrition versus other nutrition regimens, Outcome 2 All‐cause mortality in hospital.
27.3
27.3. Analysis
Comparison 27 Enteral plus parenteral nutrition versus other nutrition regimens, Outcome 3 Duration of ICU stay.
27.4
27.4. Analysis
Comparison 27 Enteral plus parenteral nutrition versus other nutrition regimens, Outcome 4 Duration of intubation.
27.5
27.5. Analysis
Comparison 27 Enteral plus parenteral nutrition versus other nutrition regimens, Outcome 5 Adverse events ‐ stress ulcer.
27.6
27.6. Analysis
Comparison 27 Enteral plus parenteral nutrition versus other nutrition regimens, Outcome 6 Adverse events ‐ diarrhoea.
27.7
27.7. Analysis
Comparison 27 Enteral plus parenteral nutrition versus other nutrition regimens, Outcome 7 Adverse events ‐ pyaemia.
27.8
27.8. Analysis
Comparison 27 Enteral plus parenteral nutrition versus other nutrition regimens, Outcome 8 Adverse events ‐ intracranial infection.
27.9
27.9. Analysis
Comparison 27 Enteral plus parenteral nutrition versus other nutrition regimens, Outcome 9 Adverse events ‐ hypoproteinaemia.
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Update of

  • doi: 10.1002/14651858.CD008687

References

References to studies included in this review

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    1. Cannon LA, Heiselman D, Gardner W, Jones J. Prophylaxis of upper gastrointestinal tract bleeding in mechanically ventilated patients. A randomized study comparing the efficacy of sucralfate, cimetidine, and antacids. Archives of Internal Medicine 1987;147(12):2101‐6. [PUBMED: 3500684] - PubMed
Chan 1995 {published data only}
    1. Chan KH, Lai EC, Tuen H, Ngan JH, Mok F, Fan YW, et al. Prospective double‐blind placebo‐controlled randomized trial on the use of ranitidine in preventing postoperative gastroduodenal complications in high‐risk neurosurgical patients. Journal of Neurosurgery 1995;82(3):413‐7. [DOI: 10.3171/jns.1995.82.3.0413] - DOI - PubMed
Cioffi 1994 {published data only}
    1. Cioffi WG, McManus AT, Rue LW 3rd, Mason AD, McManus WF, Pruitt BA Jr. Comparison of acid neutralizing and non‐acid neutralizing stress ulcer prophylaxis in thermally injured patients. Journal of Trauma 1994;36(4):544‐7. [PUBMED: 8158717] - PubMed
Conrad 2005 {published data only}
    1. Conrad SA, Gabrielli A, Margolis B, Quartin A, Hata JS, Frank WO, et al. Randomized, double‐blind comparison of immediate‐release omeprazole oral suspension versus intravenous cimetidine for the prevention of upper gastrointestinal bleeding in critically ill patients. Critical Care Medicine 2005;33(4):760‐5. [PUBMED: 15818102] - PubMed
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Darlong 2003 {published data only}
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Davies 2012 {published data only}
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De Azevedo 2000 {published data only}
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Driks 1987 {published data only}
    1. Driks MR, Craven DE, Celli BR, Manning M, Burke RA, Garvin GM, et al. Nosocomial pneumonia in intubated patients given sucralfate as compared with antacids or histamine type 2 blockers. The role of gastric colonization. New England Journal of Medicine 1987;317(22):1376‐82. [DOI: 10.1056/Nejm198711263172204; PUBMED: 2891032] - DOI - PubMed
Eddleston 1991 {published data only}
    1. Eddleston JM, Vohra A, Scott P, Tooth JA, Pearson RC, McCloy RF, et al. A comparison of the frequency of stress ulceration and secondary pneumonia in sucralfate‐ or ranitidine‐treated intensive care unit patients. Critical Care Medicine 1991;19(12):1491‐6. [PUBMED: 1959368] - PubMed
Eddleston 1994 {published data only}
    1. Eddleston JM, Pearson RC, Holland J, Tooth JA, Vohra A, Doran BH. Prospective endoscopic study of stress erosions and ulcers in critically ill adult patients treated with either sucralfate or placebo. Critical Care Medicine 1994;22(12):1949‐54. [PUBMED: 7988131] - PubMed
Ephgrave 1998 {published data only}
    1. Ephgrave KS, Kleiman‐Wexler R, Pfaller M, Booth BM, Reed D, Werkmeister L, et al. Effects of sucralfate vs antacids on gastric pathogens: results of a double‐blind clinical trial. Archives of Surgery 1998;133(3):251‐7. [PUBMED: 9517735] - PubMed
Fabian 1993 {published data only}
    1. Fabian TC, Boucher BA, Croce MA, Kuhl DA, Janning SW, Coffey BC, et al. Pneumonia and stress ulceration in severely injured patients. A prospective evaluation of the effects of stress ulcer prophylaxis. Archives of Surgery 1993;128(2):185‐92. [PUBMED: 8431119] - PubMed
Fan 2016 {published data only}
    1. Fan MC, Wang QL, Fang W, Jiang YX, Li LD, Sun P, Wang ZH. Early enteral combined with parenteral nutrition treatment for severe traumatic brain injury: effects on immune function, nutritional status and outcomes. Chinese Medical Sciences Journal 2016;31(4):213. - PubMed
Fang 2014 {published data only}
    1. Fang XW, Chang S, Zhao JH, Qian XY. Prevention and treatment of stress‐induced gastrointestinal bleeding after severe brain injury. World Chinese Journal of Digestology 2014;22(3):404‐8.
Fink 2003 {unpublished data only}
    1. Fink M, Karlstadt RG, Maroko RT, Field B. Intravenous pantoprazole (IVP) and continuous infusion cimetidine (C) prevent upper gastrointestinal bleeding (UGIB) regardless of APSII score (APACHE II) in high risk intensive care unit (ICU) patients. Gastroenterology 2003;124(4 Suppl 1):A625–6.
Fogas 2013 {published data only}
    1. Fogas JF, Kiss KK, Gyura FG, Tobias ZT, Molnar ZM. Effects of proton pump inhibitor versus H2‐receptor antagonist stress ulcer prophylaxis on ventilator‐associated pneumonia: A pilot study. Critical Care 2013;17:S150‐1.
Friedman 1982 {published data only}
    1. Friedman CJ, Oblinger MJ, Suratt PM, Bowers J, Goldberg SK, Sperling MH, et al. Prophylaxis of upper gastrointestinal hemorrhage in patients requiring mechanical ventilation. Critical Care Medicine 1982;10(5):316‐9. [PUBMED: 7042201] - PubMed
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Halloran 1980 {published data only}
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Hanisch 1998 {published data only}
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Hastings 1978 {published data only}
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Hata 2005 {published data only}
    1. Hata M, Shiono M, Sekino H, Furukawa H, Sezai A, Iida M, et al. Prospective randomized trial for optimal prophylactic treatment of the upper gastrointestinal complications after open heart surgery. Circulation Journal 2005;69(3):331‐4. [PUBMED: 15731540] - PubMed
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Israsena 1987 {published data only}
    1. Israsena S, Anantapanpong S, Kladcharoen N, Chayanand D, Limthongkul S. Sucralfate versus antacid in the prevention of stress ulcer bleeding in patients on mechanical ventilation. Journal of the Medical Association of Thailand 1987;70(12):678‐82. - PubMed
Kantorova 2004 {published data only}
    1. Kantorova I, Svoboda P, Scheer P, Doubek J, Rehorkova D, Bosakova H, et al. Stress ulcer prophylaxis in critically ill patients: a randomized controlled trial. Hepato‐gastroenterology 2004;51(57):757‐61. [PUBMED: 15143910] - PubMed
Kappstein 1991 {published data only}
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Karlstadt 1990 {published data only}
    1. Karlstadt RG, Iberti TJ, Silverstein J, Lindenberg L, Bright‐Asare P, Rockhold F, et al. Comparison of cimetidine and placebo for the prophylaxis of upper gastrointestinal bleeding due to stress‐related gastric mucosal damage in the intensive care unit. Journal of Intensive Care Medicine 1990;5(1):26‐32. [DOI: 10.1177/088506669000500106] - DOI
Kaushal 2000 {published data only}
    1. Kaushal S, Midha V, Sood A, Chopra SC, Gupta C. A comparative study of the effects of famotidine and sucralfate in prevention of upper gastro‐intestinal bleeding in patients of head injury. Indian Journal of Pharmacology 2000; Vol. 32, issue 3:246‐9. [CN‐00424209]
Khorvash 2014 {published data only}
    1. Khorvash F, Abbasi S, Meidani M, Dehdashti F, Ataei B. The comparison between proton pump inhibitors and sucralfate in incidence of ventilator associated pneumonia in critically ill patients. Advanced Biomedical Research 2014;3(52):1‐6. [DOI: 10.4103/2277-9175.125789] - DOI - PMC - PubMed
Kingsley 1985 {published data only}
    1. Kingsley AN. Prophylaxis for acute stress ulcers. Antacids or cimetidine. American Surgeon 1985;51(9):545‐7. [PUBMED: 3898949] - PubMed
Kitler 1990 {published data only}
    1. Kitler ME, Hays A, Enterline JP, Allo M, Zuidema GD. Preventing postoperative acute bleeding of the upper part of the gastrointestinal tract. Surgery, Gynecology & Obstetrics 1990;171(5):366‐72. [PUBMED: 2237719] - PubMed
Krakamp 1989 {published data only}
    1. Krakamp B, Rommel T, Edelmann M, Leidig P. Prevention of stress‐induced hemorrhage of the upper gastrointestinal tract in neurosurgical intensive care patients. A controlled, randomized double‐blind study with ranitidine alone and in combination with pirenzepine [Prophylaxe streßbedingter Blutungen aus dem oberen Gastrointestinaltrakt bei neurochirurgischen Intensivpatienten]. Medizinische Klinik 1989;84(3):133‐4. - PubMed
Kuusela 1997 {published data only}
    1. Kuusela AL, Ruuska T, Karikoski R, Laippala P, Ikonen RS, Janas M, et al. A randomized, controlled study of prophylactic ranitidine in preventing stress‐induced gastric mucosal lesions in neonatal intensive care unit patients. Critical Care Medicine 1997;25(2):346‐51. [PUBMED: 9034275] - PubMed
Lacroix 1986 {published data only}
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Laggner 1988 {published data only}
    1. Laggner AN, Lenz K, Graninger W, Gremmel F, Grimm G, Base W, et al. Prevention of stress hemorrhage in an internal medicine intensive care station: sucralfate versus ranitidine [Stressblutungsprophylaxe auf einer internen Intensivstation: Sucralfat versus Ranitidin]. Der Anaesthesist 1988;37(11):704‐10. [PUBMED: 3063134] - PubMed
Laggner 1989 {published data only}
    1. Laggner AN, Lenz K, Base W, Druml W, Schneeweiss B, Grimm G. Prevention of upper gastrointestinal bleeding in long‐term ventilated patients. Sucralfate versus ranitidine. American Journal of Medicine 1989;86(6A):81‐4. [PUBMED: 2786673] - PubMed
Lamothe 1991 {published data only}
    1. Lamothe PH, Rao E, Serra AJ, Castellano J, Woronick CL, McNicholas KW, et al. Comparative efficacy of cimetidine, famotidine, ranitidine, and mylanta in postoperative stress ulcers. Gastric pH control and ulcer prevention in patients undergoing coronary artery bypass graft surgery. Gastroenterology 1991;100(6):1515‐20. [PUBMED: 2019357] - PubMed
Larson 1989 {published data only}
    1. Larson GM, Davidson P, Brown J. Comparison of ranitidine versus placebo on 24 hour gastric pH and upper gastrointestinal (UGI) bleeding in head injuries (abstract). American Journal of Gastroenterology 1989;84:1165.
Lee 2014 {published data only}
    1. Lee TH, Hung FM, Yang LH. Comparison of the efficacy of esomeprazole and famotidine against stress ulcers in a neurosurgical intensive care unit. Advances in Digestive Medicine 2014;1(2):50‐3.
Levy 1997 {published data only}
    1. Levy MJ, Seelig CB, Robinson NJ, Ranney JE. Comparison of omeprazole and ranitidine for stress ulcer prophylaxis. Digestive Diseases and Sciences 1997;42(6):1255‐9. [PUBMED: 9201091] - PubMed
Lin 2016 {published data only}
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Lopez‐Herce 1992 {published data only}
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Luk 1982 {published data only}
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Maasoumi 2016 {published data only}
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Macdougall 1977 {published data only}
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Mahul 1992 {published data only}
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Maier 1994 {published data only}
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Martin 1980 {published data only}
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Martin 1992 {published data only}
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Martin 1993 {published data only}
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Metz 1993 {published data only}
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Mustafa 1994 {published data only}
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Ng 2012 {published data only}
    1. Ng FH, Tunggal P, Chu WM, Lam KF, Li A, Chan K, et al. Esomeprazole compared with famotidine in the prevention of upper gastrointestinal bleeding in patients with acute coronary syndrome or myocardial infarction. American Journal of Gastroenterology 2012;107(3):389‐96. [DOI: 10.1038/ajg.2011.385] - DOI - PubMed
Noseworthy 1987 {published data only}
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Ortiz 1998 {published data only}
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Pan 2004 {published data only}
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Peura 1985 {published data only}
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Phillips 1998 {unpublished data only}
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Pickworth 1993 {published data only}
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Pinilla 1985 {published data only}
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Poleski 1986 {published data only}
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Powell 1993 {published data only}
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Prakash 2008 {published data only}
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Priebe 1980 {published data only}
    1. Priebe HJ, Skillman JJ, Bushnell LS, Long PC, Silen W. Antacid versus cimetidine in preventing acute gastrointestinal bleeding. A randomized trial in 75 critically ill patients. New England Journal of Medicine 1980;302(8):426‐30. [PUBMED: 6986027] - PubMed
Prod'hom 1994 {published data only}
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Reusser 1990 {published data only}
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Rohde 1980 {published data only}
    1. Lorenz W, Fischer M, Rohde H, Troidl H, Reimann HJ, Ohmann C. Histamine and stress ulcer: new components in organizing a sequential trial on cimetidine prophylaxis in seriously ill patients and definition of a special group at risk (severe polytrauma). Klinische Wochenschrift 1980;58((3):653‐65. [PUBMED: 7442079] - PubMed
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Ruiz‐Santana 1991 {published data only}
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Ryan 1993 {published data only}
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Selvanderan 2015 {published data only}
    1. Selvanderan SP, Summers MJ, Plummer MP, Finnis ME, Ali Abdelhamid Y, Anderson MB, et al. Withholding stress ulcer prophylaxis to mechanically ventilated enterally‐fed critically ill patients appears safe: a randomised double‐blind placebo controlled pilot study. Intensive Care Medicine Experimental 2015;3:A41.
Selvanderan 2016 {published data only}
    1. Deane A, Selvanderan S, Summers M, Finnis M, Plummer M, Ali AY, et al. Pantoprazole or placebo for stress ulcer prophylaxis (Popup) study. Anaesthesia and Intensive Care 2016; Vol. 44, issue 2:303‐4. - PubMed
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Skillman 1984 {published data only}
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Somberg 2008 {published data only}
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Stothert 1980 {published data only}
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Tabeefar 2012 {published data only}
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Tryba 1985 {published data only}
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    1. Tryba M. Risk of acute stress bleeding and nosocomial pneumonia in ventilated intensive care unit patients: sucralfate versus antacids. American Journal of Medicine 1987;83(3B):117‐24. [PUBMED: 3310626] - PubMed
Tryba 1988 {published data only}
    1. Tryba M, Zevounou F, Wruck G. Stress bleeding and postoperative pneumonia in intensive care patients with ranitidine or pirenzepine [Streßblutungen und postoperative Pneumonien bei Intensivpatienten unter Ranitidin oder PirenzepinM.]. Deutsche Medizinische Wochenschrift 1988;113(23):930‐6. [DOI: 10.1055/s-2008-1067744] - DOI - PubMed
van den Berg 1985 {published data only}
    1. Berg B, Blankenstein M. Prevention of stress‐induced upper gastrointestinal bleeding by cimetidine in patients on assisted ventilation. Digestion 1985;31(1):1‐8. [PUBMED: 3979676] - PubMed
van Essen 1985 {published data only}
    1. Essen HA, Blankenstein M, Wilson JH, Berg B, Bruining HA. Intragastric prostaglandin E2 and the prevention of gastrointestinal hemorrhage in ICU patients. Critical Care Medicine 1985;13(11):957‐60. [PUBMED: 3902362] - PubMed
Wang 2015 {published data only}
    1. Wang YQ. Impact of comprehensive intestinal irritation on digestive function in mechanically ventilated critically ill patients. World Chinese Journal of Digestology 2015;23(34):5544‐8.
Wee 2013 {published data only}
    1. Wee B, Liu CH, Cohen H, Kravchuk S, Reddy K, Mukherji R. IV famotidine vs. IV pantoprazole for stress ulcer prevention in the ICU: a prospective study. Critical Care Medicine 2013;41(12):A181. [DOI: 10.1097/01.ccm.0000439969.36301.c9] - DOI
    1. Wee BC, Liu M, Cohen H, Kravchuk S, Reddy K, Mukherji R. Efficacy and safety of intravenous famotidine versus intavenous pantoprazole for stress ulcer prophylaxis in the critically ill: a prospective randomized study. Journal of Pharmacy Practice 2013;26(3):299‐300.
Weigelt 1981 {published data only}
    1. Weigelt JA, Aurbakken CM, Gewertz BL, Snyder WH 3rd. Cimetidine vs antacid in prophylaxis for stress ulceration. Archives of Surgery 1981;116(5):597‐601. [PUBMED: 7016067] - PubMed
Yildizdas 2002 {published data only}
    1. Yildizdas D, Yapicioglu H, Yilmaz HL. Occurrence of ventilator‐associated pneumonia in mechanically ventilated pediatric intensive care patients during stress ulcer prophylaxis with sucralfate, ranitidine, and omeprazole. Journal of Critical Care 2002;17(4):240‐5. [DOI: 10.1053/jcrc.2002.36761; PUBMED: 12501151] - DOI - PubMed
Zinner 1981 {published data only}
    1. Zinner MJ, Zuidema GD, Smith P[L, Mignosa M. The prevention of upper gastrointestinal tract bleeding in patients in an intensive care unit. Surgery, Gynecology & Obstetrics 1981;153(2):214‐20. [PUBMED: 7017982] - PubMed
Zinner 1989 {published data only}
    1. Zinner MJ, Rypins EB, Martin LR, Jonasson O, Hoover EL, Swab EA, et al. Misoprostol versus antacid titration for preventing stress ulcers in postoperative surgical ICU patients. Annals of Surgery 1989;210(5):590‐5. [PUBMED: 2510618] - PMC - PubMed

References to studies excluded from this review

Aanpreung 1998 {published data only}
    1. Aanpreung P, Vanprapar N, Susiva C, Parkpreaw C, Boonyachart C. A randomized clinical trial comparing the efficacy of ranitidine and famotidine on intragastric acidity in critically ill pediatric patients. Journal of the Medical Association of Thailand 1998;81(3):185‐9. [PUBMED: 9623009] - PubMed
Abe 2004 {published data only}
    1. Abe Y, Inamori M, Togawa J, Kikuchi T, Muramatsu K, Chiguchi G, et al. The comparative effects of single intravenous doses of omeprazole and famotidine on intragastric pH. Journal of Gastroenterology 2004;39(1):21‐5. [PUBMED: 14767730] - PubMed
Alaniz 2014 {published data only}
    1. Alaniz C, Hyzy RC. Time to declare a moratorium on stress ulcer prophylaxis in critically Ill. Critical Care Medicine 2014;42(9):e636‐7. - PubMed
Al‐Quorain 1994 {published data only}
    1. Al‐Quorain A, Ammar A, Al‐Awami M, Hegazi M, El‐Munshid KA, Ibrahim EM, et al. Comparison of intravenous famotidine and ranitidine in suppressing gastric acid secretion in critically ill patients. Current Therapeutic Research 1994;55(10):1263‐70.
Anonymous 2013 {published data only}
    1. Anonymous. 32nd Congress of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine, Focusing on the Brain. Acta Anaesthesiologica Scandinavica, Supplement 2013;57:no pagination. - PubMed
Anonymous 2015 {published data only}
    1. Anonymous. 33rd Congress of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine. Acta Anaesthesiologica Scandinavica 2015;59:no pagination. - PubMed
Arora 1991 {published data only}
    1. Arora A, Tandon RK, Acharya SK, Tandon BN. The role of sustained achlorhydria in bleeding peptic ulcer. Journal of Clinical Gastroenterology 1991;13(2):147‐53. [PUBMED: 2033221] - PubMed
Baccino 1987 {published data only}
    1. Baccino E, Boles JM, Guillou M, Geier B, Garo B, Robaszkiewicz M, et al. Attempt at preventive treatment of esophagitis caused by intubation during intensive care [Tentative de traitement preventif des oesophagites sur sonde en reanimation.]. Gastroenterologie Clinique et Biologique 1987;11(1):24‐8. [PUBMED: 3556957] - PubMed
Baghaie 1995 {published data only}
    1. Baghaie AA, Mojtahedzadeh M, Levine RL, Fromm RE Jr, Guntupalli KK, Opekun AR Jr. Comparison of the effect of intermittent administration and continuous infusion of famotidine on gastric pH in critically ill patients: results of a prospective, randomized, crossover study. Critical Care Medicine 1995;23(4):687‐91. [PUBMED: 7712759] - PubMed
Barth 1984 {published data only}
    1. Barth HO, Brunner G, Berg F, Dammann HG, Friedl W, Franken FH. Ranitidine versus cimetidine in preventing acute gastroduodenal bleeding: a randomized trial in 193 critically ill patients ‐ a multicentre study in Germany. Intensivmedizin 1984;21:15‐8.
Bauer 1977 {published data only}
    1. Bauer H, Doenicke A, Holle F. Prevention and treatment of upper gastrointestinal haemorrhage with cimetidine and somatostatin in intensive care patients (author's transl) [Kasuistische Mitteilung uber Moglichkeiten der Prophylaxe und Therapie gastrointestinaler Blutungen mit Cimetidin oder Somatostatin bei Schwerstkranken.]. Der Anaesthesist 1977;26(12):662‐4. [PUBMED: 304692] - PubMed
Bergmans 2001 {published data only}
    1. Bergmans DC, Bonten MJ, Gaillard CA, Paling JC, Geest S, Tiel FH, et al. Prevention of ventilator‐associated pneumonia by oral decontamination: a prospective, randomized, double‐blind, placebo‐controlled study. American Journal of Respiratory and Critical Care Medicine 2001;164(3):382‐8. [PUBMED: 11500337] - PubMed
Bhatt 2010 {published data only}
    1. Bhatt DL, Cryer BL, Contant CF, Cohen M, Lanas A, Schnitzer TJ, et al. Clopidogrel with or without omeprazole in coronary artery disease. New England Journal of Medicine 2010;363(20):1909‐17. [DOI: 10.1056/NEJMoa1007964] - DOI - PubMed
Cheadle 1985 {published data only}
    1. Cheadle WG, Vitale GC, Mackie CR, Cuschieri A. Prophylactic postoperative nasogastric decompression. A prospective study of its requirement and the influence of cimetidine in 200 patients. Annals of Surgery 1985;202(3):361‐6. [PUBMED: 4037908] - PMC - PubMed
Chernov 1971 {published data only}
    1. Chernov MS, Hale HW Jr, Wood M. Prevention of stress ulcers. American Journal of Surgery 1971;122(5):674‐7. [PUBMED: 5112074] - PubMed
Cloud 1994 {published data only}
    1. Cloud ML, Offen W. Continuous infusions of nizatidine are safe and effective in the treatment of intensive care unit patients at risk for stress gastritis. The Nizatidine Intensive Care Unit Study Group. Scandinavian Journal of Gastroenterology. Supplement 1994;206:29‐34. [PUBMED: 7863249] - PubMed
Critchlow 1987 {published data only}
    1. Critchlow JF. Comparative efficacy of parenteral histamine (H2)‐antagonists in acid suppression for the prevention of stress ulceration. American Journal of Medicine 1987;83(6a):23‐8. - PubMed
Dabiri 2015 {published data only}
    1. Dabiri Y, Fahimi F, Jamaati H, Hashemian SMR. The comparison of extemporaneous preparations of omeprazole, pantoprazole oral suspension and intravenous pantoprazole on the gastric pH of critically ill‐patients. Indian Journal of Critical Care Medicine 2015;19(1):21‐6. - PMC - PubMed
Driscoll 1993 {published data only}
    1. Driscoll DM, Cioffi WG Jr, Molter NC, McManus WF, Mason AD Jr, Pruitt BA Jr. Intragastric pH monitoring. Journal of Burn Care & Rehabilitation 1993;14(5):517‐24. [PUBMED: 8245105] - PubMed
Duma 1986 {published data only}
    1. Duma S. Prevention of stress ulcers with cimetidine and ranitidine. Comparative studies within the scope of cardiosurgical interventions [Prophylaxe von Stressulzera mit Cimetidin und Ranitidin. Vergleichende Untersuchungen im Rahmen von kardiochirurgischen Eingriffen]. Wiener Medizinische Wochenschrift (1946) 1986;136(18):467‐72. [PUBMED: 3798932] - PubMed
Estruch 1991 {published data only}
    1. Estruch R, Pedrol E, Castells A, Masanes F, Marrades RM, Urbano‐Marquez A. Prophylaxis of gastrointestinal tract bleeding with magaldrate in patients admitted to a general hospital ward. Scandinavian Journal of Gastroenterology 1991;26(8):819‐26. [PUBMED: 1771386] - PubMed
Fiorucci 1989 {published data only}
    1. Fiorucci S, Clausi GC, Farinelli M, Santucci L, Pelli MA, Morelli A. Intragastric pH monitoring during antisecretory therapy in patient with gastrointestinal bleeding. American Journal of Gastroenterology 1989;84(11):1416‐20. [PUBMED: 2816875] - PubMed
Forestier 2008 {published data only}
    1. Forestier C, Guelon D, Cluytens V, Gillart T, Sirot J, Champs C. Oral probiotic and prevention of Pseudomonas aeruginosa infections: a randomized, double‐blind, placebo‐controlled pilot study in intensive care unit patients. Critical Care (London, England) 2008;12(3):R69. [PUBMED: 18489775] - PMC - PubMed
Friedl 1985 {published data only}
    1. Friedl W, Krier C, Dammann HG, Muller P, Simon B. I.V. famotidine versus I.V. ranitidine: intragastric pH behavior in surgical intensive care patients [I.V. Famotidin versus I.V. ranitidine: intragastrales pH‐Verhalten bei chirurgischen Intensivpatienten]. Zeitschrift fur Gastroenterologie 1985;23(11):603‐7. [PUBMED: 2868579] - PubMed
Geus 1993 {published data only}
    1. Geus WP, Vinks AA, Smith SJ, Westra P, Lamers CB. Comparison of two intravenous ranitidine regimens in a homogeneous population of intensive care unit patients. Alimentary Pharmacology & Therapeutics 1993;7(4):451‐7. [PUBMED: 8218759] - PubMed
Hauer 1996 {published data only}
    1. Hauer T, Lacour M, Gastmeier P, Schulgen G, Schumacher M, et al. A prevalence survey of nosocomial infections in intensive care units [Nosokomiale Infektionen auf Intensivstationen]. Anaesthesist 1996;45:1184‐91. - PubMed
Heiselman 1995 {published data only}
    1. Heiselman DE, Hulisz DT, Fricker R, Bredle DL, Black LD. Randomized comparison of gastric pH control with intermittent and continuous intravenous infusion of famotidine in ICU patients. American Journal of Gastroenterology 1995;90(2):277‐9. [PUBMED: 7847300] - PubMed
Herrmann 1979 {published data only}
    1. Herrmann V, Kaminski DL. Evaluation of intragastric pH in acutely ill patients. Archives of Surgery 1979;114(4):511‐4. [PUBMED: 35135] - PubMed
Hollander 1973 {published data only}
    1. Hollander D, Harlan J. Antacids vs placebos in peptic ulcer therapy. A controlled double‐blind investigation. Journal of the American Medical Association 1973;226(10):1181‐5. [PUBMED: 4584411] - PubMed
Huang 2017 {published data only}
    1. Huang JX, Liu XK. Proton pump inhibitor therapy for prevention of gastrointestinal bleeding after percutaneous coronary intervention [PCI治疗术后应用质子泵抑制剂预防消化道出血效果]. World Chinese Journal of Digestology 2017;25(11):1012‐5. [DOI: 10.11569/wcjd.v25.i11.1012] - DOI
Kalfarentzos 1997 {published data only}
    1. Kalfarentzos F, Kehagias J, Mead N, Kokkinis K, Gogos CA. Enteral nutrition is superior to parenteral nutrition in severe acute pancreatitis: results of a randomized prospective trial. British Journal of Surgery 1997;84(12):1665‐9. [PUBMED: 9448611] - PubMed
Karlstadt 1993 {published data only}
    1. Karlstadt RG, Hedrich DA, Asbel‐Sethi NR, Palmer RH. Acid‐suppression profile of two continuously infused intravenous doses of cimetidine. Clinical Therapeutics 1993;15(1):97‐106. [PUBMED: 8458059] - PubMed
Ketterl 1984 {published data only}
    1. Ketterl R, Holscher AH, Weiser HF, Siewert JR. Control of the intragastric pH value in infection and peritonitis by ranitidine versus cimetidine. A double‐blind study [Kontrolle des intragastralen pH‐Wertes bei Sepsis bzw. Peritonitis durch Ranitidin versus Cimetidin‐‐Eine Doppelblindstudie]. Zeitschrift fur Gastroenterologie 1984;22(10):602‐8. [PUBMED: 6095549] - PubMed
Khan 1981 {published data only}
    1. Khan F, Parekh A, Patel S, Chitkara R, Rehman M, Goyal R. Results of gastric neutralization with hourly antacids and cimetidine in 320 intubated patients with respiratory failure. Chest 1981;79(4):409‐12. - PubMed
Klarin 2008 {published data only}
    1. Klarin B, Molin G, Jeppsson B, Larsson A. Use of the probiotic Lactobacillus plantarum 299 to reduce pathogenic bacteria in the oropharynx of intubated patients: a randomised controlled open pilot study. Critical Care (London, England) 2008;12(6):R136. [PUBMED: 18990201] - PMC - PubMed
Krag 2015 {published data only}
    1. Krag M, Perner A, Wetterslev J, Wise MP, Borthwick M, Bendel S, et al. Prevalence and outcome of gastrointestinal bleeding and use of acid suppressants in acutely ill adult intensive care patients. Intensive Care Medicine 2015;41(5):833‐45. - PubMed
Krier 1990 {published data only}
    1. Krier C, Bohrer H, Jurs G, Warth S, Just OH. Continuous intragastric pH measurement in intensive care patients treated with ranitidine and tube feeding [Kontinuierliche intragastrale pH‐Wert‐Messung bei Intensivepatienten unter Ranitidin‐ und Sondenkostgabe]. Anasthesie, Intensivtherapie, Notfallmedizin 1990;25 Suppl 1:10‐3. [PUBMED: 2106804] - PubMed
Krueger 2002 {published data only}
    1. Krueger WA, Lenhart FP, Neeser G, Ruckdeschel G, Schreckhase H, Eissner HJ, et al. Influence of combined intravenous and topical antibiotic prophylaxis on the incidence of infections, organ dysfunctions, and mortality in critically ill surgical patients: a prospective, stratified, randomized, double‐blind, placebo‐controlled clinical trial. American Journal of Respiratory and Critical Care Medicine 2002;166(8):1029‐37. [PUBMED: 12379544] - PubMed
Kuusela 1998 {published data only}
    1. Kuusela AL. Long‐term gastric pH monitoring for determining optimal dose of ranitidine for critically ill preterm and term neonates. Archives of Disease in Childhood. Fetal and Neonatal Edition 1998;78(2):F151‐3. [PUBMED: 9577289] - PMC - PubMed
Laterre 2001 {published data only}
    1. Laterre PF, Horsmans Y. Intravenous omeprazole in critically ill patients: a randomized, crossover study comparing 40 with 80 mg plus 8 mg/hour on intragastric pH. Critical Care Medicine 2001;29(10):1931‐5. [PUBMED: 11588454] - PubMed
Levine 1994 {published data only}
    1. Levine RL, Fromm RE Jr, Mojtahedzadeh M, Baghaie AA, Opekun AR Jr. Equivalence of litmus paper and intragastric pH probes for intragastric pH monitoring in the intensive care unit. Critical Care Medicine 1994;22(6):945‐8. [PUBMED: 7911416] - PubMed
Liu 2013 {published data only}
    1. Liu BL, Li B, Zhang X, Fei Z, Hu SJ, Lin W, et al. A randomized controlled study comparing omeprazole and cimetidine for the prophylaxis of stress‐related upper gastrointestinal bleeding in patients with intracerebral hemorrhage. Journal of Neurosurgery 2013;118(1):115‐20. [PUBMED: 23061387] - PubMed
Madani 2014 {published data only}
    1. Madani S, Kauffman R, Simpson P, Lehr VT, Lai ML, Sarniak A, et al. Pharmacokinetics and pharmacodynamics of famotidine and ranitidine in critically ill children. Journal of Clinical Pharmacology 2014;54(2):201‐5. - PubMed
McAlhany 1976 {published data only}
    1. McAlhany JC Jr, Colmic L, Czaja AJ, Pruitt BA Jr. Antacid control of complications from acute gastroduodenal disease after burns. Journal of Trauma 1976;16(08):645‐8. [PUBMED: 785019] - PubMed
McElwee 1979 {published data only}
    1. McElwee HP, Sirinek KR, Levine BA. Cimetidine affords protection equal to antacids in prevention of stress ulceration following thermal injury. Surgery 1979;86(4):620‐6. [PUBMED: 483170] - PubMed
Metz 2010 {published data only}
    1. Metz DC, Fulda GJ, Olsen KM, Monyak JT, Simonson SG, Sostek MB. Intravenous esomeprazole pharmacodynamics in critically ill patients. Current Medical Research Opinion 2010;26(5):1141‐8. [DOI: 10.1185/03007991003694308] - DOI - PubMed
Misra 2005 {published data only}
    1. Misra UK, Kalita J, Pandey S, Mandal SK, Srivastava M. A randomized placebo controlled trial of ranitidine versus sucralfate in patients with spontaneous intracerebral hemorrhage for prevention of gastric hemorrhage. Journal of the Neurological Sciences 2005;239(1):5‐10. [PUBMED: 16182311] - PubMed
Mojtahedzadeh 2002 {published data only}
    1. Mojtahedzadeh M, Rastegarpanah M, Rouini MR, Malekzadeh R, Khalili H, Ganji MR, et al. A comparative study of bolus administration and continuous infusion of ranitidine on gastric pH with intragastric pH‐probe. Daru 2002;10(4):153‐7.
More 1985 {published data only}
    1. More DG, Raper RF, Munro IA, Watson CJ, Boutagy JS, Shenfield GM. Randomized, prospective trial of cimetidine and ranitidine for control of intragastric pH in the critically ill. Surgery 1985;97(2):215‐24. [PUBMED: 3881838] - PubMed
Mulla 2001 {published data only}
    1. Mulla H, Peek G, Upton D, Lin E, Loubani M. Plasma aluminium levels during sucralfate prophylaxis for stress ulceration in critically ill patients on continuous venovenous hemofiltration: a randomized, controlled trial. Critical Care Medicine 2001;29(2):267‐71. [PUBMED: 11246304] - PubMed
Olsen 1995 {published data only}
    1. Olsen KM, Hiller FC, Ackerman BH, Crisp‐Landwehr K, San Pedro GS. Effect of single intravenous doses of histamine2 receptor antagonists on volume and pH of gastric acid secretions in critically ill patients. Health Advance 1995;56(8):756‐68.
Olsen 2008 {published data only}
    1. Olsen KM, Devlin JW. Comparison of the enteral and intravenous lansoprazole pharmacodynamic responses in critically ill patients. Alimentary Pharmacology & Therapeutics 2008;28(3):326‐33. [PUBMED: 19086331] - PubMed
Osteyee 1994 {published data only}
    1. Osteyee JL, Banner W Jr. Effects of two dosing regimens of intravenous ranitidine on gastric pH in critically ill children. American Journal of Critical Care 1994;3(4):267‐72. [PUBMED: 7920954] - PubMed
Pelfrene 1996 {published data only}
    1. Pelfrene E, Vandewoude K, Vogelaers D, Elewaut A, Colardyn F. The effect of cimetidine versus ranitidine on the gastric emptying rate of intensive care unit patients sustained on artificial respiration. Acta Gastro‐enterologica Belgica 1996;59(4):229‐33. [PUBMED: 9085622] - PubMed
Phillips 2001 {published data only}
    1. Phillips JO, Olsen KM, Rebuck JA, Rangnekar NJ, Miedema BW, Metzler MH. A randomized, pharmacokinetic and pharmacodynamic, cross‐over study of duodenal or jejunal administration compared to nasogastric administration of omeprazole suspension in patients at risk for stress ulcers. American Journal of Gastroenterology 2001;96(2):367‐72. [PUBMED: 11232677] - PubMed
Reid 1986 {published data only}
    1. Reid SR, Bayliff CD. The comparative efficacy of cimetidine and ranitidine in controlling gastric pH in critically ill patients. Canadian Anaesthetists' Society Journal 1986;33(3 Pt 1):287‐93. - PubMed
Ren 2015 {published data only}
    1. Ren XS, Chen YF. Pantoprazole for prevention of post‐traumatic stress ulcer [泮托拉唑应用于预防创伤后应激性溃疡的临床价值]. World Chinese Journal of Digestology 2015;23(7):1145‐8. [DOI: 10.11569/wcjd.v23.i7.1145] - DOI
Schentag 1989 {published data only}
    1. Schentag JJ, Carter CA, Welage LS. Safety and acid‐suppressant properties of histamine2‐receptor antagonists for the prevention of stress‐related mucosal damage in critical care patients. DICP: Annals of Pharmacotherapy 1989;23(10 Suppl):S36‐9. [PUBMED: 2573208] - PubMed
Simon 1984 {published data only}
    1. Simon B. Ranitidine versus cimetidine in preventing acute gastroduodenal bleeding: a randomised trial in 193 critically ill patients ‐ a multi centre study in Germany. Intensivmedizin 1984;21(1):15‐8.
Solana 2013 {published data only}
    1. Solana MJ, Lopez‐Herce J, Botran M, Urbano J, Castillo J, Garrido B. Hemodynamic effects of intravenous omeprazole in critically ill children. Anales de Pediatria 2013;78(3):167‐72. - PubMed
Sung 2003 {published data only}
    1. Sung JJ. The role of acid suppression in the management and prevention of gastrointestinal hemorrhage associated with gastroduodenal ulcers. Gastroenterology Clinics of North America 2003;32(3 Suppl):S11‐23. [PUBMED: 14556432] - PubMed
Taha 1996 {published data only}
    1. Taha AS, Hudson N, Hawkey CJ, Swannell AJ, Trye PN, Cottrell J, et al. Famotidine for the prevention of gastric and duodenal ulcers caused by nonsteroidal antiinflammatory drugs. New England Journal of Medicine 1996;334(22):1435‐9. [PUBMED: 8618582] - PubMed
Tofil 2008 {published data only}
    1. Tofil NM, Benner KW, Fuller MP, Winkler MK. Histamine 2 receptor antagonists vs intravenous proton pump inhibitors in a pediatric intensive care unit: a comparison of gastric pH. Journal of Critical Care 2008;23(3):416‐21. [PUBMED: 18725049] - PubMed
Toyota 1998 {published data only}
    1. Toyota N, Takada T, Yasuda H, Amano H, Yoshida M, Isaka T, et al. The effects of omeprazole, a proton pump inhibitor, on early gastric stagnation after a pylorus‐preserving pancreaticoduodenectomy: results of a randomized study. Hepato‐gastroenterology 1998;45(22):1005‐10. [PUBMED: 9755997] - PubMed
Udd 2005 {published data only}
    1. Udd M, Toyry J, Miettinen P, Vanninen E, Mustonen H, Julkunen R. The effect of regular and high doses of omeprazole on the intragastric acidity in patients with bleeding peptic ulcer treated endoscopically: a clinical trial with continuous intragastric pH monitoring. European Journal of Gastroenterology & Hepatology 2005;17(12):1351‐6. [PUBMED: 16292089] - PubMed
Vaduganathan 2016 {published data only}
    1. Vaduganathan M, Bhatt DL, Cryer BL, Liu, Y, Hsieh, WH, Doros G, et al. Proton‐pump inhibitors reduce gastrointestinal events regardless of aspirin dose in patients requiring dual antiplatelet therapy. Journal of the American College of Cardiology 2016;67(14):1661‐71. - PubMed
Vargas 1993 {published data only}
    1. Vargas V, Castro J, Solar F, Sanhueza H, Aguila R, Luppi M, et al. Comparative study of famotidine vs ranitidine in critically ill patients in mechanical ventilation [Estudio comparativo de famotidina vs ranitidina en pacientes criticos en ventilacion mecanica]. Revista Medica de Chile 1993;121(7):746‐51. [PUBMED: 8296077] - PubMed
Wang 1995 {published and unpublished data}
    1. Wang SC, Chen MF, Bullard MJ, Liao CC. The effectiveness of gastric pH control with bolus famotidine versus cimetidine for stress ulcer prophylaxis in a surgical intensive care unit. Current Theraputic Research 1995;56(5):530‐41.
Yao 2015 {published data only}
    1. Yao D‐K, Chen H, Wang L, Li H‐W, Wang L‐X. Comparison of intravenous plus oral pantoprazole therapy and oral pantoprazole alone for preventing gastrointestinal bleeding in acute coronary syndrome patients with high bleeding risk. Heart, Lung & Circulation 2015;24(9):885‐90. - PubMed
Zhou 2002 {published data only}
    1. Zhou Y, Qiao L, Wu J, Hu H, Xu C. Comparison of the efficacy of octreotide, vasopressin, and omeprazole in the control of acute bleeding in patients with portal hypertensive gastropathy: a controlled study. Journal of Gastroenterology and Hepatology 2002;17(9):973‐9. [PUBMED: 12167118] - PubMed

References to studies awaiting assessment

Labattut 1992 {published data only}
    1. Labattut AG, Santolalla PM, Andres AP, Ortigosa AM, Del MM, Serrano G, et al. Efficacy of sucralfate in the prevention of upper gastrointestinal stress bleeding in intensive care patients: comparison vs a control group. Clinical Intensive Care 1992;3(5 Suppl):19‐25.
Morris 2001 {published data only}
    1. Morris J, Karlstadt R, Blatcher D, et al. Intermittent intravenous pantoprazole rapidly achieves and maintains gastric pH ≥ 4.0 compared with continuous infusion H2‐receptor antagonist in intensive care unit patients. Critical Care Medicine 2001;29:A147.

References to ongoing studies

ACTRN12616000481471 {published data only}
    1. ACTRN12616000481471. Proton pump inhibitors vs. histamine‐2 receptor blockers for ulcer prophylaxis therapy in the intensive care unit [A multi‐centre, cluster randomised, crossover, registry trial comparing the safety and efficacy of proton pump inhibitors with histamine‐2 receptor blockers for ulcer prophylaxis in intensive care patients requiring invasive mechanical intervention]. anzctr.org.au/ACTRN12616000481471.aspx (first received 7 April 2016).
EUCTR2015‐000318‐24‐DK {published data only}
    1. EUCTR2015‐000318‐24‐DK. Stress ulcer prophylaxis in the intensive care unit. clinicaltrialsregister.eu/ctr‐search/search?query=EUCTR2015‐000318‐24‐DK (first received 11 March 2015).
EudraCT 2007‐006102‐19 {published data only}
    1. EudraCT 2007‐006102‐19. Omeprazole treatment for prophylaxis of gastrointestinal bleeding and gastroesophagic reflux in critically ill children [Tratamiento con omeprazol para la profilaxis de la hemorragia digestiva y el reflujo gastroesofágico en niños críticos]. clinicaltrialsregister.eu/ctr‐search/trial/2007‐006102‐19/ES (first received 23 January 2008).
IRCT201104134578N2 {published data only}
    1. IRCT201104134578N2. Ranitidine and pantoprazole in prevention of stress ulcer. http://apps.who.int/trialsearch/Trial.aspx?TrialID=IRCT201104134578N2 (accessed 24 Feburary 2012).
ISRCTN12845429 {published data only}
    1. ISRCTN12845429. DRIVE ‐ desmopressin for procedures or radiological interventions [A placebo‐controlled double blind, randomised feasibility trial of Desmopressin (DDAVP) in critical illness prior to procedures]. isrctn.com/ISRCTN12845429 (first received 30 January 2017).
Krag 2016 {published data only}
    1. Krag M, Perner A, Wetterslev J, Lange T, Wise MP, Borthwick M, et al. Stress ulcer prophylaxis in the intensive care unit trial: detailed statistical analysis plan. Acta Anaesthesiologica Scandinavica 2017;61(7):859‐68. - PubMed
    1. Krag M, Perner A, Wetterslev J, Wise MP, Borthwick M, Bendel S, et al. Stress ulcer prophylaxis with a proton pump inhibitor versus placebo in critically ill patients (SUP‐ICU trial): study protocol for a randomised controlled trial. Trials 2016;17(1):205. - PMC - PubMed
NCT00590928 {published data only}
    1. NCT00590928. Gastric pH in critically ill patients [Effect of intravenous esomeprazole versus ranitidine on gastric pH in critically ill patients ‐ a prospective, randomized, double‐blind study]. clinicaltrials.gov/show/NCT00590928 (first received 11 January 2008).
NCT00702871 {published data only}
    1. NCT00702871. A clinico‐bacteriological study and effect of stress ulcer prophylaxis on occurrence of ventilator associated pneumonia [A clinico‐bacteriological study and effect of stress ulcer prophylaxis on occurrence of ventilator associated pneumonia: a randomized prospective study]. clinicaltrials.gov/show/NCT00702871 (first received 20 June 2008).
NCT02157376 {published data only}
    1. NCT02157376. Stress ulcer prophylaxis of intravenous esomeprazole in Chinese seriously ill patients (SUP) [Effect of intravenous esomeprazole versus cimetidine in prevention of stress ulcer prophylaxis in Chinese seriously ill patients ‐ a randomized, double‐blind, parallel‐group study]. clinicaltrials.gov/show/NCT02157376 (first received 6 June 2014).
NCT02290327 {published data only}
    1. NCT02290327. Re‐evaluating the inhibition of stress erosions: gastrointestinal bleeding prophylaxis In ICU (REVISE). clinicaltrials.gov/show/NCT02290327 (first received 14 November 2014).
NCT02718261 {published data only}
    1. NCT02718261. Sup‐Icu RENal (SIREN) [Sup‐Icu RENal (SIREN) ‐ a sub‐analysis of the prospective SUP (Stress Ulcer Prophylaxis)‐ICU trial on the risk of GI‐bleeding in ICU patients receiving renal replacement therapy]. clinicaltrials.gov/show/NCT02718261 (first received 24 March 2016).
NCT03098537 {published data only}
    1. NCT03098537. Effects of enteral nutrition on stress ulcer hemorrage. Multicenter randomized controlled trial. clinicaltrials.gov/show/NCT03098537 (first received 31 March 2017).

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References to other published versions of this review

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