Web site designed and maintained by Chris Cairns  © SICS EBM Group 2004                                  

Gastric Prophylaxis

Principal investigators: Dr Chris Cairns & Dr Tim Walsh

Currently investigating the Evidence comparing Ranitidine and Sucralfate for gastric prophylaxis

Current State: Complete

Gastric Prophylaxis – The Battle of Sucralfate & Ranitidine

¹Chris Cairns, ²Tim Walsh 

¹Specialist Registrar, ²Senior Lecturer, Intensive Care Unit, Edinburgh Royal Infirmary, Lauriston Place, Edinburgh, EH3 9YW

Correspondence: Chris.Cairns@btinternet.com

 SICS EBMG web site. January 2003

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Background:

Clinically significant upper gastrointestinal haemorrhage occurs in only 2% of critically ill patients. For several years there has been debate over (1) which patients are at a significantly high risk to merit prophylactic treatment, (2) what is the most effective prophylactic treatment, (3) what complications are associated with these regimens. Most work has compared the H₂ blocker ranitidine with sucralfate. The evolution of the worldwide investigation of these questions highlights the development of EBM practice. Three early meta-analysis [1-3] came to different conclusions when investigating the differences in efficacy and complications of ranitidine and sucralfate. These demonstrated many of the limitations of meta-analysis especially when the majority of papers analyzed are poorly designed with small patient groups. The authors of the discordant meta-analysis combined forces on a joint publication [5], correcting many of the previous publications shortcomings and concluding that a large RCT was needed to resolve the question of whether there was a significant benefit in using ranitidine or sucralfate. At the same time a better understanding was developing of which patients were at higher risk of clinically significant bleeds [4].A large RCT was conducted [6] by the authors of the meta-analysis.

More recently, with the increasing rates of enteral feeding in the critically ill, the question of which patients are at significantly great enough risk of bleeding to merit prophylactic treatment has been revisited [8-9]. We reviewed the current literature and present our findings and conclusions below.

Search Strategy: Ranitidine, Sucralfate, Human, RCT & meta-analysis 

Selection Criteria: RCTs and meta-analysis after 1991 

Data Collection and analysis: PubMed search, hand search of relevant papers. Data analysed using CATmaker™ software.

 Main Results:

The incidence of clinically significant bleeding is approximately 2% in the critically ill. Patients at significant risk of clinically significant GI haemorrhage are those that are; ventilated for more than 48 hours (OR15.5), coagulopathic (OR4.3). In ventilated patients the presence of acute renal failure leads to an additional risk of bleeding (OR 2.58)

When considering prophylaxis in all patients; Ranitidine provides superior protection against bleeding than sucralfate but mortality rates are not significantly different. Rates of ventilator-associated pneumonia are higher with ranitidine but this is not statistically significant. 

When patients that have been intubated for more than 48 hours; enteral nutrition is associated with a lower risk of bleeding (OR 0.3). Ranitidine administration also lowers the risk of bleeding (OR 0.39). Ranitidine may offer some additive benefit to feeding alone.

 Reviewers Conclusions (Grades of recommendation):

• All intubated patients admitted to ICU should receive ranitidine prophylaxis especially if they are coagulopathic or in renal failure (A)

• Enteral feeding should be commenced as soon as possible (C)

• Until further data is available ranitidine should be continued even when enteral feeding is established (C)

• Discharged patients, if extubated, should have their ranitidine stopped unless they still have renal failure or are coagulopathic (D)

Areas of further research:

1.      RCT comparing enteral feeding alone with feeding and ranitidine

2.      Proton pump inhibitors

Citations with links to CATs: 

1. Tryba M. Prophylaxis of Stress Ulcer Bleeding, a Meta-analysis. J Clin Gastroenteron. 1991;13(Suppl.):S44-S55 (no cat as insufficientt data in paper)                                                                                                                                                                                    

2. Cook DJ, Witt LG, Cook RJ, Guyatt GH. Stress Ulcer Prophylaxis in the Critically Ill: A Meta-Analysis. The American Journal of Medicine. 1991. 91;519-527 cat

3. Cook DJ, L.A. Laine, G.H. Guyatt, T.A. Rafin. Nosocomial Pneumonia and the Role of Gastric pH. A Meta-Analysis. Chest 1991; 100;1: 7-13 cat

4. Cook DJ, et al for the Canadian Clinical Trails Group. Risk factors for Gastrointestinal Bleeding in Critically ill patients. The New England Journal Of Medicine. 1994;330:377-81 cat

5. Cook DJ, Reeve BK, Guyatt GH, Heyland DK, Griffiths LE, Buckingham L, Tryba M Stress Ulcer Prophylaxis in Critically Ill Patients.  JAMA. 1996. 275;4: 308-314 cat 

6.  O'Keefe GE et al. Incidence of Infectious Complications Associated With the Use Of Histamine2-Receptor Antagonists in Critically Ill Trauma Patients. Annals of Surgery. 1998. 227;(1):120-125 cat

7.  Cook DJ et al for the Canadian Critical Care Trials Group. A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation. NEJM 1998; 338:791-7 cat

8.  Cook DJ et al for The Canadian Clinical Trials Group. Risk Factors for Clinically important upper Gastrointestinal bleeding in patients requiring mechanical ventilation. Critical Care Medicine. 1999;27(12):2812-2817  cat

9.  Messori A, Troppoli S, Gorini M, Corrado A. Bleeding and pneumonia in intensive care patients given ranitidine and sucralfate for prevention of stress ulcer: meta-analysis of randomised controlled trials. BMJ 2000;321:1-7 cat

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