British Medical Journal - Ranitidine and gastrointestinal bleeding in intensive care - Brief Article - Letter to the Editor
Should prophylaxis against stress ulcer be abandoned for patients in intensive care?
EDITOR–The meta-analysis of Messori et al clearly confirms the lack of usefulness of systematic prophylaxis against stress ulcer with [H.sub.2] receptor antagonists or sucralfate,[1] but an important issue is left unanswered by this study and by the meta-analysis of Cook et al.[2] Indeed, some critically ill patients receive prophylaxis against stress ulcers for specific reasons, including brain injury (trauma, surgery, haemorrhage), steroid treatment, and coagulation abnormalities.
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Does the available literature support such prophylaxis for these patients? In other words, should intensivists prescribe stress ulcer prophylaxis for selected subgroups of patients? If the available literature does not resolve this issue, should the further trials suggested by Messori et al stratify the groups according to the patient’s condition?
Jean-Charles Preiser clinical director Clinique Reine Fabiola, 73 avenue du Centenaire, B6061 Montignies-sur-Sambre, Belgium preiserj@ulb.ac.be
[1] Messori A, Trippoli S, Vaiani M, 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;321:1103-6. (4 November.)
[2] Cook D, Reeve BK, Guyatt GH, Heyland DK, Griffith LE, Buckingham L, et al. Stress ulcer prophylaxis in critically ill patients: resolving discordant meta-analyses. JAMA 1996;275:308-14.
Occult blood loss is clinically important
EDITOR–Intensive care has always been a difficult area for research.
Firstly, patients are rarely able to give informed consent, which places increased pressure on researchers and ethics committees to ensure patients are not exposed to risk. This makes placebo controlled trials difficult even when the standard treatment has no good evidence for effect.
Secondly, the patient population is variable and often small in number, which makes comparison and recruitment of sufficient numbers for statistical analysis difficult. This is borne out by the meta-analysis by Messori et al, in which meta-analysis B assessing the effectiveness of sucralfate consisted of one paper.[1]
We also have problems with the outcome used in meta-analysis A, comparing ranitidine with placebo. In four out of five papers the outcome was acute, rapid blood loss as seen by melaena, red blood through a nasogastric tube, or haemodynamic changes. These are the signs of an acutely bleeding vessel in an ulcer, as is often seen in patients presenting to accident and emergency with haematemesis. The usual pathology in intensive treatment units is different, with the presence of multiple small ulcers, stress ulcers, causing continual, low grade blood loss, breakdown of mucosal defences, and increased need for transfusion. Few of these ulcers go on to erode gastric vessels and cause dramatic blood loss. However, 75-100% of patients with critical illness develop these within three days of being admitted to intensive treatment units, even in the absence of low perfusion states[2] We dispute the implication from the paper by Messori et al that this occult blood loss is not clinically important. A paper by Burgess et al suggested a benefit with ranitidine.[3]
The argument for prophylaxis against stress ulcer has now moved on from sucralfate with the renewed emphasis on early enteral feeding, including the instillation of enteral feed at a low rate even in patients with high nasogastric aspirates and ileus.[4]
Finally, there is the issue of prevention of aspiration by using pharmacological agents. Endotracheal intubation or tracheostomy are not absolute guardians of the airway, and leakage of material past the balloon of the airway device is a real risk, in both intensive care and anaesthesia. Ranitidine has been shown to reduce gastric acidity during periods of high risk, and its use should still be considered in the intensive treatment unit during manipulation of the airway. Overall, it is our practice to use stress ulcer prophylaxis in all patients having intensive treatment; the agent will depend on the individual patient. We find it difficult to criticise any of our colleagues’ choices in this contentious area.
Tim Dexter consultant anaesthetist
Stephen Drage specialist registrar in anaesthetics drage@clara.net Wycombe Hospital, Wycombe HP11 2TT
[1] Messori A, Trippoli S, Vaiani M, 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;321:1103-6. (4 November.)
[2] Shuman RB, Schuster DP, Zuckerman GR. Prophylactic therapy for stress ulcer bleeding: a reappraisal. Ann Intern Med 1987;106:562-7.
[3] Burgess P, Larson GM, Davidson P, Brown M, Metz CA. Effect of ranitidine on intragastric pH and stress related upper gastrointestinal bleeding in patients with severe head injury. Dig Dis Sci 1995;40:645-50.
