Current issues of ACP Journal Club are published in Annals of Internal Medicine


Respiratory failure and coagulopathy predicted gastrointestinal bleeding in adults who were critically ill

ACP J Club. 1994 July-Aug;121:24. doi:10.7326/ACPJC-1994-121-1-024

Source Citation

Cook DJ, Fuller HD, Guyatt GH, et al. Risk factors for gastrointestinal bleeding in critically ill patients. N Engl J Med. 1994 Feb 10;330:377-81.



To ascertain the incidence of and risk factors for gastrointestinal stress ulceration in patients admitted to intensive care units (ICUs).


Cohort analytic study.


4 university-affiliated medical-surgical ICUs in Canada.


2252 patients (mean age 60 y, 66% men) admitted to an ICU. Exclusion criteria were upper gastrointestinal bleeding within 48 hours before or 24 hours after admission; previous total gastrectomy, facial trauma, or epistaxis; brain death; hopeless prognosis; or death or discharge within 24 hours of admission.

Assessment of risk factors

Age, sex, admitting diagnosis, and score on the Acute Physiology and Chronic Health Evaluation (APACHE II) scale were recorded within 24 hours of admission. Daily evaluations included assessment for sepsis, hypotension, renal failure, coagulopathy, and hepatic failure; the presence of a Glasgow coma score < 5; administration of heparin, warfarin sodium, glucocorticoids, aspirin, or another nonsteroidal anti-inflammatory drug; the use of active enteral feeding; and the use of prophylaxis against stress ulceration.

Main outcome measures

Overt bleeding defined as hematemesis, gross blood or coffee grounds material in a nasogastric aspirate, hematochezia, or melena; and clinically important bleeding (causing hypotension, tachycardia, or need for transfusion).

Main results

100 patients (4.4%, 95% CI 3.6% to 5.6%) had overt bleeding episodes and 33 (1.5%, CI 1.0% to 2.1%) had clinically important bleeding. Using multiple regression analysis, 2 independent risk factors for bleeding were identified: respiratory failure requiring mechanical ventilation for > 48 hours (odds ratio [OR] 15.6) and coagulopathy (OR 4.3). Of 847 patients who had one or both of these risk factors, 31 (3.7%, CI 2.5% to 5.2%) had clinically important bleeding. Of 1405 patients without these risk factors, 2 (0.1%, CI 0.02% to 0.5%) had clinically important bleeding. The mortality rate among the patients with clinically important bleeding was 48% compared with 9% in all other patients (P < 0.001).


Prophylaxis against stress ulcers could be safely withheld from critically ill patients unless they had coagulopathy or required mechanical ventilation.

Source of funding: Ontario Ministry of Health.

For article reprint: Dr. D.J. Cook, Department of Medicine, Division of Critical Care, St. Joseph's Hospital, 50 Charlton Avenue East, Hamilton, Ontario L8N 4A6, Canada. FAX 905-521-6068.


Cook and colleagues have done us a great service by objectively clarifying that patients without either of 2 risk factors are very unlikely to benefit from stress ulcer prophylaxis. For patients without coagulopathy and respiratory failure requiring mechanical ventilation, 900 would have to be treated to prevent 1 episode of important bleeding. Even drugs with good safety profiles, such as histamine-2 antagonists, sucralfate, and antacids, have financial as well as physiologic costs. Because, at most, 0.5% (the upper limit of the 95% CI) of patients "not at significant risk" or at "extremely low risk" might have major hemorrhage, we cannot ignore these costs. When the lack of change in mortality of all critically ill patients treated with prophylactic regimens is factored in, we would likely need to justify our use of them rather than our "withholding" of medication (1).

This article comes at a time when the routine is to provide all patients admitted to the ICU with some form of prophylaxis. Stress-related mucosal damage is a complex disease. Its exact cause is unclear, but it appears that the same factors that lead to the multiple organ failure syndrome (MOFS) and death in the ICU environment are responsible. These include tissue hypoxia, effects of mediators, and a relative lack of certain metabolic substrates. Patients who are at risk for MOFS, that is, those with respiratory failure or coagulopathy, should continue to receive prophylaxis to prevent clinically important bleeding. As pointed out in the accompanying editorial (2), however, a study of high-risk patients randomly assigned to prophylaxis or no therapy needs to be done to determine if even these high-risk patients will benefit or if stress-related mucosal damage is merely a reflection of severity of illness. In the meantime, we may find a treatment of MOFS that prevents this and other complications in a more elementary way.

Christopher M. Hughes, MD
Monongahela Valley HospitalMonongahela, Pennsylvania, USA


1. Cook DJ, Witt LG, Cook RJ, Guyatt GH. Stress ulcer prophylaxis in the critically ill: a meta-analysis. Am J Med. 1991;91:519-27. [Erratum. Am J Med. 1991;91:670.]

2. Peterson WL. . Prevention of upper gastrointestinal bleeding [Editorial]. N Engl J Med. 1994;330:428-9.