Evidence-Based Medicine
June 12, 2009
Megan Brundrett
Risk Factors for Gastrointestinal Bleeding in Critically Ill Patients. Cook et al.
New England Journal of Medicine. 1994; 300:377-381.
Question: Are there specific risk factors in hospitalized patients that require GI
prophylaxis?
Background: There had been an association made that GI prophylaxis helps
prevent GI bleeding in critically ill patients. As a result, GI prophylaxis had been
widely used in the critical care setting. This study attempted to recognize the risk
factors associated with significant bleeding in order to target those with the most
risk.
Study Design: Prospective cohort study. Multicenter study.
Study Participants: 2252 patients >16 yo admitted to intensive care units at 4
university intensive care units between June 1990-July 1991.
Exclusion Criteria: Recent UGI bleed (within 48 hours or 24 hours after
admission), total gastrectomy, facial trauma, epitaxis, brain death, hopeless
prognosis, or if they died or discharged within 24 hours of admission.
Outcome Measures: Significant bleeding which is defined by gross blood or
coffee ground in NG tube that is accompanied by decrease in systolic BP of 20,
increase in HR of 20, decrease in hemoglobin by 2 requiring transfusion that did
not respond appropriately.
 These criteria were reviewed by 3 adjudicators who were not involved in
patient care.
Statistical Analysis: Simple-regression analysis of 12 potential risk factors –
which looked at variables that could be associated with bleeding. Any variable
that seemed to be statistically significant (P < 0.05) was then entered into a
multiple logistic-regression analysis and tested for interaction. Out of the multiple-
regression analysis came the variables that seemed to be independent risk
factors.
Results: 2252 patients were included in the study. 674 patients received ulcer
prophylaxis with famotidine, sulcrafate, antacids, prostaglandin, omeprazole, or a
combination of these therapies. 1578 patients did not receive GI prophylaxis. 33
total patients had significant bleeding events.
 674 patient who received GI proph – were a generally sicker population,
with an increased mortality rate, and longer length of stay, compared to
the 1578 patients that did not receive prophylaxis.
 23 patients in the GI prophylaxis group bled, and 10 patients who did not
receive prophylaxis bled.
 The only independent risk factors from the multiple regression analysis
were noted to be respiratory failure requiring mechanical ventilation for >
48 hours and coagulopathy.
 The incidence of bleeding in the group with prophylaxis was 3.4%, and the
incidence was 0.6% in the non-prophylaxis group.
 Odds ratio of mechanically ventilated was 15.6 (P <0.001)
Validity:
-- Were the patients randomized? No, prospective study.
-- Were the patients similar at the start of the study? Not really, as well as the
patients excluded from the trial seemed to be a sicker population.
-- Does the multiple regression analysis remove all the variables? No.
-- Can I use this trial to make a clinical decision? No.
Strengths:
 Attempt to determine independent risk factors to decrease wide spread
use of GI prophylaxis.
Weakness:
 Cohort study, can only show associations.

Cannot control for all variables.
 No further analysis of data – which could determine likelihood ratio.
Discussion: Mechanical ventilation was shown to be associated with increased
incidence of significant GI bleeding but this can not be assumed to be a causal
relationship. The incidence is low (1-2%) of GI bleeding in the critical care
setting, but it may be worth while to look at this in a randomized control trial.
Health care providers continue to use GI prophylaxis, likely more than needed,
for a problem that has not seemed to be worked out yet.