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Original Article
Volume 330:377-381 February 10, 1994 Number 6
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Risk Factors for Gastrointestinal Bleeding in Critically Ill Patients
Deborah J. Cook, Hugh D. Fuller, Gordon H. Guyatt, John C. Marshall, David Leasa, Richard Hall, Timothy L. Winton, Frank Rutledge, Thomas Todd, Peter Roy, Jacques Lacroix, Lauren Griffith, Andrew Willan, for The Canadian Critical Care Trials Group

 

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ABSTRACT

Background The efficacy of prophylaxis against stress ulcers in preventing gastrointestinal bleeding in critically ill patients has led to its widespread use. The side effects and cost of prophylaxis, however, necessitate targeting preventive therapy to those patients most likely to benefit.

Methods We conducted a prospective multicenter cohort study in which we evaluated potential risk factors for stress ulceration in patients admitted to intensive care units and documented the occurrence of clinically important gastrointestinal bleeding (defined as overt bleeding in association with hemodynamic compromise or the need for blood transfusion).

Results Of 2252 patients, 33 (1.5 percent; 95 percent confidence interval, 1.0 to 2.1 percent) had clinically important bleeding. Two strong independent risk factors for bleeding were identified: respiratory failure (odds ratio, 15.6) and coagulopathy (odds ratio, 4.3). Of 847 patients who had one or both of these risk factors, 31 (3.7 percent; 95 percent confidence interval, 2.5 to 5.2 percent) had clinically important bleeding. Of 1405 patients without these risk factors, 2 (0.1 percent; 95 percent confidence interval, 0.02 to 0.5 percent) had clinically important bleeding. The mortality rate was 48.5 percent in the group with bleeding and 9.1 percent in the group without bleeding (P<0.001).

Conclusions Few critically ill patients have clinically important gastrointestinal bleeding, and therefore prophylaxis against stress ulcers can be safely withheld from critically ill patients unless they have coagulopathy or require mechanical ventilation.

Gastrointestinal bleeding due to stress ulceration is an important complication in critically ill patients1,2. Prophylactic measures such as neutralization of gastric acid, reduction of gastric acid secretion, or cytoprotection are commonly recommended, on the basis of the positive results of randomized trials3,4,5,6,7,8,9,10,11,12,13,14,15. A recent meta-analysis reported a 50 percent reduction in the relative risk of clinically important bleeding among patients receiving prophylaxis16.

Prophylaxis against stress ulcers, however, is expensive17 and may have adverse effects,18 and the risk of clinically important bleeding has decreased during the past decade independently of the use of prophylaxis1,19,20,21. We undertook this prospective study to determine the incidence of clinically important gastrointestinal bleeding in a heterogeneous group of critically ill patients and to identify patients at sufficiently low risk of bleeding to obviate the need for prophylaxis.

Methods

Study Design

Consecutive patients more than 16 years old who were hospitalized between June 1990 and July 1991 at four university-affiliated medical-surgical intensive care units were considered for enrollment. Patients were ineligible if they had upper gastrointestinal bleeding (hematemesis, a nasogastric aspirate containing gross blood or "coffee grounds" material, hematochezia, or melena) within 48 hours before or 24 hours after admission, previous total gastrectomy, facial trauma or epistaxis, brain death, or a hopeless prognosis or if they died or were discharged within 24 hours after admission. Limited resources at three centers forced us to enroll subgroups of patients chosen by random allocation and to close enrollment on weekends during part of the study period.

We encouraged the attending physicians to withhold prophylaxis against stress ulcers in all patients21 except those with head injury, burns over more than 30 percent of the body-surface area, organ transplants, an endoscopic or radiographic diagnosis of peptic ulcer or gastritis in the preceding six weeks, or upper gastrointestinal bleeding three days to six weeks before admission. Prophylaxis against stress ulcers was defined as the administration of two or more doses of histamine H2-receptor antagonists, antacids, sucralfate, prostaglandin analogues, or omeprazole.

We recorded the age, sex, admitting diagnosis, and score on the Acute Physiology and Chronic Health Evaluation (APACHE II)22 scale of all eligible patients within 24 hours after admission. Daily evaluations included assessment for sepsis (defined as the presence of a core temperature >38.5 °C [>101.3 °F] or <35.0 °C [<95.0 °F], a white-cell count >15,000 per cubic millimeter or <3000 per cubic millimeter, and a positive blood culture); hypotension (either a systolic blood pressure <80 mm Hg for 2 hours or more or a decrease of >= 30 mm Hg in the systolic blood pressure); renal failure (a creatinine clearance rate <40 ml per minute, oliguria [<500 ml of urine per day], or a serum creatinine concentration >2.8 mg per deciliter [248 µmol per liter]); coagulopathy (a platelet count <50,000 per cubic millimeter, an International Normalized Ratio of >1.5 [i.e., prothrombin time >1.5 times the control value], or a partial-thromboplastin time >2.0 times the control value); hepatic failure (any two of the following: a serum bilirubin concentration >8.8 mg per deciliter [150 µmol per liter], a serum aspartate aminotransferase level >500 U per liter, a serum albumin level <41 g per liter, and clinical signs and symptoms of hepatic coma); the presence of a Glasgow coma score <5; administration of heparin or warfarin sodium, glucocorticoids (>200 mg of hydrocortisone or the equivalent per day), aspirin, or another nonsteroidal antiinflammatory drug; respiratory failure (a need for mechanical ventilation for at least 48 hours); the use of active enteral feeding; and the use of prophylaxis against stress ulceration (two or more doses).

The end points we studied16,21 were overt bleeding (defined as hematemesis, gross blood or "coffee grounds" material in a nasogastric aspirate, hematochezia, or melena) and clinically important bleeding. Clinically important bleeding was defined as overt bleeding complicated by one of the following within 24 hours after the onset of bleeding (in the absence of other causes): a spontaneous decrease of more than 20 mm Hg in the systolic blood pressure; an increase of more than 20 beats per minute in the heart rate, or a decrease of more than 10 mm Hg in the systolic blood pressure measured on sitting up; or a decrease in the hemoglobin level of more than 2 g per deciliter (1.2 mmol per liter) and subsequent transfusion, after which the hemoglobin did not increase by a value defined as the number of units transfused minus 2 g per deciliter. These criteria were applied independently by three outcome adjudicators who were not involved in patient care; disagreements were resolved by repeated reviews or by a fourth adjudicator.

Statistical Analysis

We conducted a forward stepwise logistic-regression analysis of the 12 potential risk factors evaluated daily, plus the following variables: age; APACHE score; head injury; multiple trauma; receipt of a transplant; status one week or less after a cardiovascular, thoracic, abdominal, pelvic, orthopedic, neurosurgical, or peripheral vascular procedure; surface burn; peptic ulcer or gastritis within six weeks of admission to the intensive care unit; and upper gastrointestinal bleeding three days to six weeks before admission. Variables that were significantly associated (P<0.05) with clinically important bleeding in a simple regression analysis were entered into a multiple logistic-regression analysis and tested for interaction. The analysis was repeated for the subgroup of patients who did not receive prophylaxis. All statistical tests were two-tailed.

Results

Of the 3241 patients admitted to intensive care units during the study, 413 were ineligible. Among these 413 patients, 227 had upper gastrointestinal bleeding (77 had hematemesis, 77 had grossly bloody nasogastric aspirates, 37 had nasogastric aspirates containing "coffee grounds" material, 18 had hematochezia, and 18 had melena), 25 had previously undergone total gastrectomy, 32 had facial trauma, 6 had epistaxis, 10 were brain-dead, and 113 had a hopeless prognosis. An additional 538 patients were admitted when resources were insufficient to enroll all patients; among them 299 were admitted on a weekend. Another 38 patients died or were discharged from the intensive care unit within 24 hours after admission. The characteristics of the remaining 2252 eligible patients are shown in Table 1.

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  		Table 1. Characteristics of 2828 Eligible Patients Admitted to an Intensive Care Unit.

 
Of these 2252 patients, 674 received prophylaxis against stress ulcers. Their sex distribution and APACHE scores were similar to those of the other 1578 patients, but they were slightly younger (59 vs. 60 years, P = 0.02), had longer stays in the intensive care unit (eight vs. three days, P<0.001), and had higher mortality (16.8 percent vs. 6.7 percent, P<0.001). The indications for prophylaxis against stress ulcers are shown in Table 2. The prophylactic treatment was an H2-receptor antagonist in 71.8 percent of the cases, sucralfate in 7.0 percent, antacids in 4.9 percent, a prostaglandin in 0.6 percent, omeprazole in 0.3 percent, and a combination of drugs in 15.4 percent. The median number of days of prophylaxis was as follows: H2-receptor antagonists, 2 days; sucralfate, 3 days; antacids, 2 days; prostaglandin, 1 day; omeprazole, 1 day; and multiple agents, 10 days. Of the 23 patients who bled while receiving prophylactic treatment, 3 bled within three days, 7 between three and seven days, and 13 more than one week after prophylaxis was started.

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  		Table 2. Indications for Prophylaxis against Stress Ulcer in 674 Patients Admitted to an Intensive Care Unit.

 
Of the 2252 patients, 100 had overt bleeding episodes (4.4 percent; 95 percent confidence interval, 3.6 to 5.6 percent); 87 of these 100 patients were receiving prophylaxis. Thirty-three patients had clinically important bleeding (1.5 percent; 95 percent confidence interval, 1.0 to 2.1 percent); 23 of them (69.7 percent) were receiving prophylaxis. Gastrointestinal bleeding occurred a mean (±SD) of 14 ±12 days after admission to the intensive care unit. The age, sex distribution, and APACHE scores were similar in the patients who had clinically important bleeding and those who did not (Table 3). The mortality rate among the patients with clinically important bleeding was 48.5 percent, as compared with 9.1 percent for all other patients (P<0.001) (Table 3). Agreement among the adjudicators on the presence of overt as opposed to clinically important bleeding was 81 percent after the first review and 100 percent after the second review. Agreement was 100 percent on the sources of bleeding.

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  		Table 3. Characteristics of 2252 Patients Admitted to an Intensive Care Unit, According to the Presence or Absence of Clinically Important Bleeding after Admission.

 
Among the 33 patients with clinically important bleeding, 19 had endoscopic documentation of the site of bleeding, and the site was seen at surgery in 3 other patients. The sources of bleeding in the 22 patients in whom a cause was identified were esophageal erosions (3 patients) or gastric erosions (8 patients, 3 of whom also had esophageal erosions); esophageal (1 patient), gastric (9 patients), or duodenal (7 patients) ulcers (a total of 11 patients had ulcers); esophageal and gastric varices (1 patient); Dieulafoy's vascular anomaly (1 patient); and an ileostomy anastomosis (1 patient). No upper gastrointestinal source was identified in 11 patients. Stress ulceration was present in the stomach and esophagus in four of eight patients in whom another bleeding site was identified.

The risk factors for clinically important bleeding are shown in Table 4. The only independent risk factors identified in the multiple regression analysis were respiratory failure requiring mechanical ventilation for more than 48 hours (odds ratio, 15.6) and coagulopathy (odds ratio, 4.3). Among the 33 patients with clinically important bleeding, 22 had both respiratory failure and coagulopathy, 8 had respiratory failure alone, 1 had coagulopathy alone, and only 2 patients had neither (Table 5). These two factors were predictive both in patients receiving prophylaxis (odds ratios, 18.2 and 2.6, respectively) and in those not receiving prophylaxis (odds ratios, 8.9 and 7.7, respectively). The incidence of bleeding was 3.4 percent in the group receiving prophylaxis and 0.6 percent in the group that did not receive prophylaxis, suggesting that physicians were able to identify patients at higher risk for bleeding. That the proportion of patients who had one or more risk factors was 58.0 percent among those receiving prophylaxis and 28.9 percent among those not receiving prophylaxis supports this inference.

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  		Table 4. Risk Factors for Clinically Important Bleeding among 2252 Patients Admitted to an Intensive Care Unit.

 
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  		Table 5. Clinically Important Gastrointestinal Bleeding among 2252 Patients Admitted to an Intensive Care Unit, According to the Presence or Absence of Respiratory Failure and Coagulopathy.

 
Of 847 patients at high risk (i.e., those who had respiratory failure or a coagulopathy), 31 had clinically important bleeding (3.7 percent; 95 percent confidence interval, 2.5 to 5.2 percent). In contrast, only 2 of 1405 patients at low risk (those with neither risk factor) had clinically important bleeding (0.1 percent; 95 percent confidence interval, 0.02 to 0.5 percent).

Discussion

The incidence of clinically important bleeding was less than 2 percent among the 2252 patients in this study. In the only other study known to us that prospectively evaluated clinically important bleeding in critically ill adults, the incidence was 2.0 percent in a group of high-risk patients undergoing mechanical ventilation21. In addition, our results are consistent with the estimate of 2.6 percent derived from 27 randomized trials16.

The value of previous attempts to identify risk factors for bleeding caused by stress ulceration in critically ill patients was limited by their use of chart review without documentation of reproducibility23,24 and without comparison with a control group25,26. Furthermore, although three prospective cohort studies20,27,28 and six randomized trials4,6,29,30,31,32 sought risk factors for either occult or overt bleeding, the relative risk associated with individual variables was not quantified. In only three studies in adults20,21,28 and one in children33 was the independent contribution of individual risk factors explored, and as in this study, the results indicated that coagulopathy20,21,28,33 and respiratory failure20,28,33 were associated with the risk of gastrointestinal bleeding.

The most important finding of our study is that a simple decision rule predicts the risk of bleeding and allows more selective use of prophylaxis against stress ulcers, thus avoiding the unnecessary exposure of patients to potential adverse effects. Patients who did not undergo mechanical ventilation for more than 48 hours and who had no coagulopathy, who made up 62 percent of the study group, were at extremely low risk of clinically important bleeding (0.1 percent or, at worst, 0.5 percent when the upper limit of the confidence interval is considered). Of the 1405 patients in this group, 283 (20.1 percent) received prophylaxis. A conservative estimate, based on a synthesis of the available data,16 is that if none of these patients had received prophylaxis, twice the number of patients (or, at worst, 1 percent) might have had bleeding. If prophylaxis reduces this risk by 50 percent, one would need to administer prophylaxis to more than 900 low-risk patients to prevent one episode of bleeding34. These results support the view that the risk of bleeding in patients without these two risk factors is low enough that prophylaxis can be safely withheld. A decision to restrict prophylaxis to patients with at least one risk factor for bleeding would substantially reduce the use of prophylactic agents in the critically ill.

On the other hand, our results support the use of prophylaxis in the subgroup of patients in the intensive care unit who have a coagulopathy or undergo ventilation for more than 48 hours. The risk of bleeding among these patients was 3.7 percent, despite the fact that more than half received prophylactic therapy of some type. Again applying the results of the meta-analysis, which showed a reduction of approximately 50 percent in the risk of clinically important bleeding with prophylaxis,16 and assuming that this benefit applies to all relevant subgroups, we estimate that almost twice as many of these patients would have bled if prophylaxis had been withheld, and that only about 30 high-risk patients would have to receive prophylaxis to prevent one episode of clinically important bleeding.

We think that the large heterogeneous cohort of critically ill patients that we studied, the reproducible classification of clinically important bleeding, and the precision of our estimates should provide confidence that the conclusions of this study can be applied to most critically ill patients.

Supported by the Ontario Ministry of Health. Dr. Cook is a St. Joseph's Foundation Research Scholar. Drs. Cook and Guyatt are Career Scientists of the Ontario Ministry of Health.

We are indebted to the staff of the McMaster University Methods Center who made this study possible: Susan Troyan, B.A., Peggy Austin, Suzanne Duschenne, Humaira Khan, B.A., Brenda Reeve, B.Sc., Sandie Reeve, B.A., Jennifer Whyte, B.A., and Diane VanderSchee, B.A.; to the study research nurses, including Lori Bell, Carolyn Dengate, Debra Foster, Denise Geroux, Margie Johnson, Susan Langdon, Helen Mason, John Mazzalo, Janet Shields, Maria Van Buroptedem, and Nancy Wells, for their dedication to this project; to all the participating physicians for their support; and to Debbie Maddock, Dawna Jaworsky, and Barbara Hill for assistance in the preparation of the manuscript.


Source Information

From the Faculty of Health Sciences, McMaster University, Hamilton, Ont. (D.J.C., H.D.F., G.H.G., L.G., A.W.); Toronto General Hospital and the University of Toronto, Toronto (J.C.M., T.L.W., T.J.R.T.); University Hospital and the University of Western Ontario, London, Ont. (D.L.); Victoria General Hospital and Dalhousie University, Halifax, N.S. (F.R.); Victoria General Hospital and the University of Western Ontario, London, Ont. (R.H., P.R.); and Hopital Ste.-Justine and the Universite de Montreal, Montreal (J.L.) -- all in Canada. In addition to the authors, the participants in the Canadian Critical Care Trials Group were as follows: Project Group -- H. Fuller and P. Powles, Hamilton, Ont., J. Lacroix, Montreal, J. Marshall, Toronto, T. Noseworthy, Edmonton, Alta., and L. Oppenheimer, Winnipeg, Man.; Outcome Review Committee -- D. Cook, H. Fuller, J. Hewson, J. Lang, H. Lee, and P. Powles, Hamilton, Ont., B. Guslits, Detroit, M. Heule and T. Noseworthy, Edmonton, Alta., J. Lacroix, Montreal, and J. Marshall and T. Todd, Toronto; Data Monitoring -- P. Powles, Hamilton, Ont.

Address reprint requests to Dr. Cook at the Department of Medicine, Division of Critical Care, St. Joseph's Hospital, 50 Charlton Ave. E., Hamilton, ON L8N 4A6, Canada.

References

  1. Shuman RB, Schuster DP, Zuckerman GR. Prophylactic therapy for stress ulcer bleeding: a reappraisal. Ann Intern Med 1987;106:562-567. 
  2. Gottlieb JE, Menashe PI, Cruz E. Gastrointestinal complications in critically ill patients: the intensivists' overview. Am J Gastroenterol 1986;81:227-238. [Medline]
  3. Zinner MJ, Zuidema GD, Smith PL, Mignosa M. The prevention of upper gastrointestinal tract bleeding in patients in an intensive care unit. Surg Gynecol Obstet 1981;153:214-220. [Medline]
  4. Basso N, Bagarani M, Materia A, Fiorani S, Lunardi P, Speranza V. Cimetidine and antacid prophylaxis of acute upper gastrointestinal bleeding in high risk patients: controlled, randomized trial. Am J Surg 1981;141:339-341. [CrossRef][Medline]
  5. Friedman CJ, Oblinger MJ, Suratt PM, et al. Prophylaxis of upper gastrointestinal hemorrhage in patients requiring mechanical ventilation. Crit Care Med 1982;10:316-319. [Medline]
  6. Hastings PR, Skillman JJ, Bushnell LS, Silen W. Antacid titration in the prevention of acute gastrointestinal bleeding: a controlled, randomized trial in 100 critically ill patients. N Engl J Med 1978;298:1041-1045. [Abstract]
  7. 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;79:409-412. [Free Full Text]
  8. McAlhany JC Jr, Colmic L, Czaja AJ, Pruitt BA Jr. Antacid control of complications from acute gastroduodenal disease after burns. J Trauma 1976;16:645-648. [Medline]
  9. Pinilla JC, Oleniuk FH, Reed D, Malik B, Laverty WH. Does antacid prophylaxis prevent upper gastrointestinal bleeding in critically ill patients? Crit Care Med 1985;13:646-650. [Medline]
  10. Stothert JC Jr, Simonowitz DA, Dellinger EP, et al. Randomized prospective evaluation of cimetidine and antacid control of gastric pH in the critically ill. Ann Surg 1980;192:169-174. [Medline]
  11. Weigelt JA, Aurbakken CM, Gewertz BL, Snyder WH III. Cimetidine vs antacid in prophylaxis for stress ulceration. Arch Surg 1981;116:597-601. [Abstract]
  12. Borrero E, Ciervo J, Chang JB. Antacid vs sucralfate in preventing acute gastrointestinal tract bleeding in abdominal aortic surgery: a randomized trial in 50 patients. Arch Surg 1986;121:810-812. [Abstract]
  13. Borrero E, Bank S, Margolis IB, Schulman ND, Chardavoyne R. Comparison of antacid and sucralfate in the prevention of gastrointestinal bleeding in patients who are critically ill. Am J Med 1985;79:Suppl 2C:62-64.
  14. Noseworthy TW, Shustack A, Johnston RG, Anderson BJ, Konopad E, Grace M. A randomized clinical trial comparing ranitidine and antacids in critically ill patients. Crit Care Med 1987;15:817-819. [Medline]
  15. Laggner AN, Lenz K, Graninger W, et al. Strebbluntungsprophylaxe auf einer internen Intensivstation: Sucralfat versus Ranitidin. Anaesthesist 1988;37:704-710. [Medline]
  16. Cook DJ, Witt LG, Cook RJ, Guyatt GH. Stress ulcer prophylaxis in the critically ill: a meta-analysis. Am J Med 1991;91:519-527. [Erratum, J Med 1991;91:670.] [CrossRef][Medline]
  17. Lacroix J, Infante-Rivard C, Gauthier M. Upper-gastrointestinal-bleeding (UGIB) prophylaxis: a decision-making analysis and cost/benefit analysis. Clin Invest Med 1986;9:Suppl:A22-A22.abstract 
  18. Driks MR, Craven DE, Celli BR, et al. Nosocomial pneumonia in intubated patients given sucralfate as compared with antacids or histamine type 2 blockers. N Engl J Med 1987;317:1376-1382. [Abstract]
  19. Poleski MH, Spanier AH. Cimetidine versus antacids in the prevention of stress erosions in critically ill patients. Am J Gastroenterol 1986;81:107-111. [Medline]
  20. Schuster DP, Rowley H, Feinstein S, McGue MK, Zuckerman GR. Prospective evaluation of the risk of upper gastrointestinal bleeding after admission to a medical intensive care unit. Am J Med 1984;76:623-630. [CrossRef][Medline]
  21. Cook DJ, Pearl RG, Cook RJ, Guyatt GH. The incidence of clinically important bleeding in ventilated patients. J Intensive Care Med 1991;6:167-174.
  22. Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med 1985;13:818-829. [Medline]
  23. Tryba M, Huchzermeyer H, Torok M, Zenz M, Pahlow J. Single drug and combined medication with cimetidine, antacids and pirenzipine in the prophylaxis of acute upper gastrointestinal bleeding. Hepatogastroenterology 1983;30:154-157. [Medline]
  24. Harris SK, Bone RC, Ruth WE. Gastrointestinal hemorrhage in patients in a respiratory intensive care unit. Chest 1977;72:301-304. [Free Full Text]
  25. Goodman AA, Frey CF. Massive upper gastrointestinal hemorrhage following surgical operations. Ann Surg 1968;167:180-184. [Medline]
  26. Fogelman MJ, Garvey JM. Acute gastroduodenal ulceration incident to surgery and disease: analysis and review of eighty-eight cases. Am J Surg 1966;112:651-656. [CrossRef][Medline]
  27. Skillman JJ, Bushnell LS, Goldman H, Silen W. Respiratory failure, hypotension, sepsis, and jaundice: a clinical syndrome associated with lethal hemorrhage from acute stress ulceration of the stomach. Am J Surg 1969;117:523-530. [CrossRef][Medline]
  28. Kamada T, Fusamoto H, Kawano S, Noguchi M, Hiramatsu K. Gastrointestinal bleeding following head injury: a clinical study of 433 cases. J Trauma 1977;17:44-47. [Medline]
  29. van den Berg B, van Blankenstein M. Prevention of stress-induced upper gastrointestinal bleeding by cimetidine in patients on assisted ventilation. Digestion 1985;31:1-8. [Medline]
  30. 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. N Engl J Med 1980;302:426-430. [Abstract]
  31. Groll A, Simon JB, Wigle RD, Taguchi K, Todd RJ, Depew WT. Cimetidine prophylaxis for gastrointestinal bleeding in an intensive care unit. Gut 1986;27:135-140. [Free Full Text]
  32. Tryba M, Zevounou F, Torok M, Zenz M. Prevention of acute stress bleeding with sucralfate, antacids, or cimetidine: a controlled study with pirenzepine as a basic medication. Am J Med 1985;79:Suppl 2C:55-61. 
  33. Lacroix J, Nadeau D, Laberge S, Gauthier M, Lapierre G, Farrell CA. Frequency of upper gastrointestinal bleeding in a pediatric intensive care unit. Crit Care Med 1992;20:35-42. [Medline]
  34. Laupacis A, Sackett DL, Roberts RS. An assessment of clinically useful measures of the consequences of treatment. N Engl J Med 1988;318:1728-1733. [Medline]

 

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Gastrointestinal Bleeding in Critically Ill Patients
Bardes C. L., Charlson M. E., Martin L. F., Shumate M. J., Roberts M. S., Cook D. J., Guyatt G. H., Griffith L.
Extract | Full Text  
N Engl J Med 1994; 331:51-53, Jul 7, 1994. Correspondence

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