Continuous intravenous cimetidine decreases stress-related upper gastrointestinal hemorrhage without promoting pneumonia.
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OBJECTIVES: To determine whether a continuous i.v. infusion of cimetidine, a histamine-2 (H2) receptor antagonist, is needed to prevent upper gastrointestinal (GI) hemorrhage when compared with placebo and if that usage is associated with an increased risk of nosocomial pneumonia. Due to the importance of this latter issue, data were collected to examine the occurrence rate of nosocomial pneumonia under the conditions of this study. DESIGN: A multicenter, double-blind, placebo-controlled study. INTERVENTIONS: Patients were randomized to receive cimetidine (n = 65) as an iv infusion of 50 to 100 mg/hr or placebo (n = 66). SETTING: Intensive care units in 20 institutions. PATIENTS: Critically ill patients (n = 131), all of whom had at least one acute stress condition that previously had been associated with the development of upper GI hemorrhage. MEASUREMENTS AND MAIN RESULTS: Samples of gastric fluid from nasogastric aspirates were collected every 2 hrs for measurement of pH and were examined for the presence of blood. Upper GI hemorrhage was defined as bright red blood or persistent (continuing for > 8 hrs) "coffee ground material" in the nasogastric aspirate. Baseline chest radiographs were performed and sputum specimens were collected from all patients, and those patients without clear signs of pneumonia (positive chest radiograph, positive cough, fever) at baseline were followed prospectively for the development of pneumonia while receiving the study medication. Cimetidine-infused patients experienced significantly (p = .009) less upper GI hemorrhage than placebo-infused patients: nine (14%) of 65 cimetidine vs. 22 (33%) of 66 placebo patients. Cimetidine patients demonstrated significantly (p = .0001) higher mean intragastric pH (5.7 vs. 3.9), and had intragastric pH values at > 4.0 for a significantly (p = .0001) higher mean percentage of time (82% vs. 41%) than placebo patients. Differences in pH variables were not found between patients who had upper GI hemorrhage and those patients who did not, although there was no patient in the cimetidine group who bled with a pH < 3.5 compared with 11 such patients in the placebo group. Also, the upper GI hemorrhage rate in patients with one risk factor (23%) was similar to that rate in patients with two or more risk factors (25%). Of the 56 cimetidine-infused patients and 61 placebo-infused patients who did not have pneumonia at baseline, no cimetidine-infused patient developed pneumonia while four (7%) placebo-infused patients developed pneumonia. CONCLUSIONS: The continuous i.v. infusion of cimetidine was highly effective in controlling intragastric pH and in preventing stress-related upper GI hemorrhage in critically ill patients without increasing their risk of developing nosocomial pneumonia. While the number of risk factors and intragastric pH may have pathogenic importance in the development of upper GI hemorrhage, neither the risk factors nor the intragastric pH was predictive. Therefore, short-term administration of continuously infused cimetidine offers benefits in patients who have sustained major surgery, trauma, burns, hypotension, sepsis, or single organ failure.
Aged, 80 and over
Gastric Acidity Determination
Intensive Care Units
Peptic Ulcer Hemorrhage
Severity of Illness Index
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Professor of Biostatistics & Bioinformatics
Frank is a fulltime Professor of Biostatistics and Bioinformatics at Duke University Medical Center, Affiliate Professor of Biostatistics at Virginia Commonwealth University, and Managing Partner of HunterRockhold, Inc. His 40+-year career includes senior research positions at Lilly, Merck, and GlaxoSmithKline, where he retired as Chief Safety Officer and Senior Vice President of Global Clinical Safety and Pharmacovigilance. He has held faculty appointments at six different