Continuous intravenous cimetidine decreases stress-related upper gastrointestinal hemorrhage without promoting pneumonia.
Abstract
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.
Type
Journal articleSubject
AdolescentAdult
Aged
Aged, 80 and over
Cimetidine
Critical Care
Cross Infection
Double-Blind Method
Female
Gastric Acidity Determination
Gastric Juice
Humans
Infusions, Intravenous
Intensive Care Units
Male
Middle Aged
Peptic Ulcer
Peptic Ulcer Hemorrhage
Pneumonia
Risk Factors
Severity of Illness Index
Stress, Physiological
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Show full item recordScholars@Duke
Frank Wesley Rockhold
Professor of Biostatistics & Bioinformatics
Frank is a full time Professor of Biostatistics and Bioinformatics and Faculty Director
for Biostatistics at Duke University Medical Center, Affiliate Professor of Biostatistics
at Virginia Commonwealth University, and Strategic Consultant at Hunter Rockhold,
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 h

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