Impact of multiple risk factors and ranitidine prophylaxis on the development of stress-related upper gastrointestinal bleeding: a prospective, multicenter, double-blind, randomized trial. The Ranitidine Head Injury Study Group.
OBJECTIVE
To evaluate the impact of risk factors on the development of stress-related upper gastrointestinal bleeding in severe head injury patients randomized to treatment with a 6.25 mg/hr continuous ranitidine infusion or placebo.


METHODS
Prospective, multicenter, randomized, double-blind, placebo-controlled, parallel-group study.


METHODS
Ten intensive care units in the United States.


METHODS
Patients with severe head injury, defined as having a Glasgow Coma Score of < or = 10, were eligible for enrollment.


METHODS
Ranitidine 6.25 mg/hr or saline placebo was administered by continuous infusion for a maximum of 5 days.


RESULTS
Patients were evaluated every 8 hrs for the presence of stress-related upper gastrointestinal bleeding. Bleeding developed in 15 (19%) of 81 placebo-treated patients vs. three (3%) of 86 ranitidine-treated patients (p = .002). None of the individual risk factors had a significant effect on bleeding frequency. No bleeding occurred in the four patients with one risk factor. Placebo bleeding rates in patients with 2, 3 to 5, and > 5 risk factors were 20%, 20%, and 18%, respectively. For the ranitidine-treated patients, bleeding was reported in 0%, 5%, and 0% in the 2, 3 to 5, and > 5 risk factor subgroups, respectively. Pneumonia occurred in 19% of the placebo-treated patients vs. 14% in the ranitidine treatment group.


CONCLUSIONS
The full risk to develop stress-related upper gastrointestinal bleeding was realized when two risk factors were present concomitantly. The presence of additional risk factors did not increase the occurrence of bleeding. A continuous infusion of ranitidine at 6.25 mg/hr provided significant protection from bleeding, regardless of the number of risk factors present.
Metz
C A
CA
Glaxo Pharmaceuticals, Research Triangle Park, NC 27709.
Livingston
D H
DH
Smith
J S
JS
Larson
G M
GM
Wilson
T H
TH
D000328:Adult; D006259:Craniocerebral Trauma / Q000097:blood / Q000150:complications* / Q000628:therapy; D003428:Cross Infection / Q000139:chemically induced / Q000453:epidemiology; D004311:Double-Blind Method; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000453:epidemiology* / Q000209:etiology / Q000517:prevention & control*; D015600:Glasgow Coma Scale; D006801:Humans; D015994:Incidence; D007262:Infusions, Intravenous; D008297:Male; D011014:Pneumonia / Q000139:chemically induced / Q000453:epidemiology; D011446:Prospective Studies; D011899:Ranitidine / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D012121:Respiration, Artificial / Q000009:adverse effects; D012307:Risk Factors; D013312:Stress, Physiological / Q000150:complications*
D011899:Ranitidine