Randomized, prospective trial of cimetidine and ranitidine for control of intragastric pH in the critically ill

Forty-eight critically ill patients in an intensive care unit were enrolled in a prospective study of stress ulcer prophylaxis. The H2-receptor antagonists cimetidine and ranitidine were used, patients being randomized on hospital number. Response was assessed by measuring gastric pH every 2 hours. The drugs were administered by intravenous infusion, and up to three dosage increments fo each of the drugs were titrated against the pH of the aspirated gastric juice. If one drug, in maximum dose, failed to maintain the pH above 4, the other drug was administered at maximum dose. If both drugs failed to achieve control of gastric pH, antacids were administered in an endeavor to ensure patient safety. Cimetidine was successful in maintaining the intragastric pH above 4, for the duration of the intensive care admission, in five of 28 patients. Ranitidine was successful in 10 of 20 patients. The difference between these two groups was statistically significant (p = 0.04). In patients in whom cimetidine therapy failed, ranitidine provided adequate control of pH in four of 13. Cimetidine controlled one of six patients who had failed to improve with ranitidine therapy. Plasma concentrations of both drugs were well above established acid inhibitory concentrations. However, even with much lower plasma concentrations of ranitidine, similar amounts of both drugs were present in the gastric juice, suggesting a possible explanation for the greater efficacy of ranitidine. We conclude that, although ranitidine is more effective than cimetidine, neither of these drugs is adequate for stress ulcer prophylaxis. If they ae used for this purpose in the critically ill patient, regular monitoring of gastric pH is essential to allow detection of therapeutic failures.