Stress ulceration in the intensive care unit: use of H2-receptor antagonists

H2-receptor antagonist drug therapy is the mainstay of peptic ulcer treatment in the USA. About 75% of patients in intensive care units receive parenteral H2-antagonists. The rationale for their use is that parenteral H2-antagonists offer about a four-fold protective effect compared with placebo against significant upper gastrointestinal haemorrhage. Parenteral administration of H2-receptor antagonists appears to be preferred to oral antacid or sucralfate regimens because of ease of administration and, perhaps, lower treatment costs. Recommended dosage schedules for intravenously administered H2-receptor antagonists are at fixed intervals, 6- to 8-h intervals for cimetidine and ranitidine and 12-h intervals for famotidine. These dosage schedules assume a fixed dose-response relationship (i.e. a given dose of H2-antagonist results in equivalent acid suppression throughout the circadian, or 24-h, period). However, human basal gastric acid secretion exhibits circadian variation, with peak rates occurring during the evening hours. Recent evidence from 24-h continuous intragastric pH studies in fasting patients with healed duodenal ulcer suggests that larger doses of intravenous H2-antagonists are required in the evening than in the morning to achieve equivalent acid suppression. These findings are consistent with a changing H2-antagonist dose/acid-inhibiting response over the circadian period. Continuous infusion has the advantage of providing consistent and sustained suppression of gastric acid secretion in patients at risk for stress ulceration. Results of a double-blind, randomized, crossover study indicated that equally effective suppression of acidity and time-to-onset of pharmacological effect can be achieved with and without priming bolus doses of ranitidine, and presumably other H2-receptor antagonists as well.(ABSTRACT TRUNCATED AT 250 WORDS)