Study objective: To compare the effects of intravenous bolus injection of ranitidine, continuous intravenous infusion of ranitidine, and placebo on gastric pH, acid secretion, and plasma ranitidine concentration during a 24-hour period, and to determine by survey the use, delivery methods, and costs of histamine H2-receptor antagonists in intensive care units.
Design: Double-blind, Latin-square randomized, prospective measurement of the gastric pH, acid output, and plasma ranitidine concentration over 24 hours in response to six treatment regimens in 12 patients with inactive duodenal ulcer. Eight regional hospitals were surveyed to obtain information on the use of histamine H2-receptor antagonists.
Interventions: Gastric acid secretion, pH, and plasma ranitidine were monitored for 24 hours on six separate days in response to placebo, intravenous bolus injection of ranitidine (50 mg every 8 hours and 75 mg every 12 hours), and continuous intravenous infusion of ranitidine (75, 150, and 300 mg every 24 hours).
Measurements and main results: Intravenous infusions were significantly more effective than bolus injections. After bolus injections, hourly gastric pH values fluctuated widely, from 7.6 to 1.6, whereas during continuous infusion of 150 mg and 300 mg, hourly pH values were 3.8 or greater. The gastric pH was greater than 4.0 in 75% +/- 5% and 83% +/- 6% of determinations done during continuous intravenous infusion of 150 mg and 300 mg, respectively. Fluctuations in the plasma ranitidine concentration corresponded with changes in gastric pH and acid secretion. Histamine H2-receptor antagonists were prescribed for about 75% of patients in intensive care units and were most commonly administered by bolus rather than infusion (5:1); the cost was approximately +40 per day less by infusion.
Conclusions: On the basis of both efficacy and cost, intermittent bolus injections should be discontinued and replaced by continuous intravenous infusion in hospitalized patients requiring treatment with histamine H2-receptor antagonists. If ranitidine is used, either 150 mg or 300 mg administered as a 24-hour continuous infusion is most effective.