Continuous v intermittent cimetidine infusion in critically ill hospitalized patients: role of TPN admixture as drug vehicle

Abstract

Previous studies suggest that continuous or intermittent cimetidine infusion provides a stable and sustained therapeutic blood concentration that maintains a gastric pH greater than 4.0. Twenty-seven patients receiving cimetidine were randomized to one of five treatments. Groups 1 and 2 were given cimetidine intermittently, whereas Groups 3, 4, and 5 received the drug continuously via a total parenteral nutrient (TPN) admixture. Group 1 was given 300 mg every 8 hours, and Group 2 received 300 mg every six hours. Groups 3, 4, and 5 received 600, 900, and 1200 mg per day, respectively, as a continuous infusion in the TPN admixture. Forty-eight individually prescribed TPN admixtures were used to deliver cimetidine continuously; 23 were composed of amino acids and glucose as base nutrients, whereas 25 contained amino acids, glucose, and lipids (3-in-1 or total nutrient admixtures). Serum levels of cimetidine were measured six times in 40 h (Group 1) or 42 h (Group 2-5). A two-way analysis of variance (ANOVA) revealed statistically significant differences in the serum cimetidine concentrations between groups (p less than 0.0001), but not with respect to time interval (p = 0.8687). No significant differences were noted in mean serum cimetidine concentrations between Groups 2 and 3, despite employing half the total dose in Group 3. Equivalent daily dosages were then stratified as the percentage of subtherapeutic (less than 500 ng/ml), therapeutic (500-1250 ng/ml), and supratherapeutic (greater than 1250 ng/ml) values.(ABSTRACT TRUNCATED AT 250 WORDS)