Assessment of 24-hour gastric pH measurements in trauma patients receiving intravenous famotidine by intermittent bolus versus continuous infusion administration.

OBJECTIVE: To compare the effects of intermittent bolus versus continuous infusion intravenous famotidine on gastric pH in critically ill trauma patients. DESIGN: Twenty patients were randomized to receive famotidine by intermittent bolus or continuous infusion for 24 hours. Patients fasted during the study period. Hourly gastric pH measurements were made using an indwelling sensor/sump tube. SETTING: The study was conducted in a university teaching hospital. PARTICIPANTS: Adult patients admitted to the neurosurgical or surgical/trauma intensive care unit within 72 hours of traumatic injury were enrolled in the study if they had two consecutive hourly gastric pH readings of < 4 without receiving antacids, sucralfate, or histamine2-antagonists. MAIN OUTCOME MEASURES: Groups were compared with regard to (1) total dose of famotidine received/24 hours, and (2) number of dosage changes required to maintain a gastric pH value of > or = 4. RESULTS: The median dose of famotidine required to maintain a gastric pH > or = 4 was 50 mg/24 h (25th-75th percentiles = 40-55 mg) in the intermittent bolus group compared with 42 mg/24 h (25th-75th percentiles = 42-52 mg) in the continuous infusion group (p = 0.9577). A dosage increase was required by 5 of 8 patients (62 percent) receiving intermittent bolus therapy, whereas only 2 of 8 patients (25 percent) in the continuous infusion group required a dosage adjustment (p = 0.315, power = 0.318). CONCLUSIONS: Intravenous famotidine (40-50 mg/d) effectively controlled gastric pH in critically ill trauma patients. Patients treated with intermittent bolus therapy required slightly more drug and more frequent dosage adjustments to achieve a gastric pH > or = 4. These differences did not reach statistical significance.

Influence of histamine receptors on basal left ventricular contractile tone in humans: assessment using the H2 receptor antagonist famotidine and the beta-adrenoceptor antagonist esmolol as pharmacologic probes.

Histamine has a positive inotropic action in humans. Recent controversial data have suggested that histamine2 (H2) receptor blockade depresses overall left ventricular systolic performance in healthy volunteers. To explore the possibility that H2 receptors positively influence basal left ventricular contractile tone, 10 normal subjects were studied by using imaging and Doppler echocardiography and calibrated subclavian pulse data in a blinded, randomized, two-period crossover trial with measurements obtained at the end of each 7-day period. Oral drug administration consisted of either the potent H2 antagonist famotidine (40 mg/day) or placebo. Left ventricular circumferential end-systolic wall stress-rate-corrected velocity of fiber shortening (Vcfc) relations were generated over a range of loads with methoxamine. Contractility was assessed by using Vcfc at a common end-systolic wall stress. During each study, data were obtained before and during high dose intravenous esmolol administration to determine the contributions, if any, of sympathetic reflex responses. Famotidine did not alter blood pressure, left ventricular percent fractional shortening, circumferential end-systolic wall stress, stroke volume index, cardiac index, total vascular resistance or ventricular contractile state in comparison with placebo but did decrease heart rate by 3 beats/min (p less than 0.05). With beta-adrenergic blockade, no differences in contractility were evident between esmolol alone and famotidine plus esmolol. Thus, H2 receptor blockade with famotidine does not alter myocardial mechanics or cardiac sympathetic tone, suggesting that in humans basal left ventricular contractile state is not physiologically dependent on the H2-mediated effects of histamine.