Parenteral antisecretory drug therapy in patients with Zollinger-Ellison syndrome

Forty-six patients with Zollinger-Ellison syndrome were studied prospectively to determine a safe and effective method and criterion for controlling gastric acid hypersecretion during periods when oral antisecretory agents could not be used. In each patient it was possible to reduce acid secretion to less than or equal to 10 mEq/h after an i.v. bolus of 150 or 300 mg of cimetidine and a stepwise titration of cimetidine given by continuous infusion. The mean dose given by i.v. infusion was 2.9 mg/kg body wt.h but there was a wide range (0.5-7.0 mg/kg body wt.h) and the minimal dose had to be determined individually for each patient. The minimal i.v. cimetidine dose did not correlate with basal or maximal acid output or fasting gastrin concentration, but correlated closely with either the previous oral dose of cimetidine (r = 0.96, p less than 0.001) or the previous oral dose of ranitidine or famotidine (r = 0.95, p less than 0.001). To study the efficacy and safety of an i.v. infusion of cimetidine, 34 patients undergoing surgery were maintained on i.v. cimetidine for a mean of 12 days (range 1-83 days). One-half of the patients did not require dose adjustment, whereas the remainder required an average of 2 adjustments, usually in the first 3 postoperative days. No patient developed complications attributable to gastric acid hypersecretion in the postoperative period, and there was no detectable neurologic, hematologic, or hepatic toxicity. This study demonstrates that a continuous i.v. infusion of cimetidine adequately inhibits gastric acid hypersecretion in patients with Zollinger-Ellison syndrome. However, high doses were frequently required, the dose had to be determined in a stepwise fashion individually for each patient, and the i.v. dose correlated with the previous oral dose. Reducing acid secretion to less than or equal to 10 mEq/h was a safe criterion during surgery and continuous i.v. cimetidine was safe and effective in achieving this degree of control for up to 83 days.