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.