• W A Bowler, C Hostettler, D Samuelson, B S Lavin, and E C Oldfield.
• Department of Internal Medicine, Naval Hospital, San Diego, California 92134-5000.
• Am. J. Med. 1992 Mar 1; 92 (3): 249-53.

ObjectiveTo determine the frequency of gastrointestinal toxicity due to intravenous (IV) erythromycin and to attempt to decrease this toxicity by prolonging the infusion time of erythromycin and/or pretreating with the peripheral anticholinergic, glycopyrrolate 0.1 mg IV.DesignRandomized, double-blind, placebo-controlled trial.SettingGeneral medical wards of a tertiary medical center.PatientsA total of 51 hospitalized patients 18 years of age or older who were prescribed IV erythromycin lactobionate (EMLB) 500 mg every 6 hours by their attending physicians.InterventionsEach of eight consecutive infusions of EMLB was randomly assigned to one of four groups: control--30-minute infusion/placebo pretreatment; 60/P--60-minute infusion/placebo pretreatment; 30/G--30-minute infusion/glycopyrrolate pretreatment; and 60/G--60-minute infusion/glycopyrrolate pretreatment.Main Outcome MeasuresEach infusion was accompanied by a questionnaire in which patients rated the magnitude of nausea and vomiting on a scale of 1 (no toxicity) to 9 (severe toxicity). Scores for both nausea and vomiting were added together for a total toxicity score ranging from 2 to 18. A total score of greater than 8 was defined as clinically important.ResultsThe 51 patients received a total of 356 infusions with gastrointestinal toxicity occurring in 27 of 51 (53%) patients. Among patients under the age of 40, 22 of 33 (67%) experienced toxicity compared with only five of 18 patients (28%) over the age of 40 (p = 0.018). Clinically important toxicity was seen in 19 of 51 patients (37%), including five who withdrew during the study because of severe nausea and vomiting. In this group, the combination of a 60-minute erythromycin infusion and glycopyrrolate pretreatment decreased clinically important toxicity by 79% from 47% to 10%, a statistically and clinically significant 37% (95% CI, 14% to 60%) difference (p = 0.007).ConclusionsGastrointestinal toxicity associated with the IV infusion of erythromycin is common and is more likely to occur in younger patients. A 1-hour infusion of erythromycin combined with pretreatment with glycopyrrolate, 0.1 mg IV, is effective in reducing this toxicity.

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