T. F. Boerner

Inhibition of alfentanil metabolism by erythromycin.

To investigate a possible connection between erythromycin administration and reduced elimination of alfentanil, a controlled crossover study of alfentanil pharmacokinetics was undertaken. Six subjects were monitored for alfentanil plasma levels for 8 hours after alfentanil was administered. These measurements were obtained after a 0‐, 1‐, and 7‐day course of erythromycin. Elimination half‐life increased significantly (p < 0.01) after 7 days from the control value of 84.0 ± 8.2 minutes to 131.4 ± 43.5 minutes. Clearance was decreased significantly (p < 0.05) from 3.9 ± 0.8 ml/kg/min to 2.9 ± 1.2 ml/kg/min after 7 days. Values after 1 day were intermediate. Distribution volume did not change significantly. Subjects differed sharply in their sensitivity to erythromycin. Because of the interaction between erythromycin and alfentanil, we recommend that patients who are receiving erythromycin should be given alfentanil in reduced amounts or should avoid the drug completely.

Time-course of respiratory depression after an alfentanil infusion-based anesthetic

Postoperative respiratory depression after alfentanil administration has been described in several case reports. The effects of a prolonged alfentanil infusion on the CO2 response curve or cognitive function have not been studied. Twenty-one ASA physical status I or II patients were studied after a prolonged alfentanil infusion (>90 min) to determine the incidence of postoperative respiratory depression, arterial O2 desaturation, and impairment of cognitive function. Each patients recovery was observed at 30-min intervals for evidence of respiratory depression (utilizing the Read CO2 rebreathing method), desaturation by pulse oximetry (severe desaturation defined as arterial O2 saturation <90%), and cognitive function (utilizing Trieger dot and digit substitution tests). Plasma samples were also examined for secondary elevations in alfentanil plasma concentrations. Significant depression of the CO2 response curve and cognitive function was found up to 1 h postoperatively. Arterial O2 desaturation was seen in 11 of 21 patients (52%). No correlation was found between arterial O2 desaturation and cognitive function scores or CO2 rebreathing results. Increased depression of the CO2 response curve was not necessarily associated with severe desaturation episodes. A secondary increase in plasma alfentanil concentration was detected in 5 of the 21 patients (24%), but these patients did not experience further depression of the CO2response curve. We conclude that prolonged alfentanil administration may result in severe arterial O2desaturation with significant depression of the hyper-capnic respiratory drive during the first hour in the postanesthesia care unit, even though the majority of our patients were easily aroused in response to verbal stimuli.