Ventilatory depression related to plasma fentanyl concentrations during and after anesthesia in humans

Twenty-four patients were allocated randomly into four groups for the study of the pharmacokinetics of, and effects on postoperative ventilation of, two doses of fentanyl (10 micrograms/kg or 25 micrograms/kg) administered at the start of general anesthesia in which ventilation was controlled at a fixed volume, but arterial PCO2 was adjusted to a range of either 38-42 torr, or 20-25 torr. During the first 2 hr after anesthesia, ventilatory depression (CO2 responsiveness decreased to less than 50% of awake values, PaCO2 greater than 48 torr) occurred only in patients who had received 25 micrograms/kg fentanyl, and was more marked in patients who were hyperventilated to a low PaCO2 during anesthesia. Plasma fentanyl concentrations associated with 50% depression of CO2 responsiveness were in the range 1.5-3.0 ng/ml, the lower values found in patients hyperventilated to a low PaCO2. Whole-body clearance of fentanyl was significantly decreased by hypocapnic hyperventilation.