Fentanyl-induced ventilatory depression: effects of age.

To determine whether infants are more sensitive than older patients to the ventilatory-depressant effects of fentanyl, patients were anesthetized with fentanyl and nitrous oxide (N2O) and ventilatory depression was assessed following elimination of N2O and in the immediate postoperative period. Three groups of patients were studied: infants (1-12 mo old, n = 14), children (1-5 yr old, n = 14), and adults (23-38 yr old, n = 13). Skin-surface PCO2 was measured to determine the peak PCO2 occurring at the end of anesthesia when end-tidal N2O concentration was less than 6%. Naloxone was administered if PCO2 exceeded 70 mmHg. During recovery from anesthesia, ventilatory pattern was recorded using impedance pneumography to determine the longest breath-to-breath interval and the number of episodes of central apnea (defined as breath-to-breath intervals greater than or equal to 10 s in infants and children and greater than or equal to 20 s in adults). Elevation of PCO2 correlated with increasing plasma fentanyl concentrations but did not differ between groups. Four patients (two infants, one child, and one adult) required naloxone. The only subject who had a low plasma fentanyl concentration but required naloxone was a 6-wk-old infant; this was the only subject younger than 3 mo. For each range of fentanyl concentrations, the incidence of apnea increased with age, as did the number of episodes of apnea per subject. Fentanyl-induced ventilatory depression, as assessed by elevation of resting PCO2 during emergence from anesthesia and disruption of ventilatory pattern during recovery from anesthesia, is not greater in infants older than 3 mo than in children and adults.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics of fentanyl in neonatal humans and lambs: effects of age.

To determine whether the clearance of fentanyl in neonates varies with age, the authors determined the pharmacokinetics of fentanyl in 14 humans ages 1-71 days and 15 lambs ages 3-37 days. In humans, fentanyl, 54.1 +/- 2.3 (mean +/- SD) micrograms/kg, was administered as a 2-min iv infusion; in lambs, fentanyl, 50 micrograms/kg, was administered as an iv bolus. Ventilation was controlled to maintain end-tidal or arterial PCO2 normal, and potent inhaled anesthetics were not administered; in humans, additional anesthesia was provided with iv morphine. Arterial or venous samples were obtained for 12 h, and plasma concentrations of fentanyl were determined by radioimmunoassay. Plasma concentration versus time data were fitted to two- and three-compartment pharmacokinetic models, and clearance, volume of distribution at steady-state (Vdss), and elimination half-life were determined. Clearance increased with age in both humans and lambs. Two humans who had intraabdominal surgery had no clearance of fentanyl: plasma concentrations of fentanyl remained constant for approximately 10 h after an initial distribution phase. In lambs, but not in humans, Vdss increased with age; elimination half-life did not change with age in either lambs or humans. The authors conclude that at least two factors--postnatal age and the type of surgery--affect fentanyl clearance during the neonatal period. The effect of other factors, such as inhaled anesthetics, remains to be determined.

Pre-induction of anesthesia in pediatric patients with nasally administered sufentanil.

To evaluate nasally administered sufentanil, 1.5-4.5 micrograms/kg, for pre-induction (i.e., pre-medication/induction) of anesthesia in pediatric patients, the authors studied ASA PS 1 or 2 patients scheduled for elective surgery. Eighty children, ages 6 months to 7 yr, were randomized to receive sufentanil (1.5, 3.0, or 4.5 micrograms/kg) or placebo (normal saline, 0.03 ml/kg) nasally over 15-20 s. Induction of anesthesia was completed with 5% halothane and O2 via facemask. After tracheal intubation, anesthesia was maintained with N2O (60-70%) and halothane, as clinically indicated. A blinded observer remained with the child from prior to drug administration until discharge from the recovery room. Patients given sufentanil were more likely to separate willingly from their parents and be judged as calm at or before 10 min compared to those given saline. Ventilatory compliance during induction of anesthesia decreased markedly in 25% of subjects given sufentanil, 4.5 micrograms/kg. Subjects given sufentanil moved or coughed less during tracheal intubation and required less halothane compared to those given placebo. During recovery, patients given sufentanil cried less and fewer needed analgesics; recovery times were similar for all groups. However, patients given sufentanil, 4.5 micrograms/kg, had a higher incidence of vomiting in the recovery room and during the first postoperative day. The authors conclude that nasally administered sufentanil, 1.5 or 3.0 micrograms/kg, facilitates separation of children from parents, has minimal side effects, may improve intubating conditions, and can provide postoperative analgesia.