ALFENTANIL

Fetal Risk Summary

No reports linking the use of alfentanil during pregnancy with congenital abnormalities have been located, but experience in the 1st trimester has not been reported. The narcotic is not teratogenic in rats and rabbits (1,2). An embryocidal effect was observed with doses 2.5 times the upper human dose administered for 10–30 days, but this may have been related to maternal toxicity (1).

Alfentanil rapidly crosses the placenta to the fetus (3,4 and 5). A 1986 report described the pharmacokinetics and placental transfer of alfentanil after a single 30-µg/kg IV dose administered to five women scheduled for cesarean section (group A) and during a continuous epidural infusion (30–µg/kg loading dose followed by 30-µg/kg/hour infusion) given to five women for vaginal delivery (group B) (3). The ratio of total alfentanil in umbilical vein to maternal blood in the combined 10 women was 0.29 (0.31 and 0.28 for groups A and B, respectively). The fetal:maternal ratio of free (unbound) alfentanil, however, was 0.97, reflecting the decreased a1-acid glycoprotein (the most important binding protein for the drug) levels in the fetuses compared with the mothers (3).

Alfentanil was administered as a continuous infusion (30 µg/kg/hour with as-needed bolus doses of 30 µg/kg) via an extradural catheter to 16 women undergoing vaginal delivery (4). The umbilical vein:maternal ratios in six patients varied between 0.221 and 0.576 (mean 0.33). For all 16 newborns, the mean (range) Apgar scores at 1, 3, and 5 minutes were 8.56 (range 7–10), 9.60 (range 8–10), and 9.80 (range 9–10), respectively, and were comparable to a control group. However, neurobehavioral assessment of the newborns using the Amiel-Tison score at 15–30 minutes of life indicated a significant decrease, compared with that of control newborns, in passive and active tone and total score. Primary reflexes and general assessment were not statistically different from those of control newborns. No abnormal feeding habits or behavior changes were noted on later evaluation, presumably after the effects of the narcotic had dissipated.

In 21 women scheduled for elective cesarean section, alfentanil (10 µg/kg IV) administered before the induction of anesthesia significantly decreased the pressor response to laryngoscopy and endotracheal intubation in comparison to 16 control patients (p<0.01) (5). At delivery, the mean total alfentanil fetal:maternal ratio was 0.32, but based on the lower a1-acid glycoprotein levels in the newborns (33% of maternal levels), the calculated unbound alfentanil concentrations in the newborns and mothers were approximately equal (5).

Other reports have described the use of IV alfentanil immediately before the induction of anesthesia for cesarean section to lessen the hypertensive effects of tracheal intubation in women with preeclampsia (6,7 and 8) or as a single epidural injection (1 mg) in combination with a continuous epidural infusion of bupivacaine before vaginal delivery (9). As with other opioid agonist analgesics, neonatal respiratory depression is a potential complication, but it can be quickly reversed with naloxone.

[*Risk Factor D if used for prolonged periods or in high doses at term.]

Breast Feeding Summary

Alfentanil is excreted into breast milk. Nine non-breast-feeding women undergoing postpartum tubal ligation were administered alfentanil, 50 µg/kg IV (10). An additional 10 µg/kg was given if needed. Colostrum was collected from the right breast 4 hours after the last injection of alfentanil and from the left breast at 28 hours. The mean level of alfentanil in the colostrum at 4 hours was 0.88 ng/mL (range 0.21–1.56 ng/mL), and the mean level at 28 hours was 0.05 ng/mL (range 0.11–0.26 ng/mL). The clinical significance of the drug level in milk to the nursing infant at either time is unknown but is probably nil.

References

1. Product information. Alfenta. Janssen Pharmaceutica, Inc. 1992.
2. Fujinaga M, Mazze RI, Jackson EC, Baden JM. Reproductive and teratogenic effects of sufentanil and alfentanil in Sprague-Dawley rats. Anesth Analg 1988;67:166–9.
3. Gepts E, Heytens L, Camu F. Pharmacokinetics and placental transfer of intravenous and epidural alfentanil in parturient women. Anesth Analg 1986;65:1155–60.
4. Heytens L, Cammu H, Camu F. Extradural analgesia during labour using alfentanil. Br J Anaesth 1987;59:331–7.
5. Cartwright DP, Dann WL, Hutchinson A. Placental transfer of alfentanil at caesarean section. Eur J Anaesthesiol 1989;6:103–9.
6. Ashton WB, James MFM, Janicki P, Uys PC. Attenuation of the pressor response to tracheal intubation by magnesium sulphate with and without alfentanil in hypertensive proteinuric patients undergoing caesarean section. Br J Anaesth 1991;67:741–7.
7. Rout CC, Rocke DA. Effects of alfentanil and fentanyl on induction of anaesthesia in patients with severe pregnancy-induced hypertension. Br J Anaesth 1990;65:468–74.
8. Batson MA, Longmire S, Csontos E. Alfentanil for urgent caesarean section in a patient with severe mitral stenosis and pulmonary hypertension. Can J Anaesth 1990;37:685–8.
9. Perreault C, Albert JF, Couture P, Meloche R. Epidural alfentanil during labor, in association with a continuous infusion of bupivacaine. Can J Anaesth 1990;37:S5.
10. Giesecke AH Jr, Rice LJ, Lipton JM. Alfentanil in colostrum. Anesthesiology 1985;63:A284.