Autonomic (Skeletal Muscle Relaxant)
PREGNANCY RECOMMENDATION: Limited Human Data—No Relevant Animal Data
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
Vecuronium has been used as an adjunct to general anesthesia during gamete intrafallopian transfer (GIFT) procedures and cesarean sections. It has also been used in the 2nd and 3rd trimesters by direct IV and IM fetal dosing to produce paralysis during various procedures. No adverse effects attributable to vecuronium on pregnancy rates, the fetus, or the newborn have been reported in these studies. Small amounts of vecuronium cross the placenta, even though this transfer is inhibited by the drug’s low lipid solubility and ionization at physiologic pH. Animal reproduction studies have not been conducted with vecuronium, and no studies, animal or human, have reported its use during organogenesis. Based on this lack of information, the embryo risk from exposure to vecuronium during organogenesis cannot be determined. Use in later times of gestation, however, appears to carry little, if any, risk to the fetus or newborn.
FETAL RISK SUMMARY
The muscle relaxant vecuronium bromide is a nondepolarizing neuromuscular blocking agent that acts by competing for cholinergic receptors at the motor end plate (1). This quaternary ammonium compound belongs to the same general subclass (aminosteroidal) of neuromuscular blockers as pancuronium, pipecuronium, rapacuronium, and rocuronium (2). Vecuronium is indicated as an adjunct to general anesthesia, to facilitate endotracheal intubation, and to provide skeletal muscle relaxation during surgery or mechanical ventilation (1). Reproduction studies of vecuronium in experimental animals have not been located.
The pharmacokinetics of vecuronium in pregnancy was summarized in a 1998 review (3). At term, the elimination half-life of a 0.04 mg/kg dose was 36 minutes, approximately twice as long as atracurium but half the time of pancuronium (3).
The molecular weight (about 638) suggests that vecuronium will cross the placenta, but the ionization and low lipid solubility should limit the exposure of the embryo and fetus. Small amounts of vecuronium do cross the human placenta at term (4–8). In 20 women undergoing general anesthesia for cesarean section, vecuronium (60–80 mcg/kg) was administered between 5 and 21 minutes before delivery (4). The venous cord:maternal ratio averaged 0.11. No neonatal adverse effect was noted as evidenced by normal 1- and 5-minute Apgar scores (4). Others have reported an identical (0.11) umbilical vein:maternal vein ratio (5,6). In these studies, the mean vecuronium-to-delivery interval was 6–7 minutes. No adverse effects on the newborns were observed, as noted by the Apgar scores at 1 and 5 minutes, and the Neurologic and Adaptive Capacity Scores (NACS) determined at 15 minutes, 2, and 24 hours after birth (6).
A 1990 report described the use of vecuronium in 21 patients who were delivered at 36–41 weeks’ gestation by elective cesarean section (7). In one group, 11 women received a 0.01 mg/kg IV priming dose, followed 4–6 minutes later by a 0.1 mg/kg IV dose. The second group of 10 women received a single IV dose of 0.2 mg/kg. The mean induction to delivery time intervals in the two groups was 9 and 11 minutes, respectively. The mean umbilical (UV) and maternal (MV) venous plasma concentrations of vecuronium in group 1 were 73 and 515 ng/mL, respectively, a UV/MV ratio of 0.14, whereas in group 2 the values were 107 and 838 ng/mL, respectively, a ratio of 0.13. The mean birth weights in the two groups were 3443 and 3405 g, respectively. The percentage of newborns having Apgar scores <7 in groups 1 and 2 at 1 minute were 70% and 50%, respectively, and at 5 minutes 100% and 90%, respectively. There were no significant differences between the two groups in the 1- and 24-hour NACS, or in individual tests of passive and active tone within the overall NACS profile. However, the data suggested that vecuronium caused residual effects in the infants (7). A number of other reports have discussed the safe use of vecuronium during cesarean section (8–12).
In a 1999 report, investigators concluded that a more accurate estimation of vecuronium placental transfer during cesarean section would be shown by the ratio of umbilical vein (UV) to maternal artery (MA) concentrations (13). Following an intubation dose of 0.11 mg/kg, the mean UV/MA ratio was 0.056 at an intubation-to-umbilical-cord clamping (I-D) interval of 280 seconds. As expected, the ratio decreased as the I-D interval shortened.
Vecuronium (1–10 mg) has been used as an adjunct to general anesthesia in GIFT procedures (14). No effect on the pregnancy rate following GIFT was noted.
In a 1983 study, 19 newborns of mothers who had received vecuronium before delivery by cesarean section were compared with 9 newborns whose mothers had not received the agent (15). No significant difference in the Apgar scores at 1 and 5 minutes were observed between the two groups. In addition, vecuronium had no effect on maternal plasma cholinesterase activity (15).
A 1988 case study described the direct fetal administration of vecuronium under ultrasound guidance for fetal magnetic resonance imaging at 33 weeks’ gestation of a brain defect (16). The dose used was 0.2 mg (0.1 mg/kg). A 3540-g male infant was delivered at 39 weeks’ with Apgar scores of 10 and 10 at 1 and 5 minutes, respectively. Examination at 9 days of age confirmed the defect (16).
The successful anesthetic management of a woman at 32 weeks’ gestation with dextrocardia, situs inversus, a double-outlet right ventricle, ventricular septal defect, and severe pulmonary stenosis was described in a 1994 report (17). No adverse effects attributable to vecuronium (0.1 mg/kg) were observed in the growth-restricted (0.94 kg) infant, who was doing well at 2 weeks of age. Vecuronium (10 mg) was used to assist mechanical ventilation in another case involving a woman at 36 weeks’ gestation in labor who had developed severe respiratory distress secondary to myocardial infarction related to cocaine use (18). The mother also received fentanyl and midazolam. Four hours later, the woman delivered a live female infant. Specific information on the infant’s condition was not given.
A 1998 case report described respiratory muscle rigidity in a newborn that was attributed to fentanyl (see Fentanyl) (19). In addition to other drugs, the mother had received vecuronium (7 mg) at 31 weeks’ gestation.
Vecuronium was used to paralyze 14 fetuses during 17 intrauterine intravascular exchange transfusions (20). The mean gestational age was 29.2 weeks (range 22–35 weeks) and the mean estimated fetal weight was 1610 g (range 500–2500 g). The dose used (0.1 mg/kg) resulted in a mean onset of paralysis of 97.6 seconds (range 45–150 seconds) with a mean duration, as determined by maternal perception of fetal movements, of 122 minutes. The duration of paralysis was not correlated with gestational age. No maternal or fetal adverse effects were noted. All fetuses were delivered alive at a mean 35.8 weeks’ gestation (20). In another 1992 report, vecuronium (0.15 mg/kg IV or IM) was used in nine intrauterine procedures involving five fetuses (21). The authors noted that whereas vecuronium caused no fetal heart rate changes, pancuronium caused increased fetal heart rates and decreased beat-to-beat variability for 2.5 hours postdose.
Two pregnant women undergoing general anesthesia for cesarean section developed difficulty with breathing after receiving IV priming doses of vecuronium (10 and 13.7 mcg/kg) (22). Rapid sequence induction was initiated and healthy infants with normal Apgar scores were delivered.
BREASTFEEDING SUMMARY
No reports describing the use of vecuronium during lactation have been located. However, even if such use was reported, it is doubtful if clinically significant amounts of vecuronium would be excreted into breast milk. The molecular weight (about 638) is low enough, but the low lipid solubility and ionization at physiologic pH would inhibit its excretion into milk. These factors suggest that vecuronium represents no risk to a breastfeeding infant.
References
1.Product information. Norcuron. Organon, 2002.
2.Muscle relaxants. In: Parfitt K, ed. Martindale. 32nd ed. London: Pharmaceutical Press, 1999:1302.
3.Guay J, Grenier Y, Varin F. Clinical pharmacokinetics of neuromuscular relaxants in pregnancy. Clin Pharmacokinet 1998;483–96.
4.Demetriou M, Depoix JP, Diakite B, Fromentin M, Duvaldestin P. Placental transfer of ORG NC45 in women undergoing caesarean section. Br J Anaesth 1982;54:643–5.
5.Dailey PA, Fisher DM, Shnider SM, Baysinger CL, Shinohara Y, Miller RD, Abboud TK, Kim KC. Pharmacokinetics, placental transfer, and neonatal effects of vecuronium (ORG NC45) administered prior to delivery (abstract). Anesthesiology 1982;57:A391.
6.Dailey PA, Fisher DM, Shnider SM, Baysinger CL, Shinohara Y, Miller RD, Abboud TK, Kim KC. Pharmacokinetics, placental transfer, and neonatal effects of vecuronium and pancuronium administered during Cesarean section. Anesthesiology 1984;60:569–74.
7.Hawkins JL, Johnson TD, Kubicek MA, Skjonsby BS, Morrow DH, Joyce TH III. Vecuronium for rapid-sequence intubation for Cesarean section. Anesth Analg 1990;71:185–90.
8.Baraka A, Jabbour S, Tabboush Z, Sibai A, Bijjani A, Karam K. Onset of vecuronium neuromuscular block is more rapid in patients undergoing caesarean section. Can J Anaesth 1992;39:135–8.
9.Teviotdale BM. Vecuronium-thiopentone induction for emergency caesarean section under general anaesthesia. Anaesth Intensive Care 1993;21:288–91.
10.Brimacombe J, Berry A. Vecuronium for emergency caesarean section. Anaesth Intens Care 1994;22:119.
11.Teviotdate B. Vecuronium for emergency caesarean section. Reply. Anaesth Intens Care 1994;22:119–20.
12.Das S, Bhattacharjee M, Maitra S. Study of neonatal status after use of vecuronium as a muscle relaxant in caesarean section. J Indian Med Assoc 1993;91:54–6.
13.Iwama H, Kaneko T, Tobishima S, Komatsu T, Watanabe K, Akutsu H. Time dependency of the ratio of umbilical vein/maternal artery concentrations of vecuronium in Caesarean section. Acta Anaesthesiol Scand 1999; 43:9–12.
14.Pierce ET, Smalky M, Alper MM, Hunter JA, Amrhein RL, Pierce EC Jr. Comparison of pregnancy rates following gamete intrafallopian transfer (GIFT) under general anesthesia with thiopental sodium or propofol. J Clin Anesth 1992;4:394–8.
15.Baraka A, Noueihed R, Sinno H, Wakid N, Agoston S. Succinylcholine-vecuronium (ORG NC 45) sequence for Cesarean section. Anesth Analg 1983;62:909–13.
16.Daffos F, Forestier F, MacAleese J, Aufrant C, Mandelbrot L, Cabanis EA, Iba-Zizen MT, Alfonso JM, Tamraz J. Fetal curarization for prenatal magnetic resonance imaging. Prenat Diagn 1988;8:312–4.
17.Rowbottom SJ, Gin T, Cheung LP. General anaesthesia for Caesarean section in a patient with uncorrected complex cyanotic heart disease. Anaesth Intens Care 1994;22:74–8.
18.Liu SS, Forrester RM, Murphy GS, Chen K, Glassenberg R. Anaesthetic management of a parturient with myocardial infarction related to cocaine use. Can J Anaesth 1992;39:858–61.
19.Lindemann R. Respiratory muscle rigidity in a preterm infant after use of fentanyl during Caesarean section. Eur J Pediatr 1998;157:1012–3.
20.Leveque C, Murat I, Toubas F, Poissonnier MH, Brossard Y, Saint-Maurice C. Fetal neuromuscular blockade with vecuronium bromide: studies during intravascular intrauterine transfusion in isoimmunized pregnancies. Anesthesiology 1992;76:642–4.
21.Watson WJ, Atchison SR, Harlass FE. Comparison of pancuronium and vecuronium for fetal neuromuscular blockade during invasive procedures. J Matern Fetal Med 1996;5:151–4.
22.Cherala S, Eddie D, Halpern M, Shevdi K. Priming with vecuronium in obstetrics. Anaesthesia 1987;42:1021.