General Anesthetic
PREGNANCY RECOMMENDATION: Compatible
BREASTFEEDING RECOMMENDATION: Limited Human Data—Probably Compatible
PREGNANCY SUMMARY
Methohexital sodium is commonly used for induction of general anesthesia for cesarean sections and for electroconvulsive therapy (ECT). The drug can cause dose-related fetal heart rate slowing and respiratory depression and sedation in the newborn. Moreover, reported experience in the 1st trimester is lacking. The animal reproduction studies found no fetal harm.
FETAL RISK SUMMARY
Methohexital sodium is a rapid, ultra short-acting barbiturate anesthetic. It is indicated for IV induction of anesthesia before the use of other general anesthetic agents. In pediatric patients older than 1 month it is given either rectally or as an IM injection (1).
Reproduction studies have been conducted in pregnant rats and rabbits. Doses that were 4 and 7 times the human dose revealed no fetal harm. Studies for carcinogenic or mutagenic potential have not been conducted. There was no evidence of impaired fertility in animals (1).
Consistent with the molecular weight (about 284), methohexital sodium crosses the human placenta (2,3). Women undergoing a cesarean section were given a 1 mg/kg IV dose (2). The mean umbilical vein serum concentration in newborns 5 minutes after injection was 0.02 mcg/mL. No adverse effects in the newborns were observed (2). In a 2000 report, perfused human term placentas were used to study the bidirectional (mother to fetus and fetus to mother) transfer of methohexital sodium (3). Although protein binding significantly affected the degree of transfer, the drug readily crossed the placenta in both directions.
A study reported in 1974 evaluated two doses of methohexital sodium, 1.0 and 1.4 mg/kg, in 26 women undergoing an elective cesarean section (4). In the group that received the lower dose, fewer infants required assisted ventilation, took less time to establish regular respiration, and had higher Apgar scores. A letter to the editor commented on this study and thought that the data suggested a greater degree of acidemia in the infants exposed to the higher maternal dose (5).
A 2009 review of ECT in pregnancy noted that the most frequently used anesthetic agent for ECT was methohexital sodium (6). Although not teratogenic, the agent does cause dose-related fetal heart rate slowing and newborn sedation. These effects can be minimized, however, by using low doses (0.5–1.0 mg/kg).
BREASTFEEDING SUMMARY
Methohexital sodium is excreted into breast milk. Nine women undergoing tubal sterilization 32–341 days after giving birth received 120 or 150 mg IV methohexital sodium for induction of general anesthesia (7). Milk and maternal blood samples were drawn 1–2 hours after induction in five women and 2–4 hours in four. Subsequent samples were drawn at 8–10 hours and 24–28 hours. The highest milk concentration (407 ng/mL) was drawn 63 minutes after induction. The mean milk:blood ratio was 1.1 at 1–2 hours. The drug was undetectable in milk in four women at 8–10 hours and undetectable in milk or blood at 24 hours. The maximum dose to a nursing infant in a 100-mL feeding 1 hour after induction was estimated to be 0.04 mg. This amount did not warrant interruption of breastfeeding (7).
References
1.Product information. Brevital. JHP Pharmaceuticals, 2009.
2.Varga VJ, Machay T, Paulin F, Balazs M, Fedak L. Changes in serum level of methohexital (Brietal) in mothers and newborns during cesarean section. Zbl Gynakol 1983;105:297–9.
3.Herman NL, Li A-T, Johnson RF, Bjoraker RW, Downing JW, Jones D. Transfer of methohexital across the perfused human placenta. J Clin Anesth 2000;12:25–30.
4.Holdcroft A, Robinson MJ, Gordon H, Whitwam JG. Comparison of effect of two induction doses of methohexitone on infants delivered by elective caesarean section. Br Med J 1974;2:472–5.
5.Downing JW. Effect of methohexitone on infants delivered by caesarean section. Br Med J 1974;3:411.
6.Anderson EL, Reti IM. ECT in pregnancy: a review of the literature from 1941 to 2007. Psychosom Med 2009;71:235–42.
7.Borgatta L, Jenny RW, Gruss L, Ong C, Barad D. Clinical significance of methohexital, meperidine, and diazepam in breast milk. J Clin Pharmacol 1997;37:186–92.