Hypnotic
PREGNANCY RECOMMENDATION: Limited Human Data—Animal Data Suggest Risk
BREASTFEEDING RECOMMENDATION: Limited Human Data—Probably Compatible
PREGNANCY SUMMARY
The human pregnancy experience with etomidate is limited to women undergoing cesarean section. A 1988 review found no reports of congenital malformations in children of women anesthetized with this agent (1). The animal data suggest risk (embryo–fetal death), but the dose was based on body weight and may not be relevant. However, no structural anomalies have been observed in animals. When used immediately before birth, etomidate causes a transient decrease in newborn cortisol concentrations. The clinical significance of this effect is unknown. Although the data are limited, use of etomidate for induction of general anesthesia at or near term does not appear to represent a risk of fetal or newborn harm.
FETAL RISK SUMMARY
Etomidate is a rapid, short-acting hypnotic drug without analgesic activity that is given as an IV injection. Etomidate is indicated for the induction of general anesthesia. The agent is metabolized in the liver to inactive metabolites. Blood concentrations of etomidate decrease rapidly up to 30 minutes after injection and thereafter more slowly with an elimination half-life about 75 minutes (2, 3).
Reproduction studies have been conducted in rats and rabbits. In rats, doses that were ≥1 times the human dose (based on body weight) were embryocidal. In rats and rabbits, doses that were 1–16 and 5–15 times the human dose, respectively, resulted in decreased pup survival. The highest doses caused maternal toxicity including death. No teratogenicity has been observed in animals (2, 3).
Studies for carcinogenicity and mutagenicity have not been conducted. No impairment of fertility was noted in male and female rats (2, 3).
It is not known if etomidate crosses the human placenta early in pregnancy but it does at term. A 1988 abstract described seven women undergoing elective cesarean section (4). General anesthesia was induced with a 0.3 mg/kg IV dose of etomidate. The elimination half-life was 132 minutes. At delivery, the fetal:maternal ratio was 0.51. Etomidate was detected in the urine of the newborns up to 16 hours after birth (4). One study reported an umbilical:maternal vein ratio of 0.5 after use of the drug for cesarean section in 20 women (5). Apgar scores were ≥7 and 9/10 at 1 and 5 minutes, respectively. Another study measured an umbilical:maternal ratio of 0.48 in 20 women at cesarean section (6). A 1992 study of 20 women undergoing cesarean section also found that the drug crossed to the fetus (7). All of these results are consistent with the relatively low molecular weight (about 244) of etomidate.
In one of the studies described above, etomidate was associated with a transient reduction in neonatal cortisol concentrations in comparison with a methohexitone group (6). The difference between the two groups was most evident 2 hours after birth. There was no difference at 5 hours. The decrease was thought to be secondary to inhibition of cortisol synthesis in the adrenal cortex, a known effect of etomidate (6). In another study, 11 mothers undergoing elective cesarean sections were given 0.3 mg/kg etomidate for induction of general anesthesia (8). Serum cortisol in the newborns was compared with 11 newborns of mothers who had been given thiopentone for induction. At 1 hour of age, the cortisol concentrations were significantly lower (p<0.001) in the etomidate group (8).
One of the first reports describing the use of etomidate for induction of general anesthesia before cesarean section was published in 1984 (9). Seventy-two women received the agent and no clinical effects were observed in the newborns. Other reports also have described the use of etomidate for this purpose, apparently without harm to the newborns (10–14).
BREASTFEEDING SUMMARY
No reports describing the use of etomidate during human lactation have been located. Such studies are not expected because of the indication for the drug. However, the drug crosses the placenta when given for cesarean section (4–7). In one study involving 20 women who had received a single 0.3 mg/kg IV dose, etomidate was detected in the colostrum (7). Mean colostrum drug concentrations at 30 and 120 minutes after the dose were 79.3 ng/mL (range 0–420 ng/mL) and 16.2 ng/mL (range 0–60 ng/mL), respectively. Etomidate was not detected in any sample 4 hours after the dose. The colostrum:plasma ratio at 30 minutes was 1.2; at 120 minutes, plasma concentrations were undetectable (7). Because of the very small amounts of colostrum that are available at these times, the risk to a nursing infant probably is nil.
References
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3.Product information. Amidate. Hospira, 2009.
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14.Duman A, Sarkilar G, Dayioglu M, Özden M, Görmüs N. Use of remifentanil in a patient with Eisenmenger syndrome requiring urgent cesarean section. Middle East J Anesthesiol 2010;20:577–80.