Hypnotic
PREGNANCY RECOMMENDATION: Limited Human Data—Animal Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: Limited Human Data—Probably Compatible
PREGNANCY SUMMARY
A number of studies have described the use of propofol during cesarean section. The drug has caused transient newborn depression. No reports describing the use of the drug during the 1st and 2nd trimesters have been located.
FETAL RISK SUMMARY
Propofol is a hypnotic agent used for the IV induction and maintenance of anesthesia (1–20). Reproduction studies in rats and rabbits at doses 6 times the recommended human induction dose have revealed no evidence of impaired fertility or fetal harm (21).
The pharmacokinetics of propofol in women undergoing cesarean section was reported in 1990 (1). Propofol rapidly crosses the placenta and distributes in the fetus (2–12). The fetal:maternal (umbilical vein:maternal vein) ratio is approximately 0.7. Doses were administered either by IV bolus, by continuous infusion, or by both methods.
Several studies have examined the effect of maternal propofol anesthesia on infant Apgar scores, time to sustained spontaneous respiration, and Neurological and Adaptive Capacity Score (NACS) or the Early Neonatal Neurobehavioural Scale (ENNS) (1,2,4,5,7,8,11–18). Most investigators reported no difference in the Apgar scores of infants exposed to propofol either alone or when compared with other general anesthesia techniques, such as thiopental with enflurane or isoflurane (2,5,7,8,14–18). Moreover, no correlation was found between the Apgar scores and umbilical arterial or venous concentration of propofol (2,5,8,11,15).
In one study, infants (N = 20) exposed to a maternal propofol dose of 2.8 mg/kg had significantly lower Apgar scores at 1 and 5 minutes compared with infants (N = 20) whose mothers were treated with thiopental 5 mg/kg (13). The Apgar scores in both groups were significantly lower when compared with infants born by spontaneous vaginal delivery. The induction-to-delivery and uterine incision-to-delivery intervals in the two treatment groups were nearly identical. Five propofol-exposed infants had profound muscular hypotonus at birth and at 5 minutes, and one newborn was somnolent (13). Propofol-exposed infants were evaluated using the ENNS and were found to have a depression in alert state, pinprick and placing reflexes, and mean decremental count in Moro and light reflexes 1 hour after birth but not at 4 hours (13). Five (25%) of the infants exhibited generalized irritability and continuous crying at 1 hour, but not at 4 hours.
In contrast, most studies found no difference in the NACS or time to sustained spontaneous respiration between various groups with propofol IV bolus doses of 2.5 mg/kg or when continuous infusion doses were no higher than 6 mg/kg/hr (2,5,8,14–16). Higher doses, such as 9 mg/kg/hr, were correlated with a depressed NACS (8,12,14–16,18).
BREASTFEEDING SUMMARY
Small amounts of propofol are excreted into breast milk and colostrum following use of the agent for the induction and maintenance of maternal anesthesia during cesarean section (3). Two groups of women were studied. The first group consisted of four women who had received a mean IV propofol dose of 2.55 mg/kg at a mean of 25.9 minutes before delivery. The mean total dose received by patients in this group was 155.5 mg. The second group consisted of three women who had received a mean IV dose of 2.51 mg/kg plus a mean infusion of 5.08 mg/kg/hr. The mean total dose in this group was 247.4 mg, and the mean time to delivery was 20.2 minutes. Breast milk or colostrum samples were collected at various intervals from 4 to 24 hours after delivery. Propofol concentrations in the seven patients varied between 0.048 and 0.74 mcg/mL, with the highest levels predictably occurring at 4–5 hours in group 2. In one patient from group 2, the milk/colostrum concentration was 0.74 mcg/mL at 5 hours and fell to 0.048 mcg/mL (6% of the initial sample) at 24 hours. These amounts were considered negligible when compared with the amounts the infants received before birth from placental transfer of the drug (3).
References
1.Gin T, Gregory MA, Chan K, Buckley T, Oh TE. Pharmacokinetics of propofol in women undergoing elective caesarean section. Br J Anaesth 1990;64:148–53.
2.Dailland P, Lirzin JD, Cockshott ID, Jorrot JC, Conseiller C. Placental transfer and neonatal effects of propofol administered during cesarean section (abstract). Anesthesiology 1987;67:A454.
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19.Costantino P, Emanuelli M, Muratori F, Sebastiani M. Propofol versus thiopentone as induction agents in cesarean section. Minerva Anestesiol 1990;56:865–70.
20.Alberico FP. Propofol in anesthesia induction for cesarean section. Minerva Anestesiol 1990;56:871.
21.Product information. Diprivan. AstraZeneca, 2000.