2164 Injectable anesthetics

Etomidate, ketamine, methohexital, propofol, and thiopentone (ithiopental) are among the injectable anesthetics. If administered intravenously, injectable anesthetics reach their maximum concentrations immediately. The concentration in plasma falls rapidly due to rapid redistribution and excretion. After use in labor, the longer the time between the injection of the anesthetic and the infant's birth, the lower the concentration in the newborn, and the less the possible transient effects of these agents. As a rule, they can all be used in pregnancy. The main drugs will be discusscd individually.

This non-barbiturate imidazole derivative is inactivated by nonspecific esterases. It is an inhibitor of steroid biosynthesis, and has been found to reduce scrum Cortisol concentrations in neonates following the use of ctomidatc during delivery without any long-term consequences (Reddy 1988). Etomidate does not have cardio-depressive characteristics. Its half-life is very short, being in the serum for about 3 minutes. The brief duration of the effect, like that of barbiturates, is dependent on redistribution from the brain, with its large blood supply, to tissues such as muscle and fat, which are less wcll-vascularized. There arc no epidemiologic studies on the administration of ctomidatc in prcgnancy, and there has been no long-term follow-up. Animal studies regarding congenital anomalies are inconclusive, and even high doses were not teratogenic in rats (USP DI 2003. Doenicke 1977).

Recommendation. Etomidate may be used In pregnancy, but If it is used in labor then the baby should be observed for possible respiratory depressant effects.

Ketamine (Ketalar) is a fast-acting anesthetic agent that has a good analgesic effect and little effect on respiration. There are no epidemiologic studies in man evaluating its possible effects on fetal development. Due to its enhancement of sympathomimetic sensitivity. ketamine administration can be associated with marked cardiovascular effects such as increased heart rate and blood pressure. Ketamine increases the uterine tone and the frequency of uterine contractions in a dose-related fashion (Krissel 1994). High doses may depress fetal functions and hence distort fetal monitoring during parturition (Baraka 1990, Reich 1989). Use of ketamine during cesarean section has in several cases led to clinically important panic disorders, which restricts its use during birth. In addition, neonatal behavioral alterations, including reduction in sucking.

have also been described in infants whose mothers were given kct-amine for cesarean section (Hodgkinson 1978). In a study on 20 women who received ketamine for cesarean section, no neonatal depression was observed if the induction-to-delivery and incision-to-delivery times were short, but complications occurred if these intervals were longer than 10 and 1.5 minutes respectively (Baraka 1990), Most animal studies regarding congenital anomalies are negative (Abdel-Rahman 2000) even with doses 10-25 times the human dose. On microscopic evaluation, however, several tissues have shown degenerative changes in the offspring of rats treated in pregnancy with ketamine (Kochar 1986).

Recommendation. It seems preferable not to use ketamine during pregnancy. As ketamine can increase blood pressure, it is especially contraindi-cated in cases of hypertension or pre-edampsia in pregnancy, and with uterine hyperactivity or suspicion of fetal hypoxia during labor.

Propofol is a general anesthetic administered intravenously. It crosses the human placenta with cord blood levels at term approximately 70% those of maternal blood (Dailland 1990). Similar findings have also been reported for samples taken during gestational weeks 12-18 (Jauniaux 1998). All studies except one on pregnancy rates in ova collection for in vitro fertilization following propofol anesthesia demonstrated no adverse effects on the rate of pregnancy (Beilin 1999, Christiaens 1998).

There are several reports which conclude that propofol used during delivery has no adverse effects on neonatal well-being (d'AIessio 1998, Moore 1989). These either have no controls or are compared to infants exposed to thiopental, and in most cases the conclusions are based on Apgar scores or the lack of need for ventilatory assistance. One of these reports, using the early neonatal neurobehavioral scale (ENNS), found newborns exposed to propofol for cesarean section to have a decrement in some areas of neurobehavioral status when compared with children exposed to thiopental (Celleno 1989, d'AIessio 1998). These effects were always transitory. In another study by Gin (1993), propofol was found to be superior to thiopental when used for anesthesia in women undergoing cesarean section. Animal studies reported by the manufacturer appear negative in the doses used for anesthesia.

Recommendation. Propofol may be used in obstetrics to initiate anesthesia for operations during pregnancy and labor, or for ova transfer and IVF, Newborns should be observed for a depressive effect on the breathing if used in labor.

Sodium thiopentone (thiopental) and methohexital (sodium brevital)

Sodium thiopentone is a thiobarbiturate characterized by its rapid action. Thiopentone accumulates in the brain, owing to this organ's large blood supply, where it acts rapidly. Subsequent redistribution to muscle and fat causes the concentration in the brain to fall rapidly below the threshold of anesthetic effectiveness, enabling rapid awakening. There seems to be only one epidemiologic human study showing that this drug, when serving for anesthesia in 152 women, did not increase the rate of congenital anomalies (Heinonen 1977).

Thiobarbituratcs can be detected in fetal blood as rapidly as 1 minute after injection, at a concentration only slightly less than that in the mother's blood, but its concentrations in the fetal brain are low as it is rapidly taken up by the fetal liver. With low doses (i.v. up to 5mg/kg) during labor, no fetal impairment is expected. With higher doses, neonatal respiratory depression may occur (Langanke 1987).

Methohexital (sodium brevital, barbital) is also a short-acting barbiturate, administered intravenously as an adjunct anesthetic during surgical procedures, including cesarean section. No human data regarding the safety of this drug in pregnancy arc available, but it is widely used without any reported deleterious effects on pregnancy outcome (Cohen 1971). It readily crosses the placenta in both directions, thus fetal concentrations are similar to those in the mother (Herman 2000).

In animal studies, both drugs did not seem to increase the rate of congenital anomalies among the offspring of mice, rats or rabbits treated with this drug during pregnancy (Persaud 1965).

Recommendation. Short-acting barbiturates like sodium thiopentone may be used to initiate anesthesia for operations during pregnancy. When given during labor, newborns should be observed for a depressive effect on breathing.

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