General and local anesthetics and muscle relaxants

Due to their lipid solubility, general anesthetic agents rapidly cross the blood–brain barrier and the placenta. In addition to their sleep-inducing effect in the brain, they also frequently have a depressant effect on the respiratory center. Thus, during the perinatal phase, there is a risk of hypoxia from neonatal respiratory depression. Fortunately there is no indication that an uncomplicated general anesthetic can lead to developmental disorders. Based on our current knowledge, the commonly used injection or inhalation anesthetics do not have teratogenic properties. However, impairments of respiration and circulation arising in the course of maternal anesthesia, stronger uterine contractions or events such as malignant hyperthermia can also harm the fetus.

Although there are only limited epidemiological data on individual anesthetics, the effects of surgery under anesthesia on pregnant women have been examined in some larger studies. When various anesthetics were combined, none of these older studies found significant indications of damaging effects ( ). In animal experiments, some anesthetic agents have shown neurotoxic effects on the developing brain ( ), possibly through interaction at the glutamate N -methyl- d -aspartate (NMDA) receptor. Substantial debate continues as to whether these animal results are applicable to humans, because in humans, the exposure are generally a single anesthetic and are usually of shorter duration in relation to brain development than in these animal experiments ( ). The results from studies conducted in young children, mostly retrospective to date, are not uniform. It is difficult to control for confounders like pre-existing diseases which might contribute to the incidence of repeat operations ( ). Large prospective multicenter studies are currently being conducted to clarify these questions, e.g. the PANDA study (Pediatric Anesthesia and Neurodevelopment Assessment, www.kidspandastudy.org ) or the GAS study (compare also http://www.smarttots.org/research/relatedstudies.html ). Results are not expected before 2015.

Local anesthetics that are either injected or sprayed on tissue were long considered the agents of choice during pregnancy because it was assumed that the anesthetics remain at the site of administration and so would not pass to the fetus. However, even with this form of anesthesia, complications cannot be ruled out since local anesthetics also reach the fetus following adsorption into the mother’s circulation, depending on the location and vascularization at the injection site ( ).

Muscle relaxants used in connection with surgical procedures are quaternary ammonia salts which, under physiological conditions, are available in a highly ionized form and therefore pass through the placenta only relatively slowly. Nevertheless, they reach the fetus in detectable amounts. Overall, no differences were found in the Apgar scores or the postpartum neurological adaptation of the newborns after caesarean section regardless of whether the mother had had general anesthesia with desflurane or sevoflurane or epidural anesthesia ( ).