BACKGROUND:There is concern that maternal anesthesia during pregnancy impairs brain development of the human fetus. Xenon is neuroprotective in pre-clinical models of anesthesia-induced neurotoxicity in neonates. It is not known if xenon also protects the developing fetal brain when administered in addition to maternal sevoflurane-anesthesia during pregnancy.OBJECTIVE:To investigate the effects of sevoflurane and xenon on neurobehaviour and neurodevelopment of the offspring in a pregnant rabbit model.METHODS:Pregnant rabbits on post-conception day 28 (term = 31d) underwent two hours of general anesthesia with 1 minimum alveolar concentration (MAC) of sevoflurane in 30% oxygen (n = 17) or 1 MAC sevoflurane plus 50-60 % xenon in 30% oxygen (n = 10) during a standardized laparotomy while receiving physiological monitoring. A sham-group (n = 11) underwent monitoring alone for two hours. At term, the rabbits were delivered by caesarean section. On the first postnatal day, neonatal rabbits underwent neurobehavioral assessment using a validated test battery. Following euthanasia, the brains were harvested for neurohistological analysis. A mixed effects-model was used for statistical analysis.RESULTS:Maternal cardiopulmonary parameters during anesthesia were within the reference range. Fetal survival rates were significantly higher in the sham-group as compared to the sevoflurane-group and the fetal brain/body weight ratio was significantly lower in the sevoflurane-group as compared with the sham- and xenon-group. Pups antenatally exposed to anesthesia had significantly lower motor and sensory neurobehavioral scores when compared to the sham-group (mean ± SD; sevo: 22.70 ± 3.50 vs. sevo+xenon: 22.74 ± 3.15 vs. sham: 24.37 ± 1.59; overall p = 0.003; sevo: 14.98 ± 3.00 vs. sevo+xenon: 14.80 ± 2.83 vs. sham: 16.43 ± 2.63; overall p = 0.006; respectively). Neuron density, neuronal proliferation and synaptic density were reduced in multiple brain regions of the exposed neonates. The co-administration of xenon had no measurable neuroprotective effects in this model.CONCLUSIONS:In rabbits, sevoflurane anesthesia for a standardized laparotomy during pregnancy resulted in impaired neonatal neurobehavior and a decreased neuron count in several regions of the neonatal rabbit brain. Co-administration of xenon did not prevent this effect.

(Am J Obstet Gynecol. 2019;221:355.e1–355.e19) Approximately 0.2% to 2% of pregnant women in the United States and Europe undergo nonobstetric surgery each year. These procedures are often performed under general anesthesia (GA). Clinicians, researchers, and organizations have expressed concern about the potential adverse effects of anesthesia on the developing brain of an infant or fetus. Previous clinical research studies have indicated varying conclusions, but there is a general consensus that the developing brain is most vulnerable when the brain is at peak growth, beginning mid-gestation, and continues after delivery. While earlier animal studies have explored the effects of neonatal anesthesia only, little research has explored the effects of GA administered for surgery, as well as the effect of surgery itself during pregnancy. This study investigated whether the combination of maternal anesthesia and surgery, using a rabbit model, would lead to poorer neurological outcomes at birth, as well as behavioral and cognitive debilitation in the time after delivery.

BackgroundXenon has repeatedly been demonstrated to have only minimal hemodynamic side effects when compared to other anesthetics. Moreover, in experimental models, xenon was found to be neuroprotective and devoid of developmental neurotoxicity. These properties could render xenon attractive for the anesthesia in neonates and infants with congenital heart disease. However, experience with xenon anesthesia in children is scarce. AimsWe hypothesized that in children undergoing cardiac catheterization, general anesthesia with a combination of sevoflurane with xenon results in superior hemodynamic stability, compared to sevoflurane alone. MethodsIn this prospective, randomized, single-blinded, controlled clinical trial, children with a median age of 12 [IQR 3-36] months undergoing diagnostic/interventional cardiac catheterization were randomized to either general anesthesia with 50-65vol% xenon plus sevoflurane or sevoflurane alone. The primary outcome was the incidence of intraprocedural hemodynamic instability, defined as the occurrence of: (i) a heart rate change >20% from baseline; or (ii) a change in mean arterial blood pressure >20% from baseline; or (iii) the requirement of vasopressors, inotropes, chronotropes, or fluid boluses. Secondary endpoints included recovery characteristics, feasibility criteria, and safety (incidence of emergence agitation and postoperative vomiting. ResultsAfter inclusion of 40 children, the trial was stopped as an a priori planned blinded interim analysis revealed that the overall rate of hemodynamic instability did not differ between groups [100% in both the xenon-sevoflurane and the sevoflurane group. However, the adjuvant administration of xenon decreased vasopressor requirements, preserved better cerebral oxygen saturation, and resulted in a faster recovery. Xenon anesthesia was feasible (with no differences in the need for rescue anesthetics in both groups). ConclusionOur observations suggest that combining xenon with sevoflurane in preschool children is safe, feasible, and facilitates hemodynamic management. Larger and adequately powered clinical trials are warranted to investigate the impact of xenon on short- and long-term outcomes in pediatric anesthesia.