The first national survey of anesthesia techniques for fetal therapies in Japan.

PURPOSE: The aim of this study was to survey the frequency of various anesthetic techniques used in the anesthetic management of both the mother and fetus during fetal therapies in Japan. METHODS: We sent a postal survey to the institutions with physicians who held membership of the Japan Society of Fetal Therapy to describe maternal and fetal anesthetic management during fetal therapies performed from January 2016 to March 2017. The therapies included were thoracoamniotic shunting (TAS), intrauterine transfusion (IUT), radiofrequency ablation (RFA), fetoscopic laser photocoagulation (FLP), fetoscopic endotracheal occlusion (FETO), and ex utero intrapartum treatment (EXIT). Survey respondents were asked to specify the standard anesthetic technique used in each of these procedures done during the study period. RESULTS: The most common anesthetic techniques used in each therapy were sedation/analgesia with local anesthesia in TAS (31%), local anesthesia alone in IUT (47%), neuraxial anesthesia in RFA (50%), FLP (66%) and FETO (100%), and general endotracheal anesthesia in EXIT. Fetal analgesia was utilized in 61% of TAS, 33% of IUT, 10% of RFA, 22% of FLP, 100% of FETO, and 50% of EXIT. In all fetal therapies, the most common route of administration for fetal anesthesia was maternal administration. CONCLUSION: In this first published description of the frequency of various anesthetic techniques used during fetal therapies in Japan, we found that anesthetic techniques varied depending on the degree of invasiveness to the mother and fetus. Fetal anesthesia was not always performed, and the most common route for fetal anesthesia was maternal administration.

EARLY gestational exposure to isoflurane causes persistent cell loss in the dentate gyrus of adult male rats.

BACKGROUND: Our previous research showed that 4 h of maternal anesthesia with isoflurane during early gestation in pregnant rats leads to a deficit in spatial memory of adult male offspring. Because spatial memory is predominantly a hippocampally-mediated task, we asked the question if early gestational exposure to isoflurane affects development of the hippocampus in the offspring. FINDINGS: Previously behaviorally characterized adult male rats that were exposed to isoflurane during second trimester were sacrificed at 4 months of age (N = 10 and 13, control and isoflurane groups, respectively) for quantitative histology of hippocampal subregions. Sections were stained with cresyl violet and the total number of cells in the granular layer of the dentate gyrus and the pyramidal cell layer in the CA1 region were determined by a blinded observer using unbiased stereological principles and the optical fractionator method. Data were analyzed using Student's t test; P < 0.05 was accorded statistical significance. Stereological examination revealed 9% fewer cells in the granular layer of the dentate gyrus of isoflurane-exposed adult rats compared to controls (1,002,122 ± 84,870 vs. 1,091,829 ± 65,791, respectively; Mean ± S.D, *P = 0.01). In contrast, there were no changes in the cell number in the CA1 region, nor were there changes in the volumes of both regions. CONCLUSIONS: Our results show that maternal isoflurane anesthesia in rodents causes region-specific cell loss in the hippocampus of adult male offspring. These changes may, in part, account for the behavioral deficits reported in adult rats exposed to isoflurane in utero.

Multiple Exposures to Sevoflurane General Anesthesia During Pregnancy Inhibit CaMKII/CREB Axis by Downregulating HCN2 to Induce an Autism-Like Phenotype in Offspring Mice.

The objective of this investigation was to examine the impact of multiple exposures to general anesthesia (GA) with sevoflurane on the offspring of pregnant mice, as well as to elucidate the underlying mechanism. Neurodevelopmental assessments, including various reflexes and behavioral tests, were conducted on the offspring in the GA group to evaluate neuronal cell development. Furthermore, neonatal mouse neuronal cells were isolated and transfected with a high-expression CREB vector (pcDNA3.1-CREB), followed by treatment with sevoflurane (0.72 mol/L), ZD7288 (50 µmol/L), and KN-62 (10 µmol/L), or a combination of these compounds. The expression of relevant genes was then analyzed using qRT-PCR and western blot techniques. In comparison to the sham group, neonatal mice in the GA group exhibited significantly prolonged latencies in surface righting reflex, geotaxis test, and air righting reflex. Furthermore, there was a notable deceleration in the development of body weight and tail in the GA group. These mice also displayed impairments in social ability, reduced reciprocal social interaction behaviors, diminished learning capacity, and heightened levels of anxious behaviors. Additionally, synaptic trigger malfunction was observed, along with decreased production of c-Fos and neurotrophic factors. Sevoflurane was found to notably decrease cellular c-Fos and neurotrophic factor production, as well as the expression of HCN2 and CaMKII/CREB-related proteins. The inhibitory effects of sevoflurane on HCN2 or CaMKII channels were similar to those observed with ZD7288 or KN-62 inhibition. However, overexpression of CREB mitigated the impact of sevoflurane on neuronal cells. Repetitive exposure to sevoflurane general anesthesia while pregnant suppresses the CaMKII/CREB pathway, leading to the development of autism-like characteristics in offspring mice through the reduction of HCN2 expression.

Effects of Pregnancy Anesthesia on Fetal Nervous System.

The effects of general anesthesia on the developing brain remain a great concern in the medical field and even in the public, and most researches in this area focus on infancy and childhood. In recent years, with the continuous development of medical technology, the number of operations during pregnancy is increasing, however, studies on general anesthesia during pregnancy are relatively lacking. The mid-trimester of pregnancy is a critical period, and is regarded as a safe period for surgery, but it is a fragile period for the development of the central nervous system and is particularly sensitive to the impact of the environment. Our research group found that general anesthesia may have adverse effects on fetal neurodevelopment during the mid-trimester. Therefore, in this review, we summarize the characteristics of anesthesia during pregnancy, and the related research of the anesthesia's impacts on the development of central nervous system were introduced.

Cerebral Oxygenation in Neonates Immediately after Cesarean Section and Mode of Maternal Anesthesia.

BACKGROUND: Cerebral regional oxygen saturation (crSO2) during immediate transition and resuscitation immediately after birth is of increasing interest. OBJECTIVES: The aim of the present study was to assess whether the type of maternal anesthesia during cesarean section (CS; general anesthesia vs. spinal anesthesia) has an influence on cerebral oxygenation during immediate neonatal transition after birth. METHODS: Secondary outcome parameters of prospective observational studies were analyzed. Neonates born by CS from November 2009 to September 2016 at the Medical University of Graz (Austria) were eligible. Term and preterm neonates were included, provided that: (1) crSO2 was measured by near-infrared spectroscopy, and (2) peripheral arterial oxygen saturation (SpO2) and heart rate (HR) were measured by pulse oximetry during the first 15 min after birth. Administration of supplemental oxygen was recorded and cerebral fractional tissue oxygen extraction (cFTOE) was calculated out of crSO2 and SpO2. For comparison, term and preterm neonates with maternal general anesthesia were matched to neonates with maternal spinal anesthesia during CS. RESULTS: Out of 760 eligible neonates, 64 term (38.8 ± 0.9 weeks of gestation; 32 neonates in each group) and 54 preterm neonates (32.0 ± 2.9 weeks of gestation; 27 neonates in each group) were included. In term neonates, maternal general anesthesia was associated with lower initial SpO2, HR values, and Apgar scores. The fraction of inspired oxygen (FiO2) was statistically significantly higher in the general anesthesia group. Nevertheless, crSO2 and cFTOE did not differ statistically significantly between the groups. In preterm neonates there were no statistically significant differences in SpO2, HR, crSO2, and cFTOE between the general and spinal anesthesia groups. Apgar scores at 1 min were statistically significantly lower and FiO2 was statistically significantly higher in the general anesthesia group. CONCLUSION: Cerebral tissue oxygenation in neonates during immediate transition after birth was similar after maternal general and spinal anesthesia during CS, despite differences in SpO2, HR, and supplemental oxygen in term neonates and differences in supplemental oxygen in preterm neonates.

General Anesthesia During the Third Trimester: Any Link to Neurocognitive Outcomes?

Rodent studies on the effect of general anesthesia during the third trimester on neurocognitive outcomes are mixed, but primate studies suggest that a clinically relevant exposure to anesthetic agents during the third trimester can trigger neuronal and glial cell death. Human studies are conflicting and the evidence is weak. This is an up-to-date review of the literature on the neurodevelopmental effects of anesthetic agents administered during the third trimester. Early brain development and critical periods of neurodevelopment as it relates to neurotoxicity are highlighted. Rodent, nonhuman primate, and population studies are discussed and placed in the context of clinical practice.

Effects of maternal enflurane exposure on NR2B expression in the hippocampus of their offspring

This work aims to study the pathogenesis of learning and memory impairment in offspring rats resulting from maternal enflurane anesthesia by focusing on the expression of the N-methyl-d-aspartic acid receptor subunit 2B (NR2B) in the hippocampus of the offspring. Thirty female Sprague-Dawley rats were randomly divided into three groups: control (C group), 4 h enflurane exposure (E1 group), and 8 h enflurane exposure (E2 group) groups. Eight to ten days after the initiation of pregnancy, rats from the E1 and E2 groups were allowed to inhale 1.7% enflurane in 2 L/min oxygen for 4 h and 8 h, respectively. Rats from the C group were allowed to inhale 2 L/min of oxygen only. The Morris water maze was used to assay the learning and memory function of the offspring on postnatal days 20 and 30. RT-PCR and immunohistochemistry assays were then used to measure the mRNA levels and protein expression of NR2B, respectively. Relative to offspring rats from the C group, those from the E1 and E2 groups exhibited longer escape latencies, lesser number of crossings over the platform, and less time spent in the target quadrant in the spatial exploration test (P < 0.05). In addition, the mRNA and protein expression levels of NR2B in the hippocampus of offspring rats in the E1 and E2 groups were down-regulated (P < 0.05). No significant differences between the E1 and E2 groups were observed (P > 0.05) in terms of mRNA levels and protein expression of NR2B. The cognitive function of the offspring is impaired when maternal rats are exposed to enflurane during early pregnancy. A possible mechanism of this effect is related to the down-regulation of NR2B expression.

Este trabalho objetiva o estudo da patogênese de deficiência no aprendizado e memória de prole de ratos resultante da anestesia maternal por enflurano, por meio da expressão da subunidade 2B do receptor do ácidoN-metil-D-aspártico (NR2B) no hipocampo dos filhotes. Dividiram-se, aleatoriamente, 30 fêmeas de ratos Sprague-Dawley em três grupos: controle (grupo C), exposição ao enflurano por 4 h (grupo E1) e por 8 h (grupo E2). De oito a 10 dias após o início da gravidez, os ratos dos grupos E1 e E2 inalaram enflurano 1,7% em 2 L/min de oxigênio, por 4 h e 8 h, respectivamente. Ratos do grupo C inalaram apenas 2 L/min de oxigênio. O labirinto de água de Morris foi empregado para analisar as funções de aprendizado e memória da cria em 20 e 30 dias após o nascimento. Utilizaram-se ensaios de RT-PCR e de imuno-histoquímica para medir os níveis de mRNA e expressão da proteína do NR2B, respectivamente. Em comparação com os ratos controle do grupo C, aqueles dos grupos E1 e E2 exibiram latências de escape mais longas, menor número de travessias na plataforma e menos tempo gasto no quadrante alvo no teste de exploração espacial (P < 0,05). Adicionalmente, os níveis de expressão de mRNA e de proteína do NR2B no hipocampo dos filhotes nos grupos E1 e E2 estavam reduzidos (P < 0,05). Não se observaram diferenças significativas entre os grupos E1 e E2 (P < 0,05) quanto aos níveis de mRNA e à expressão de proteína de NR2B. A função cognitiva dos filhotes é prejudicada quando as mães são expostas ao enflurano durante o início da gravidez. O mecanismo possível para esse efeito está relacionado à diminuição na expressão de NR2B.