Neuroendocrine,epigenetic, and intergenerational effects of general anesthetics

The progress of modern medicine would be impossible without the use of general anesthetics (GAs). Despite advancements in refining anesthesia approaches, the effects of GAs are not fully reversible upon GA withdrawal. Neurocognitive deficiencies attributed to GA exposure may persist in neonates or endure for weeks to years in the elderly. Human studies on the mechanisms of the long-term adverse effects of GAs are needed to improve the safety of general anesthesia but they are hampered not only by ethical limitations specific to human research, but also by a lack of specific biological markers that can be used in human studies to safely and objectively study such effects. The latter can primarily be attributed to an insufficient understanding of the full range of the biological effects induced by GAs and the molecular mechanisms mediating such effects even in rodents, which are far more extensively studied than any other species. Our most recent experimental findings in rodents suggest that GAs may adversely affect many more people than is currently anticipated. Specifically, we have shown that anesthesia with the commonly used GA sevoflurane induces in exposed animals not only neuroendocrine abnormalities (somatic effects), but also epigenetic reprogramming of germ cells (germ cell effects). The latter may pass the neurobehavioral effects of parental sevoflurane exposure to the offspring, who may be affected even at levels of anesthesia that are not harmful to the exposed parents. The large number of patients who require general anesthesia, the even larger number of their future unexposed offspring whose health may be affected, and a growing number of neurodevelopmental disorders of unknown etiology underscore the translational importance of investigating the intergenerational effects of GAs. In this mini review, we discuss emerging experimental findings on neuroendocrine, epigenetic, and intergenerational effects of GAs.     

二氧化碳吸收剂中水分对七氟醚分解反应的影响

目的　研究模拟紧闭反应器内干燥的二氧化碳 (CO2 )吸收剂及自身含水对七氟醚分解的影响。方法　在紧闭反应器 (1 6 0ml)内 ,分别装钠石灰、钡石灰、干燥钠石灰和干燥钡石灰 (各 2 5g)。在密闭状态下注入液态的七氟醚 4 0 0 μl,放入 5 0℃水浴内反应 6h ,分别在 5、1 5、30、4 5、6 0min、以后每 30分钟至 36 0分钟采样 ,用气相色谱法分析。测定七氟醚的分解产物。结果　钠石灰组出现复合物A、B ,在其他组七氟醚产生 5种分解产物。复合物A∶干燥钡石灰 >干燥钠石灰 >钡石灰和钠石灰组。干燥钡石灰组明显高于其他两组 (P <0 0 5 )。复合物B∶干燥钡石灰组 <钡石灰组 <干燥钠石灰组 (P <0 0 5 )。复合物C、D、E ,以干燥钡石灰组最为明显 (P <0 0 5 )。各组均未检测到CO。结论　在 5 0℃的紧闭反应器内 ,七氟醚与干燥的CO2 吸收剂反应剧烈 ,未产生CO ;国产钠石灰优于钡石灰 ,在紧闭容器内自身含水可以抑制分解反应     

脑状态指数在七氟醚或丙泊酚诱导时的变化

目的 观察七氟醚或丙泊酚麻醉时脑状态指数(CSI)的变化.方法 30例腹腔镜手术患者随机均分成七氟醚组(S组)和丙泊酚组(P组).麻醉诱导:S组吸入2%的七氟醚,每隔1分钟增加1%;P组每隔1分钟重复给予15 mg丙泊酚,直至患者意识消失.记录患者诱导期的CSI数值,并对患者的镇静程度采用警觉/镇静评分(OAA/S)标准评分.结果 S组与P组术前CSI基础值差异无统计学意义,随着麻醉的加深,两组的CSI数值均明显下降(P<0.01),至OAA/S 1分时S组与P组的CSI数值较OAA/S 5分时明显下降(P<0.05或P<0.01),S组与P组的CSI与OAA/S的相关系数r分别为0.843和0.812.结论 CSI监测可反映七氟醚或丙泊酚麻醉时的麻醉深度.     

七氟醚、异氟醚对阿曲库铵肌松恢复的影响

目的 观察七氟醚、异氟醚对阿曲库铵肌松恢复的影响.方法 选择75例Ⅰ或Ⅱ级成年择期全麻手术病人随机均分为三组.Ⅰ组丙泊酚4～10 mg·kg-1·h-1泵入;Ⅱ、Ⅲ组分别吸入呼气末浓度为1 MAC的七氟醚、异氟醚.诱导插管后阿曲库铵均以30μg·kg-1·min-1的速度静脉泵入.使用Biomter加速度仪监测肌松恢复情况,记录T1恢复至25%,75%及TOFr恢复至0.7的时间.结果 Ⅱ、Ⅲ组T1恢复至25%、75%的时间及TOFr恢复至0.7的时间均比Ⅰ组显著延长(P＜0.05).恢复指数(T1从25%至75%的时间)三组比较差异无统计学意义.结论 七氟醚、异氟醚均可增加阿曲库铵残余肌松作用.     

七氟醚后处理对局灶性脑缺血-再灌注损伤的保护作用

目的评价在缺血后期及再灌注早期吸入不同浓度的七氟醚行后处理对大鼠局灶性脑缺血-再灌注损伤的保护作用及其剂量依赖性。方法雄性SD大鼠50只,随机分为空白对照组、吸氧组和0.5、1.0、1.5MAC七氟醚后处理组,每组10只。采用大脑中动脉线栓法阻闭(middle cerebral artery occlusion,MCAO)120min后再灌注72h制备局灶性脑缺血模型。各七氟醚后处理组于再灌注即刻的前20min和后10min给予不同浓度七氟醚吸入。再灌注后的24、48和72h行神经功能评分(NDS),并于最后一次评分后测定脑梗死容积比。结果0.5、1.0和1.5MAC组的脑梗死容积比分别为0.39±0.03,0.31±0.03和0.24±0.03(P<0.05),明显小于对照组0.53±0.05(P<0.05)。吸氧组为0.51±0.05,与对照组比差异无统计学意义。各个时间点七氟醚后处理组NDS明显优于对照组和吸氧组。结论在局灶性脑缺血-再灌注的缺血后期和再灌注早期吸入0.5、1.0和1.5MAC七氟醚行后处理均具有脑保护作用,并呈现剂量依赖性。     

异氟醚和七氟醚麻醉对患者心率变异性的影响

目的研究异氟醚和七氟醚麻醉对患者心率变异性(HRV)的影响。方法60例择期颅脑手术患者,用动态心电图仪记录麻醉诱导前、插管后10 min、停药时、停药后1、2 h和4 h的HRV。结果ISO1组(异氟醚,年龄<60岁)和ISO2组(异氟醚,年龄≥60岁)插管后10 min、停药时、停药后1、2 h的低频功率(LF)、高频功率(HF)值均显著低于麻醉诱导前(P<0.05)。SEV1组(七氟醚,年龄<60岁)和SEV2组(七氟醚,年龄≥60岁)的LF、HF值在插管后10 min、停药时、停药后1 h均显著低于麻醉诱导前(P<0.05)。ISO组插管后各时点的LF、HF值均显著低于SEV组(P<0.05)。结论异氟醚对患者的交感神经和迷走神经都有明显的抑制作用,而对于交感神经和副交感神经活性的均衡性没有显著的影响。异氟醚对于交感神经和迷走神经的抑制作用比七氟醚更为明显。     

腹部手术患者吸入七氟醚与异氟醚麻醉恢复的比较

目的比较腹部手术患者吸入七氟醚与异氟醚麻醉恢复的情况。方法全麻下行开腹手术患者40例,随机分为2组（n=20）：七氟醚组（S组）及异氟醚组（Ⅰ组）。麻醉诱导后行气管插管,机械通气。诱导后吸入纯氧,氧流量2 L/min,30min后调整为1 L/min。手术开始前,调整吸入麻醉药的呼气末浓度为1.0 MAC。麻醉维持：吸入七氟醚或异氟醚,间断静脉注射罗库溴铵和芬太尼,维持血压和心率波动幅度不超过基础值30%。缝皮结束时,停止吸入七氟醚或异氟醚,纯氧流量调整为5 L/min。记录睁眼时间（停止吸入麻醉药到睁眼的时间）、拔除气管导管时间（停止吸入麻醉药到拔除气管导管的时间）、Aldrete评分达到9分时间（从停止吸入麻醉药计时）及麻醉后恢复室（PACU）停留时间。记录吸入麻醉药用量。结果与Ⅰ组比较,S组睁眼时间、拔除气管导管时间、Aldrete评分达到9分时间及PACU停留时间缩短（P〈0.05）,吸入麻醉药的总用量和单位时间用量差异无统计学意义（P〉0.05）。结论与异氟醚比较,吸入七氟醚患者麻醉恢复较快,且麻醉恢复质量较好。     

七氟醚预处理对体外循环冠状动脉旁路移植术病人围术期心肌的保护作用

目的探讨七氟醚预处理对体外循环(CPB)下冠状动脉旁路移植术(CABG)病人心肌的保护作用。方法择期CPB下CABG病人40例,ASAⅡ级或Ⅲ级,随机分为2组(n=20):七氟醚组(S组)或异丙酚组(P组)。麻醉维持:P组靶控输注异丙酚,血浆靶浓度2～3μg/L,静脉输注芬太尼2～3μg·kg~(-1)·h~(-1);S组夹闭主动脉前,吸入0.5%～2%七氟醚,静脉输注芬太尼2～3μg·kg~(-1)·h~(-1),夹闭主动脉后靶控输注异丙酚,血浆靶浓度2～3μg/L,静脉输注芬太尼2～3μg·kg~(-1)·h~(-1)。于切皮前即刻、CPB前即刻、CPB后即刻、回ICU后即刻、6、12h记录心率(HR)、平均动脉压(MAP)、肺动脉楔压(PCWP)、中心静脉压(CVP)、心脏指数(CI)、体循环血管阻力指数(SVRI)。于麻醉诱导前、回ICU后即刻、6、12、24h采集静脉血,测定血清心肌肌钙蛋白I(cTnI)浓度。记录术后不良事件的发生情况。结果2组各时点MAP、PCWP、CVP、HR和SVRI比较差异无统计学意义(P>0.05);与切皮前即刻和P组比较,S组回ICU后各时点CI升高(P<0.05)。与P组比较,S组回ICU后各时点cTnI浓度降低(P<0.05)。2组病人术后均无死亡;2组心肌梗塞、房颤和心肌缺血的发生率差异无统计学意义(P>0.05);S组cTnI浓度>2ng/ml的发生率低于P组(P<0.05)。结论七氟醚预处理对体外循环下冠状动脉旁路移植术病人围术期心肌具有一定的保护作用。     

Correlation between renal function and pharmacokinetic parameters of inorganic fluoride following sevoflurane anesthesia

We studied the correlation between renal function and pharmacokinetic parameters of inorganic fluoride following sevoflurane anesthesia. In 30 neurosurgical patients aged 40–70 years, anesthesia was induced with midazolam and sevoflurane and maintained with sevoflurane and nitrous oxide in oxygen. Serum and urine inorganic fluoride (F⁻) levels and β₂-microglobulin (BMG), blood urea nitrogen (BUN), and serum creatinine (Cr) were measured during and after anesthesia. The decrease rate of serum F⁻ level and the area under the curve (AUC) of serum F⁻ were calculated. Correlations among sevoflurane dosage, duration of administration, peak serum F⁻ level, AUC, the decrease rate of serum F⁻ level, and the maximum values in BUN, Cr, and urine BMG during the study were investigated. Urine BMG increased significantly after surgery but returned to the preoperative level in a week. BUN, Cr, and serum BMG remained within normal ranges during the study. Sevoflurane dosage and duration of administration were significantly correlated with AUC and the maximum value of urine BMG, but not with the peak serum F⁻ level or the decrease rate of serum F⁻. AUC was significantly correlated with the maximum value of urine BMG. In sevoflurane anesthesia, sevoflurane dosage, duration of administration, and AUC affected urine BMG level, but not peak serum F⁻.