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.     

学龄期儿童前房深度发育状况分析

目的了解7~14岁学龄期儿童前房深度发育情况。探索其与屈光度数间的关系。方法收集2012年6月至2014年6月眼科门诊7~14岁儿童为研究对象，共计521例（1042只眼）。采用IOLMaster人工晶状体生物测量仪测量各屈光参数，同时测量身高、体重。散瞳后验光测得静态屈光度。分析前房深度发育情况及不同屈光状态的学龄期儿童前房深度发育情况。结果（1）随着年龄的增长，7~14岁学龄期的儿童前房深度随之增长，差异具有统计学意义（P＜0.01）。同一年龄段儿童的左右眼之间的均值相近，且生长发育趋势相近（均P＞0.05）。（2）随着年龄的增长，男女的前房深度均逐渐增大，同一年龄段男性前房深度大于女性前房深度（均P＜0.01）。（3）儿童前房深度与身高正相关（P＜0.01）。（4）前房深度随近视度数增高而增大，低度近视组与中度近视组及高度近视组差异有统计学意义（P＜0.05）。结论学龄期儿童的前房深度的发育受到身高、性别及屈光度数的影响，与身高呈正相关，同一年龄段，男性前房深度大于女性。双眼前房深度发育同步。低中度近视的儿童前房深度增大。     

Etomidate for Rapid-sequence Intubation in Young Children: Hemodynamic Effects and Adverse Events

OBJECTIVES: Physicians commonly use etomidate for adult rapid-sequence intubation (RSI), but the manufacturer does not recommend its use for children under 10 years of age due to a lack of data. The authors present their experience with etomidate for pediatric RSI in order to further develop its risk-benefit profile in this age group. METHODS: Trained abstractors reviewed the medical records for all children under 10 years old who received etomidate for RSI between July 1996 and April 2001. RESULTS: 105 children, with an average age of 3 (+/-2.9) years, received a median dose of 0.32 (+/-0.12) mg/kg of etomidate. The systolic blood pressure increased an average of 4 mm Hg (95% CI = -3.3 to 9.2); the diastolic blood pressure increased 7 mm Hg (95% CI = -3.1 to 11) within 10 minutes of receiving etomidate. The heart rate increased an average of 10 beats/min (95% CI = 4.0 to 17.4). Complications included three patients who vomited within 10 minutes of etomidate administration. There were no cases of documented myoclonus, status epilepticus, or new-onset seizures. Thirty-eight patients received corticosteroids during the hospital course, none for suspected adrenal insufficiency. Three patients died, all from severe brain injury. CONCLUSIONS: In children less than 10 years old, etomidate seems to produce minimal hemodynamic changes, and appears to have a low risk of clinically important adrenal insufficiency, myoclonus, and status epilepticus. The association between etomidate and emesis (observed in less than 3% of enrolled patients) remains unclear. For clinical situations in which minimal blood pressure changes during RSI are critical, etomidate appears to have a favorable risk-benefit profile for children under 10 years old.     

分瓶法测定果蝇吸入麻醉药半数麻醉有效浓度

目的　建立测定果蝇吸入麻醉药半数麻醉有效浓度 (ED50 )的方法学。方法　在 11个 32 5ml的三角烧瓶中各放入 30只雄性果蝇 ,分别加入不同容量的异氟醚标准气 ,使 11个烧瓶中异氟醚浓度分布在零效应浓度与百分之百效应浓度之间。以果蝇失去附壁及运动能力为标准计算各瓶中被麻醉果蝇数 ,用正规法计算出ED50 。结果　 11次实验在 2 5及 5 0min时的量 -效关系曲线均呈S形 ,用各自的对数浓度与概率单位作图都呈直线相关 ,相关系数分别为 0 .972± 0 .0 14和 0 .971± 0 .0 2 5 ,ED50 值分别为 (0 .5 1± 0 .0 6 8) %和 (0 .4 7± 0 .0 85 ) % ,变异系数分别为 13.3%和 18.0 %。结论　本法稳定性较好 ,实用可行     

乳剂依托咪酯对心脏手术病人麻醉诱导期循环功能的影响

目的　本文应用乳剂依托咪酯,观察其对心脏手术病人麻醉诱导期的循环影响。方法　选择心脏手术病人80例,心功能Ⅲ～Ⅳ级,随机分为两组,每组2 0例:Ⅰ组(水剂组) :水剂依托咪酯0 2 5mg kg-1;Ⅱ组(乳剂组) :乳剂依托咪酯0 2 5mg kg-1。记录麻醉前、注射依托咪酯前、后,气管插管后1min和3min时段的各监测参数。观察不自主肌肉颤动,注射疼痛感及过敏反应等不良反应。结果　显示两种剂型的依托咪酯各时间点的SBP、DBP、MAP、HR各组间无显著差异(P >0 0 5 )。两组在注射依托咪酯后SBP、DBP、MAP、HR轻度下降,但与注射前均无统计学差异(P >0 0 5 )。不自主肌肉运动Ⅰ组8例、Ⅱ组6例:两组间无显著差异(P >0 0 5 )。静脉注射处疼痛Ⅰ组14例、Ⅱ组1例,两组间显著差异(P >0 0 5 )。结论　乳剂依托咪酯具有麻醉诱导平稳,心血管影响轻微,副作用少在应用上优于水剂依托咪酯,可用于高龄及心脏功能受损害患者的麻醉诱导。     

不同针刺深度对前列腺增生症大鼠重量指数的影响及形态学观察

目的与方法 采用深刺和浅刺对丙酸睾酮所致前列增生症（BPH）大鼠模型进行干预，研究其作用殊同。结果 针刺组前列腺，膀胱指数明显小于模型组；形态学观察，针刺组较模型组增生明显减轻，腺上皮呈单层柱状，腺体数目明显减少，间质充血，钙化明显减轻，结缔组织无增生，腺腔内分泌物减少。深刺组好于浅刺组。结论 深刺对实验性BPH大鼠的干预作用好于浅刺方法。     

离体模式下地氟醚、异氟醚和氟烷通过氧合器应用的药代动力学研究

目的研究在离体模式下地氟醚、异氟醚和氟烷通过氧合器应用的药代动力学。方法选择成人型膜式氧合器，预充生理盐水2000ml，连接动静脉端形成环路。将预先配制在钢瓶内的2．4％地氟醚、0．46％异氟醚及0．308％氟烷混合气体输送至氧合器，气体流量3Umin，泵流量4Umin，温度30℃。在摄入及排出的0、1、2、4、8、16、32min采集氧合器入气口、排气口及动脉端样本，测定吸入麻醉药分压。结果在摄入阶段及排出阶段，动脉端溶液中三种吸入麻醉药分压迅速上升或下降，用药后8min时，三种药物的动脉端样本分压与吸入气分压之比(Pa／Pi)均达50％以上，停药后8min动脉端样本分压与动脉端样本分压峰值之比(Pa／Pa0)均降至10％以下。三种药物之间在同一时间点Pa／Pi及Pa／17aO均有显著性差异(P＜0．05)。各吸入麻醉药动脉端样本与氧合器排气口中分压之间呈线性相关关系(r=0．99)。结论(1)Bentley膜式氧合器具有快速转运吸入麻醉药的性能；(2)地氟醚、异氟醚及氟烷通过氧合器应用后摄取和排出速率随着药物的水／气分配系数的增高而减慢；(3)通过监测氧合器排气口中吸入麻醉药分压可以快速、准确地估计液相中吸入麻醉药分压。     

Control of post anaesthetic shivering with nefopam hydrochloride in mildly hypothermic patients after neurosurgery

Postoperative shivering may be prevented by maintaining normothermia intraoperatively or it may be treated using specific drugs. The aim of this study was to compare the efficacy of nefopam hydrochloride (nefopam) to that of clonidine and meperidine in patients undergoing elective neurosurgical procedures. Three groups of patients were included in the study. Patients in group A (60) received i.v., at random, 20 mg of nefopam, 50 mg of meperidine or 150 μg of clonidine in the immediate postoperative period. The incidence of shivering and the time at which shivering ceased were noted, along with central temperature and main haemodynamic changes. Group B (20) received i.v., at random, either 10 mg of nefopam or saline before awakening from anaesthesia. The effects of nefopam on central temperature, oxygen consumption (Vo₂), carbon dioxide production (VcO₂), basal metabolic rate (BMR) and energy expenditure (EE) were investigated. Group C (10) received i.v. 20 mg of nefopam during surgery: cerebrospinal fluid pressure (CSFP), cerebral perfusion pressure (CPP) and electroencephalogram (EEG) were monitored. In group A nefopam stopped shivering in 95% of patients when compared to meperidine and clonidine, which were effective in 32% and 40% of patients respectively. In group B, only 10% of patients receiving nefopam had postoperative shivering, Vo2, VcO2 and EE were significantly lower in patients treated with nefopam than those in the control group. No changes in CSFP, CPP or EEG were observed in group C. In conclusion, nefopam seems to be more effective than clonidine or meperidine in quickly suppressing shivering, without producing significant adverse reactions.