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.     

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。     

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.     

Clinical office anesthesia: The use of propofol for the induction and maintenance of general anesthesia

Ambulatory surgery has become routine for many plastic surgery procedures. Anesthesia techniques including general anesthesia by inhalation and intravenous infusion and the dissociative technique have all been used successfully for outpatient anesthesia. Propofol (Diprivan), a relatively new agent, has proven to be a safe and effective general anesthesia agent for outpatient surgery. We report on our experience with propofol as an induction agent and continuous drip for general anesthesia maintenance in 100 consecutive outpatient, plastic surgery procedures performed in an office facility. Assessment factors were recovery-room time, nausea and vomiting in the recovery room and at home, hallucinations, patients' recollection of anesthesia experience, and overall patient satisfaction.     

Intubating conditions provided by propofol and alfentanil - acceptable, but not ideal

Background: The use of muscle relaxants to facilitate intubation is associated with several side effects regardless of whether depolarizing or non-depolarizing drugs are used. In the present study we compared the intubating conditions, haemodynamic responses and changes in oxygen saturation following induction with alfentanil and propofol or alfentanil, thiopental and suxamethonium.
Methods: Eighty patients (ASA I or II) were in a double-blind manner assigned to receive either of the two induction methods. Intubating conditions were assessed on the basis of jaw relaxation, ease of insertion of the endotracheal tube and coughing on intubation. Heart rate, systolic arterial pressure and oxygen saturation were monitored throughout the procedure.
Results: The use of alfentanil and propofol resulted in significantly lower scored intubation points. Systolic arterial pressure decreased and heart rate increased significantly in the alfentanil-thiopental-suxamethonium group as compared to the alfentanil-propofol group. There were no significant changes in oxygen saturation.
Conclusion: The results show that propofol and alfentanil in combination provides haemodynamic stability and unaltered oxygen saturation but less optimal intubating conditions.     

恒猴精索内注射长效局麻药后对睾丸和附睾的影响

在13只恒河猴精索内注射长效局麻药后,睾丸发生明显变化;而且给药剂量不同,睾丸曲精小管改变的程度和恢复正常的时间亦不同。睾丸间质细胞无明显变化;睾酮分泌不减少,无毒性反应。对临床男性节育应用及生殖生理研究均具有意义。     

深低温对吸入麻醉药的MAC,心脏麻醉指数和心肌稳定性的影响

目的:研究深低温对吸入麻醉药MAC、心脏麻醉指数和心肌稳定性的影响。方法:新西兰白兔40只,随机分为氟烷、安氟醚、异氟醚和七氟醚组。采用夹尾试验法测定常温下(38℃±0.5℃)的最低肺泡有效浓度(MAC)。行体表降温后测定深低温下(23℃±0.5 ℃)的MAC。维持深低温增加吸入性麻醉药的浓度,同时用50Hz、25V电压胸外电击心脏。记录出现室颤或室性心律失常时的肺泡呼气末吸入麻醉药浓度。结果:从38℃到23℃兔体温每降低1℃,MAC下降值为:氟烷5.1％、安氟醚3.6％、异氟醚4.4％、七氟醚4.3％;氟烷、安氟醚、异氟醚和七氟醚心脏麻醉指数分别为4.4、3.18、6.25和4.6,异氟醚明显高于其它麻醉药;麻醉药浓度8MAC以内安氟醚和氟烷发生室颤的机率(100％)明显高于七氟醚和异氟醚(40％)。结论:异氟醚是深低温麻醉的最佳选择用药,而安氟醚则不宜用于低温麻醉。