不同剂量氯胺酮复合顺式阿曲库铵预注对肌松效应的影响

目的比较顺式阿曲库铵预注、不同剂量氯胺酮复合顺式阿曲库铵预注对顺式阿曲库铵起效时间、血流动力学的影响。方法选择全麻下行择期手术的患者120例随机分成4组,即Ⅰ(生理盐水0.5ml)组、Ⅱ(顺式阿曲库铵0.01mg/kg)组、Ⅲ(顺式阿曲库铵0.01mg/kg预注复合氯胺酮0.5mg/kg)组、Ⅳ(顺式阿曲库铵0.01mg/kg预注复合氯胺酮1mg/kg)组,预注、预处理3min后,Ⅰ组静注插管剂量顺式阿曲库铵0.15mg/kg,Ⅱ、Ⅲ、Ⅳ组静注剩余插管剂量顺式阿曲库铵0.14mg/kg。使用四个成串刺激(TOF),待T1达最大抑制程度时行气管插管,记录肌松起效时间,同时观察HR、BP的变化。结果Ⅱ、Ⅲ、Ⅳ组肌松起效时间明显短于Ⅰ组(P0.05),且Ⅲ、Ⅳ组起效时间较Ⅱ组短(P0.05),但Ⅲ、Ⅳ组起效时间比较无统计学意义(P0.05);各组麻醉诱导期间均无明显心血管不良反应。结论氯胺酮0.5mg/kg复合顺式阿曲库铵0.01mg/kg、氯胺酮1mg/kg复合顺式阿曲库铵0.01mg/kg均能进一步缩短肌松起效时间,且无明显心血管不良反应。     

地佐辛超前镇痛对鼻内镜手术患者全麻气管拔管不良反应的干预作用

目的：探讨地佐辛超前镇痛对全麻条件下鼻内镜手术后预防气管拔管时不良反应的可行性及安全性。方法：美国麻醉师协会（ASA）评分Ⅰ～Ⅱ级,行择期鼻内镜手术患者60例,随机分为试验组和对照组（n=30）。常规心电监测后用咪达唑仑0．04mg／kg,芬太尼5／μg／kg,丙泊酚2mg／kg,阿曲库铵0．6mg／kg行麻醉诱导,丙泊酚加七氟醚静吸复合维持麻醉。试验组手术开始前15min肌肉注射地佐辛0．1mg／kg,对照组则给予同等容量的生理盐水。记录术前、术中、拔管时及拔管后的收缩压、舒张压、心率及血氧饱和度、苏醒时间、拔管时躁动、寒战情况以及术后24h疼痛情况。结果：术后气管拔管时试验组收缩压、舒张压及心率显著低于对照组（P〈0．05）,且试验组术后24h疼痛视觉模拟评分（VAS）明显低于对照组（P〈0．05）。结论：地佐辛超前镇痛用于鼻内镜手术,能有效保持气管拔管时血流动力学的平稳,减少不良反应的发生,减轻患者疼痛。     

右美托咪啶复合芬太尼及七氟烷用于脑肿瘤手术的麻醉效果及对血流动力学的影响

目的:探讨右美托咪啶复合芬太尼及七氟烷用于脑肿瘤手术的麻醉效果及对血流动力学的影响。方法:择期全麻下行脑肿瘤切除术患者40例,随机分为右美托咪啶组(D组)和丙泊酚组(P组)各20例。麻醉诱导前D组静脉输注右美托咪啶0.5μg/kg,P组给予同等容量的生理盐水,均15 min泵注完成。静脉注射咪唑安定、芬太尼、顺式阿曲库铵、依托咪酯行麻醉诱导。术中均用芬太尼、七氟烷、顺式阿曲库铵维持麻醉,D组持续静脉输注右美托咪啶0.2~1.0μg·kg-1·h-1,P组给予丙泊酚3~10 mg·kg-1·h-1,调整右美托咪啶及丙泊酚用量,使BIS值维持于40~50。于麻醉用药前(基础值)(T0)、麻醉诱导气管插管前(T1)、气管插管后(T2)、切开硬脑膜(T3)、取瘤(T4)、术毕(T5)、拔气管导管时(T6)记录心率(HR)、血压(SBP、DBP)。记录手术时间、输液量、出血量、苏醒时间、拔管时间及拔管后10 min警觉/镇静(OAA/S)评分。结果:与T0比较,D组T1、T3、T4时SBP、DBP明显降低(P0.05),HR明显减慢(P0.05),但仍接近正常值,P组T1时SBP、DBP明显降低(P0.05),HR明显减慢(P0.05),T2、T5、T6时SBP、DBP明显升高(P0.05),HR明显加快(P0.05)。与P组比较,T2~T6时D组SBP、DBP明显低于P组(P0.05),HR明显慢于P组(P0.05)。D组苏醒时间、拔管时间明显短于P组(P0.05),拔管后10min OAA/S评分显著高于P组(P0.05)。结论:右美托咪啶或丙泊酚复合芬太尼、七氟烷麻醉用于脑肿瘤手术均能够提供满意的麻醉效果,右美托咪啶能抑制气管插管、拔管等引起的血流动力学反应,术后苏醒快且苏醒质量高。     

顺式阿曲库铵在小儿全身麻醉中对气道功能的影响

目的:比较顺式阿曲库铵和阿曲库铵在小儿全麻中对气道功能的影响。方法:选取72名3-9岁患儿,男42例,女30例,采用随机表法将其分为观察组和对照组,每组36例。两组麻醉诱导都采用异丙酚,芬太尼,咪达唑仑。观察组使用顺式阿曲库铵0.15mg/kg,对照组组阿曲库铵0.5 mg/kg,比较两组小儿在插管后5 min、10 min、15 min、20 min患儿P_(ET)CO_2、P-PEAK、听诊呼吸音(粗、细湿啰音)、SPO_2变化四项指标来研究顺式阿曲库铵和阿曲库铵对呼吸系统的影响。结果:观察组注药后5 min、10 min、15 min、20 min时间点P_(ET)CO_2,P-PEAK变化趋势不明显,听诊呼吸音、SPO_2无明显变化(P0.05)。对照组在注药后的4个时间段P_(ET)CO_2、P-PEAK、听诊呼吸音、SPO_2有显著变化,随时间延长,P_(ET)CO_2,P-PEAK有明显增高,SPO_2逐渐下降情况(P0.05)。观察组和对照组相比,5 min、10 min、15 min、20 min各时间点观察组SPO_2高于对照组,PETCO_2、P-PEAK明显低于对照组,啰音发生的概率低于对照组,各时间点各项指标比较差异有统计学意义(P0.05)。结论:顺式阿曲库铵术中对小儿气道功能影响较小,肌松作用理想,可广泛应用于小儿临床麻醉。     

右旋美托咪啶用于食道癌手术麻醉的临床研究

目的：观察右旋美托咪啶用于食道癌手术麻醉的临床研究。方法：100例美国麻醉医师协会（ASA）Ⅰ-Ⅱ级择期行食道癌手术患者,随机分为生理盐水组（A组）和右旋美托咪啶组（B组）（n=50）,麻醉诱导前10min分别静脉注射右旋美托咪啶1μg／kg、生理盐水10ml后,两组麻醉诱导和维持相同。随后持续注射右旋美托咪啶0．4μg／kg·h直至手术结束前30min,观察与记录麻醉诱导前（T0）、插管即刻（T1）、拔管后1min（T2）、5min（T3）、10min（T4）平均动脉压（MAP）、心率（HR）、血氧饱和度（SaO2）、中心静脉压（CVP）、丙泊酚用量、芬太尼用量及不良反应。结果：T0、T1、T2,T3、T4A组与B组比较,MAP明显下降、HR明显减慢（P〈0．05）,丙泊酚和芬太尼用药量B组显著少于A组（P〈0．05）。B组术后咽喉疼痛、呛咳躁动发生率也明显低于A组（P〈0．05）。结论：右旋美托咪啶可减轻食道癌手术气管插管与拔管的心血管反应、减少麻醉药用量,减少胸科手术后咽喉疼痛、呛咳躁动的发生率。     

瑞芬太尼复合丙泊酚静脉全麻与异氟醚吸入全麻在小儿眼科手术中比较

目的：比较瑞芬太尼复合丙泊酚静脉全麻用于小儿眼科手术麻醉的安全性、有效性及可控性。方法：选择择期眼科手术的小儿40例,随机分为两组：瑞芬太尼复合丙泊酚静脉全麻组（RP组）和异氟醚吸入全麻组（Ⅰ组）,每组20例。麻醉诱导采用咪唑安定0．05mg·kg^-1,丙泊酚2mg·kg^-1,维库溴胺0．1mg·kg^-1,观察组用瑞芬太尼2μg·kg^-1,对照组用芬太尼3μg·kg^-1,气管插管后机械通气,RP组麻醉维持采用静脉持续输注瑞芬太尼0．1μg·kg^-1min^-1和丙泊酚,Ⅰ组麻醉维持用异氟醚吸入,术中根据麻醉深度调整异氟醚吸入浓度和丙泊酚输注速度。观察围术期两组血流动力学变化、自主呼吸恢复、气管拔管和清醒的时间,苏醒后躁动和恶心呕吐的发生率。结果：两组病人平均动脉压（MAP）变化：两组T1、T2、T3、T4与T0比较,MAP明显降低（P〈0．05）,T5与T0比较,MAP无明显差异（P〉0．05）;组间比较,两组在T0、T1、T2、T3、T4、T5点,MAP无明显差异（P〉0．05）。两组病人心率（HR）变化：Ⅰ组：T3、T4、T5与T0比较,心率显著增快（P〈0．05）,RP组：T1、T2、T3、T4与T0比较,心率明显降低（P〈0．05）,T5与T0比较,心率变化无明显差异（P〉0．05）。组间比较,两组在T0心率无明显差异,T1、T2、L、T4、T5观察组与对照组比较,心率明显降低（P〈0．01）。麻醉苏醒时间比较：RP组与Ⅰ组比较,病人自主呼吸恢复时间、意识恢复时间和拔管时间均明显缩短（P〈0．05）。RP组术后躁动、恶心呕吐发生率,均低于Ⅰ组（P〈0．05）。结论：瑞芬太尼复合丙泊酚静脉全麻可为小儿眼科手术提供稳定血流动力学状态,快速苏醒,适用于小儿眼科手术麻醉。     

雷米芬太尼联合丙泊酚对妇科腹腔镜手术患者的血流动力学及麻醉苏醒的影响

目的:探讨雷米芬太尼联合丙泊酚对妇科腹腔镜手术患者的血流动力学及麻醉苏醒的影响。方法:将116例拟行妇科腹腔镜手术患者随机分为观察组和对照组,观察组给予雷米芬太尼联合丙泊酚全凭静脉麻醉,对照组给予芬太尼联合丙泊酚全凭静脉麻醉。比较两组术中平均动脉压(MAP)、心率(HR)、血气分析指标、患者麻醉后睁眼时间、拔管时间及答问切题时间。结果:麻醉诱导后两组平均动脉压(MAP)及心率(HR)均显著下降(P0.05);观察组插管即刻及插管后2 min MAP及HR显著低于对照组(P0.05);观察组麻醉后睁眼时间、拔管时间、答问切题时间显著早于对照组(P0.05);与气腹前相比,气腹10 min、20 min及60min的PaCO2均升高(P0.05),两组各时点其他血气分析指标比较无显著差别(P0.05)。结论:妇科腹腔镜手术给予雷米芬太尼联合丙泊酚全凭静脉麻醉,可显著减轻插管应激心血管反应,保持血流动力学稳定,效果优于芬太尼联合丙泊酚麻醉。     

氟比洛芬酯用于小儿斜视手术的临床研究

目的观察氟比洛芬酯用于小儿斜视手术术后镇痛的有效性和安全性。方法将60例择期行斜视手术的息儿随机分为两组,每组30例。所有患儿均采用丙泊酚、瑞芬太尼靶控输注（TCI）全凭静脉麻醉方法。诱导采用丙泊酚效应室靶浓度为3μg／ml,瑞芬太尼血浆靶控浓度为3ng／ml,达预设浓度后静注维库溴铵0．1mg／kg,气管插管后行机械通气;麻醉维持为丙泊酚2～4μg／ml,瑞芬太尼3～4ng／ml,必要时追加维库溴铵。镇痛组于手术结束前15min缓慢静脉注射氟比洛芬酯1mg／kg（用生理盐水稀释至5m1）,对照组于麻醉拔管后缓慢静注生理盐水5ml,两组注射时间均为2rain。记录苏醒时间、拔管时间、恢复室停留时间,观察有无恶心、呕吐、嗜睡、躁动及呼吸抑制等不良反应的发生。观察术后1、2、4、8、12、24h的镇痛评分,同时记录各时点的平均动脉血压、心率、血氧饱和度。结果对照组患儿术后1、2、4、6、8h的MAP、HR值均较镇痛组高（P〈0．05）;两组术后12、24h的MAP、HR值比较差异无统计学意义（P〉0．05）。两组患儿术后各时点Spoz比较差异无统计学意义（P〉0．05）。对照组患儿的苏醒时间和拔管时间均较镇痛组延长（P〈0．05）。但两组患儿恢复室停留时间比较差异无统计学意义（P〉0．05）。对照组患儿术后1、2、4、6、8h的VAS值均较镇痛组高（P〈0．05）;两组术后12、24h的VAS值比较差异无统计学意义（P〉0．05）。对照组患儿术后躁动明显较镇痛组多（P〈0．05）。镇痛组患儿出现恶心、呕吐各1例,而对照组出现恶心2例,呕吐3例,但差异无统计学意义（P〉0．05）。结论氟比洛芬酯起效快,镇痛作用时间长,血流动力学稳定,苏醒期平稳,不抑制中枢,不影响患儿的麻醉苏醒,提高了患儿术后的舒适度。氟比洛芬酯用于小儿斜视手术安全、有效。     

丙泊酚复合麻醉在实验犬外科手术中的效果观察

目的丙泊酚复合麻醉应用于实验犬外科手术,进行效果评价。方法成年健康杂种犬13只,雌雄不限。术前30 min肌内注射阿托品0.5 mg,吗啡10 mg,进行气管插管,静脉注射氯胺酮50 mg,静脉注射丙泊酚首次剂量5 mg/kg体重,维持剂量1 mg/kg。结果丙泊酚复合麻醉,平均麻醉起效时间40 s,首次剂量平均维持17.3min,重复给药平均维持13.6 min,无死亡。丙泊酚有较强的麻醉效果,诱导时间短,起效快,恢复快速平稳,而且无副作用。结论丙泊酚复合麻醉适合于犬的外科手术实验,是一种较为理想的麻醉方法。     

小剂量利多卡因在无痛宫腔镜术中的应用

目的：观察静注利多卡因在无痛宫腔镜术的应用效果。方法：120例择期宫腔镜手术患者,随机均分为L、C两组。L组麻醉诱导前缓慢静脉推注利多卡因1mg／kg;C组以生理盐水替代。两组均静注丙泊酚1—1．5mg／kg进行麻醉诱导至睫毛反射消失,术中酌情追加丙泊酚。麻醉开始后,询问患者是否有静脉注射痛,观察记录术中及术后疼痛情况。结果：两组术中血压、心率平稳。L组较C组丙泊酚注射痛及术中术后疼痛程度减轻（P〈0．05）。结论：利多卡因复合丙泊酚用于无痛宫腔镜不良反应小,有利于病人术后恢复。     

Identification of Propofol Binding Sites in a Nicotinic Acetylcholine Receptor with a Photoreactive Propofol Analog

Propofol, a widely used intravenous general anesthetic, acts at anesthetic concentrations as a positive allosteric modulator of γ-aminobutyric acid type A receptors and at higher concentration as an inhibitor of nicotinic acetylcholine receptors (nAChRs). Here, we characterize propofol binding sites in a muscle-type nAChR by use of a photoreactive analog of propofol, 2-isopropyl-5-[3-(trifluoromethyl)-3H-diazirin-3-yl]phenol (AziPm). Based upon radioligand binding assays, AziPm stabilized the Torpedo nAChR in the resting state, whereas propofol stabilized the desensitized state. nAChR-rich membranes were photolabeled with [³H]AziPm, and labeled amino acids were identified by Edman degradation. [³H]AziPm binds at three sites within the nAChR transmembrane domain: (i) an intrasubunit site in the δ subunit helix bundle, photolabeling in the nAChR desensitized state (+agonist) δM2-18′ and two residues in δM1 (δPhe-232 and δCys-236); (ii) in the ion channel, photolabeling in the nAChR resting, closed channel state (−agonist) amino acids in the M2 helices (αM2-6′, βM2-6′ and -13′, and δM2-13′) that line the channel lumen (with photolabeling reduced by >90% in the desensitized state); and (iii) at the γ-α interface, photolabeling αM2-10′. Propofol enhanced [³H]AziPm photolabeling at αM2-10′. Propofol inhibited [³H]AziPm photolabeling within the δ subunit helix bundle at lower concentrations (IC₅₀ = 40 μm) than it inhibited ion channel photolabeling (IC₅₀ = 125 μm). These results identify for the first time a single intrasubunit propofol binding site in the nAChR transmembrane domain and suggest that this is the functionally relevant inhibitory binding site.     

Propofol directly increases tau phosphorylation

In Alzheimer's disease (AD) and other tauopathies, the microtubule-associated protein tau can undergo aberrant hyperphosphorylation potentially leading to the development of neurofibrillary pathology. Anesthetics have been previously shown to induce tau hyperphosphorylation through a mechanism involving hypothermia-induced inhibition of protein phosphatase 2A (PP2A) activity. However, the effects of propofol, a common clinically used intravenous anesthetic, on tau phosphorylation under normothermic conditions are unknown. We investigated the effects of a general anesthetic dose of propofol on levels of phosphorylated tau in the mouse hippocampus and cortex under normothermic conditions. Thirty min following the administration of propofol 250 mg/kg i.p., significant increases in tau phosphorylation were observed at the AT8, CP13, and PHF-1 phosphoepitopes in the hippocampus, as well as at AT8, PHF-1, MC6, pS262, and pS422 epitopes in the cortex. However, we did not detect somatodendritic relocalization of tau. In both brain regions, tau hyperphosphorylation persisted at the AT8 epitope 2 h following propofol, although the sedative effects of the drug were no longer evident at this time point. By 6 h following propofol, levels of phosphorylated tau at AT8 returned to control levels. An initial decrease in the activity and expression of PP2A were observed, suggesting that PP2A inhibition is at least partly responsible for the hyperphosphorylation of tau at multiple sites following 30 min of propofol exposure. We also examined tau phosphorylation in SH-SY5Y cells transfected to overexpress human tau. A 1 h exposure to a clinically relevant concentration of propofol in vitro was also associated with tau hyperphosphorylation. These findings suggest that propofol increases tau phosphorylation both in vivo and in vitro under normothermic conditions, and further studies are warranted to determine the impact of this anesthetic on the acceleration of neurofibrillary pathology.     

Propofol Pharmacokinetics and Estimation of Fetal Propofol Exposure during Mid-Gestational Fetal Surgery: A Maternal-Fetal Sheep Model

Background

Measuring fetal drug concentrations is extremely difficult in humans. We conducted a study in pregnant sheep to simultaneously describe maternal and fetal concentrations of propofol, a common intravenous anesthetic agent used in humans. Compared to inhalational anesthesia, propofol supplemented anesthesia lowered the dose of desflurane required to provide adequate uterine relaxation during open fetal surgery. This resulted in better intraoperative fetal cardiac outcome. This study describes maternal and fetal propofol pharmacokinetics (PK) using a chronically instrumented maternal-fetal sheep model.

Methods

Fetal and maternal blood samples were simultaneously collected from eight mid-gestational pregnant ewes during general anesthesia with propofol, remifentanil and desflurane. Nonlinear mixed-effects modeling was performed by using NONMEM software. Total body weight, gestational age and hemodynamic parameters were tested in the covariate analysis. The final model was validated by bootstrapping and visual predictive check.

Results

A total of 160 propofol samples were collected. A 2-compartment maternal PK model with a third fetal compartment appropriately described the data. Mean population parameter estimates for maternal propofol clearance and central volume of distribution were 4.17 L/min and 37.7 L, respectively, in a typical ewe with a median heart rate of 135 beats/min. Increase in maternal heart rate significantly correlated with increase in propofol clearance. The estimated population maternal-fetal inter-compartment clearance was 0.0138 L/min and the volume of distribution of propofol in the fetus was 0.144 L. Fetal propofol clearance was found to be almost negligible compared to maternal clearance and could not be robustly estimated.

Conclusions

For the first time, a maternal-fetal PK model of propofol in pregnant ewes was successfully developed. This study narrows the gap in our knowledge in maternal-fetal PK model in human. Our study confirms that maternal heart rate has an important influence on the pharmacokinetics of propofol during pregnancy. Much lower propofol concentration in the fetus compared to maternal concentrations explain limited placental transfer in in-vivo paired model, and less direct fetal cardiac depression we observed earlier with propofol supplemented inhalational anesthesia compared to higher dose inhalational anesthesia in humans and sheep.