右美托咪定对脑功能区手术术中唤醒质量的影响

目的 评价右美托咪定对丙泊酚和舒芬太尼麻醉下脑功能区手术术中唤醒质量的影响。方法 拟行术中唤醒试验的脑功能区手术患者40例,年龄18~65岁,ASA分级Ⅰ或Ⅱ级,采用完全随机法将患者随机分为2组：对照组和右美托咪定组,每组20例。右美托咪定组麻醉诱导前10 min静脉输注右美托咪定1 μg?kg^-1,对照组则静脉输注等量生理盐水,此后2组均靶控输注丙泊酚和舒芬太尼诱导与维持。丙泊酚血浆靶浓度为3~5 μg?mL^-1,维持脑电双频指数(BIS)45~55;舒芬太尼效应室靶浓度0.1~0.2 ng?mL^-1。麻醉维持期,右美托咪定组右美托咪定速率下调到0.4 μg?kg^-1?h^-1,对照组则静脉输注等量生理盐水。硬脑膜打开后,2组均停止输注丙泊酚及肌松药,并将舒芬太尼效应室靶浓度调整为0.1 ng?mL^-1;此时右美托咪定组右美托咪定速率下调到0.1 μg?kg^-1?h^-1,而对照组给予输注等量生理盐水。同时,记录唤醒前麻醉时间、唤醒前麻醉药用量、唤醒时间、唤醒期间并发症以及术中知晓等的发生情况。结果 所有患者均成功实施唤醒,并顺利完成手术。与对照组比较,右美托咪定组唤醒前丙泊酚用量减少,唤醒试验期间高血压、心动过速、头痛和术中知晓的发生率均降低,唤醒时间缩短,差异均具有有统计学意义(P<0.05)。BIS值差异无统计学意义(P>0.05)。结论 右美托咪定可以缩短脑功能区手术患者的唤醒时间,提高唤醒试验质量。     

经腹子宫全切术患者不同剂量右美托咪啶硬膜外麻醉镇静效果观察

摘 要 目的： 观察不同剂量右美托咪啶在硬膜外麻醉经腹子宫全切术中的镇静效果和安全性。方法: 硬膜外麻醉经腹子宫全切术择期患者120例随机分为4组,即不同剂量右美托咪啶镇静组（D1组,D2组,D3组）和咪达唑仑镇静组（M组）。D1组、D2组、D3组在手术前10 min静脉泵注右美托咪啶0.5μg·kg^-1,随之分别以0.4,0.6,0.8 μg·(kg·h)^-1维持输注;M组患者在手术前10 min静脉泵注咪达唑仑0.06 mg·kg^-1,随之以0.04 mg·(kg·h)^-1维持输注。比较各组患者入室时（T0）、确定硬膜外麻醉阻滞效果满意时（T1）、镇静药物泵注后10 min（T2）、20 min（T3）、40 min（T4）、手术结束时（T5）的平均动脉压（MAP）、心率（HR）、呼吸频率（RR）和血氧饱和度（SpO₂）,以及镇静药物使用时间和手术时间。评估各时点镇静程度,及术后患者手术期间遗忘程度、药品不良反应和麻醉服务满意度。结果:T3时点后,D3组HR显著低于其余3组（P＜0.05）;T2时点后,4组HR均明显低于T0时（P＜0.05和P＜0.01）。M组T3、T4 时点RR显著低于其余3组（P＜0.05）。与T0时比较,T2时点后,各组患者均取得显著镇静效果（P＜0.05和P＜0.01）;D3组T3、T4时镇静评分显著优于D1组和M组（P＜0.05）。4组患者均未出现明显药品不良反应。结论: 硬膜外麻醉经腹子宫全切术应用右美托咪啶维持镇静无类似输注咪达唑仑后发生呼吸抑制的风险,但剂量宜低于0.8 μg·(kg·h)^-1。     

右美托咪定对开颅动脉瘤夹闭术患者的脑保护作用

目的 观察右美托咪定(dexmedetomidine,DEX)对开颅动脉瘤夹闭术患者围术期炎症因子及神经损伤标记物表达的影响,研究其脑保护作用。方法 择期开颅动脉瘤夹闭术患者60例,随机数表法将其均分为对照组和右美托咪啶组。右美托咪啶组患者麻醉诱导前给予DEX 1 μg·kg^-1,然后以0.5 μg·kg^-1·h^-1速度持续输注至手术结束;对照组患者在同时段给予等量生理盐水。分别于麻醉后切皮前(T0)、载瘤动脉阻断开始时(T₁)、载瘤动脉阻断结束时(T₂)、手术结束时(T₃)、手术结束后24 h(T₄)及手术结束后72 h(T₅)6个时间点从颈静脉球部采集血液标本,采用ELISA法检测肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白介素-6(interleukin-6,IL-6)、白介素-10(interleukin-10,IL-10)、星形胶质细胞S100蛋白的β亚型(beta isoform of S100 protein in astrocytes,S-100β蛋白)及神经元特异性烯醇化酶(neuronspecific enolase,NSE)。结果 T₁~T₃ 2组TNF-α、IL-6、IL-10、S-100β及NSE均高于组内T₀(P<0.05),右美托咪啶组TNF-α、IL-6、S-100β及NSE均低于同时点对照组(P<0.05),右美托咪啶组IL-10均高于同时点对照组(P<0.05);T₄时间点,除右美托咪啶组TNF-a、S-100β及NSE外,2组各指标均高于组内T₀(P<0.05),右美托咪啶组IL-6及NSE低于同时点对照组(P<0.05),右美托咪啶组IL-10高于同时点对照组(P<0.05);T₅时间点,对照组IL-6及右美托咪啶组IL-6和IL-10高于组内T₀(P<0.05)。结论 DEX可以在一定程度上抑制开颅动脉瘤夹闭术患者围术期促炎因子和神经损伤标记物表达,同时促进抗炎因子表达,具有脑保护作用。     

不同剂量右美托咪定滴鼻在麻醉诱导前的应用比较

目的 探讨右美托咪定(dexmedetomidine,DEX)滴鼻在麻醉诱导前应用的最佳剂量。方法 择期手术的120例患者随机分为对照组和DEX 0.5,1.5,2.5 μg·kg^-1组,术前30 min分别滴鼻生理盐水和相应剂量DEX。观察DEX滴鼻后30 min镇静评分、插管后血流动力学变化(平均动脉压和心率)和不良事件发生例数、拔管时间、拔管后镇痛评分、拔管后发生躁动情况。结果 DEX各剂量滴鼻后患者30 min OAA/S评分均下降(P<0.05);DEX 1.5 μg·kg^-1组滴鼻后30 min HR和MAP下降(P<0.05);插管即刻,对照组、DEX 0.5 μg·kg^-1组HR和MAP上升,DEX 2.5 μg·kg^-1组HR和MAP下降(P<0.05);DEX 1.5 μg·kg^-1组及DEX 2.5 μg·kg^-1组心动过速、高血压发生例数减少(P<0.05);DEX 2.5 μg·kg^-1组心动过缓、低血压发生例数增多(P<0.05),拔管时间延长(P<0.05);DEX 1.5和2.5 μg·kg^-1组拔管后镇痛VAS评分、发生躁动例数下降(P<0.05)。结论 麻醉诱导前30 min经鼻滴入DEX 1.5 μg·kg^-1可以平稳完成气管插管,同时减少各种不良反应。     

不同剂量右美托咪定用于心房颤动经导管射频消融术中的疗效

摘 要 目的：探讨不同负荷剂量右美托咪定用于心房颤动经导管射频消融术中的临床疗效和安全性。方法: 接受导管射频消融手术的房颤患者63例随机分为3组,分别接受大负荷剂量的右美托咪定1 μg·kg^-1（HDex组）,小负荷剂量的右美托咪定0.5 μg·kg^-1（LDex组）和等量0.9%氯化钠注射液（NS组）,均静脉输注10 min。HDex组与LDex组负荷剂量后予维持剂量右美托咪定0.4 μg·kg^-1·h-1至手术结束,NS组予等量0.9%氯化钠注射液。3组患者在手术开始时均予局部麻醉,静脉联合泵注芬太尼（1 μg·kg^-1·h-1）至手术结束。记录3组入室时(T0)、给负荷量后(T1)、手术开始时(T2)、射频消融开始后10 min(T3)、射频消融结束后10 min(T4)的收缩压（SBP）、舒张压（DBP）、心率（HR）、Ramsay镇静评分。记录术中面罩辅助通气发生次数、因疼痛需调整芬太尼用量而中断手术次数、手术时间。结果: T1、T2、T3、T4时,HDex组、LDex组Ramsay镇静评分收缩压、舒张压、心率与NS组比较差异有统计学意义（P<0.05）。在T1时,HDex比LDex组收缩压、舒张压、心率下降更显著（P<0.05）。HDex组发生2例心动过缓,2例术中面罩辅助通气。NS组发生2例因疼痛调整芬太尼用量而中断手术。结论: 在与芬太尼联用时,临床上予0.5 μg·kg^-1小负荷剂量的右美托咪定即可满足心房颤动经导管射频消融术的镇静、镇痛需要,且不良反应少。     

右美托咪定用于老年患者低位硬膜外麻醉22例

目的 观察右美托咪定用于老年患者低位硬膜外麻醉镇静的适合剂量和安全性. 方法选择拟行经尿道前列腺电切术的老年患者48例,随机分为右美托咪定组和对照组各24例. 两组患者均接受1.5%利多卡因连续硬膜外麻醉. 右美托咪定组患者于手术开始前10 min缓慢泵注负荷剂量右美托咪定0.5 μg. kg^-1,并以起始剂量0.2 μg.kg^-1.h^-1泵注维持,泵注速度每次增减0.1 μg.kg^-1.h^-1以维持跳动 镇静(RASS)评分为-2分. 对照组患者不给予静脉镇静用药. 观察并记录镇静评分、生命体征变化及术后并发症. 结果 右美托咪定组22例患者完成研究观察. 右美托咪定组患者都能达到良好的镇静状态;给予右美托咪定镇静后,各观察时间点心率明显降低(P<0.05);同时有更好的舒适度评价和低术后寒战发生率. 推荐右美托咪定用于老年患者低位硬膜外麻醉镇静的维持剂量为0.2～0.3 μg.kg^-1.h^-1. 结论 静脉泵注0.5 μg.kg^-1右美托咪定负荷剂量后,继以0.2～0.3 μg.kg^-1.h^-1维持,可安全有效地用于老年患者低位硬膜外麻醉的镇静.     

盐酸右美托咪啶对开胸手术患者麻醉苏醒期躁动的镇静作用

目的 研究盐酸右美托咪啶对开胸手术患者麻醉苏醒期躁动的镇静作用. 方法 全麻苏醒期躁动的开胸患者47例,给予盐酸右美托咪啶,用0.9%氯化钠注射液配制成4 μg.mL^-1的浓度,20 min给予1.0 μg.kg^-1的负荷量,之后使用微量泵以0.2～0.7 μg.kg^-1.h^-1的速度输注维持,维持Ramsay评分＞3分,监测各项指标. 结果镇静效率为(87.5±4.2)%,镇静时间内平均输注速度为(0.64±0.12) μg.kg^-1.h^-1,镇静前后平均动脉压(MAP)、呼吸率(RR)及心率(HR)明显下降,而中心静脉压(CVP)及血氧饱和度(SpO2)无明显差异. 结论 盐酸右美托咪啶对开胸手术患者麻醉苏醒期躁动有较好的镇静作用.     

不同剂量右美托咪啶用于小儿腹腔镜手术的临床研究

目的 探讨三种剂量右美托咪啶用于小儿腹腔镜手术中的麻醉效果及安全性。 方法 择期行腹腔镜手术的患儿 80例,随机分为四组,每组20例。对照组(C 组)患儿插管后微泵静脉注射生理盐水0. 1ml.kg_-1.h_-1,低、中、高剂量右美托咪啶组(D1、D2、D3组)患儿插管后分别用微泵静脉注射右美托咪啶0.2μg.kg_-1.h_-1, 0.5μg.kg_-1.h_-1,0.7μg.kg_-1.h_-1。记录患儿入室时( T1)、麻醉诱导后( T2) 、手术开始10min(T3) 、术 毕 (T4) 的 平 均 动 脉 压( MAP) 、心率(HR) ; 苏醒时间,拔管时间、PACU停留时间; 苏醒期疼痛评分; 术后躁动发生人数、比例; 术后患儿呼吸抑制、心动过缓、恶心、呕吐等不良反应发生情况。 结果 T3、T4时间点D1、D2、D3组患儿HR明显低于T1(P<0.05),也明显低于同时间点C组患儿(P<0.05),四组患儿T2时间点MAP均显著低于T1(P<0.05);术后疼痛评分D1、D2、D3组明显低于对照组(P<0.05),而D3组又明显低于D1和D2组(P<0.05);苏醒期躁动发生率D1、D2、D3组明显低于对照组(P<0.05),而D3组又明显低于D1和D2组(P<0.05)。四组患儿均未有出现呼吸抑制和心动过缓。C组有一例患儿发生恶心呕吐。 结论 0.7μg/kg右美托咪啶微泵静脉注射用于小儿腹腔镜手术,血流动力学稳定,镇痛效果好,减少苏醒期躁动发生率,不良反应少,更适用于临床。     

右美托咪啶与依托咪酯对脑功能区手术患者术中麻醉唤醒的疗效比较

目的：评价右美托咪啶与依托咪酯用于治疗脑功能区手术患者术中麻醉唤醒的疗效。方法：将院内收治的60例行脑功能区手术患者分为实验组和对照组,其中实验组给予右美托咪啶用于麻醉唤醒,对照组给予依托咪酯用于麻醉唤醒,比较两组患者唤醒时间、唤醒质量和唤醒期间不良反应的发生情况。结果：两组患者唤醒时间,经比较其差异无统计学意义（P〉0.05）;实验组患者Ⅰ级-Ⅱ级比例高于对照组,Ⅲ级-Ⅳ级比例低于对照组,经比较其差异有统计学意义（P〈0.05）;实验组患者唤醒期间心动过速、心动过缓、高血压、低血压、体动、呛咳和恶心的发生率低于对照组,经比较其差异有统计学意义（P〈0.05）;两组患者呼吸抑制和对唤醒过程有记忆的发生率,经比较其差异无统计学意义（P〉0.05）。结论：右美托咪啶与依托咪酯对脑功能区手术患者术中麻醉唤醒均有确切效果,经比较前者唤醒质量与唤醒期间不良反应的发生率比后者优。     

不同浓度舒芬太尼联合咪达唑仑在机械通气COPD患者中的效果

目的 探讨不同浓度舒芬太尼联合咪达唑仑对机械通气COPD患者治疗后的疗效和影响。方法 从2012年5月至2015年5月ICU机械通气COPD患者中,选取120例,随机分成A、B、C、D 4组,每组30例,A组舒芬太尼(0.6 μg/kg负荷量,0.6 μg·kg^-1·h^-1 维持量)联合咪达唑仑(50 μg/kg负荷量,40~200 μg·kg^-1·h^-1维持量),B组舒芬太尼(0.4 μg/kg负荷量,0.4 μg·kg^-1·h^-1 维持量)联合咪达唑仑(50 μg/kg负荷量,40~200 μg·kg^-1·h^-1维持量),C组舒芬太尼(0.2 μg/kg负荷量,0.2 μg·kg^-1·h^-1 维持量)联合咪达唑仑(50 μg/kg负荷量,40~200 μg·kg^-1·h^-1维持量),D组咪达唑仑(50 μg/kg负荷量,40~200 μg·kg^-1·h^-1维持量)。结果 4组治疗后,浅快呼吸指数(f/VT)、心率(HR)都下降显著,氧合指数(PO₂/FiO₂)、镇静评分值(Ramsay评分)升高显著, A、B、C组平均动脉压(MAP)下降显著,4组患者的呼吸功能指标差异差异无统计学意义。不同浓度的舒芬太尼治疗后,A、B、C组HR较D组下降更明显(P<0.05),C组与A组比较,有统计学意义(P<0.05),A、B、C组的MAP明显低于D组(P<0.05),C组与A组比较,差异有统计学意义(P<0.05)。各时间点Ramsay评分,A、B、C组均高于D组,差异具有统计学意义(P<0.05)。总镇静时间和机械通气时间,A、B、C组明显低于D组,差异具有统计学意义(P<0.05)。停药后,4组患者的清醒时间没有明显差别。结论 舒芬太尼联合咪达唑仑对机械通气COPD患者效果较好,且中等浓度即可满足临床需要,值得推广。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.