高龄患者椎管内麻醉应用右美托咪啶的镇静效果观察

摘 要 目的：观察椎管内麻醉高龄患者应用右美托咪啶的镇静效果。方法: 52例行椎管内麻醉手术治疗的高龄患者随机分为观察组和对照组,每组26例。麻醉成功后,对照组患者静脉泵注0.9%氯化钠注射液,观察组患者则静脉泵注右美托咪啶。比较两组患者T0（麻醉前）、T1（给药后10 min）、T2（给药后30 min）、T3（给药后60 min）、T4（手术结束）等时点的血压（BP）、呼吸频率（RR）、血氧饱和度（SpO2与心率（HR）变化,Ramsay镇静评分及药品不良反应情况。结果:两组患者的HR、RR及SpO2均维持在正常范围内,观察组患者T2与T3时点SBP、HR显著低于T0,也低于对照组同时点(P＜0.05);观察组患者在T2～T4时点Ramsay镇静评分均显著低于T0,也低于对照组同时点(P＜0.05）;观察组药品不良反应发生率明显低于对照组(P＜0.05)。结论:右美托咪啶用于老年患者的椎管内麻醉手术,辅助效果显著,在维持血流动力学稳定的基础上使患者充分镇静,能减少不良反应发生,安全性高,值得临床推广应用。     

Population Pharmacokinetic/Pharmacodynamic Model for the Sedative Effects of Flibanserin in Healthy Volunteers

Purpose

Flibanserin is being developed for treating hypoactive sexual desire disorder in women; the main side effect is sedation. The analysis objective was to relate flibanserin plasma concentrations with acute sedative effects using a population pharmacokinetic/pharmacodynamic (PK/PD) model.

Methods

The population model was developed with NONMEM based on data from 24 healthy volunteers. ??Drowsiness?? was serially assessed by a Visual Analogue Scale (VAS) on a baseline day and after morning oral administration of 100?mg flibanserin together with PK sampling.

Results

PK was best described by a three-compartment disposition model and transit compartments accounting for the lag time in absorption. VAS ??drowsiness?? baseline profiles were modeled using linear splines with three breakpoints located at clock times at first and last observation, and at the median of the observation time across subjects. The drug effect followed a sigmoidal E_MAX model using predicted effect site concentrations (C_e). The VAS vs. C_e relationship was very steep and effect site and plasma concentration-time profiles were very similar thus suggesting little delay between the occurrence of maximum flibanserin plasma concentrations and drowsiness.

Conclusions

At effect site concentrations lower than ??200?ng/mL that are reached approximately 4?h after administration, flibanserin shows hardly any effect on the VAS ??drowsiness?? scale.     

在老年股骨头置换术中应用腰麻硬膜外联合麻醉的效果分析

目的探讨腰麻硬膜外联合麻醉应用于老年股骨头置换术的临床效果。方法 91例行股骨头置换术的老年患者被随机分为实验组(n=46)和对照组(n=45),对照组给予硬膜外麻醉,实验组给予腰麻硬膜外联合麻醉。结果实验组下肢运动阻滞程度评分,Ramsay以及术中MAP和HR指标均显著优于对照组,显示了更好的临床效果(P<0.05)。结论腰麻硬膜外联合麻醉应用于老年股骨头置换术,能显著提高临床效果,改善患者生活质量,值得在临床上应用和推广。     

Gene Therapy: A Pharmacokinetic/Pharmacodynamic Modelling Overview

Since gene therapy started over 20 years ago, more than one-thousand clinical trials have been carried out. Nonviral vectors present interesting properties for their clinical application, but their efficiency in vivo is relatively low, and further improvements in these vectors are needed. Elucidating how nonviral vectors behave at the intracellular level is enlightening for vector improvement and optimization. Model-based approach is a powerful tool to understand and describe the different processes that gene transfer systems should overcome inside the body. Model-based approach allows for proposing and predicting the effect of parameter changes on the overall gene therapy response, as well as the known application of the pharmacokinetic/pharmacodynamic modelling in conventional therapies. The objective of this paper is to critically review the works in which the time-course of naked or formulated DNA have been quantitatively studied or modelled.     

Population Pharmacokinetic/Pharmacodynamic Modelling of the Analgesic Effects of Tramadol in Pediatrics

Background and Purpose The efficacy of tramadol (T) in children is not clearly understood because it is still unknown the ability of that population to form the active metabolite O-demethyltramadol (M1) and, whether or not the parent compound has a contribution to the efficacy. The aim was to develop a population pharmacokinetic/pharmacodynamic model for T in pediatrics, identifying the main active components.Materials and Methods One hundred four children, mean age (4.55 years) received intravenously 1 mg/kg dose of T over 2.5 min at the end of surgery. If pain relief was inadequate, then an additional 0.33 mg/kg dose was given at 15, 30 and/or 45 min. Plasma samples and analgesic responses such as crying and movement were measured during a 6-h period.Results The estimates of the apparent volumes of distribution of the central compartment and at steady state and total plasma clearance of T were 8 l, 46.2 l, and 15.2 l/h, respectively. M1 formation clearance represented only a minor elimination pathway of T. Effect site concentrations of T and M1 were found to be the best predictors of the movement and crying responses, respectively. Steady-state plasma concentration levels of T and M1 of 100 and 15 ng/ml were associated with a 95% probability of adequate pain relief.Conclusions Children have the ability to produce enough M1 to achieve proper pain relief. The response variables investigated give further evidence that not only the opioid effects of the metabolite are relevant, also the non-opiod effects of tramadol seem to give a significant contribution in its clinical use.     

丙泊酚在重症哮喘机械通气患者中的镇静效果观察

目的探讨丙泊酚在重症哮喘机械通气中的镇静效果。方法采用有创机械通气治疗的重症哮喘患者36例,随机分为治疗组18例给予丙泊酚镇静,对照组18例给予咪唑安定镇静,二组均给予容量辅助/控制通气模式,根据病情调整呼吸机参数,其余治疗哮喘的方法相同。结果治疗组和对照组的治愈率分别为92.86%和90.15%无统计学差异。但气管插管时间治疗组为(2.4±0.33)d,对照组为(3.6±0.25)d,平均住ICU时间治疗组和对照组分别为(4.3±0.16)d,(5.5±0.18)d,呼吸机相关性肺炎(VAP)发生率分别为5.56%和11.11%均有明显的统计学差异。结论丙泊酚镇静在重症哮喘机械通气中具有起效快、苏醒迅速的特点,它可以减少带呼吸机时间,缩短住ICU时间,减少呼吸机相关性肺炎的发生率。     

盐酸羟考酮与芬太尼分别复合丙泊酚对喉显微手术患者麻醉效果的比较

目的：比较盐酸羟考酮与芬太尼分别复合丙泊酚对喉显微手术的麻醉效果。方法：喉显微手术患者120例,年龄22～65岁,体重42～85 kg,ASA分级Ⅰ～Ⅱ级,随机均分2组（n=60例）。所有病人均采用全凭静脉麻醉。常规去氮给氧依次静注丙泊酚2.0 mg·kg^-1+芬太尼3.0 μg·kg^-1（F组）或丙泊酚2.0 mg·kg^-1盐酸羟考酮0.1 mg·kg^-1（O组）,以1.0 mL·s^-1的速率静脉推注芬太尼或盐酸羟考酮后,观察1 min内患者的呛咳反应,然后再给予米库氯胺2.0 mg·kg^-1,待肌松完全后行气管插管。记录入室前（T₀）、静注芬太尼或盐酸羟考酮后1 min（T₁）、插管后1 min（T₂）、插管后5 min（T₃）、拔管后3 min（T₄）,记录平均动脉压（MAP）、心率（HR）并采集静脉血用放免法检测皮质醇（Cor）、用高效液相色谱-电化学法测定去甲肾上腺素（NE）、用己糖激酶法测定血糖（Glu）,同时记录麻醉诱导时两组患者呛咳反应（FIC）发生率;麻醉苏醒和离开手术室时间及恶心呕吐、呛咳躁动、咽喉疼痛、呼吸抑制等不良反应发生率。结果：F组、O组在T₂、T₃、T₄时点NE、Cor、Glu、MAP、HR虽有所升高,但与T₀相比,差异无统计学意义（P＞0.05）;在T₁时点,F组MAP明显升高、HR明显加快,NE、Cor、Glu分泌水平也明显增加,O组T₀与T₁时点相比,差异有明显的统计学意义（P＜0.05）;F组患者FIC的发生率18例（30%）明显高于O组的0例（P＜0.05）;术后呼吸抑制F组发生率6例（10%）明显高于O组的1例（1.7%）（P＜0.05）;恶心、呕吐发生率F组10例（16.7%）明显高于O组的2例（3.3%）（P＜0.05）;两组清醒时间、离开手术室时间差异无统计学意义;两组咽喉疼痛、苏醒期呛咳躁动等不良反应发生率差异无统计学意义（P＞0.05）。结论：盐酸羟考酮（0.1 mg·kg^-1）作为全麻诱导辅助药可以增强心血管稳定性、降低围手术期的应激反应,避免FIC的发生,降低了不良反应的发生。     

腰硬联合麻醉在高龄患者全髋关节置换术中的应用

目的观察腰麻硬膜外联合麻醉(CSEA)应用于高龄患者全髋关节置换术的麻醉效果,以及对高龄患者的血压、心率、血氧饱和度的影响,与硬膜外麻醉比较,是否更具有优越性.方法选择行全髋关节置术的高龄患者70例,随机分为腰硬联合麻醉组(Ⅰ组)和硬膜外麻醉组(Ⅱ组),对两种麻醉方法的麻醉起效时间、麻醉效果、生命体征变化、低血压及其他并发症的发生率等进行比较.结果腰硬联合麻醉比单纯硬膜外麻醉完全率高,麻醉起效时间及手术时间缩短,麻醉后低血压发生率低.结论两种麻醉方法对高龄老人髋关节置换术均有效,麻醉完全率腰硬联合比单纯硬膜外高.     

纳布啡在剖宫产术后静脉自控镇痛患者中的镇痛镇静效果分析

目的:探讨纳布啡在剖宫产术后静脉自控镇痛患者中的镇痛镇静效果.方法:选择2019年6月至2020年3月于萍乡市安源区妇幼保健院产科行剖宫产手术的401例产妇,采用随机数表法分为布托啡诺组(n=200)和纳布啡组(n=201),两组术后均行静脉自控镇痛.比较两组不同时点疼痛视觉模拟量表(VAS)评分[包括术后2?h(T1...     

丙泊酚用于儿童核磁共振检查麻醉效果与安全性的系统评价

目的：评价丙泊酚静脉麻醉用于儿童核磁共振检查的临床麻醉效果和安全性。方法：计算机检索国内外相关数据库文献资料,并辅以手工检索相关文献的参考文献目录,全面收集丙泊酚用于儿童核磁共振检查的麻醉效果的临床随机对照试验文献,由两名评价员独立筛选、提取资料并对其进行质量评价,分析总结丙泊酚的临床麻醉效应。结果：共纳入5篇文献（共529名患者,年龄范围是1～18岁）,由于存在临床异质性（如对照药物与给药方法不同）,未进行Meta分析,仅进行描述性分析;与右美托咪定或戊巴比妥等有效药物相比,丙泊酚用于儿童核磁共振检查的麻醉效果与安全性基本相同,苏醒时间更快,个别会出现低血压、呼吸抑制等不良反应;比较断续滴定法与持续维持法、麻醉达成后维持或不维持给药等方法,不同的丙泊酚给药方法均具有同等麻醉效果与安全性。结论：丙泊酚静脉麻醉用于儿童磁共振检查的优势在于复苏时间短,苏醒快;因个别病例存在呼吸抑制和血压降低的风险,需进行严密的生命体征监测;采用不同给药方法实施麻醉,麻醉效果与安全性相同,可结合实际情况选择使用。     

舒芬太尼联合咪达唑仑用于机械通气患者镇静的临床观察

目的：评价机械通气时采用舒芬太尼与咪达唑仑联合镇静的效果和安全性。方法：选择ICU中需要镇静的机械通气患者106例,随机分为舒芬太尼-咪达唑仑组（MSF组）、咪达唑仑组（M组）。两组均在给予负荷剂量后用微量注射泵持续静脉泵入药物方式镇静。监测用药初期（0、15、30 min）两组患者呼吸及循环参数的变化,以后每2小时评估镇静深度,以MAAS镇静评分3分、ATICE人机顺应性评分≥3分为镇静目标,优先保证人机顺应性进行药物输注速度的调整;并于24 h停药后观察苏醒时间、相关并发症、用药量及镇静满意度和人机顺应性满意度。结果：两组患者的基线参数比较差异均无统计学意义（P〉0.05）;两组镇静15 min和30 min的心率、呼吸频率、气道峰压明显低于用药前（P〈0.05,P〈0.01或P〈0.001）;MSF组收缩压较镇静前下降（P〈0.05）,但两组舒张压镇静前后无明显变化（P〉0.05）;M＋F组的镇静满意程度、人机顺应满意程度明显高于M组（P〈0.01,P〈0.05）。M＋F组的恢复时间明显短于M组（P〈0.01）;MSF组咪达唑仑的用药量少,相关并发症少。结论：机械通气患者使用舒芬太尼联合咪达唑仑镇静具有良好的镇静效果,提高人机顺应性,适当改善通气效果,且用药安全。     

腰硬联合麻醉在高龄患者经尿道前列腺电切术中的麻醉效果分析

目的探讨腰硬联合麻醉在高龄患者经尿道前列腺电切术中的麻醉效果及安全性。方法选择70例行尿道前列腺电切术的高龄患者,随机分为观察组与对照组各35例。观察组给予患者腰麻-硬膜外联合麻醉,对照组给予患者连续硬膜外麻醉,观察两组患者的麻醉效果及安全性。结果观察组患者在感觉阻滞起效时间、痛觉阻滞持续时间、运动阻滞起效时间、运动阻滞持续时间等方面明显短于对照组,具有显著性差异(P<0.05)。观察组患者没出现辅助静脉镇痛药和改全麻,也没出现腰麻后头痛和神经系统并发症。对照组患者有3例因麻醉不全、有痛感而给予辅助静脉镇痛药,有1例患者因不能耐受手术而改气管插管全麻。观察组麻醉效果明显优于对照组,具有显著性差异(P<0.05)。结论腰硬联合麻醉应用于高龄患者经尿道前列腺电切术安全可靠,效果确切,值得基层医院推广应用。     

A Double-Blind Study of the Sedative Effects of the Thalidomide Enantiomers in Humans

This study investigated the sedative effects of the enantiomers of thalidomide in humans. Since the enantiomers undergo chiral inversion in vivo this entailed application of suitable statistical methodology to distinguish the effects of each enantiomer in the presence of the other one. Six healthy male volunteers received single oral doses of (+)-(R)-thalidomide, (–)-(S)-thalidomide or racemic thalidomide in a double-blind study, and the results of this study were compared with those of a similar study where three subjects received (+)-(R)-thalidomide, (–)-(S)-thalidomide or placebo in a double-blind fashion. Blood samples for analysis of (+)-(R)-thalidomide and (–)-(S)-thalidomide were obtained. Prior to sampling it was noted whether the subject was awake or asleep, and his feelings of tiredness and heaviness were estimated using Borg scales. After blood sampling continuous reaction time was measured by a 10-min series of auditory signals. The concentration–effect relationships were analyzed by logistic regression techniques and Cox regression for the reaction time data. The (+)-(R)-thalidomide concentrations, but not the (–)-(S)-thalidomide concentrations, exhibited significant positive influences on all sedative effects studied (sleep, tiredness, and reaction times). In some of the analyses of reaction times the (–)-(S)-thalidomide concentrations had a significant effect in the opposite direction. The time course and intensity of sedative effect is thus influenced by which enantiomer is administered and by the kinetics of in vivo chiral inversion.     

Pharmacodynamic Modelling of Placebo and Buprenorphine Effects on Event‐Related Potentials in Experimental Pain

The purpose of the study was to investigate placebo and buprenorphine effects on event‐related potentials (ERPs) in experimental pain and the potential benefit of population pharmacodynamic modelling in data analysis. Nineteen healthy volunteers received transdermal placebo and buprenorphine in a cross‐over study. Drug plasma concentrations and ERPs after electrical stimulation at the median nerve with intensity adjusted to pain detection threshold were recorded until 144 hrs after administration. Placebo and concentration‐effect models were fitted to data using non‐linear mixed‐effects modelling implemented in NONMEM (V7.2.0.). Pharmacodynamic models were developed to adequately describe both placebo and buprenorphine ERP data. Models predicted significant placebo effects, but did not predict significant effects related to buprenorphine concentration. Models revealed that ERPs varied both between subjects and between study occasions. ERPs were found to be reproducible within subjects and occasions as population variance was found to be eight times higher than the unexplained variances. Between‐subject variance accounted for more than 75% of the population variance. In conclusion, pharmacodynamic modelling was successfully implemented to allow for placebo and variability correction in ERP of experimental pain. Improved outcome of ERP studies can be expected if variation between subjects and study occasions can be identified and described.     

盐酸丙帕他莫复合靶控输注异丙酚用于人工流产术的效应室靶浓度测定

目的:测定盐酸丙帕他莫复合靶控输注(TCI)异丙酚用于人工流产术的50%和95%有效浓度(EC_(50)和EC_(95))。方法:选择30例美国麻醉师协会(ASA)Ⅰ级孕6～12周接受无痛人工流产术患者,术前30min静脉滴注盐酸丙帕他莫2g,TCI异丙酚效应室靶浓度采用改良序贯法确定,根据上一例患者术中有无明显体动反应,下一例患者增加或减少0.5mg·mL-1,用概率单位回归分析法计算出EC_(50)和EC_(95)及相应的95%可信区间(CI)。结果:复合盐酸丙帕他莫2g时,异丙酚的EC_(50)为4.81mg·mL~(-1),95%CI为4.34～5.19mg·mL~(-1);EC_(95)为5.86mg·mL~(-1),95%CI为5.34～9.68mg·mL~(-1)。结论:复合盐酸丙帕他莫2g用于人工流产术,靶控输注异丙酚效应室靶浓度为5.86mg·mL~(-1)较适宜。     

右美托咪定对颅脑损伤患者的镇静效果及不良反应观察

目的：探讨右美托咪定对颅脑损伤患者的镇静效果及其不良反应。方法：90例ICU病房收治的颅脑损伤患随机分为观察组和对照组各45例,观察组予右美托咪定注射液镇静治疗,对照组予咪达唑仑镇静治疗。比较两组患者的镇静效果、机械通气时间、停药后至唤醒所需要时间和药品不良反应发生情况。结果：两组患者均顺利完成治疗,观察组达到目标镇静的平均时间、达到目标镇静次数,需要干预治疗达到目标镇静次数均明显优于对照组,且观察组面部表情评分降低程度明显优于对照组,差异均有统计学意义（P〈0.05）;观察组的机械通气时间和停药至唤醒所需时间也明显短于对照组,差异有统计学意义（P〈0.05）;两组患者发生不良反应和需要干预的例数差异无统计学意义（P〉0.05）。结论：右美托咪定对ICU颅脑损伤患者的镇静效果显著,唤醒时间短,无呼吸抑制,且能更好地维持循环稳定,值得临床推广。     

异丙酚吗啡和咪唑安定用于机械通气镇静效果对比研究

目的对比观察异丙酚、吗啡和咪唑安定用于ICU患者机械通气的镇静效果。方法选择急性呼吸衰竭需机械通气12h以上或并发急性呼吸窘迫综合征的ICU患者320例,随机分为3组,其中异丙酚组160例,吗啡组45例,咪唑安定组115例。异丙酚组:先静注异丙酚1.5mg/kg行镇静诱导,然后改用输液泵持续静注异丙酚1~4mg/(kg.h)。吗啡组以0.15mg/(kg.d)计算吗啡量,老年及危重患者酌情减量,超过60mg不再追加量。将吗啡用5%葡萄糖稀释至24m l,用微量泵以1m l/h的速度持续静脉泵入。咪唑安定组:先静脉注射咪唑安定0.06mg/kg行镇静诱导,再以0.05~0.15mg/(kg.h)的剂量用输液泵持续静脉内泵入。结果总镇静时间异丙酚组为(27.2±8.2)h,吗啡组为(23.8±6.7)h咪唑安定组为(26.5±5.5)h;药物起效时间异丙酚组为(29.3±7.6)s,吗啡组为(28.5±6.3)s,咪唑安定组为(65.1±11.3)s,异丙酚组、吗啡组和咪唑安定组比较有显著性差异(P<0.01)。达到满意镇静深度时间异丙酚组为(25±11)m in,吗啡组为(8±3)m in,咪唑安定组(35±17)m in。停药清醒后再入睡者:异丙酚组为0例,吗啡组为0例,咪唑安定组为3例(P<0.05)。停药后出现恶心者:异丙酚组为4例(2.50%),吗啡组为5例(11.11%),咪唑安定组为20例(17.39%),P<0.05。异丙酚组有6例出现血压下降,4例出现心率减慢。结论异丙酚、吗啡和咪唑安定用于ICU危重患者的镇静都能达到良好的镇静效果,可根据不同需要来选择用药使ICU患者取得满意的镇静效果。     

A Compartmental Analysis of the Pharmacokinetics of Propofol in Sheep

Conventional compartmental pharmacokinetic analysis may provide inaccurate prediction of drug concentrations after rapid iv administration. To examine this, compartment and effect compartment analysis was applied to measured arterial and brain concentrations of propofol in sheep after iv administration at a range of doses and dose rates. Although arterial and brain concentrations were reasonably well fitted to compartmental and effect compartment models for individual doses and dose rates, the structure and parameters of all models differed with changes in both dose and rate of administration. There were large discrepancies between predicted and measured arterial and brain concentrations when these models were used to predict drug concentrations across doses and dose rates. These data support the limitations of this type of modeling in the setting of rapid propofol administration.