ICU慢性阻塞性肺疾病患者撤机后镇静对呼吸循环功能的影响

目的观察右美托咪啶对ICU慢性阻塞性肺疾病患者撤机后镇静作用。方法成功撤机12 h的慢性阻塞性肺疾病患者48例,给予右美托咪啶负荷剂量1.0μg.kg-1,滴定维持剂量0.2～0.7μg.kg-1.h-1,保持患者Ramsay镇静深度评分3～4分,给药0、30 min、1、2 h监测INBP、HR、SpO2、PETCO2。结果与0 min比较,30 min、1、2 h SBP明显下降(P0.05),HR明显下降(P0.05),完成实验的患者在任何时间点均SBP90 mmHg,HR60 mmHg,无微循环灌注不足表现,PETCO2无明显改变(P0.05)。结论右美托咪啶用于ICU慢性阻塞性肺疾病患者撤机后镇静未产生明显呼吸抑制,血压和心率轻度降低。     

右美托咪定及其分别复合氯胺酮、咪达唑仑滴鼻用于患儿术前镇静的比较研究

[摘要]目的：比较右美托咪定单独或分别复合咪达唑仑、氯胺酮作为儿童术前用药的镇静效果及安全性。方法：选择美国麻醉医师协会（ASA）Ⅰ~Ⅱ级行择期手术患儿75例,年龄2~12岁,随机分为右美托咪啶组（D组）、右美托咪定复合咪达唑仑组（DM组）和右美托咪定复合氯胺酮组（DK组）。术前30 min右美托咪啶1 μg/kg、右美托咪啶1 μg/kg+咪达唑仑0.2 mg/kg和右美托咪定1 μg/kg+氯胺酮3 mg/kg分别滴鼻给药,观察给药后5 min（T1）、10 min（T2）、15 min（T3）、20 min（T4）、25 min（T5）、30 min（T6）时患儿的心率（HR）、收缩压（SBP）、舒张压（DBP）、呼吸频率（RR）、氧饱和度（SpO2）和Ramsay镇静评分。结果：与D组比较,DK和DM组T1~T6时心率降低（P<0.05）;与D组、DK组比较,DM组T1~T6时收缩压降低（P<0.05）;与D组、DK组比较,DM组T1~T6时舒张压降低（P<0.05）。与D组比较,DK组和DM组T1~T6时镇静评分升高（P<0.05）;与DM组比较,DK组T2~T6时镇静评分降低（P<0.05）,无镇静过度。结论：在小儿麻醉前给予右美托咪定 1 μg/kg +氯胺酮3 mg/kg滴鼻可以产生良好的镇静效果且无滴鼻刺激性。     

右美托咪定与丙泊酚在慢性阻塞性肺疾病患者中镇静疗效评价

目的：在有创机械通气的慢性阻塞性肺疾病（AECOPD）患者中,对比右美托咪啶与丙泊酚的镇静效果及疗效。方法：选取104例相关患者分为丙泊酚组和右美托咪啶组,随机、单盲法试验。根据躁动-镇静评分（RASS）、谵妄评定方法判断两组镇静效果及谵妄发生率,并对比两组呼吸机使用时间和入住ICU时间。结果：两组患者在达到目标镇静范围内百分比无显著性差异;但在起效时间上存在明显差异。谵妄发生率差异也具有统计学意义。右美托咪啶组对比丙泊酚组表现为心动过缓发生率较高;而低血压发生率右美托咪啶组则低于丙泊酚组。脱机时间：右美托咪啶组平均为3.2天;丙泊酚组平均为6.1天,差异具有统计学意义。ICU留住时间,右美托咪啶组平均为5.1天,丙泊酚组平均为10.2天,差异有统计学意义。结论：右美托咪因具有清醒镇静,易唤醒的特点,使得其在AECOPD患者的镇静中优于丙泊酚。     

右美托咪定用于重度子痫前期患者剖宫产术前镇静的效果

目的：评价右美托咪定用于重度子痫前期患者剖宫产术前镇静的效果。方法选择重度子痫前期孕妇102例,孕周≥34周,体重60～100 kg,年龄25～39岁,ASAⅡ或Ⅲ级,孕妇随机分为2组：右美托咪定组及安定组。右美托咪定组患者于术前泵注右美托咪定负荷剂量1μg／kg,泵注10 min后改为0Ζ．25μg· kg－1· min－1持续泵注2 h,安定组于术前采用肌内注射安定10 mg镇静,2组均静脉输注硫酸镁。记录患者用药前及用药后30 min、2 h、麻醉前收缩压、舒张压、心率及胎心率监测,乌拉地尔用量,患者麻醉前Ramsay 镇静评分,检测患者麻醉前及手术开始时血清皮质醇、超氧化物歧化酶（ SOD）、丙二醛（ MDA）浓度,记录新生儿娩出1 min时的Apgar评分。结果2组治疗前、治疗后30 min、2 h收缩压、舒张压、心率和胎心比较,差异无统计学意义（ P ＞0．05）。2组治疗后收缩压水平呈逐渐下降趋势（ P ＜0．05）,安定组治疗后舒张压水平呈逐渐下降趋势（ P ＜0．05）,右美托咪定组治疗后30 min、2 h舒张压均低于治疗前（ P ＜0．05）,治疗后2 h舒张压低于治疗后30 min,但差异无统计学意义（ P ＞0．05）。2组患者术前乌拉地尔用量、麻醉前Ramsay 评分及新生儿Apgar评分的比较差异有统计学意义（ P ＜0．05）。2组手术开始时血清皮质醇、MDA水平高于麻醉前,SOD水平低于麻醉前,差异有统计学意义（ P ＜0．05）。右美托咪定组麻醉前、手术开始时皮质醇、MDA水平低于安定组,SOD水平高于安定组,差异有统计学意义（ P ＜0．05）。结论右美托咪定可安全用于重度子痫前期患者的术前镇静,减少术前乌拉地尔用量,且降低患者应激反应。     

右美托咪啶在颈丛神经阻滞甲状腺手术中的对比研究

目的：观察颈丛阻滞甲状腺手术辅以右美托咪啶或杜氟合剂的临床效果。方法择期甲状腺手术患者60例,随机分为两组：右美托咪啶组（D组）、杜氟合剂组（P组）,每组20例。神经阻滞后D组泵注右美托咪啶负荷量1μg/kg,恒速10 min,持续量0.5μg/（kg·h）, P组静脉推注杜冷丁50 mg,氟哌利多2.5 mg。记录基础值（T0）、颈丛阻滞后10 min（T1）、20 min（T2）、30 min（T3）及手术结束时（T4）的收缩压（SBP）、舒张压（DBP）、心率（HR）。结果D组较P组T1~T4各指标均明显降低,差异具有统计学意义（P〈0.05）。结论甲状腺手术辅以右美托咪啶比辅以杜氟合剂镇静、镇痛效果好,能有效抑制颈丛阻滞导致的心血管不良反应。     

右美托咪啶、丙泊酚与咪达唑仑辅助于臂丛阻滞麻醉的比较

目的 比较右美托咪啶、丙泊酚与咪达唑仑辅助于臂丛阻滞麻醉中的镇静效果及对呼吸循环的影响.方法 选择60例ASA Ⅰ ～Ⅱ级拟行上肢手术的患者,随机分为3组,每组各20例.超声引导下臂丛阻滞成功后,右美托咪定组（D组）患者给予右美托咪啶0.5μg/kg静脉泵注10 min后按0.2～0.7 μg/（kg·h）的速率维持;丙泊酚组（P组）给予丙泊酚2 mg/kg静脉注射后以2～4 mg/（kg·h）维持;咪达唑仑组（M组）静脉注射咪达唑仑0.05 mg/kg后以0.05～0.1 mg/（kg·h）维持.调整各组患者的输注速度使镇静目标维持Ramsay镇静评分为3～4分.术中监测不同时间点的心率（HR）、平均动脉压（MAP）、血氧饱和度（SpO2）、呼吸频率（RR）、脑电双频（BIS）指数值、Ramsay镇静评分,并记录术中出现的不良反应.结果 在相同镇静评分下,D组的BIS值明显低于P、M组（P＜0.05）;3组均出现不同程度的血压下降和心率减慢,D组HR下降较P、M组明显（P＜0.05）,P组MAP下降较D、M组明显（P＜0.05）;P、M组RR减慢较D组明显,需要辅助呼吸的比例明显高于D组（P＜0.05）.结论 丙泊酚和咪达唑仑能明显抑制呼吸,而右美托咪啶对呼吸和循环的影响小,辅助于臂丛阻滞麻醉镇静效果比较好,但易诱发心动过缓.     

丙泊酚和右美托咪啶对于重症监护病房患者镇静效果的比较分析

目的：对照分析丙泊酚和右美托咪啶对重症监护患者的临床镇痛效果。方法：选取重症颅脑外伤躁动患者44例为研究对象,设为丙泊酚镇静组;同期选取同症患者44例作为参照对象,设为右美托咪啶镇静组,对比观察两组的镇静效果、不良反应等指标。结果：丙泊酚组患者达到镇静满意的时间和停药后唤醒时间明显短于右美托咪啶组,两组差异有统计学意义（P＜0.05）。机械通气时间,丙泊酚组与右美托咪啶组差异不明显,无统计学意义（P＞0.05）。右美托咪啶组心动过缓的发生率更高,丙泊酚组呼吸抑制、注射部位疼痛的发生率较高,差异有统计学意义(P＜0.05)。结论：对于重症颅脑外伤躁动患者而言,给予丙泊酚和右美托咪定都能够起到显著的镇静效果,丙泊酚药物见效快,用药时间短,有时会出现呼吸抑制现象,右美托咪啶抑制呼吸并不明显,但是心动过缓现象时有发生。因此临床用药过程中应该根据具体病情给药。     

右旋美托咪啶在高血压患者围麻醉期间的影响

目的 观察右旋美托咪啶对高血压患者围麻醉期间的影响.方法 选择2009年9月-2010年8月在我院行全麻手术的原发性高血压患者25例为研究对象,随机分为对照组(12例)和右旋美托咪啶组(13例);右旋美托咪啶组采用微量泵将4μg/ml浓度的右旋美托咪定以0.6 ml/(kg·h)速度静脉泵入,对照组以同样方法泵入0.9%氯化钠溶液;分别观察并记录入室时、给药后5 min、麻醉后30 min、麻醉后2 h血压、心率及脉搏血氧饱和度(SpO2).结果 麻醉后对照组2例使用麻黄碱,5例使用盐酸尼卡地平;右旋美托咪啶组3例使用麻黄碱,无1例使用盐酸尼卡地平和阿托品.对照组患者入室后收缩压、心率均有所增加,泵药15min后舒张压有所下降;右旋美托咪啶组心率、收缩压和舒张压无明显变化,组间比较差异有统计学意义(P＜0.05),入室后两组SpO2无明显下降,两组间比较差异无统计学意义(P＞0.05).结论 右旋美托咪啶可对高血压患者产生明显的镇静作用和轻度的中枢降压效果,增强围麻醉期循环稳定,减少阿片类药物的用量,而且不产生呼吸抑制作用,可防止患者术后高血压恶化,防止心脑血管意外的发生.     

氯胺酮复合右美托咪啶在烧伤切痂植皮麻醉中的应用

目的探讨氯胺酮复合右美托咪啶在烧伤切痂植皮术非气管插管麻醉中的效果。方法 60例择期切痂植皮手术患者,ASAⅠ-Ⅱ级,随机均分为氯胺酮复合右美托咪啶组(KD组)和氯胺酮复合丙泊酚组(KP组)。术中均保留自主呼吸,并用面罩给氧。记录心率、血压、脉搏血氧饱和度、心肌耗氧指数、氯胺酮用量、手术时间、苏醒时间、围术期镇静评分及出现的不良反应。结果与KP组相比,KD组右美托咪啶给药后10min收缩压增高(P<0.05),氯胺酮给药后5、10min降低(P<0.05),在氯胺酮给药后5、10、15min心率-收缩压乘积(RPP)降低(P<0.05),术后1h镇静评分增高(P<0.05),苏醒时间缩短(P<0.05)。结论烧伤切痂植皮术用氯胺酮复合右美托咪啶麻醉较复合丙泊酚能更好的维持血流动力学稳定,减少术中心肌氧耗,促进早期苏醒。     

脑电双频指数指导下右美托咪啶和丙泊酚用于颅脑损伤患者镇静作用的比较

目的比较和评估右美托咪啶(DEX)和丙泊酚用于ICU内进行机械通气的颅脑损伤患者镇静的效果和安全性。方法将61例行机械通气的颅脑损伤患者分为两组,右美托咪啶组(D组)合丙泊酚组(P组)。所有患者入室后行脑电双频指数(BIS)及心电图、上臂血压、脉搏血氧饱和度(SpO2)检查,按镇静方法完全随机分为两组:D组33例,右美托咪啶负荷量0.5μg/kg,以0.2μg/(kg·h)静脉恒速输注;P组28例,以丙泊酚负荷量1mg/kg,维持剂量0.4mg/(kg·h)静脉恒速输注。两组均将脑电双频指数控制在≤85,并以此为标准调整输注计量维持镇静过程,同时记录剂量的调整。记录心率(HR)、平均动脉压的变化,记录两组患者机械通气时间、拔管时间唤醒所需时间,镇静过程平均动脉压和心率变化并记录患者的Ramsay镇静评分(RSS评分)。结果与镇静前比,镇静后各时间点Ramsay评分明显升高,BIS值显著下降,差异有统计学意义(P0.05)。D组心动过缓和低血压的发生率分别为0,3.03%(1/33),明显低于P组10.7%(3/28),17.8%(5/28),差异有统计学意义(P0.01)。D组患者从进入ICU至开始脱机时间为(62.0±4.0)h,与P组(67.0±5.0)h比较,差异无统计学意义。P组患者ICU内住院时间(115.4±2.0)h,脱机时间(3.6±1.5)h,拔管时间(2.3±1.2)h,D组患者ICU平均住院(112.3±4.0)h,脱机时间(3.5±1.3)h及拔管时间(2.2±1.1)h,D组与P组组间比较有统计学意义。结论对于ICU内颅脑损伤患者使用右美托咪啶和丙泊酚镇静安全有效,右美托咪啶较丙泊酚能够有效的减轻气道-循环反射,可有效提高患者的苏醒时间。右美托咪啶对血流动力的影响优于丙泊酚,且在脱机和拔管时间方面右美托咪啶优于丙泊酚,右美托咪啶镇静效果好,易唤醒,在脑电双频指数的指导下右美托咪啶更有优势。     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.     

Biochemical and molecular characterisation of cubozoan protein toxins

Class Cubozoa includes several species of box jellyfish that are harmful to humans. The venoms of box jellyfish are stored and discharged by nematocysts and contain a variety of bioactive proteins that are cytolytic, cytotoxic, inflammatory or lethal. Although cubozoan venoms generally share similar biological activities, the diverse range and severity of effects caused by different species indicate that their venoms vary in protein composition, activity and potency. To date, few individual venom proteins have been thoroughly characterised, however, accumulating evidence suggests that cubozoan jellyfish produce at least one group of homologous bioactive proteins that are labile, basic, haemolytic and similar in molecular mass (42-46 kDa). The novel box jellyfish toxins are also potentially lethal and the cause of cutaneous pain, inflammation and necrosis, similar to that observed in envenomed humans. Secondary structure analysis and remote protein homology predictions suggest that the box jellyfish toxins may act as α-pore-forming toxins. However, more research is required to elucidate their structures and investigate their mechanism(s) of action. The biological, biochemical and molecular characteristics of cubozoan venoms and their bioactive protein components are reviewed, with particular focus on cubozoan cytolysins and the newly emerging family of box jellyfish toxins.     

Dose tolerability of chronically inhaled voriconazole solution in rodents

Invasive pulmonary aspergillosis (IPA) is a fungal disease of the lung associated with high mortality rates in immunosuppressed patients despite treatment. Targeted drug delivery of aqueous voriconazole solutions has been shown in previous studies to produce high tissue and plasma drug concentrations as well as improved survival in a murine model of IPA. In the present study, rats were exposed to 20 min nebulizations of normal saline (control group) or aerosolized aqueous solutions of voriconazole at 15.625 mg (low dose group) or 31.25 mg (high dose group). Peak voriconazole concentrations in rat lung tissue and plasma after 3 days of twice daily dosing in the high dose group were 0.85 ± 0.63 μg/g wet lung weight and 0.58 ± 0.30 μg/mL, with low dose group lung and plasma concentrations of 0.38 ± 0.01 μg/g wet lung weight and 0.09 ± 0.06 μg/mL, respectively. Trough plasma concentrations were low but demonstrated some drug accumulation over 21 days of inhaled voriconazole administered twice daily. Following multiple inhaled doses, statistically significant but clinically irrelevant abnormalities in laboratory values were observed. Histopathology also revealed an increase in the number of alveolar macrophages but without inflammation or ulceration of the airway, interstitial changes, or edema. Inhaled voriconazole was well tolerated in a rat model of drug inhalation.