丙泊酚复合雷米芬太尼或咪唑安定在无痛胃镜检查中的麻醉效果

目的比较丙泊酚复合雷朱芬太尼或咪唑安定在无痛胃镜检查中的麻醉效果。方法选择胃镜检查患者120例,随机分为A．B．C3组,每组40例。分别给予丙泊酚,丙泊酚与雷米芬太尼、丙泊酚与咪唑安定。观察术中患者丙泊酚用量,苏醒情况及不良反应。结果丙泊酚复合雷米芬太尼或咪唑安定后,可明显减少丙泊酚用量,增强镇痛效果,减少不良反应的发生,但与味唑安定复合苏醒时间延长。结论丙泊酚复合雷束芬太尼用于无痛胃镜检查安全有效。     

Self-administration of methohexital,midazolam and ethanol: effects on the pituitary–adrenal axis in rhesus monkeys

Rationale There is disagreement in the literature with respect to how drugs of abuse affect the functioning of the hypothalamic–pituitary–adrenal (HPA) axis, and whether these changes in endocrine function may be related to the rewarding effects of these drugs.Objectives To determine whether reinforcing drugs with different mechanisms of action affect HPA axis function at doses at which they serve as reinforcers.Methods Seven monkeys (6 male) were randomly assigned to self-administer methohexital—a barbiturate (n=4), midazolam—a benzodiazepine (n=3), or ethanol (n=5). Each monkey had a surgically implanted indwelling venous catheter, and was trained to respond on a fixed ratio of 30 lever presses to receive an injection of drug or saline. Blood samples were obtained before, during, and after the self-administration sessions for the measurement of ACTH and cortisol by radioimmunoassay.Results Although methohexital, midazolam, and ethanol all maintained self-administration behavior across a range of doses, they differed in their effects on ACTH and cortisol. Ethanol inhibited ACTH and cortisol secretion. Methohexital and midazolam both tended to decrease ACTH and cortisol at large doses, and increase these hormones at small doses, but the HPA effects of neither drug differed significantly from when saline was available.Conclusions The neutral overall effect of methohexital and midazolam on HPA activity is consistent with other monkey and human studies, whereas the inhibitory effect of self-administered ethanol in the monkey contrasts with both the rat and human literature. The data in this study suggest that a change in HPA axis activity is not a requirement for drug-reinforced behavior in monkeys.Results from this paper were first presented at the annual meeting of ISPNE, Quebec City, Canada, in August 2001.     

咪达唑仑治疗儿童癫痫持续状态及惊厥频繁发作的临床研究

目的研究咪达唑仑持续静脉滴注治疗癫痫持续状态[SE,包括难治性癫痫(R SE)]及频繁惊厥发作(FCS)的临床疗效,同时探讨其安全有效剂量及副作用。方法选取收入院的SE及FCS患儿205例为观察对象,随机分为两组,治疗组103例,给予咪达唑仑持续静脉滴注;对照组102例,应用传统的一线抗癫痫药(AED s)治疗。同时将两组疗效进行对照研究,观察治疗组的最大、最小用药剂量,副反应,51例患儿进行脑电图监测。结果治疗组疗效明显高于对照组(P<0.01),治疗组的咪达唑仑安全有效剂量为1￣8μg.kg-1.m in-1,在治疗剂量下未见明显副作用,37例痫样放电随着临床发作的终止消失,14例随着发作次数的减少而减少。结论持续静脉滴注咪达唑仑治疗SE及FCS安全、可靠、有效,且常规一线AEDs治疗无效后该药仍有效,故该药可推荐为治疗癫痫持续状态及频繁惊厥发作的最佳选择。     

咪达唑仑联合不同剂量盐酸纳布啡用于重度肥胖患者无痛胃镜检查的效果

〔摘 要〕 目的：探讨咪达唑仑联合不同剂量盐酸纳布啡用于重度肥胖患者无痛胃镜检查的效果。 方法：选择南昌市第五医院 2018 年 1 月至 2020 年 7 月期间接受无痛胃镜检查的 126 例重度肥胖患者,按随机数字表法分为对照组和观察组,各 63 例。观察组应用 2.5 mg 纳布啡复合咪达唑仑;对照组应用 5 mg 纳布啡复合咪达唑仑。比较两组患者的镇痛与镇静情况、苏醒时间、体动与并发症。 结果：两组患者在苏醒后 5 min 的视觉模拟评分法（VAS）评分、麻醉诱导后 2 min 的Ramsay 镇静评分比较,差异无统计学意义（P ＞ 0.05）;在苏醒后 30 min 两组患者的 VAS 评分较苏醒后 5 min 下降,差异具有统计学意义（P ＜ 0.05）;但苏醒后 30 min 两组患者的 VAS 评分比较,差异无统计学意义（P ＞ 0.05）。内镜入喉时,两组患者的的 Ramsay 镇静评分均较麻醉诱导后 2 min 升高,差异具有统计学意义（P ＜ 0.05）;但内镜入喉时两组患者的Ramsay 镇静评分比较,差异无统计学意义（P ＞ 0.05）。观察组患者的完全苏醒时间为（5.03 ± 1.04）min,短于对照组的（5.50 ± 1.20）min,差异具有统计学意义（P ＜ 0.05）。两组患者均无严重体动发生,且一般体动的发生率比较,差异无统计学意义（P ＞ 0.05）;观察组患者的并发症发生率为 7.94 %,低于对照组的 20.63 %,差异具有统计学意义（P ＜ 0.05）。 结论：重度肥胖患者行无痛胃镜检查应用 2.5 mg 或 5 mg 的盐酸纳布啡复合咪达唑仑均可有效镇静镇痛,体动发生情况少,但低剂量的盐酸纳布啡可减少并发症的发生,且利于患者苏醒。     

Differential effects of ethanol and midazolam upon the devaluation of an aversive memory in infant rats.

In infant rats, low doses of ethanol (EtOH) have been found to attenuate the aversive representation of an unconditioned stimulus (US) as assessed through a revaluation paradigm. This may be explained by early anxiolytic properties of EtOH. The present set of experiments was aimed at analyzing possible mechanisms of these putative antianxiety effects of EtOH. In the first experiment, EtOH's effects upon the expression of citric acid-induced distress calls were compared with varying doses of midazolam (MDZ), a fast-acting gamma-aminobutyric acid type A (GABA(A)) agonist. Similar calming effects of 0.5 g/kg EtOH and 0.09 mg/kg MDZ were observed. Both drugs were then assessed in their capability to alter the expression of a conditioned aversion by devaluing the US. Aversive conditioning was conducted on postnatal day 14 (PD14) by pairing a lemon odor (conditioned stimulus, CS) with intraoral stimulation of citric acid (US). Control animals experienced both stimuli in an explicitly unrelated fashion. On PD15, pups were briefly exposed to the citric acid solution under the effects of 0.5 g/kg EtOH, 0.09 mg/kg MDZ, or the respective vehicle for each drug. Pups were then tested in a two-way odor preference test (lemon vs. cineole). Both vehicle- and MDZ-treated animals spent significantly less time near the lemon CS, thus expressing a citric acid-mediated odor aversion. This conditioned response was completely inhibited in pups that received 0.5 g/kg EtOH. Locomotor patterns at test were not affected by either EtOH or MDZ administration. A higher dose of MDZ (0.18 mg/kg, intraperitoneal) was also ineffective in attenuating the aversive memory. In summary, EtOH's devaluating capabilities are not shared by MDZ, indicating that these effects of EtOH may not be GABA mediated. Appetitive motivational properties of EtOH or non-GABA(A)-mediated antianxiety effects [i.e., N-methyl-D-aspartic acid (NMDA) related] could underlie this devaluation effect of EtOH.     

Evaluation of the novel antiepileptic drug,AWD 131-138, for benzodiazepine-like discriminative stimulus and reinforcing effects in squirrel monkeys

AWD 131-138 [1-(4-chlorophenyl)-4-morpholino-imidazolin-2-one], a new low-affinity partial benzodiazepine receptor agonist with potent anticonvulsant and anxiolytic properties in rodent models, was studied in squirrel monkeys trained to discriminate intramuscular (i.m.) injections of midazolam (0.3 mg/kg) from injections of vehicle. Diazepam produced midazolam-like responding at cumulative doses of 1.0 and 3.0 mg/kg i.m. and decreased rates of responding at 3.0 mg/kg (plasma levels of about 400 ng/ml). In contrast, AWD 131-138 did not produce midazolam-like responding or alter response rates at cumulative doses up to 18.0 mg/kg i.m. (plasma levels over 2100 ng/ml). Other monkeys were trained to intravenously (i.v.) self-administer cocaine (56.0 microg/kg/injection). When AWD 131-138 (10-100 microg/kg/injection) was studied by substitution, responding declined to vehicle substitution levels within three sessions. At the dose of 100 microg/kg i.v. AWD 131-138, sufficient drug was self-administered during the first session (about 3.5 mg/kg) to produce plasma levels above 1000 ng/ml, yet responding over the next two sessions dropped to vehicle levels. The failure of AWD 131-138 to produce benzodiazepine-like discriminative effects and the absence of drug self-administration behavior when substituted for cocaine suggest that its abuse liability is low.     

咪达唑仑与芬太尼联合用于ICU机械通气患者镇静的临床观察

目的观察咪达唑仑与芬太尼联合用于ICU患者镇静的作用。方法对30例ICU机械通气患者给予咪达唑仑和芬太尼联合镇静,维持理想的镇静深度3～4级,观察各项镇静指标。结果镇静效率为(87±8.8)%,镇静期间咪达唑仑的平均输注速度为(0.14±0.02)mg/(kg.h)。镇静期间血压、心率平稳,且明显低于镇静前;镇静期间的血氧饱和度则明显高于镇静前。停药后完全清醒时间为(90±24.8)min,拔除气管插管时间为(140±36.6)min。拔管后1h血气正常。结论咪达唑仑与芬太尼联合用于ICU机械通气患者可获得满意的镇静效果。     

咪唑安定辅助硬膜外麻醉的临床观察

目的:比较咪唑安定与氟哌啶硬膜外辅助用药的作用.方法:40例病人随机分为二组,每组20例.麻醉完善后,组Ⅰ给予哌替啶1 mg/kg,加咪唑安定0.05mg/mg.组Ⅱ静注哌替啶1 mg/kg,加氟哌利多0.05mg/kg.结果:两组用药前与用药后5、10、15分钟平均动脉压心率均稍降,Ⅱ组比Ⅰ组明显.两组病人用药前与用药后5、10、15分钟呼吸SpO2均有一定程度的下降,且以Ⅱ组为著.结论:咪唑安定加哌替啶作为硬膜外麻醉辅助用药,无明显的呼吸及循环抑制作用,对术中镇静及对抗内脏牵拉反应有较为满意的作用.     

灯盏花素对大鼠CYP3A4体内活性的影响

目的以咪达唑仑作为探针药物,研究灯盏花素对大鼠细胞色素P450 3A4(CYP3A4)体内活性的影响,为临床合理用药提供参考。方法将SD大鼠随机分为3组,对照组、灯盏花素低剂量组和高剂量组。低剂量组和高剂量组每天分别尾静脉给予灯盏花素粉针剂0.18 mg/100 g及0.54 mg/100 g,共10 d,对照组给予生理盐水。各组分别于第11天注射咪达唑仑溶液,于给药前及给药后不同时间点眼内眦静脉取血0.8 ml,使用高效液相色谱(HPLC)法测定血浆中咪达唑仑的浓度。结果静脉给予大鼠灯盏花素粉针剂10 d后,与对照组相比,低剂量组和高剂量组咪达唑仑的AUC、MRT和tφ均显著高于对照组(P<0.05),CL显著低于对照组(P<0.05);灯盏花素高剂量组与低剂量组无显著性差异。结论灯盏花素可明显抑制大鼠CYP3A4的体内活性。     

丙泊酚、氯胺酮全凭静脉麻醉应用于烧伤病人的临床研究

目的:研究微量注射泵输注丙泊酚和氯胺酮全凭静脉麻醉在烧伤患者切痂植皮手术中的临床效果。方法:选择期手术患者,随机分为丙泊酚、氯胺酮组(P·K组)和咪达唑仑、氯胺酮组(M·K组)。P·K组术前10min首次静注丙泊酚2mg·kg和氯胺酮2mg·kg。M·K组术前10min首次静注咪达唑仑0 2mg·kg、氯胺酮2mg·kg ,随后两组以微量注射泵输注控制在P·K组丙泊酚6 6 . 6 6 μg·kg-1·min-1和氯胺酮4 1 .6 6 μg·Kg-1·min-1。记录注药后5、10min、切痂、取皮、植皮及停药后5、10min各时段无创血压(MAP)心率(HR)脉搏氧饱和度(SpO2 )及两组氯胺酮用药量变化。结果:P·K组氯胺酮用药量比M·K组少,P·K组MAP和HR无明显变化(P >0 . 0 5 ) ,M·K组MAP、HR均较麻醉前升高(P <0 . 0 1) ,两组SpO2 于诱导注药后均有一过性下降,数分钟恢复正常,两组比较差异无显著意义(P >0 . 0 5 )。结论:微量注射泵输注丙泊酚和氯胺酮全凭静脉麻醉安全可行,副作用小,可控性强,适用于烧伤患者切痂植皮手术。