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。     

不同浓度的咪唑安定对兔离体气管平滑肌收缩的影响

目的研究不同浓度的咪唑安定对离体气管平滑肌的舒张作用,以明确咪唑安定在10-5mol/L浓度时是否能够产生较为明显的舒张作用。方法用高浓度氯化钾、乙酰胆碱、电脉冲三种刺激因素诱发兔离体气管平滑肌收缩,并观察三种不同浓度的咪唑安定对其的影响。结果1.5×10-5mol/L的咪唑安定对三种刺激因素诱发的气管平滑肌收缩不产生明显抑制作用;1.5×10-4mol/L和3.0×10-4mol/L的咪唑安定可显著抑制上述三种刺激因素诱发的气管平滑肌收缩(P<0.05或P<0.01),普萘洛尔和中枢性苯二氮卓艹类受体阻断药氟马西尼不能拮抗咪唑安定对气管平滑肌的舒张作用。结论咪唑安定在10-5mol/L左右的浓度时对兔离体气管平滑肌收缩不能产生明显的抑制作用。     

Benzodiazepine ligands,nociception and ‘defeat’ analgesia in male mice

Recent studies have indicated that defeat experience induces acute non-opioid analgesia in intruder mice. To investigate the potential involvement of benzodiazepine receptors in this biologically-relevant form of environmentally-induced antinociception, we initially assessed the effects of some benzodiazepine ligands on basal nociception (tail-flick assay). Chlordiazepoxide (5–30 mg/kg), midazolam (0.625–5 mg/kg), diazepam (0.5–4 mg/kg), Ro15-1788 (5–80 mg/kg) and CGS8216 (5 mg/kg) were found to be ineffective in altering basal nociception. However, higher doses of CGS8216 (10–20 mg/kg) induced significant analgesia, an effect also observed with the -carboline derivatives FG7142 (5–20 mg/kg) and DMCM (1–2 mg/kg). Time-course analyses revealed that the onset of CGS8216 analgesia was slower than for FG7142 and DMCM, but that all three drugs produced long-lasting elevations in tailflick latencies. The analgesic effects of FG7142 and DMCM were completely reversed by Ro15-1788 (20 mg/kg) and by chlordiazepoxide (20 mg/kg), suggesting mediation by benzodiazepine receptor mechanisms. Although CGS8216 analgesia was also reversed by Ro15-1788, it was unaffected by chlordiazepoxide; however, diazepam (5 mg/kg) did significantly attenuate the reaction. Further studies indicated that the antinociceptive consequences of defeat experience were dose-dependently blocked by Ro15-1788 (10–40 mg/kg) and by diazepam (0.5–2 mg/kg). Surprisingly, however, neither chlordiazepoxide (5–20 mg/kg) nor midazolam (1.25–2.5 mg/kg) blocked defeat analgesia under present test conditions. Although several issues remain unresolved, present findings would not be inconsistent with the proposal that stimuli associated with the acute stress of defeat experience release an endogenous ligand which acts in an inverse agonist-like manner at benzodiazepine sites.     

咪达唑仑对剖宫产术初产妇情绪和记忆的影响

目的 探讨咪达唑仑对剖宫产手术产妇情绪和记忆的影响.方法 72例择期剖宫产术产妇随机分成4组,Ⅰ、Ⅱ和Ⅲ组麻醉前30 min分别肌注咪达唑仑0.05、0.06和0.07 mg/kg,Ⅳ组肌注生理盐水1.5 ml,同时肌肉注射阿托品0.01 mg/kg.于注药前和注药后30 min进行焦虑视觉类比试验(AVAT)、状态焦虑问卷(SAI)测试及Ramsay镇静水平评估.将麻醉准备到手术结束过程分为5阶段,每项告知产妇,记录剖宫产术后4 h产妇能准确回忆的项目.结果 注药后30 min时,Ⅰ～Ⅲ组AVAT分别下降36.4%、43.2%和43.1%;SAI分别下降20.9%、24.8%和26.9%,均获得Ramsay 2～4级镇静水平.Ⅰ～Ⅲ组和Ⅳ组比较记忆保留组间差异均有统计学意义(P均＜0.01).Ⅰ～Ⅲ组以遗忘静脉穿刺过程的居多,4组产妇对椎管内麻醉穿刺和新生儿娩出后性别识别两过程全部记忆完觋整.结论 剖宫产手术前给予咪达唑仑0.05～0.07 mg/kg,对产妇有良好的镇静和抗焦虑作用,对外显记忆有一定程度的影响,其中对信息量小和关注程度低的信息能产生顺行性遗忘作用,能保留信息量大和关注程度高的信息的完整记忆.     

Defensive reactions are counteracted by midazolam and muscimol and elicited by activation of glutamate receptors in the inferior colliculus of rats

 The inferior colliculus is involved in conveying auditory information of an aversive nature to higher cortical structures. Gradual increases in the electrical stimulation of this structure produce progressive aversive responses from vigilance, through freezing, until escape. Recently, we have shown that microinjections of NMDA into the inferior colliculus mimic these aversive effects and that the neural substrates responsible for learned escape behavior in the inferior colliculus are regulated by GABA−benzodiazepine mechanisms. In the present study, we extend these observations showing that unlearned aversive responses are also depressed by muscimol and midazolam, both GABA-benzodiazepine agonists, and that microinjection of glutamate, an excitatory amino acid, into the inferior colliculus can trigger freezing responses. Electrical stimulation of the inferior colliculus of rats placed inside an open field allowed the determination of thresholds for the aversive responses, alertness, freezing and escape. Systemic administration (3 and 5.6 mg/kg) as well as microinjections into the inferior colliculus of the anxiolytic compound midazolam (10, 20 and 40 nmol) caused increases in threshold for these aversive responses. Similar results were obtained following microinjections of the GABA-A agonist muscimol (0.1, 1 and 5 nmol) into this brainstem structure. Microinjections of low doses of glutamate (5 nmol), presumed to activate mainly AMPA/kainate receptors, into the ventrolateral division of the central nucleus of the inferior colliculus of rats placed inside a circular arena induced aversive reactions, characterized by freezing responses. However, higher doses of glutamate caused no apparent effects. GDEE, an AMPA/kainate receptor antagonist, inhibited, whereas AP7, a NMDA receptor antagonist, did not influence these responses. It is suggested that GABA-benzodiazepine processes modulate the expression of defensive reactions in the inferior colliculus and that activation of fast-acting excitatory amino acid receptors in this midbrain region can trigger the initial steps of the defense reaction without eliciting the motor explosive behavior usually seen following the activation of NMDA receptors. Received: 13 May 1998 / Final version: 12 August 1998     

Lack of accumulation of midazolam in plasma and lipoprotein fractions during intravenous lipid infusions in patients on artificial respiration

Summary Severely ill patients often require total parenteral nutrition including intravenous liqid emulsions concurrently administered with lipophilic drugs. Therefore we investigated whether therapeutic application of a mixed medium chain/long chain triglyceride infusion affects the disposition of midazolam necessary for sedation in patients on artificial respiration. The concentrations of midazolam were measured in unfractionated plasma, and in lipoprotein fractions isolated from ex vivo blood samples, including determination of triglycerides and cholesterol; the albumin level was also analysed.Midazolam in the VLDL fraction was only 0.246 g·ml^–1, whereas the total plasma concentration averaged 1.101 g·ml^–1, and the midazolam content of the LDL plus HDL fractions amounted to 1.771 g·ml^–1. Albumin in these lipoprotein fractions was just as unequally distributed. A lipid infusion resulted in a significant elevation of total triglycerides from 157 to 221 mg·dl^–1 and VLDL-triglycerides from 77 to 155 mg·dl^–1. The triglyceride content of the LDL plus HDL fraction rose from 102 to 139 mg·dl^–1. At the same time the midazolam concentration in unfractionated plasma and in the VLDL and the LDL + HDL fractions decreased to 0.899 g·ml^–1, 0.130 g·ml^–1, and 1.265 g·ml^–1, respectively. Cholesterol and albumin concentrations were not affected.The data show for the first time that a significant increase in plasma triglycerides during an intravenous lipid infusion does not result in accumulation of midazolam in lipoproteins, probably because albumin binding of the drug is very strong. The lack of midazolam trapping is important with respect to the safety of concurrent use of lipophilic drugs and intravenous lipid infusions.     

Clinical experience with continuous intravenous sedation using midazolam and fentanyl in the paediatric intensive care unit

Twenty-four patients in a paediatric intensive care unit mostly undergoing cardiac surgery, received a midazolam dosage between 50–400 g/kg per hour as a continuous intravenous infusion partly in combination with fentanyl [0,5–2,5 g/kg per hour] for analgesia and sedation. The mean duration of midazolam infusion was 11.6 days (range 38h–40 days). Blood samples for the HPLC assay of serum midazolam concentration were taken and the clearance estimated. The efficiency of sedation in correlation to the midazolam concentration was evaluated by a clinical sedation score. Serum midazolam concentrations between 100–400 g/l were sufficient for sedation. Dosage had to be increased during therapy according to an increased midazolam clearance. The evaluation of the sedation score showed that sedation of artifically ventilated infants and young children can be established by continuous intravenous infusion of midazolam.Dedicated to the 65th birthday of Prof.Dr. Erich Gladtke     

不同静脉和吸入麻醉药对罗库溴铵肌肉松弛作用的影响

目的：研究不同静脉和吸入麻醉药对罗库溴铵肌肉松弛作用的影响。方法：５０例病人分为５组，观察并比较了静脉麻醉药咪唑安定、异丙酚和吸入麻醉药（１．２ＭＡＣ）安氟醚、异氟醚和七氟醚对罗库溴铵肌肉松弛作用的影响，以及罗库溴铵对血流动力学的影响。结果：肌松作用起效时间５组间无显著差异，平均为４４．５～４９．１秒。其临床维持时间、７５％恢复时间和恢复指数三种吸入麻醉药组均显著长于两种静脉麻醉药组（Ｐ＜０．０１），而三种吸入麻醉药组间和两种静脉麻醉药组间则无显著差异。咪唑安定组和异丙酚组的肌松作用临床维持时间平均为３６．２～４１．５分钟。罗库溴铵静脉给药后血压、心率维持平稳。结论：罗库溴铵具有起效快、中等作用维持时间和血流动力学稳定的特点，但与高浓度吸入麻醉药合用可使其作用时间明显延长。     

The hedonic impact and intake of food are increased by midazolam microinjection in the parabrachial nucleus

Benzodiazepines have been reported to induce eating when administered into the brainstem of rats (either the fourth ventricle or the parabrachial nucleus). Benzodiazepines in the brainstem also have been reported to enhance the hedonic impact of taste, as measured by hedonic/aversive taste reactivity patterns, when administered to the fourth ventricle. The present study examined whether the parabrachial nucleus in particular is a brainstem site of the benzodiazepine-produced enhancement of eating and palatability. Food intake (cereal mash) was measured after brainstem microinjections of midazolam or vehicle (0.0, 7.5, and 15.0 microg) into the parabrachial nucleus, the nucleus of the solitary tract, the pedunculopontine tegmental nucleus, or the fourth ventricle (60 microg). We used the taste reactivity paradigm to measure hedonic/aversive affective reactions elicited from rats by oral infusions of a bittersweet solution (7% sucrose-0.01% quinine). Positive hedonic reactions and negative aversive reactions to sucrose-quinine were also measured after microinjections of midazolam (0.0, 7.5, and 15 microg) into the parabrachial nucleus. Midazolam increased food intake and selectively enhanced positive hedonic taste reactivity patterns to the bittersweet solution when microinjections were delivered to the parabrachial nucleus. When administered to the other brainstem sites at the same doses, however, midazolam had no effect. We therefore conclude that the parabrachial nucleus can mediate the benzodiazepine-induced enhancement of the hedonic impact of taste as well as mediating the enhancement of eating behavior.