Traitement pharmacologique de l’état de mal réfractaire

Status epilepticus (SE) refractory to benzodiazepines and other antiepileptic agents is managed with intravenous anesthetic compounds, such as thiopental, propofol or midazolam. These drugs display quite different pharmacodynamic and pharmacokinetic properties, but have not been prospectively compared to date. Their use is clearly advocated for the treatment of generalized convulsive SE, whereas partial-complex, or absence SE are generally managed less aggressively, in consideration of their better prognosis. The most important aspect seems to be related to the correct use of these anesthetics in the right context, rather than the choice of one specific compound. An electroencephalographic burst-suppression should be targeted for about 24 hour, before progressive weaning of the dosage under EEG monitoring. If this approach proves unsuccessful, the use of other drugs, including inhalational anesthetics, has been described.     

咪达唑仑用于新生儿机械通气镇静的疗效观察

目的比较咪达唑仑与鲁米那和(或)地西泮在新生儿机械通气治疗中的镇静效果。方法将2005年1月至2006年12月机械通气治疗中应用鲁米那和(或)地西泮的新生儿20例(对照组)与2007年1月至2008年12月应用咪达唑仑的新生儿25例(治疗组)进行对比,比较两组的镇静效果、脱机时间。结果治疗组25例达理想镇静22例(88%),非理想镇静3例(12%),对照组20例达理想镇静12例(60%),非理想镇静8例(40%),差异有显著性。治疗组脱机时间(80.2±32.3)h,对照组脱机时间(103.5±16.9)h,差异有显著性。治疗组无明显不良反应。结论在新生儿机械通气过程中应用咪达唑仑1～5μg/(kg.h)持续微量输液泵静脉滴注,与鲁米那和(或)地西泮相比,咪达唑仑具有镇静效果好、脱机时间短、停药后苏醒快的优点。     

咪达唑仑和芬太尼用于腰硬联合麻醉镇静的临床观察

目的：观察不同剂量咪达唑仑加芬太尼用于腰硬联合麻醉镇静的临床效果。方法：80例ASAⅠ～Ⅱ级下腹部手术患者随机分为Ⅰ、Ⅱ、Ⅲ、Ⅳ4组,分别采用0．02、0．04、0．06和0．08mg／kg咪达唑仑辅助芬太尼0．001mg／kg进行腰硬联合麻醉镇静,以改良警觉／镇静评分法（OAA／S）记录给药不同时间患者的镇静程度、遗忘程度,观察术中患者生命体征的变化。结果：给药后5minⅠ组、Ⅱ组OAA／S评分明显高于Ⅲ组、Ⅳ组（P〈0．05）,给药后10、30、60minⅠ组OAA／S评分明显高于Ⅱ、Ⅲ、Ⅳ组（P〈0．05～0．01）。给药后30minⅡ、Ⅲ、Ⅳ组遗忘作用均优于Ⅰ组,Ⅲ、Ⅳ组优于Ⅱ组（P〈0．05）,给药后120minⅢ、Ⅳ组遗忘作用优于Ⅰ、Ⅱ组（P〈0．05）。镇静、遗忘程度依次为Ⅳ组〉Ⅲ组〉Ⅱ组〉Ⅰ组。4组各生命体征指标差异无统计学意义（P〉0．05）,均未发生严重的血压下降,Ⅳ组呼吸抑制发生率最高。结论：0．04～0．06mg／kg咪达唑仑辅助0．001mg／kg芬太尼较适用于腰硬联合麻醉的镇静、遗忘剂量。     

Stress-induced hyperthermia is reduced by rapid-acting anxiolytic drugs independent of injection stress in rats

Background

Stress-induced hyperthermia (SIH) is the transient rise in body temperature after encountering a stressor. The SIH response can be blocked by administration of various anxiolytic drugs prior to inducing stress. However, a drug injection involves handling and injection stress and therefore induces a SIH response itself. In the standard SIH test, drugs are therefore injected 60 min before stress induction to allow injection-induced hyperthermia to decline. This makes it difficult to study putative anxiolytic compounds with a short half-life. The present study therefore aimed to compare the effects of standard (stressful) and stress-free anxiolytic drug administration on the subsequent SIH response with a 10-minute injection-stressor interval.

Methods

Anxiolytic drugs with short half-lives (midazolam, 8-OH-DPAT, nicotine) were injected subcutaneously in rats using either a stressful (manual injection) or stress-free injection (subcutaneous cannula) method 10 min before novel cage stress. Body temperature and locomotor activity were measured using telemetric transmitters.

Results

Stressful and stress-free drug administration resulted in comparable drug effects on the stress-induced hyperthermia and locomotor responses in rats.

Conclusion

The present study shows that both stressful and stress-free drug injection shortly before a stressor results in reproducible attenuation of the SIH response in rats. In rats, a short injection-stressor interval can therefore be applied using the SIH model, enabling the study of putative anxiolytic drugs with short half-lives.     

A preclinical model of binge eating elicited by yo-yo dieting and stressful exposure to food: effect of sibutramine,fluoxetine, topiramate,and midazolam

Rationale  Preclinical models are needed to investigate the neurobiology and psychobiology of binge eating and to identify innovative pharmacotherapeutic strategies. Objectives  A modification of the model based on the combination of cyclic caloric restrictions and acute stress was developed to further increase its face validity and reliability and, for the first time, to assess its predictive value. Materials and methods  Four groups of female rats were employed: group 1 was normally fed and not stressed on the test day (25th); group 2 was fed normally but was exposed to an acute stress on day 25; group 3 was exposed to three cycles (4 days 66% of chow intake + 4 days food ad libitum) of yo-yo dieting but not stressed; and group 4 was exposed to cyclic yo-yo dieting and then stressed. All groups were fed highly palatable food (HPF) for 2 h on days 5–6 and 13–14. Acute stress was elicited by exposing rats to HPF, but preventing them from access to it for 15 min. Results  The combination of cyclic food restriction and stressful exposure to food markedly increased HPF intake. Sibutramine and fluoxetine inhibited food intake in all conditions. Topiramate selectively inhibited compulsive HPF intake in rats submitted to caloric restriction and stress. Midazolam increased HPF intake. Conclusions  Pharmacological results suggest that this model, in addition to face validity as an isomorphic model of human binge eating, is endowed with good predictive validity.     

咪达唑仑对顺铂诱发猫呕吐的预防作用

目的 探讨咪达唑仑预防顺铂诱发猫恶心、呕吐的效果.方法 健康杂种家猫18只,随机分为3组：单纯模型组（顺铂组,C组）、格拉斯琼组（G组）和咪达唑仑组（M组）,每组6只,分别静注生理盐水3ml、格拉斯琼0.15mg/kg和咪达唑仑0.50mg/kg,20min后顺铂3mg/kg腹腔注射.观察动物镇静程度和10h内恶心、呕吐情况.结果 顺铂能诱发猫产生严重的恶心、呕吐反应;G组和M组猫干呕潜伏期延长,恶心、呕吐次数减少（P＜0.01）.结论 猫静脉注射咪达唑仑0.5 mg/kg能预防顺铂诱发的恶心、呕吐.     

鞘内注射咪唑安定对福尔马林致痛大鼠镇痛作用ED50的测定

目的：研究在福尔马林致痛大鼠模型鞘内注射咪唑安定镇痛作用的半数有效剂量（ED50）及其对痛行为的影响。方法：选择鞘内成功置管的雄性SD大鼠32只,随机分为4组（n=8）：对照组（C组）、生理盐水组（NS组）、致痛前给药组（M1组）及致病后给药组（M2组）。鞘内置管后5d,NS组、M1组及M2组大鼠于左后足掌部皮下注射5％福尔马林100μL致痛,致痛前10min,NS组鞘内注射20μL生理盐水,MI组鞘内注射咪唑安定22μg,C组鞘内注射20μL生理盐水,足底注射100μL生理盐水作为对照。采用大鼠缩腿、舔爪时间之和作为行为学观察指标。结果：NS组、M1组与M2组第二相缩腿、舔瓜累计时间显著长于C组（P〈0．01）;M1组与M2组的缩腿、舔爪累计时间短于NS组（P〈0．01）;且M1组短于M2组（P〈0．01）。结论：在福尔马林致病大鼠模型中鞘内注射咪唑安定镇痛作用的ED50为21．8μg,咪唑安定具有超前镇痛效应。     

Low-dose fentanyl and midazolam in outpatient surgical abortion up to 18 weeks of gestation

Background

We investigated the safety of a conscious sedation protocol using intravenous fentanyl and midazolam by direct venous injection in women who underwent outpatient surgical abortion up to 18 weeks of gestation.

Study Design

This retrospective cohort study evaluated 1433 abortion procedures performed on women who received intravenous conscious sedation between April 1, 2001, and December 31, 2006. Women were allowed oral intake before the procedure. De-identified data were abstracted from charts using a standardized extraction form. Primary outcomes evaluated were need for reversal agents, need to obtain emergency intravenous access, pulmonary aspiration, need for oxygen supplementation and hospitalization for any reason.

Results

Of the 1433 procedures, 410 women received sedation with continuous intravenous access, and 1023 women received sedation by direct venous injection. More than 95% of women received fentanyl 100 mcg combined with 1-2 mg of midazolam. We identified four (0.3%) instances of adverse events, none of which occurred as a result of oversedation. No women experienced oral content aspiration.

Conclusions

Intravenous conscious sedation with fentanyl and midazolam is safe for outpatient surgical abortion in women without cardiovascular compromise up to 18 weeks of gestation. The risk of aspiration or oversedation requiring reversal agents is rare and does not warrant universal direct venous access or restriction of oral intake.     

丙泊酚和咪唑安定用于重症监护室患者的观察

目的观察丙泊酚和咪唑安定对ICU呼吸机治疗患者的镇静效果,为危重患者镇静用药提供依据。方法选择在ICU呼吸机治疗的患者40例,随机分为两组。丙泊酚组21例,先静注丙泊酚1．5mg／kg镇静诱导,然后改用微量注射泵持续注射丙泊酚,根据Ramsay氏分级标准调整用量;咪唑安定组19例,先静注咪唑安定0．05mg／kg镇静诱导,然后改用微量注射泵持续注射咪唑安定,根据不同镇静分级调整用量。分别记录Ramsay氏分级Ⅲ～Ⅵ级时的用药量及用药前后、苏醒时的心率、血压、脉搏血氧饱和度和停药后苏醒时间,停药后再入睡和恶心发生情况。结果两组患者随镇静程度的加深而用药量增加,但呼吸、循环无明显抑制。丙泊酚组较咪唑安定组苏醒时间快,且苏醒后再入睡及出现恶心患者明显减少。结论丙泊酚和咪唑安定都能达到ICU患者所需的镇静要求。丙泊酚苏醒快,且苏醒后再入睡和恶心的发生明显少于咪唑安定。     

HPLC法测定人体内咪达唑仑血药浓度

目的建立人体血浆中同时测定咪达唑仑HPLC测定法。方法采用HPLC法,色谱柱为Hypersil ODS C18柱(250mm×4.6mm,5μm),流动相为甲醇:水(60:40)(含0.1%二乙胺,0.05%磷酸溶液),流速为1.0ml/min,柱温为室温,检测波长225nm。结果咪达唑仑在0.25~4μg/ml内呈良好的线性关系(r=0.9997),咪达唑仑最低检测浓度为50ng/ml,回收率96.81%~100.98%,萃取回收率87.69%~92.99%。日内、日间RSD(n=3)均小于5.89%。结论本方法简便、准确,可靠,可用于人体血浆中测定咪达唑仑的浓度。