咪达唑仑联合声门下吸痰对呼吸机相关性肺炎的临床价值

目的探讨静脉持续泵入咪达唑仑状态下经声门下吸痰在呼吸机相关性肺炎(ventilation-associated pneumonia,VAP)患者治疗中的临床应用价值。方法以2011年1月—2012年12月收治的共60例VAP患者为研究对象,按随机数字表法分为A组、B组、C组各20例。A组给予ICU常规物理治疗,包括翻身、叩背及常规吸痰(患者自主咳嗽基础上经口腔、鼻腔、人工气道声门上),B组给予ICU常规物理治疗包括翻身、叩背及经声门下吸痰,C组给予咪达唑仑持续静脉泵入下施予同B组相同的处理方法。计量资料采用单因素方差分析,多个实验组与一个对照组比较采用最小显著差法,多个实验组之间采用q检验,P0.05为差异有统计学意义。结果三组患者在治疗后第7天WBC、CRP、PaO2[A组(14.68±5.81)×10~9/L、(68.64±10.68)mg/L、(62.64±8.42)mm Hg(1 mm Hg=0.133 kPa),B组(13.78±4.54)×10~9/L、(72.48±12.13)mg/L、(64.80±8.85)mm Hg,C组(9.86±3.49)×10~9/L、(45.67±9.08)mg/L、(70.98±8.75)mm Hg]测定差异均有统计学意义(均P0.05),而PaCO2测定差异均无统计学意义(P0.05)。C组连续1周内吸痰时不良事件发生次数、机械通气天数[(28.38±2.57)次/周、(9.24±2.18)d]均明显低于A组[(38.68±4.87)次/周、(14.56±3.32)d]、B组[(35.45±3.36)次/周、(13.48±2.98)d],差异均有统计学意义(均P0.05)。结论静脉持续泵入适量咪达唑仑状态下未加重二氧化碳潴留,可增加患者对声门下吸痰的耐受性,二者配合作用下有助于肺内分泌物的排出,有利于VAP患者炎症指标的控制并可缩短机械通气治疗时间。     

小剂量氯氨酮和咪唑安定对减轻硬膜外腔穿刺痛和术后镇痛的效应

目的　研究硬膜外腔穿刺前应用小剂量氯氨酮和咪唑安定 ,观察其镇静和有无预先镇痛的效果及安全性。方法　 6 0例择期行硬膜外腔麻醉 (复合全身麻醉 )的上腹部手术病人 ,随机分为两组 :氯氨酮和咪唑安定组 (TM组 ) 30例 ,手术前 1 5 min静脉给予氯氨酮 0 .3m g/ kg和咪唑安定 1 mg,用药 5 min后施行硬膜外腔穿刺 ,继之持续静脉输注氯按酮 3μg· kg- 1 · min- 1 和咪唑安定 0 .1μg· kg- 1 · min- 1 至手术结束前 1 5 min;对照组 (NS组 ) 30例静脉注射同等容量的生理盐水。患者术后均采用自控硬膜外镇痛 (PCEA) ,观察两组用药后 1 min、3min和 5 min时的镇静程度 (Ramsay分级评分 ) ,血压、心率、呼吸频率和脉搏血氧饱和度和术后 3、6、1 2、2 4、4 8h随访 PCEA用量、视觉模拟镇痛评分 (VAS)及患者有无精神异常。结果　TM组术后 3h和 6 h PECA用量显著少于 NS组 ,VAS评分明显低于NS组 ,Ramsay氏评分明显高于 NS组 ,其它监测指标均在正常范围 ,两组未有精神异常发生。结论　硬膜外腔穿刺前 ,预先静脉注射小剂量氯氨酮和咪唑安定 ,可明显减轻硬膜外穿刺痛 ,提高术后早期 PCEA镇痛质量 ,安全可靠     

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.     

HPLC法测定人血浆中咪达唑仑的浓度

目的:建立以高效液相色谱法测定人血浆中咪达唑仑浓度的方法。方法:以安定为内标,色谱柱为Agilent Eclipse XDB C18,流动相为0.02mol·L-1NaH2PO4水溶液(pH7.6,内含0.02%三乙胺)-乙腈(52∶48),流速为1.0mL.min-1,检测波长为223nm,灵敏度为0.001AUFS,进样量为50μL,柱温为40℃。结果:咪达唑仑血浆浓度在10~1 600ng·mL-1范围内线性关系良好(r=0.999 1),最低检测限为1ng·mL-1;日内、日间RSD≤7.25%。结论:本方法简便、灵敏、准确、快速,检测范围广,可用于咪达唑仑的血药浓度监测及临床药动学研究。     

右美托咪定与咪达唑仑对依托咪酯全麻诱导时肌阵挛影响的对比研究

目的：对比观察右美托咪定与咪达唑仑预处理对依托咪酯诱导时肌阵挛的影响。方法：选择120例ASA为Ⅰ~Ⅱ级妇科全麻手术患者,随机分为右美托咪定组、咪达唑仑组和对照组,每组各40例;分别静注右美托咪定0.5μg/kg（4μg/ml）、咪达唑仑0.03 mg/kg（0.24 mg/ml）和等量（0.125 ml/kg）生理盐水（5 min注射完毕）。5 min后,静脉注射依托咪酯0.3 mg/kg（1 min注射完毕）,观察并记录有无肌阵挛发生及肌阵挛的严重程度。结果：右美托咪定组和咪达唑仑组分别经静脉预先注射0.5μg/kg和0.03 mg/kg后,再给予依托咪酯诱导时肌阵挛的发生率分别为5%和7.5%,而对照组肌阵挛的发生率为55%,差异有统计学意义（P〈0.01）。结论：以右美托咪定0.5μg/kg和咪达唑仑0.03 mg/kg预处理都可明显降低依托咪酯诱导时肌阵挛的发生率,且两者预处理的效果相当。右美托咪定在辅助麻醉方面具有镇静、镇痛,减少麻醉剂用量、稳定血流动力学、无呼吸抑制等特点,更适合与依托咪酯联合使用作为全麻诱导用药。     

咪达唑仑持续静脉维持治疗儿童癫(癎)持续状态副作用观察

目的观察咪达唑仑持续静脉维持治疗癫持续状态(SE)的副作用。方法应用咪达唑仑持续静脉维持治疗SE患儿38例,开始静脉注射0.1～0.2mg/kg,随后以0.1～0.4mg/(kg.h)持续静脉维持,根据发作状态调整剂量大小。结果26例SE患儿应用咪达唑仑维持治疗后癫发作停止。2例患儿因基础疾病死亡。副作用主要有呼吸道分泌物增多、下呼吸道感染、心率增快、意识障碍及尿潴留等。未见明显致死性副作用发生。结论应用咪达唑仑治疗SE安全有效。     

Effects of hydroxysafflor yellow A on the activity and mRNA expression of four CYP isozymes in rats

Ethnopharmacological relevance

In traditional therapy with Chinese medicine, hydroxysafflor yellow A (HSYA), a main active component isolated from the dried flower of Carthamus tinctorius L., is the principal efficiency ingredient of Safflor Yellow Injection. Now HSYA has been demonstrated to have good pharmacological activities of antioxidation, myocardial and cerebral protective and neuroprotective effects. The purpose of this study was to find out whether HSYA influences the effect on rat cytochrome P450 (CYP) enzymes (CYP1A2, CYP2C11, CYP2D4 and CYP3A1) by using cocktail probe drugs in vivo; the influence on the levels of CYP mRNA was also studied.

Materials and methods

A cocktail solution at a dose of 5 mL/kg, which contained phenacetin (20 mg/kg), tolbutamide (5 mg/kg), dextromethorphan (20 mg/kg) and midazolam (10 mg/kg), was given as oral administration to rats treated with short or long period of intravenous HSYA via the caudal vein. Blood samples were collected at a series of time-points and the concentrations of probe drugs in plasma were determined by HPLC–MS/MS. The corresponding pharmacokinetic parameters were calculated by the software of DAS 2.0. In addition, real-time RT-PCR was performed to determine the effect of HSYA on the mRNA expression of CYP1A2, CYP2C11, CYP2D4 and CYP3A1 in rat liver.

Results

HSYA had significant inhibition effects on CYP1A2 and CYP2C11 in rats as oriented from the pharmacokinetic profiles of the probe drugs. Furthermore, HSYA had no effects on rat CYP2D4. However, CYP3A1 enzyme activity was induced by HSYA. The mRNA expression results were in accordance with the pharmacokinetic results.

Conclusions

HSYA can either inhibit or induce activities of CYP1A2, CYP2C11 and CYP3A1. Therefore, co-administration of some CYP substrates with HSYA may need dose adjustment to avoid an undesirable herb–drug interaction.     

口服、肌注与鼻腔内给咪达唑仑对小儿七氟烷麻醉恢复期躁动的影响

目的 对口服、肌注与鼻腔内给咪达唑仑对小儿七氟烷麻醉恢复期躁动的影响进行分析.方法 选取在本院行扁桃体联合腺样体切除术治疗的患儿76例,按照随机数字表法将本批患者分为4组,分别为对照组(C组)、肌内注射咪达唑仑组(IM组)、鼻腔内给予咪达唑组(IN组)以及口服咪达唑仑组(0组),每组19例.C组在麻醉前30 min口服10％葡萄糖溶液10 ml,lM组、O组、IN组咪达唑仑剂量分别为0.15、0.45、0.25 mg·kg-1,利用七氟烷进行相应的麻醉诱导,并在静脉注射相应的瑞芬太尼以及七氟烷对其麻醉效果给与维持.对脱离父母的难易程度以及父母的满意度进行评分,EA发生情况采用患儿麻醉恢复期躁动表化评分表(PAED)进行评估.结果 C组(1分:17例;2分:2例;3分:0例;4分:0例)与O组(1分:0例;2分:15例;3分:4例;4分:0例)、IN组(1分:0例;2分:6例;3分:13例;4分:0例)以及IM组(1分:0例;2分:7例;3分:12例;4分:0例)相比,其在脱离父母难易程度、父母满意度所获评分提升,其相应的PAED评分及EA的发生率均降低(均P＜ 0.05);与0组相比,其相应的脱离父母难易程度上的评分明显升高,在父母的满意度方面的评分降低(均P＜ 0.05),其在EA发生率以及PAED的评分上差异均无统计学意义(均P＞0.05).结论 通过口服、肌注与鼻腔内给相应的咪达唑仑,对于预防小儿七氟烷EA的发生在效果上具有相似之处,并且通过口服的方式用药更容易被接受.     

地佐辛复合右美托咪定在清醒患者纤维支气管镜气管插管术中的应用

目的 探讨地佐辛复合右美托咪定在重症医学科清醒患者纤维支气管镜气管插管术中的镇痛镇静效果及安全性.方法 将本科2015年1月至2016年12月180例需行气管插管机械通气的清醒患者采用随机数字表法分为A、B、C三组,各60例.A组静脉泵注咪达唑仑0.1 mg/kg;B组静脉泵注地佐辛0.1 mg/kg+咪达唑仑0.05 mg/kg;C组静脉泵注地佐辛0.1 mg/kg+右美托咪定1μg/kg.观察并比较插管前(T1)、插管时(T2)、插管后10 min(T3)患者心率(HR)、呼吸频率(RR)、平均动脉压(MAP)、指端血氧饱和度(SpO2)以及插管过程中患者躁动情况(MAAS评分)、气管插管后10 min患者的镇静效果(Ramsay评分)、转入时疾病严重程度评分(APACHEⅡ评分).结果 3组T3时间点HR均较T1时间点显著下降[A组:(99.0±5.2)次/min比(101.2±7.6)次/min,P＜0.05;B组:(97.3±6.1)次/min比(103.0±9.5)次/min,P＜0.05;C组:(94.4±7.2)次/min比(100.0±8.8)次/min,P＜0.05].3组RR在T2时间点均较同组T1时间点显著下降[A组:(27.1±2.6)次/min比(28.5±3.6)次/min,P＜0.05;B组:(26.3±2.8)次/min比(28.1±3.3)次/min,P＜0.05;C组:(25.1±3.5)次/min比(27.6±3.1)次/min,P＜0.05].B组T3时间点MAP较同组T1、T2时间点下降[(71.2±8.8) mmHg(1 mmHg=0.133 kPa)比(74.3±8.0) mmHg,P＜0.05;(71.2±8.8) mmHg比(74.3±8.8) mmHg,P＜0.05].C组T2时间点MAP较同组T1、T3时间点下降[(68.4±8.1) mmHg比(73.2±6.3),P＜0.05;(68.4±8.1) mmHg比(72.8±7.6) mmHg,P＜0.05].T1时间点,3组HR、RR、MAP差异无统计学意义(均P＞0.05).T2时间点,C组MAP较A、B两组显著下降[(68.4±8.1)mmHg比(73.6±8.6),P＜0.05;(68.4±8.1) mmHg比(74.3±8.8) mmHg,P＜0.05].T3时间点,C组HR较A、B两组显著下降[(94.4±7.2)次/min比(99.0±5.2)次/min,P＜0.05;(94.4±7.2)次/min比(97.3±6.1)次/min,P＜0.05].插管过程中B、C两组MAAS评分均显著低于A组[(3.2±1.0)比(3.9±1.0),P＜ 0.05;(3.0±1.0)比(3.9±1.0),P＜0.05],但B、C组间差异无统计学意义(P＞0.05).气管插管后10 min,A组Ramsay评分显著低于B、C两组[(2.4±0.9)比(2.7±0.9),P＜0.05;(2.4±0.9)比(2.8±0.9),P＜0.05],但B、C两组比较差异无统计学意义(P＞0.05).结论地佐辛复合咪达唑仑或右美托咪定较单纯使用咪达唑仑可显著改善清醒患者气管插管的耐受性并提高镇静效果;地佐辛复合右美托咪定用于清醒患者气管插管镇痛镇静效果确切.     

右美托咪定或咪达唑仑复合0.375%左旋布比卡因对超声引导下臂丛神经阻滞效果比较

目的 比较右美托咪定或咪达唑仑加入0.375%左旋布比卡因用于超声引导下臂丛神经阻滞效果。方法 选择2014年1月至2016年12月皖北煤电集团总医院行前臂或手部手术的ASAⅠ～Ⅱ级患者120例,随机分为3组,每组40例。左旋布比卡因组（L组）接受0.375%左旋布比卡因30 mL,左旋布比卡因+咪达唑仑组（LM组）接受0.375%左旋布比卡因30 mL+咪达唑仑（50 μg/kg）,左旋布比卡因+右美托咪定组（LD组）接受0.375%左旋布比卡因30 mL+右美托咪定（1 μg/kg）。评估痛觉和运动阻滞起效时间、痛觉和运动阻滞维持时间、镇痛时间以及不良反应。结果 3组患者的痛觉、运动阻滞起效时间、维持时间、镇痛时间差异有统计学意义（P<0.05）。与L组相比,LM组和LD组痛觉、运动阻滞起效时间缩短,痛觉、运动阻滞维持及镇痛时间延长,差异有统计学意义（P<0.05）。与LM组相比,LD组痛觉、运动阻滞起效时间缩短,痛觉、运动阻滞维持及镇痛时间延长,差异有统计学意义（P<0.05）。LM组患者的Ramsay镇静评分高于LD组,但差异无统计学意义（P>0.05）。3组患者的不良反应发生率差异无统计学意义（P>0.05）。结论 右美托咪定、咪达唑仑复合左旋布比卡因用于超声引导下臂丛神经阻滞中,能缩短痛觉、运动阻滞起效时间,延长痛觉和运动阻滞维持时间及镇痛时间。相比咪达唑仑,右美托咪定的效果更好。