小剂量氯氨酮复合芬太尼术后静脉镇痛在老年病人中的应用

目的观察小剂量氯氨酮复合芬太尼术后静脉镇痛应用于老年病人的临床效果和并发症,并与单纯芬太尼进行比较。方法选择行胸腹部手术后老年(年龄≥65岁)患者80例,随机分为两组,每组40例。氯氨酮-芬太尼组(联合组):氯氨酮0.5mg/ml 芬太尼5.0μg/ml 咪唑安定50μg/ml;单纯芬太尼组:芬太尼7.5μg/ml 咪唑安定50μg/ml。各组镇痛泵中药物均用生理盐水稀释至200ml。观察各组患者术后镇痛48h内的静息镇痛评分、镇静评分以及恶心呕吐、皮肤瘙痒、幻觉的发生情况。结果两组用药总量及PCA量均相似(P>0.05)。两组术后各时段静息镇痛评分均无显著性差异(P>0.05)。联合组在各时段的镇静效果明显地优于单纯芬太尼组(P<0.05)。在术后镇痛48h内,联合组的恶心、呕吐、皮肤瘙痒发生率明显低于单纯芬太尼组(P<0.05),两组患者均无幻觉发生。结论小剂量氯氨酮用于老年病人术后镇痛可明显减少芬太尼的剂量,并使恶心呕吐、皮肤瘙痒的发生率降低,而镇痛效果并无差异。     

小儿术前口服咪达唑仑复合液对围术期焦虑的影响

目的:观察小儿术前口服咪达唑仑复合液对围术期焦虑和行为改变的影响.方法:选择小儿择期手术60例,随机分为3组,每组20例.A组:口服咪达唑仑0.5 mg/kg;B组:口服咪达唑仑0.5 mg/kg和氯胺酮5 mg/kg;C组:口服咪达唑仑0.8 mg/kg和氯胺酮5 mg/kg.观察对口服药的接受程度、起效时间、镇静程度和抗焦虑情况、心率、呼吸、脉搏、血氧饱和度变化,以及术后精神状态和有无并发症等.结果:3组患儿均很好地接受口服用药;术中呼吸、脉搏、血氧饱和度稳定,无术后精神状态和并发症;C组起效时间更短;C组镇静和抗焦虑的作用较强,与A组比较差异有统计学意义(P＜0.05).结论:术前口服咪达唑仑复合液(咪达唑仑)0.8 mg/kg和氯胺酮5 mg/kg混合液,其镇静和抗焦虑效果好,不良反应少,是较理想的小儿术前用药.     

Sex Differences in the Behavioral,Molecular, and Structural Effects of Ketamine Treatment in Depression

Major depressive disorder (MDD) is a common psychiatric illness that manifests in sex-influenced ways. Men and women may experience depression differently and also respond to various antidepressant treatments in sex-influenced ways. Ketamine, which is now being used as a rapid-acting antidepressant, is likely the same. To date, the majority of studies investigating treatment outcomes in MDD do not disaggregate the findings in males and females, and this is also true for ketamine. This review aims to highlight that gap by exploring pre-clinical data—at a behavioral, molecular, and structural level—and recent clinical trials. Sex hormones, particularly estrogen and progesterone, influence the response at all levels examined, and sex is therefore a critical factor to examine when looking at ketamine response. Taken together, the data show females are more sensitive to ketamine than males, and it might be possible to monitor the phase of the menstrual cycle to mitigate some risks associated with the use of ketamine for females with MDD. Based on the studies reviewed in this article, we suggest that ketamine should be administered adhering to sex-specific considerations.     

Molecular mechanisms for the antidepressant-like effects of a low-dose ketamine treatment in a DFP-based rat model for Gulf War Illness

Exposure to organophosphates (OP) during the First Gulf War is among one of the factors for Gulf War Illness (GWI) development in veterans and it has been challenging to treat GWI symptoms with existing therapies. Ketamine produces a rapid-onset and sustained antidepressant response, but there is no evidence whether ketamine treatment is effective for GWI depression. Repeated, low-dose exposure to diisopropyl fluorophosphate (DFP) mimic Gulf War related OP exposures and produces a chronic depressive state in rats. In this study, DFP-exposed rats treated with ketamine (10 mg/kg, i.p.) exhibited antidepressant-like effect on the Forced Swim Test at 1-h. This effect persisted at 24-h post ketamine, a time-point by which it is eliminated from the brain suggesting involvement of mechanisms that affect long-term synaptic plasticity. Western blot analysis showed significantly lower Brain-Derived Neurotrophic Factor (BDNF) levels in DFP rat brains. Ketamine produced a nonsignificant increase in BDNF expression at 1-h but produced a larger, significant (2.2-fold) increase at 24-h in DFP rats. We previously reported chronic hippocampal calcium elevations ([Ca²⁺]_i) in DFP rats. Ketamine-treated DFP rats exhibited significantly lower [Ca²⁺]_i at 1-h but not at 24-h. Interestingly, treatment with ANA-12, a TrkB-BDNF receptor antagonist, in DFP rats blunted ketamine’s antidepressant-like effect at 24-h but not at 1-h. These experiments suggest that in a rat model of DFP-induced depression, inhibition of the NMDAR-Ca²⁺ contributes to the rapid-onset antidepressant effects of ketamine while the antidepressant actions that persisted at 24-h post ketamine administration involve upregulation of BDNF signaling.     

Influence of mTOR signaling pathway on ketamine-induced injuries in the hippocampal neurons of rats

Objective: To explore the influences of mammalian target of rapamycin (mTOR) signaling pathway on ketamine-induced apoptosis, oxidative stress and Ca²⁺ concentration in the hippocampal neurons of rats.

Methods: The primary hippocampal neurons isolated from fetal Sprague Dawley rats were treated with ketamine (0, 50, 100 and 500 μM) for 4 days to observe its effect on mTOR signaling pathway and apoptosis of rat hippocampal neurons. Then, the hippocampal neurons were divided into C (Control), R (Rapamycin, an inhibitor of mTOR signaling pathway), K (Ketamine) and R + K (Rapamycin + Ketamine) groups to detect the apoptosis, reactive oxygen species (ROS) production, and Ca²⁺ concentration via the terminal transferase uridyl nick end labelling (TUNEL) assay, dichloro-dihydro-fluorescein diacetate (DCFH-DA) method and Fluo-3 acetoxymethyl ester (Fluo-3AM) staining, respectively. The expressions of mTOR signaling pathway and apoptosis-related proteins in hippocampal neurons were examined by qRT-PCR and Western blot.

Results: Ketamine could dose-dependently promote the apoptosis of rat hippocampal neurons with upregulation of p-mTOR and its downstream regulators (p-4E-BP-1 and p-p70S6K). However, ketamine-induced apoptosis in hippocampal neurons was reversed significantly by the administration of rapamycin, as evident by the decrease in expressions of pro-apoptotic proteins (Bax and cleaved Caspase-3) and the increase in anti-apoptotic protein (Bcl-2). Meanwhile, the ROS generation and Ca²⁺ concentration was inhibited accompanied with reduced malonildialdehyde levels but elevated superoxide and glutathione peroxidase activities.

Conclusion: Inhibition of mTOR signaling pathway protected rat hippocampal neurons from ketamine-induced injuries via reducing apoptosis, oxidative stress, as well as Ca²⁺ concentration.

Abbreviations: mTOR: mammalian target of rapamycin; SD: Sprague-Dawley; SPF: Specific-pathogen free; ROS: reactive oxygen species; TUNEL: terminal transferase uridyl nick end labelling; DCFH-DA: Dichloro-dihydro-fluorescein diacetate; Fluo-3A: Fluo-3 acetoxymethyl ester; NMDAR: non-competitive N-methyl-D-aspartame glutamate receptor; 4E-BP1: 4E binding protein 1; p70S6K: p70 S6 Kinase; PCR: Polymerase chain reaction; MDA: malonildialdehyde; GSH-PX: glutathione peroxidase; ANOVA: One-way Analysis of Variance.     

氯胺酮复合异丙酚静脉全麻在小儿先天性心脏病介入治疗中的应用及对心钠素的影响

目的 研究氯胺酮复合异丙酚静脉全麻在小儿先天性心脏病介入治疗中的安全性和有效性及对心钠素(atrial natriuretic peptide,ANP)的影响.方法 选择美国麻醉医师协会(ASA)Ⅰ～Ⅱ级小儿先天性心脏病介入治疗患儿40例,年龄2～7岁,体重11～25 kg.随机分为2组,每组各20例.氯胺酮组为持续泵注氯胺酮,异丙酚组为持续泵注异丙酚.测定入室后(T1)、麻醉维持15 min(T2)时ANP浓度,并同时记录心率、血氧饱和度(SpO2).结果 氯胺酮组有2例一过性呼吸抑制,异丙酚组有1例,经托下颌面罩吸氧缓解,2组间SpO2差异无统计学意义(P＞0.05).心率和ANP变化一致,氯胺酮组在T2高于T1(P＜0.05), 异丙酚组变化不明显,2组间比较氯胺酮组在T2高于异丙酚组(P＜0.05).结论 异丙酚对ANP影响不明显,氯胺酮复合异丙酚静脉全麻是小儿先天性心脏病介入治疗手术的一种较好的麻醉方法.     

氯胺酮对SD大鼠后代学习记忆功能影响的实验研究

目的研究孕期大鼠接受氯胺酮全身麻醉对其后代学习记忆功能的影响。方法将30只怀孕SD大鼠随机均分成氯胺酮组和对照组,每组15只。氯胺酮组怀孕SD大鼠经尾静脉持续输注氯胺酮麻醉2h,对照组则给予等体积的生理盐水。于出生后20d和30d用Morris水迷宫测试各大组所产子鼠的学习记忆功能,用透射电子显微镜观察两组子鼠海马组织超微结构。结果出生后20d和30d氯胺酮组子鼠逃避潜伏期较对照组长,出生后30d氯胺酮组子鼠第2次水迷宫试验所测得的逃避潜伏期明显较对照组长,差异有统计学意义（P〈0．05）,氯胺酮组子鼠海马组织神经元超微结构出现明显异常。结论母体孕期接受氯胺酮全身麻醉对SD大鼠后代学习记忆功能有损害作用,其机制与氯胺酮可引起后代海马区神经元损害有关。     

氯胺酮对新生大鼠海马齿状回NMDA受体亚型表达的影响

目的 观察海马齿状回N-甲基-D-天冬氨酸(N-methyl-D-aspartate,NMDA)受体亚型蛋白表达的变化.方法 生后7 d SD大鼠24只,分为2组:给药后即刻组(PND7)和给药后3周组(PND28).2组根据给药剂量不同再各分为3组(n=4),即C组:空白对照组,腹腔注射生理盐水; K1组:诱导剂量100 mg/kg,连续麻醉6 h; K2组:诱导剂量50 mg/kg, 连续麻醉6 h;维持剂量按诱导剂量的1/2追加.PND7组麻醉后24 h内处死,PND28组在相同环境中饲养3周(即生后28 d)后处死.免疫组织化学ABC法进行细胞染色.结果 在海马齿状回,PND7组中处理组NR2A、2B亚型蛋白表达均比对照组有增加的趋势(P<0.05), 但NR2C亚型变化不大.PND 28组中NR2A亚型处理组同样比对照有所增加(P<0.05),但NR2B、2C亚型变化不大.各亚型中K1、K2处理组之间均没有显著性差异(P>0.05).结论 氯胺酮对发育阶段大鼠海马的NMDA受体亚型蛋白的表达具有上调作用,进而可能对大鼠神经系统的发育产生一定影响.     

小剂量氯胺酮复合丙泊酚、瑞芬太尼用于无痛胃镜检查的效果及安全性

目的探讨氯胺酮复合丙泊酚、瑞芬太尼在无痛胃镜检查中的临床效果。方法将42例ASAⅠ～Ⅱ级患者随机分成两组,均行胃镜检查A组采用瑞芬太尼丙泊酚麻醉,B组采用氯胺酮、瑞芬太尼麻醉。观察两组丙泊酚使用剂量,术中OAA/S评分,苏醒时间及并发症。结果丙泊酚首次剂量、总剂量A组〉B组（P〈0．05）,两组OAA／S评分无明显差异;两组苏醒时间（出镜一呼之睁眼）无显著差异;两组窦缓（HR〈60次／min）、注射痛发生率A组〉B组（P〈0．05）,低氧血症（SpO2〈90％）发生率无明显差异,两组均无术中知晓、喉痉挛、恢复期兴奋、烦躁。结论瑞芬太尼加丙泊酚麻醉可明显减慢心率,复合小剂量氯胺酮能减少丙泊酚的首次剂量和总量,不影响麻醉效果、苏醒和恢复,并明显降低窦缓和诱导期注射痛的发生,是无痛胃镜检查术较为适用的麻醉方法。