氯胺酮麻醉前不同时间肌内注射阿托品对小儿呼吸道的影响

目的探讨氯胺酮麻醉前不同时间肌内注射阿托品对小儿呼吸道的影响。方法将2012年1月至2013年6月在廊坊市第四人民医院住院的100例患儿按随机数字表法分为两组:A组(50例)于氯胺酮麻醉前30~60 min肌内注射阿托品(0.02 mg/kg),B组(50例)阿托品(0.02 mg/kg)与氯胺酮同时间肌内注射。两组患儿均于氯胺酮肌内注射2~4 min后入室准备手术,术中观察记录两组患儿呼吸道和肺部的听诊变化及脉搏血氧饱和度(Sp O2)变化。结果 A组Ⅰ级(即呼吸道未受影响)44例,Ⅱ级以上(即呼吸道受到不同程度影响)6例,阳性率为12%(6/50);B组Ⅰ级33例,Ⅱ级以上17例,阳性率为34%(17∕50)。两组患儿呼吸道受影响程度的比较,差异有统计学意义(P<0.01)。结论小儿氯胺酮麻醉前30 min肌内注射阿托品,能有效降低氯胺酮对患儿呼吸道的影响,提高术中患儿的安全系数。     

氯胺酮静脉全身麻醉复合罗哌卡因骶管阻滞对腹股沟疝患儿术中应激反应的影响

目的探讨氯胺酮静脉全身麻醉复合罗哌卡因骶管阻滞对腹股沟疝患儿术中应激反应的影响。 方法选取2015年11月至2017年12月，保定市儿童医院82例腹股沟疝患儿的临床资料，通过随机数字表法分为对照组与试验组，每组患儿41例。对照组采用氯胺酮静脉全身麻醉，试验组采用氯胺酮静脉全身麻醉复合罗哌卡因骶管阻滞。统计2组麻醉前（T1）、麻醉后10 min（T2）、术后即刻（T3）、术后8 h（T4）应激反应指标[皮质醇、白细胞介素-6（interleukin 6，IL-6）]水平、氯胺酮用量、苏醒时间、术后5、60、120 min时疼痛的改良面部表情评分（facial expression scoring，FLACC）及苏醒期躁动评分（awakening period score，AS）、不良反应发生率。 结果T2时2组血清皮质醇、IL-6水平较T1时期增高，但试验组低于对照组（P<0.05），T3及T4时2组血清皮质醇、IL-6水平较T2时期降低，但试验组低于对照组（P<0.05）；试验组氯胺酮用量少于对照组、苏醒时间短于对照组（P<0.05）；术后5、60、120 min试验组FLACC及AS分值低于对照组（P<0.05）；试验组呕吐（7.32%）、躁动（12.20%）、嗜睡（9.76%）发生率低于对照组（P<0.05）。 结论腹股沟疝患儿手术治疗过程中采取氯胺酮静脉全身麻醉复合罗哌卡因骶管阻滞，可减少氯胺酮用量，缩短苏醒时间，减轻术中应激反应程度，还有利于减轻术后疼痛感及躁动程度，且可降低不良反应发生率。     

Agmatine as a novel candidate for rapid-onset antidepressant response

Major depressive disorder (MDD) is a disabling and highly prevalent mood disorder as well as a common cause of suicide. Chronic stress, inflammation, and intestinal dysbiosis have all been shown to play crucial roles in the pathophysiology of MDD. Although conventional antidepressants are widely used in the clinic, they can take weeks to months to produce therapeutic effects. The discovery that ketamine promotes fast and sustaining antidepressant responses is one of the most important breakthroughs in the pharmacotherapy of MDD. However, the adverse psychomimetic/dissociative and neurotoxic effects of ketamine discourage its chronic use. Therefore, agmatine, an endogenous glutamatergic modulator, has been postulated to elicit fast behavioral and synaptogenic effects by stimulating the mechanistic target of rapamycin complex 1 signaling pathway, similar to ketamine. However, recent evidence has demonstrated that the modulation of the NLR family pyrin domain containing 3 inflammasome and gut microbiota, which have been shown to play a crucial role in the pathophysiology of MDD, may also participate in the antidepressant-like effects of both ketamine and agmatine. This review seeks to provide evidence about the mechanisms that may underlie the fast antidepressant-like responses of agmatine in preclinical studies. Considering the anti-inflammatory properties of agmatine, it may also be further investigated as a useful compound for the management of MDD associated with a pro-inflammatory state. Moreover, the fast antidepressant-like response of agmatine noted in animal models should be investigated in clinical studies.     

Can we increase the speed and efficacy of antidepressant treatments? Part II. Glutamatergic and RNA interference strategies

In the second part we focus on two treatment strategies that may overcome the main limitations of current antidepressant drugs. First, we review the experimental and clinical evidence supporting the use of glutamatergic drugs as fast-acting antidepressants. Secondly, we review the involvement of microRNAs (miRNAs) in the pathophysiology of major depressive disorder (MDD) and the use of small RNAs (e.g.., small interfering RNAs or siRNAs) to knockdown genes in monoaminergic and non-monoaminergic neurons and induce antidepressant-like responses in experimental animals.The development of glutamatergic agents is a promising venue for antidepressant drug development, given the antidepressant properties of the non-competitive NMDA receptor antagonist ketamine. Its unique properties appear to result from the activation of AMPA receptors by a metabolite [(2 S,6 S;2 R,6 R)-hydroxynorketamine (HNK)] and mTOR signaling. These effects increase synaptogenesis in prefrontal cortical pyramidal neurons and enhance serotonergic neurotransmission via descending inputs to the raphe nuclei. This view is supported by the cancellation of ketamine's antidepressant-like effects by inhibition of serotonin synthesis.We also review existing evidence supporting the involvement of miRNAs in MDD and the preclinical use of RNA interference (RNAi) strategies to target genes involved in antidepressant response. Many miRNAs have been associated to MDD, some of which e.g., miR-135 targets genes involved in antidepressant actions. Likewise, SSRI-conjugated siRNA evokes faster and/or more effective antidepressant-like responses. Intranasal application of sertraline-conjugated siRNAs directed to 5-HT_1A receptors and SERT evoked much faster changes of pre- and postsynaptic antidepressant markers than those produced by fluoxetine.     

Rapid antidepressant effect of S-ketamine in schizophrenia

Rapid anti-suicidal and antidepressant effects of ketamine have repeatedly been confirmed in unipolar and bipolar depression. Although meaningful antidepressant efficacy of ketamine has also been shown in depressed patients with a history of psychotic symptoms, its administration in psychotic disorders has largely been neglected due to its potential to exacerbate dissociative or psychotic symptoms. Presenting a case of a young female inpatient suffering from schizophrenia with a severe post-psychotic depression, we demonstrate a robust anti-suicidal and antidepressant effect of S-ketamine infusions administered thrice weekly for 3 weeks in total. Importantly, no relevant psychotic or dissociative symptoms occurred during the whole augmentation treatment period leading to a sustained remission of depressive symptoms and suicidality. Our safe and effective experience with intravenous S-ketamine might encourage researchers and clinicians to widen its administration range beyond the diagnosis of depression to enrich the current knowledge of ketamine effects in psychotic disorders.     

Regulation of cytochrome P450 gene expression by ketamine: a review

Introduction: Although used as an anesthetic drug for decades, ketamine appears to have garnered renewed interest due to its potential therapeutic uses in pain therapy, neurology, and psychiatry. Ketamine undergoes extensive oxidative metabolism by cytochrome P450 (CYP) enzymes. Considerable efforts have been expended to elucidate the ketamine-induced regulation of CYP gene expression. The safety profile of chronic ketamine administration is still unclear. Understanding how ketamine regulates CYP gene expression is clinically meaningful.

Areas covered: In this article, the authors provide a brief review of clinical applications of ketamine and its metabolism by CYP enzymes. We discuss the effects of ketamine on the regulation of CYP gene expression, exploring aspects of cytoskeletal remodeling, mitochondrial functions, and calcium homeostasis.

Expert opinion: Ketamine may inhibit CYP gene expression through inhibiting calcium signaling, decreasing ATP levels, producing excessive reactive oxygen species, and subsequently perturbing cytoskeletal dynamics. Further research is still needed to avoid possible ketamine–drug interactions during long-term use in the clinic.     

异丙酚、氯胺酮对腭裂患儿全麻手术中心率变异性的影响

目的:研究异丙酚与氯胺酮麻醉对小儿自主神经功能的影响。方法:35例ASAⅠ~Ⅱ级腭裂手术患儿,随机分为2组:插管后Ⅰ组(氯胺酮组,n=17)静注氯胺酮(1~2mg/kg),Ⅱ组(异丙酚组,n=18)异丙酚4~8mg/(kg·h)微量泵输注。监测麻醉前(T0)、插管后5min(T1)、切皮(T2)、手术开始后1h(T3)、术毕(T4)及拔管后(T5)低频(LF)、高频(HF)、低频高频比(LF/HF)和总功率(LF HF)及MAP、HR、SpO2各值。结果:T1~T4各时点LF、HF、LF/HF及LF HF显著降低(P<0.05)。拔管后HRV各值基本恢复至术前水平(P>0.05)。2组比较,T2~T5各时点Ⅱ组HRV各值明显低于I组(P<0.05)。T2~T5HR、MAPⅡ组明显低于I组(P<0.05)。T5时点SpO22组明显低于T0~T4(P<0.05)。Ⅰ组拔管时间、清醒时间明显较Ⅱ组长(P<0.05),且躁动哭闹及术后恶心呕吐发生率明显高于Ⅱ组(P<0.05)。结论:异丙酚在麻醉中降低血压、心率和抑制自主神经功能的作用强于氯胺酮,术后拔管时间、苏醒时间、恶心呕吐及躁动哭闹的发生明显优于氯胺酮。     

N-甲基-D-天冬氨酸受体与抑郁症

抑郁症(major depressive disorder,MDD)是一类以心境抑郁、兴趣减退为主要临床表现的精神障碍疾病。其病因机制不清,具有高发病率、高复发率及高自杀率特点。当下主流的单胺类假说不能充分阐明其病理学特征,部分抑郁症患者对现有抗抑郁药治疗应答不佳。N-甲基-D-天冬氨酸受体(N-methyl-D-aspartate receptor,NMDAR)拮抗剂和γ-氨基丁酸A(γ-aminobutyric acid A,GABAA)受体正向变构调节剂具有潜在快速抗抑郁效果,可能是抑郁症发病的新机制和临床治疗的突破口。NMDAR具有双向调节作用,适当激活可促进树突发育、神经元生长和长时程增强,但过度刺激会引起毒性反应,导致突触萎缩和神经元死亡。此外,炎症反应可诱导NMDAR功能改变从而产生抑郁症状。目前临床上新型抗抑郁药物NMDAR拮抗剂氯胺酮可能通过促进脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)释放增加、激活雷帕霉素靶蛋白复合物1(mammalian target of rapamycin complex 1,mTORC1)信号通路,进而促进蛋白质合成、增强突触可塑性,从而起到快速抗抑郁和延缓抑郁复发的作用,但由于MDD患者NMDAR基因变异性较大,其潜在功能多态性影响临床症状表现和药物敏感性。本文通过梳理分析国内外最新研究,综述NMDAR功能异常与抑郁症发病、抗抑郁治疗作用以及临床应用现状,以期为抑郁症患者精准治疗提供理论基础。     

听觉诱发电位指数对无痛人流术麻醉深度的调控

目的评价异丙酚和异丙酚复合氯胺酮用于无痛人工流产的临床效果。方法50例早期妊娠分成异丙酚组（Ⅰ组）和异丙酚复合氯胺酮组（Ⅱ组）各25例，观察两组用药总量、手术各时点听觉诱发电位指数（AAI）、呼吸循环参数改变。采用A—LINE无创麻醉深度监测仪监测AAI值。结果Ⅰ组异丙酚用量明显多于Ⅱ组；两组AAI值在给药后及整个手术期间均明显降低（P〈0．01），Ⅱ组AAI下降的时间及恢复时间滞后于Ⅰ组，Ⅰ组在术后7分钟、Ⅱ组在术后10分钟升至给药前水平；给药后两组平均动脉压（MAP）均有下降（P〈0．05）；Ⅱ组与Ⅰ组相比，SpO2在给药后、手术开始时、手术1分钟及术后1、4分钟时差异有显著性意义（P〈0．05）；Ⅰ组在给药后、手术前4分钟与术后前4分钟SpO2降低（P〈0．05），Ⅱ组SpO2在给药后各时点无明显变化；Ⅰ组术中体动6例，Ⅱ组中无体动。结论AAI的监测更能保证手术的顺利进行和患者的安全。     

不同麻醉药物诱导用于小儿气管镜检异物取出术的比较

目的比较七氟醚、丙泊酚和氯胺酮麻醉诱导用于小儿支气管镜检异物取出术的效果。方法急诊支气管镜检异物取出术患儿30例,年龄9~58个月,采用随机数字表法将患儿分为三组:七氟醚组(S组),丙泊酚组(P组)和氯胺酮组(K组),每组10例。S组采用8%七氟醚吸入诱导;P组采用丙泊酚2.5mg/kg缓慢静脉注射诱导;K组采用氯胺酮5mg/kg肌肉注射诱导;三组诱导至意识消失后均以保留自主呼吸为准则,喉镜开口实施利多卡因咽喉部表面麻醉;术中采用靶控输注丙泊酚和瑞芬太尼维持麻醉,面罩吸氧后置入气管镜。记录一次置入气管镜成功率,置入气管镜前后即刻HR和SpO2,置入气管镜时间、气管镜检时间和术后苏醒时间,置入气管镜和术中不良反应发生情况。结果 S组和P组成功置入气管镜的时间、术后苏醒时间明显短于K组(P0.05);S组一次置管成功率明显高于K组(P0.05)。三组患儿不良反应发生率差异无统计学意义。结论与丙泊酚静脉注射和氯胺酮肌肉注射麻醉诱导比较,七氟醚诱导麻醉在婴幼儿气管镜检异物取出术中具有诱导快、苏醒快等优点。