剖宫产术中小剂量氯胺酮应用预防产后抑郁的疗效评价

发布时间：2018-04-02 07:21

本文选题：产后　切入点：抑郁症　出处：《南方医科大学》2017年硕士论文

【摘要】：背景:产后抑郁是分娩常见的并发症,并已经成为了重要的公共卫生问题。传统的抗抑郁药作用于单胺氧化酶系统,需要数周才能起效,且临床有效性低。近十几年来有越来越多的临床研究发现亚剂量的氯胺酮(0.5 mg/kg)具有快速抗抑郁的作用,其作用机制可能是氯胺酮介导了突触的可塑性从而能引起长期的行为学变化。另外,有临床研究表明疼痛是产后抑郁的危险因素,而有meta分析显示小剂量氯胺酮应用可以降低术后疼痛强度和预防慢性疼痛,其机制可能与NMDA受体被拮抗从而减少中枢敏化和痛觉过敏有关。从氯胺酮以上两个作用机制来看,我们认为氯胺酮可能具有预防产后抑郁的作用,因此我们设计了一项前瞻性、随机、双盲的临床试验来评价剖宫产术中小剂量的氯胺酮应用是否具有预防产后抑郁的作用。方法:本研究是一项随机、双盲、安慰剂对照、前瞻性的临床试验。所有的受试者被随机分配到氯胺酮组或生理盐水组。新生儿娩出后5min内由麻醉医师给产妇静脉推注0.25 mg/kg氯胺酮或等量生理盐水。受试者基本情况的数据采集包括年龄、体重指数(Body Mass Index,BMI)、此次妊娠相关的情况。术中的数据由麻醉医师完成,包括去氧肾上腺素用量、术中出血量、手术持续时间、新生儿信息,并在给完试验药物后5分钟、15分钟和出室的时候询问受试者是否存在瘙痒、恶心、呕吐、头痛、幻觉、眩晕、嗜睡、复视,同时进行镇静评分(Ramsay评分)。主要结局指标为产后第3天和6 周的 EPDS 评分(Edinburgh Postnatal Depression Scale score)。次要结局指标为产后第3天和6周的NRS(Numeric Rating Scale)疼痛评分。结果:共纳入330例受试者,受试者的基本资料数据两组之间没有统计学意义。术中采集的产妇信息和新生儿的信息在两组之间也没有统计学意义。与对照组相比,氯胺酮组在给药后5分钟的头痛、幻觉、头晕、嗜睡、复视症状比对照组多,镇静评分3分的发生率比对照组高。给药后15分钟呕吐、幻觉、头晕、嗜睡、复视症状比对照组多,镇静评分(Ramsay评分)3分的发生率两组之间没有统计学差异。出手术间时两组之间氯胺酮相关的副作用没有统计学差异。两组之间在术后第3天产后抑郁的发生率和NRS评分没有统计学差异,术后6周产后抑郁的发生率没有统计学差异。氯胺酮组在术后第6周的NRS疼痛评分要显著低于对照组(P=0.014)。结论:氯胺酮0.25 mg/kg剖宫产术中应用不能有效地预防产后抑郁,但能够减少剖宫产术后第6周疼痛的发生。有部分受试者在给药后会出现氯胺酮相关的副作用,但缓解迅速,不延迟出室时间。
[Abstract]:Background: postpartum depression is a common complication of childbirth and has become an important public health problem.Traditional antidepressants act on monoamine oxidase systems, which take several weeks to take effect and have low clinical efficacy.In recent years, more and more clinical studies have found that the sub-dose of ketamine (0.5 mg / kg) has a rapid antidepressant effect, and its mechanism may be that ketamine mediates synaptic plasticity and causes long-term behavioral changes.In addition, clinical studies have shown that pain is a risk factor for postpartum depression, and meta analysis shows that low doses of ketamine can reduce postoperative pain intensity and prevent chronic pain.The mechanism may be related to the antagonism of NMDA receptor, which reduces central sensitization and hyperalgesia.From the above two mechanisms of ketamine, we think that ketamine may have a role in preventing postpartum depression, so we designed a prospective, randomized,A double blind clinical trial was conducted to evaluate whether low-dose ketamine use during cesarean section could prevent postpartum depression.Methods: this study was a randomized, double-blind, placebo-controlled, prospective clinical trial.All subjects were randomly assigned to either the ketamine group or the saline group.The anesthesiologist intravenously injected 0.25 mg/kg ketamine or the same amount of normal saline into the parturient after delivery.The subjects' basic data collection included age, body Mass index, and pregnancy related information.The intraoperative data were performed by the anesthesiologist, including the amount of norepinephrine, the amount of blood lost during the operation, the duration of the operation, the information on the newborn, and the subjects were asked if they had itching 5 minutes, 15 minutes after the trial and when they left the room.Nausea, vomiting, headache, hallucination, vertigo, lethargy, diplopia, sedation score and Ramsay score.The main outcome index was the EPDS score on the 3rd and 6th week postpartum.The secondary outcome was the NRS(Numeric Rating scale score on the 3rd and 6th week postpartum.Results: a total of 330 subjects were included, and there was no statistical significance between the two groups.There was also no statistical significance between the maternal and neonatal information collected during the operation.Compared with control group, ketamine group had more symptoms of headache, hallucination, dizziness, drowsiness, and diplopia, and the incidence of sedation score 3 was higher than that of control group 5 minutes after administration of ketamine.There was no significant difference in the incidence of vomiting, hallucination, dizziness, lethargy, diplopia symptoms, sedation score and Ramsay score between the two groups 15 minutes after administration.There was no significant difference in ketamine-related side effects between the two groups at the time of operation.There was no significant difference in the incidence of postpartum depression and NRS score between the two groups on the third day after operation, but there was no significant difference in the incidence of postpartum depression at 6 weeks after operation.The NRS pain score in ketamine group was significantly lower than that in control group at 6 weeks postoperatively.Conclusion: ketamine 0.25 mg/kg during cesarean section can not effectively prevent postpartum depression, but can reduce the incidence of pain 6 weeks after cesarean section.Some subjects had ketamine-related side effects after administration, but the response was rapid, without delay.
【学位授予单位】：南方医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R614

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