Hashiya Mai, Okubo Yusuke, Kato Tsuguhiko
Department of Anesthesiology, National Center for Child Health and Development, Tokyo, Japan.
Department of Social Medicine, National Center for Child Health and Development, Tokyo, Japan.
J Cardiothorac Vasc Anesth. 2023 Jun;37(6):1013-1020. doi: 10.1053/j.jvca.2023.02.013. Epub 2023 Feb 16.
Dexmedetomidine use decreases adverse neurocognitive outcomes in adults undergoing cardiovascular surgery, but its effect has been unclear in children with congenital heart disease.
The authors conducted a systematic review using the PubMed, Embase, and Cochrane Library databases for randomized controlled trials (RCTs) that compared intravenous dexmedetomidine with normal saline during pediatric cardiac surgery under anesthesia. Published randomized controlled trials that evaluated children aged <18 years who underwent congenital heart surgery were included. Nonrandomized trials, observational studies, case series and case reports, editorials, reviews, and conference papers were excluded. The quality of the included studies was assessed using the Cochrane revised tool for assessing risk-of-bias in randomized trials. Meta-analysis was performed to estimate the effects of intravenous dexmedetomidine on brain markers (neuron-specific enolase [NSE], S-100β protein) and inflammatory markers (interleukin-6, tumor necrosis factor [TNF]-α, nuclear factor kappa-B [NF-κB]) during and after cardiac surgery, using random-effect models for standardized mean difference (SMD).
Seven RCTs involving 579 children were eligible for the following meta-analyses. Most children underwent cardiac surgery for atrial or ventricular septum defects. Pooled analyses (5 treatment groups in 3 RCTs with 260 children) showed that dexmedetomidine use was associated with reduced serum levels of NSE (pooled SMD, -0.54; 95% CI, -0.96 to -0.12) and S-100β (pooled SMD, -0.85; 95% CI, -1.67 to -0.04) within 24 hours after the surgery. Also, dexmedetomidine use was associated with reduced levels of interleukin-6 (pooled SMD, -1.55; 95% CI, -2.82 to -0.27; 4 treatment groups in 2 RCTs with 190 children). In contrast, the authors observed similar levels of TNF-α (pooled SMD, -0.07; 95% CI, -0.33 to 0.19; 4 treatment groups in 2 RCTs with 190 children) and NF-κB (pooled SMD, -0.27; 95% CI, -0.62 to 0.09; 2 treatment groups in 1 RCT with 90 children) between the dexmedetomidine and control groups.
The authors' findings support the effect of dexmedetomidine on reductions in brain markers among children who undergo cardiac surgery. Further studies would be needed to elucidate its clinically meaningful effects using cognitive functions in the long term, and its effects among children who undergo more complex cardiac surgeries.
右美托咪定可降低接受心血管手术的成人出现不良神经认知结局的风险，但其对先天性心脏病患儿的影响尚不清楚。
作者使用PubMed、Embase和Cochrane图书馆数据库进行了一项系统评价，纳入在小儿心脏手术麻醉期间将静脉注射右美托咪定与生理盐水进行比较的随机对照试验（RCT）。纳入已发表的评估年龄<18岁的先天性心脏病手术患儿的随机对照试验。排除非随机试验、观察性研究、病例系列和病例报告、社论、综述及会议论文。使用Cochrane修订的随机试验偏倚风险评估工具对纳入研究的质量进行评估。采用随机效应模型计算标准化均数差（SMD），进行荟萃分析以评估静脉注射右美托咪定对心脏手术期间及术后脑标志物（神经元特异性烯醇化酶[NSE]、S-100β蛋白）和炎症标志物（白细胞介素-6、肿瘤坏死因子[TNF]-α、核因子κB[NF-κB]）的影响。
7项涉及579名儿童的RCT符合以下荟萃分析的条件。大多数儿童接受了房间隔或室间隔缺损的心脏手术。汇总分析（3项RCT中的5个治疗组，共260名儿童）显示，使用右美托咪定与术后24小时内血清NSE水平降低（汇总SMD，-0.54；95%CI，-0.96至-0.12）和S-100β水平降低（汇总SMD，-0.85；95%CI，-1.67至-0.04）相关。此外，使用右美托咪定与白细胞介素-6水平降低相关（汇总SMD，-1.55；95%CI，-2.82至-0.27；2项RCT中的4个治疗组，共190名儿童）。相比之下，作者观察到右美托咪定组和对照组之间TNF-α（汇总SMD，-0.07；95%CI，-0.33至0.19；2项RCT中的4个治疗组，共190名儿童）和NF-κB（汇总SMD，-0.27；95%CI，-0.62至0.09；1项RCT中的2个治疗组，共90名儿童）水平相似。
作者的研究结果支持右美托咪定对接受心脏手术患儿脑标志物降低的作用。需要进一步研究以阐明其对长期认知功能的临床意义，以及其在接受更复杂心脏手术患儿中的作用。
