Clinical Anaesthesia & Paediatrics, Acute & Perioperative Pain Service, Department of Anaesthesia, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 2001, Cincinnati, OH 45229, USA.
Pharmacogenomics. 2014 Feb;15(3):277-84. doi: 10.2217/pgs.13.248.
Effective perioperative analgesia is lacking for children owing to interindividual variations and underdosing of opioids caused by fear of adverse effects. We investigated the role of COMT SNPs on postoperative pain management in children.
One hundred and forty nine children undergoing adenotonsillectomy were enrolled. The associations of four COMT SNPs (rs6269, rs4633, rs4818 and rs4680) with postoperative pain were analyzed and outcome measures included maximum pain scores, need for postoperative opioid interventions and postoperative morphine requirements.
We detected an association of postoperative opioid intervention need with all four COMT SNPs. Minor allele carriers of COMT SNPs were approximately three-times more likely to require analgesic interventions than homozygotes of major alleles (p-value range: 0.0031-0.0127; odds ratio range: 2.6-3.1). In addition, significant association was detected between maximum Face, Leg, Activity, Consolability, Cry (FLACC) pain scores and three COMT SNPs (rs6269, rs4633 and rs4680). Haplotype 1 (ATCA: 51.3%) and Haplotype 2 (GCGG: 36.2%) are more frequent. Haplotype 2 was associated with higher odds of intravenous analgesic intervention need in postanesthesia recovery unit with an odds ratio of 2.6 (95% CI: 1.2-5.4; p-value = 0.022).
COMT SNPs may play a significant role in interindividual variation in postoperative pain perception and postoperative morphine requirements in children. Original submitted 16 August 2013; Revision submitted 13 December 2013.
由于个体差异和对不良反应的恐惧导致阿片类药物剂量不足,儿童围手术期镇痛效果不佳。我们研究了 COMT 单核苷酸多态性(SNP)在儿童术后疼痛管理中的作用。
共纳入 149 例行腺样体扁桃体切除术的儿童。分析了四个 COMT SNP(rs6269、rs4633、rs4818 和 rs4680)与术后疼痛的关系,观察指标包括最大疼痛评分、术后阿片类药物干预需求和术后吗啡用量。
我们发现,所有四个 COMT SNP 均与术后阿片类药物干预需求相关。COMT SNP 次要等位基因携带者需要镇痛干预的可能性是主要等位基因纯合子的近 3 倍(p 值范围:0.0031-0.0127;比值比范围:2.6-3.1)。此外,还发现 COMT 的三个 SNP(rs6269、rs4633 和 rs4680)与最大面部、腿部、活动、安抚、哭泣(FLACC)疼痛评分显著相关。单体型 1(ATCA:51.3%)和单体型 2(GCGG:36.2%)更为常见。单体型 2 与术后恢复室静脉镇痛干预需求的高几率相关,比值比为 2.6(95%可信区间:1.2-5.4;p 值=0.022)。
COMT SNP 可能在儿童术后疼痛感知和术后吗啡需求的个体差异中起重要作用。