O'Byrne Michael L, Baxelbaum Keith, Tam Vicky, Griffis Heather, Pennington Maryjane L, Hagerty Alyssa, Naim Maryam Y, Nicolson Susan C, Shillingford Amanda J, Sutherland Tori N, Hampton Lyla E, Gebregiorgis Nebiat G, Nguyen Thuyvi, Ramos Elizabeth, Rossano Joseph W
Division of Cardiology, The Children's Hospital of Philadelphia, Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA; Leonard Davis Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Clinical Futures, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; Cardiovascular Outcomes, Quality, and Evaluative Research Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Data Science and Biostatistics Unit, Department of Biomedical and Health Informatics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
J Am Coll Cardiol. 2024 Sep 10;84(11):1010-1021. doi: 10.1016/j.jacc.2024.06.033.
Opioids are commonly used to provide analgesia during and after congenital heart surgery. The effects of exposure to opioids on neurodevelopment in neonates and infants are not well understood.
This study sought to evaluate the associations between cumulative opioid exposure (measured in morphine mg equivalent) over the first year of life and 2-year neurodevelopmental outcomes (Bayley Scales of Infant and Toddler Development-Third/Fourth Edition [Bayley-III/IV] cognitive, language, and motor scores).
A single-center retrospective cohort study of infants undergoing congenital heart surgery was performed. Adjustment for measurable confounders was performed through multivariable linear regression.
A total of 526 subjects were studied, of whom 32% underwent Society for Thoracic Surgeons-European Association for Cardio-Thoracic Surgery category 4 or 5 operations. In unadjusted analyses, higher total exposure to opioids was associated with worse scores across all 3 Bayley-III/IV domain scores (all P < 0.05). After adjustment for measured confounders, greater opioid exposure was associated with lower Bayley-III/IV scores (cognitive: β = -1.0 per log-transformed morphine mg equivalents, P = 0.04; language: β = -1.2, P = 0.04; and motor: β = -1.1, P = 0.02). Total hospital length of stay, prematurity, genetic syndromes, and worse neighborhood socioeconomic status (represented either by Social Vulnerability Index or Childhood Opportunity Index) were all associated with worse Bayley-III/IV scores across all domains (all P < 0.05).
Greater postnatal exposure to opioids was associated with worse neurodevelopmental outcomes across cognitive, language, and motor domains, independent of other less modifiable factors. This finding should motivate research and efforts to explore reduction in opioid exposure while preserving quality cardiac intensive care.
阿片类药物常用于先天性心脏病手术期间及术后镇痛。阿片类药物暴露对新生儿和婴儿神经发育的影响尚不清楚。
本研究旨在评估生命第一年累积阿片类药物暴露量（以吗啡毫克当量衡量）与2岁时神经发育结局（贝利婴幼儿发育量表第三/四版[贝利-III/IV]认知、语言和运动评分）之间的关联。
对接受先天性心脏病手术的婴儿进行单中心回顾性队列研究。通过多变量线性回归对可测量的混杂因素进行校正。
共研究了526名受试者，其中32%接受了胸外科医师协会-欧洲心胸外科学会4级或5级手术。在未校正的分析中，阿片类药物总暴露量越高，贝利-III/IV所有三个领域的评分越差（所有P<0.05）。校正测量的混杂因素后，阿片类药物暴露量越高，贝利-III/IV评分越低（认知：每对数转换后的吗啡毫克当量β=-1.0，P=0.04；语言：β=-1.2，P=0.04；运动：β=-1.1，P=0.02）。住院总时长、早产、遗传综合征以及较差的社区社会经济地位（以社会脆弱性指数或儿童机会指数表示）均与所有领域的贝利-III/IV评分较差相关（所有P<0.05）。
出生后较高的阿片类药物暴露量与认知、语言和运动领域较差的神经发育结局相关，独立于其他较难改变的因素。这一发现应促使开展研究并努力探索在保持优质心脏重症监护的同时减少阿片类药物暴露量。
