Perioperative Precision Medicine: Translating Science to Clinical Practice to Improve Safety and Efficacy of Opioids in Neonates, Children and Nursing Mothers

围手术期精准医学：将科学转化为临床实践，提高阿片类药物对新生儿、儿童和哺乳期母亲的安全性和有效性

• 批准号: 10676237
• 负责人: Senthilkumar Sadhasivam
• 金额: $ 108.16万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-03 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10676237
• 关键词: ABCB1 gene; Absence of pain sensation; Acceleration; Acute; Address; Adult; Adverse effects; Analgesics; Anoxic Encephalopathy; Brain Death; Breastfed infant; Breathing; CYP2B6 gene; CYP2D6 gene; Caring; Case Study; Cesarean section; Cessation of life; Child; Chronic; Clinical; Codeine; Dependence; Deterioration; Discipline of Nursing; Dose; Drug Kinetics; Economic Burden; Effectiveness; Electronic Health Record; Enzymes; Genetic Risk; Genetic Variation; Genomics; Genotype; Guidelines; Heritability; Hydrocodone; Individual; Infant; Infrastructure; Insurance Coverage; Knowledge; Length of Stay; Life; Link; Liver; Metabolism; Methadone; Methods; Mothers; N-Methylaspartate; Newborn Infant; Nursing infant; Operative Surgical Procedures; Opiate Addiction; Opioid; Opioid Analgesics; Other Genetics; Outcome; Outpatients; Oxycodone; Oxymorphone; Pain; Pain management; Patients; Perioperative; Population; Postoperative Nausea and Vomiting; Postoperative Pain; Postoperative Period; Postpartum Depression; Productivity; Protocols documentation; Public Health; Publishing; Risk; Safety; Science; Spinal Fusion; Surgical Management; Testing; Tramadol; Translating; Translational Research; Variant; Ventilatory Depression; Vulnerable Populations; Woman; adverse outcome; antagonist; chronic pain; clinical decision support; clinical practice; cost effectiveness; digital; digital tool; electronic patient reported outcomes; evidence base; follow-up; genetic risk factor; genetic variant; high risk; improved; infant death; innovation; inpatient surgery; multidisciplinary; neonate; nursing mothers; opioid epidemic; opioid mortality; opioid overdose; opioid use; pain relief; personalized care; personalized decision; personalized intervention; practice setting; precision medicine; prescription opioid; prevent; public health relevance; risk prediction; socioeconomics; surgical pain; translational barrier; translational potential

Project Summary: Perioperative opioid adverse effects--from common but less-serious post-operative nausea and vomiting to the more serious respiratory depression and death—are current but preventable challenges in managing surgical pain. Severe surgical pain is still poorly managed, yet clinicians must also avoid unpredictable and life-threatening opioid adverse effects as well as long-term opioid use/misuse. This application innovatively proposes to translate evidence into a proactive clinical practice to optimize post- surgical pain control and decrease opioid-related adverse effects. Current evidence shows that opioid me- tabolism, opioids’ analgesic and adverse effects are influenced by genetic variations. The FDA warns against the use of codeine and tramadol in children (due to postoperative anoxic brain injuries and deaths) and in nursing mothers (due to serious breathing problems and infantile death). Preoperative genotyping and personalized analgesia are not practiced despite evidence, regulatory warnings, CPIC guidelines, cost- effectiveness and insurance coverage for CYP2D6 testing due to translational bottlenecks, lack of infra- structure and knowledge gaps in how to personalize opioid use and dose precisely for optimal outcomes. Thus, there is an urgent and unmet critical need for a perioperative precision analgesia infrastructure to overcome the translational barriers and to improve safety and effectiveness of opioids in children and nurs- ing mothers. Personalizing analgesia based on genetic risks will reduce opioid use, adverse-effects, and accelerate value-based care opportunities. However, these opportunities are constrained by lack of trans- lational platforms and major gaps in our understanding of how to personalize and precisely dose opioids. In this collaborative CTSA project, we propose to overcome the translational barriers by developing an inno- vative perioperative precision analgesia platform (PPAP) to reduce serious adverse outcomes of opioids, and improve safety of opioids in: 1) children undergoing painful surgery, and 2) nursing mothers and their infants. We have robust evidence and implementation expertise on genetic risk factors including CYP2D6 and other genetic variations for opioids’ analgesic efficacy and opioid-related serious adverse effects, meth- ods of implementation of genotypes with clinical decision support in electronic health records, genotype- based perioperative opioid use and innovative digital tools for electronic patient reported outcomes at all participating CTSA hubs. This application with innovative preoperative genotyping, integrated personalized decision support aims to enhance understanding of opioid metabolism, personalized opioid selection, pre- cision dosing, and clinical outcomes in neonates, children, and nursing mothers, and to disseminate findings to other CTSA hubs. A unified CTSA-wide PPAP will enable genetic risk predictions and personalized in- terventions to maximize pain relief while minimizing opioid use and adverse effects in millions of children and nursing mothers undergoing surgery each year.

项目总结：围手术期阿片类药物不良反应——常见但不太严重的术后不良反应