OPTIMIZING OUTPATIENT ANESTHESIA: IMPROVING ANALGESIA AND REDUCING OPIOID MISADVENTURE

优化门诊麻醉：改善镇痛并减少阿片类药物事故

• 批准号: 10087912
• 负责人: Evan D. Kharasch
• 金额: $ 50.52万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10087912
• 关键词: Absence of pain sensation; Acute; Address; Adverse effects; Ambulatory Surgical Procedures; American; Americas; Anesthesia procedures; Caring; Cellular Phone; Cessation of life; Chronic; Clinical Research; Clinical Trials; Country; Data; Day Surgery; Development; Dose; Double-Blind Method; Effectiveness; Epidemic; Face; General Anesthesia; Goals; Healthcare; Heroin; Home; Hospitals; Hour; Human; Incidence; Inpatients; Medical; Methadone; Neurofibrillary Tangles; Operative Surgical Procedures; Opiate Addiction; Opioid; Outcome; Outpatients; Overdose; Pain; Pain intensity; Pain management; Patients; Perioperative; Pharmaceutical Preparations; Pharmacotherapy; Policies; Population; Postoperative Pain; Postoperative Period; Public Health; Randomized; Recovery; Reporting; Research; Risk Factors; Safety; Surgeon; System; Tablets; Telephone; Testing; Therapeutic; Time; Work; addiction; chronic pain; cohort; compare effectiveness; experience; functional independence; fundamental research; health related quality of life; improved; innovation; inpatient surgery; multimodality; novel; opioid epidemic; opioid misuse; opioid mortality; opioid overdose; opioid use; overdose death; pain reduction; pain relief; patient safety; pill; postoperative recovery; prescription opioid; prescription opioid abuse; prescription opioid misuse; prospective; side effect; surgical pain; trend

PROJECT SUMMARY/ABSTRACT The overall long-term objectives of this research are to: (1) reduce the over-prescribing of postoperative discharge opioids which contribute to the population reservoir of unused pills available for patient misuse, and for the diversion and misadventure which are contributing to the devastating public health problem of opioid addiction, overdose, and death; and (2) improve pain treatment, decrease postoperative opioid requirements, increase patient safety, and diminish opioid-related adverse and side effects after outpatient surgery. Our research fundamentally challenges long-practiced yet untested notions that opioids of short duration are the best way to treat surgical pain and to help patients. Anesthesiologists and surgeons face the challenge that surgical pain is inadequately treated in >80% of patients, 10-50% of whom develop chronic postsurgical pain, for which acute postoperative pain is the single greatest risk factor. Opioids are the primary pharmacotherapy for surgical pain, yet with increased use of short-duration opioids, surgical pain treatment has not improved over the past two decades. In contrast, three decades of clinical research and experience shows that a single intraoperative dose of a long-duration opioid (i.e. methadone), which sustains therapeutic drug concentrations, produces better analgesia than repeated doses of short-duration opioids and reduces further opioid requirements, in inpatient surgery. Nevertheless, in outpatient surgery, methadone has never been evaluated, and the potential benefits of methadone in outpatient surgery regarding better postoperative pain, side effects, safety, and reduced opioid consumption remain unrealized. This is a missed opportunity. We will test the innovative, paradigm-shifting hypothesis that in outpatient surgery, intraoperative anesthesia with methadone, compared with conventional short-duration opioids, achieves better analgesia, with similar or diminished side effects, reduces development of chronic postsurgical pain, improves postoperative recovery, and most importantly, decreases postoperative opioid consumption. Demonstrating reduced opioid consumption and hence diminishing prescribing of take-home opioids could shrink the population reservoir of unused opioids available for diversion and misuse, and reduce addiction, overdose, and death. This hypothesis will be tested in two prospective, randomized, double-blind clinical trials, with separate outpatient cohorts of short-stay (overnight <24 hours) and same-day surgery. We will compare general anesthesia with single-dose methadone vs as needed short-duration opioids, evaluate intraoperative and postoperative opioid use, opioid side effects, short-term and long-term postoperative pain, and overall quality of recovery for up to 1 year. Successful completion of the aims portends improved outpatient surgical care, enhanced patient recovery, and reduced postoperative opioid use. An ensuing revolutionary redesign of anesthesia care, and transformational approach to and reduction of postoperative opioid prescribing, would shrink the pool of prescription opioids in America, and help address one of the primary contributory factors to the opioid epidemic.

项目摘要/摘要 这项研究的总体长期目标是：（1）减少术后过度处方 排放阿片类药物会导致可用于患者滥用的未使用药丸的人口库， 为了导致阿片类药物毁灭性的公共卫生问题的转移和不幸 成瘾，服药过量和死亡； （2）改善疼痛治疗，减少术后阿片类药物需求， 提高患者的安全性，并减少门诊手术后与阿片类药物相关的不良反应和副作用。我们的 研究从根本上挑战了长期以来却没有测试的观念，即短期阿片类药物是 治疗外科疼痛和帮助患者的最佳方法。麻醉师和外科医生面临着一个挑战 在> 80％的患者中，手术疼痛治疗不足，其中10-50％会出现慢性术后疼痛， 急性术后疼痛是最大的危险因素。阿片类药物是主要的药物治疗 对于手术疼痛，随着使用短期阿片类药物的使用增加，手术疼痛治疗尚未改善 在过去的二十年中。相比之下，三十年的临床研究和经验表明一个单一 术中长持续阿片类药物（即美沙酮）的术中剂量，该剂量维持治疗药物浓度， 产生比重复剂量的短期阿片类药物更好的镇痛作用，并减少阿片类药物 要求，在住院手术中。然而，在门诊手术中，美沙酮从未得到评估过， 以及美沙酮在门诊手术中的潜在益处，术后疼痛，副作用， 安全性和减少的阿片类药物消费量仍未实现。这是一个错过的机会。我们将测试 创新的，范式转移的假设在门诊手术中，术中麻醉，美沙酮， 与常规的短期阿片类药物相比，取得更好的镇痛作用，侧面相似或减少 影响，减轻慢性术后疼痛的发展，改善术后康复，大多数 重要的是，减少术后阿片类药物消耗。证明阿片类药物的消费减少和 因此，降低家居阿片类药物的处方可能会缩小未使用阿片类药物的人口储藏 可用于转移和滥用，并减少成瘾，用药过量和死亡。该假设将进行检验 在两个前瞻性，随机，双盲临床试验中 （隔夜<24小时）和当天手术。我们将将全身麻醉与单剂量进行比较 美沙酮与需要的短期阿片类药物，评估术中和术后阿片类药物，阿片类药物 副作用，短期和长期术后疼痛以及长达1年的总体恢复质量。 成功完成目标预示了改善门诊手术护理，增强的患者康复和 减少术后阿片类药物的使用。随之而来的革命性重新设计麻醉护理和变革性 术后阿片类药物处方的方法和减少，将缩小处方阿片类药物的池 美国，有助于解决阿片类药物流行的主要因素之一。

项目成果

Response to the Comment on "Postoperative Opioid Prescribing and Pain".

对“术后阿片类药物处方和疼痛”评论的回应。

• DOI: 10.1097/sla.0000000000003653
• 发表时间: 2020
• 期刊: Annals of surgery
• 影响因子: 9
• 作者: Pagé,MGabrielle;Clarke,Hance;Kudrina,Irina
• 通讯作者: Kudrina,Irina

Intraoperative Methadone in Next-day Discharge Outpatient Surgery: A Randomized, Double-blinded, Dose-finding Pilot Study.

次日出院门诊手术中的术中美沙酮：一项随机、双盲、剂量探索试点研究。

• DOI: 10.1097/aln.0000000000004663
• 发表时间: 2023
• 期刊: Anesthesiology
• 影响因子: 8.8
• 作者: Kharasch,EvanD;Brunt,LMichael;Blood,Jane;Komen,Helga
• 通讯作者: Komen,Helga

Methadone Disposition: Implementing Lessons Learned.

美沙酮处置：吸取经验教训。

• DOI: 10.1002/jcph.1427
• 发表时间: 2019
• 期刊: Journal of clinical pharmacology
• 影响因子: 2.9
• 作者: Kharasch,EvanD;Greenblatt,DavidJ
• 通讯作者: Greenblatt,DavidJ

Opioid-free Anesthesia: Reply.

无阿片类药物麻醉：答复。

• DOI: 10.1097/aln.0000000000003912
• 发表时间: 2021
• 期刊: Anesthesiology
• 影响因子: 8.8
• 作者: Kharasch,EvanD;Clark,JDavid
• 通讯作者: Clark,JDavid