Optimizing the use of ketamine to reduce chronic postsurgical pain

优化氯胺酮的使用以减少慢性术后疼痛

基本信息

批准号：
10527397
负责人：
Lisa Doan
金额：
$ 10.61万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-17 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10527397
关键词：
Absence of pain sensation Acetaminophen Acute Acute Pain Agreement American Anxiety Bolus Infusion Breast-Conserving Surgery Brief Pain Inventory Chronic Clinical Clinical and Translational Science Awards Conduction Anesthesia Consent Forms Continuous Infusion Data Analyses Data Collection Databases Development Double-Blind Method Effectiveness Emergency Medicine Enrollment Goals Guidelines Hospitals Hour Incidence Information Dissemination Infrastructure Infusion procedures Intervention Ketamine Link Lymph Node Dissections Machine Learning Mastectomy Measures Medicine Mental Depression Methods Modeling Mood Disorders Moods Nature Neuropathy Non-Steroidal Anti-Inflammatory Agents Operative Surgical Procedures Opiate Addiction Pain Pain management Patients Perioperative Phase Placebos Play Postoperative Care Postoperative Pain Postoperative Period Prevention Protocols documentation Questionnaires Randomized Randomized Controlled Trials Recommendation Recovery Recovery of Function Regimen Reporting Risk Risk Factors Role Saline Severities Short-Form McGill Pain Questionnaire Site Societies Statistical Data Interpretation Syndrome System Testing Time Training Treatment Efficacy Treatment Protocols United States National Institutes of Health Universities Washington Woman anxiety treatment arm base breast surgery cancer pain chronic pain cohort combat cost effective data management effectiveness research effectiveness study effectiveness testing effectiveness trial efficacy testing functional disability high reward high risk improved innovation machine learning model malignant breast neoplasm multimodality opioid epidemic opioid sparing opioid use pain catastrophizing participant retention payment pilot trial precision medicine predictive marker prevent primary endpoint recruit secondary analysis secondary endpoint success surgical pain three-arm study treatment effect treatment response treatment risk

项目摘要

Chronic pain contributes significantly to the current opioid epidemic. Up to 20% of postoperative patients develop chronic postsurgical pain (CPSP). CPSP is highly associated with chronic opioid use and dependence, and yet routine multimodal analgesia as a combination of acetaminophen, NSAIDs, and anti-neuropathic agents is only moderately effective in preventing CPSP. The incidence for CPSP is particularly high in patients undergoing mastectomy or breast conserving surgery with lymph node dissections (25-60%). This specific postsurgical pain condition is known as post-mastectomy pain syndrome (PMPS), and a recent study showed that 1 in 10 patients continue to use opioids 3 months after surgery. We aim to study the effectiveness of perioperative ketamine for the prevention of PMPS, within the NIH HEAL Pain Management Effectiveness Research Network (Pain ERN). Our rationale is that ketamine can reduce key risks for CPSP including acute pain severity, anxiety and depression, and pain catastrophizing, and in doing so can prevent the development of PMPS. Mechanistically, ketamine is known to enhance endogenous cortical control of pain and mood. There is strong clinical evidence for perioperative ketamine infusion in reducing postsurgical pain, and for a single ketamine bolus (0.3-0.5mg/kg) to treat depression and anxiety associated with postsurgical pain. However, studies are urgently needed to test the efficacy of ketamine in the perioperative period for preventing CPSP, particularly PMPS, in a large cohort of patients and to assess clinical variables predictive for chronic pain severity and for treatment effects. We aim to conduct a multi-site, three-arm RCT to study the effectiveness of ketamine in reducing the incidence and severity of PMPS. 750 patients after mastectomy or breast conserving surgery with lymph node dissection will be randomized to receive either a standard continuous ketamine infusion starting after induction (bolus of 0.35mg/kg followed by infusion at the rate of 0.25mg/kg/hr) and continued for 3 hours after surgery, a regimen of single-bolus ketamine (0.6mg/kg) administered right after surgery, or placebo (saline) control. To maintain the pragmatic nature of an effectiveness trial, all patients will receive routine postoperative multimodal analgesia. Compatible with recent NIH recommendations, we will assess pain, function and mood over 12 months after surgery. We will use Brief Pain Inventory (BPI) severity score at 3 months after surgery as primary endpoints. Secondary endpoints include pain incidence, BPI, short- form McGill's Pain Questionnaire, opioid use, NIH PROMIS scales, Hospital Anxiety and Depression Scale, Pain Catastrophizing Scale, and Breast Cancer Pain Questionnaire. We will also build precision medicine models to analyze clinical variables associated with CPSP and with success of ketamine treatment. Agreements have been reached with 11 sites, including 7 Clinical and Translational Science Awards (CTSA) hubs, NYU, Columbia, Einstein, BWH, Washington University at St. Louis, Duke, and Univ. Washington, to carry out this study successfully.

慢性疼痛在很大程度上导致了当前阿片类药物的流行。高达 20% 的术后患者发生慢性术后疼痛（CPSP）。 CPSP 与慢性阿片类药物使用和依赖密切相关，但常规多模式镇痛是对乙酰氨基酚、非甾体抗炎药和抗神经病药物的组合药物在预防 CPSP 方面仅具有中等效果。 CPSP 在患者中的发生率特别高接受乳房切除术或保乳手术及淋巴结清扫术（25-60%）。这个具体术后疼痛被称为乳房切除术后疼痛综合征 (PMPS)，最近的一项研究表明十分之一的患者在手术后 3 个月继续使用阿片类药物。我们的目标是研究有效性围术期氯胺酮预防 PMPS，符合 NIH HEAL 疼痛管理有效性研究网络（疼痛 ERN）。我们的理由是氯胺酮可以降低 CPSP 的主要风险，包括急性疼痛的严重程度、焦虑和抑郁以及疼痛的灾难性，这样做可以防止病情的发展的 PMPS。从机制上讲，氯胺酮可以增强内源性皮质对疼痛和情绪的控制。那里是围手术期氯胺酮输注可减轻术后疼痛的强有力的临床证据，并且单次氯胺酮推注（0.3-0.5mg/kg）用于治疗与术后疼痛相关的抑郁和焦虑。然而，迫切需要研究来测试氯胺酮在围手术期预防 CPSP 的功效，特别是 PMPS，在一大群患者中进行，并评估预测慢性疼痛的临床变量严重程度和治疗效果。我们的目标是进行多中心、三臂随机对照试验来研究氯胺酮可降低 PMPS 的发生率和严重程度。 750 名乳房切除或保乳患者淋巴结清扫手术将随机接受标准连续氯胺酮治疗诱导后开始输注（0.35mg/kg 推注，然后以 0.25mg/kg/hr 的速率输注）和手术后持续 3 小时，术后立即给予单次推注氯胺酮 (0.6mg/kg) 方案手术或安慰剂（盐水）对照。为了保持有效性试验的务实性质，所有患者将术后常规接受多模式镇痛。与最近的 NIH 建议兼容，我们将评估术后 12 个月内的疼痛、功能和情绪。我们将使用简短疼痛量表 (BPI) 严重程度术后 3 个月的评分作为主要终点。次要终点包括疼痛发生率、BPI、短期形成麦吉尔疼痛问卷、阿片类药物使用、NIH PROMIS 量表、医院焦虑和抑郁量表、疼痛灾难化量表和乳腺癌疼痛问卷。我们还将打造精准医疗模型来分析与 CPSP 和氯胺酮治疗成功相关的临床变量。已与 11 个中心达成协议，其中包括 7 个临床和转化科学奖 (CTSA) 中心，纽约大学、哥伦比亚大学、爱因斯坦大学、BWH、华盛顿大学圣路易斯分校、杜克大学和大学。华盛顿, 至成功地开展这项研究。