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

• 批准号: 10490898
• 负责人: Lisa Doan
• 金额: $ 120.69万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 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/10490898
• 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

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.

慢性疼痛对当前的阿片类药物流行产生了重大贡献。多达20％的术后患者 发展慢性术后疼痛（CPSP）。 CPSP与慢性阿片类药物的使用和依赖性高度相关， 然而，常规的多模式镇痛作为对乙酰氨基酚，NSAID和抗神经性的组合 代理仅在防止CPSP方面有效。患者的CPSP发病率特别高 用淋巴结清扫术进行乳房切除术或乳房保存手术（25-60％）。这个具体 外科疼痛病被称为术后术后疼痛综合征（PMP），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。我们旨在研究 NIH治愈疼痛管理有效性，围手术期氯胺酮用于预防PMP 研究网络（疼痛ERN）。我们的理由是，氯胺酮可以减少CPSP的关键风险 疼痛的严重程度，焦虑和抑郁以及疼痛灾难性，这样做可以防止发展 PMP。从机械上讲，氯胺酮已知可以增强内源性皮质控制疼痛和情绪。那里 是围手术期氯胺酮输注的有力临床证据 氯胺酮（0.3-0.5mg/kg）治疗与术后疼痛有关的抑郁症和焦虑。然而， 迫切需要进行研究以测试围手术期在防止CPSP的疗效， 特别是PMP，在大量患者中，评估慢性疼痛的临床变量 严重程度和治疗效果。我们旨在进行多站点的三臂RCT来研究 氯胺酮减少PMP的发病率和严重程度。乳房切除术或乳房保存后750名患者 淋巴结清扫术的手术将随机分配以接受标准连续氯胺酮 从诱导后开始输注（推注为0.35mg/kg，然后以0.25mg/kg/hr的速度输注）和 手术后持续3个小时，一项单支氯胺酮（0.6mg/kg）的治疗方案 手术或安慰剂（盐水）控制。为了维持有效性试验的务实性质，所有患者将 接受常规的术后多模式镇痛。与最近的NIH建议兼容，我们将 在手术后12个月内评估疼痛，​​功能和情绪。我们将使用简短的疼痛清单（BPI）严重性 在手术后3个月作为主要终点。次要终点包括疼痛发生率，BPI，短 - 麦吉尔的疼痛问卷，阿片类药物使用，NIH Promis量表，医院焦虑和抑郁量表， 疼痛灾难性量表和乳腺癌疼痛问卷。我们还将建立精密医学 分析与CPSP相关的临床变量以及与氯胺酮治疗成功相关的模型。 已经达成了11个站点的协议，其中包括7项临床和转化科学奖（CTSA） 枢纽，纽约大学，哥伦比亚，爱因斯坦，BWH，华盛顿大学，圣路易斯，杜克大学和大学。华盛顿，去 成功进行这项研究。