Strategies for Persistent Agitated Delirium in Palliative Care

姑息治疗中持续性激越性谵妄的策略

• 批准号: 10319942
• 负责人: David Hui
• 金额: $ 43.44万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10319942
• 关键词: Achievement; Acute; Address; Advanced Malignant Neoplasm; Adverse effects; Affect; Age; Agitation; Antipsychotic Agents; Benzodiazepines; Biological Markers; Cancer Patient; Caregivers; Characteristics; Clinical; Clinical Trials; Combined Modality Therapy; Complex; Consent; Coupled; Data; Decision Making; Delirium; Delusions; Distress; Dose; Double-Blind Method; Effectiveness; Enrollment; Frequencies; Goals; Hallucinations; Haloperidol; Health Professional; Hour; Hyperactivity; Interleukin-10; Interleukin-6; Interleukin-8; Intervention; Intervention Studies; Lorazepam; Mission; Monitor; Nurses; Outcome; Outcome Measure; Palliative Care; Participant; Patient Care; Patient Monitoring; Patients; Pharmaceutical Preparations; Physicians; Placebos; Prediction of Response to Therapy; Proxy; Public Health; Quality of life; Questionnaires; Randomized Controlled Trials; Research; Role; Rotation; Scheme; Sedation procedure; Severities; Standardization; Symptoms; Syndrome; Testing; Therapeutic; Time; Titrations; United States National Institutes of Health; Withdrawal; arm; effective therapy; end of life; end of life care; evidence base; experience; high risk; improved; innovation; intervention effect; neuropsychiatry; novel; novel marker; novel strategies; novel therapeutics; palliate; palliation; palliative; patient population; patient-clinician communication; predictive marker; response; response biomarker; sex; treatment effect; treatment strategy

PROJECT SUMMARY Delirium is the most common and distressing neuropsychiatric syndrome in cancer patients. It has a negative effect on symptom assessment, patient-clinician communication, decision making, and survival. Approximately 50% of patients with hyperactive or mixed delirium continue to experience agitation despite low-dose haloperidol, which can be particularly distressing to patients and caregivers. Neuroleptic dose escalation, benzodiazepine rotation, combination therapy, and neuroleptic withdrawal may provide good control of agitation. However, no delirium trials have ever been completed to directly compare these options; such trials are urgently needed to improve the quality of life of patients with this devastating syndrome. Our long-term goal is to develop evidence-based therapy for the palliation of delirium in cancer patients. The proposed study is a high-impact, 4-arm, multi-center, double-blind, double-dummy, randomized controlled trial to compare the effect of neuroleptic dose escalation, benzodiazepine rotation, combination therapy, and neuroleptic withdrawal in the treatment of persistent agitated delirium in cancer patients admitted to acute palliative care units (APCUs). We hypothesize that benzodiazepine rotation and combination therapy are particularly effective against agitated delirium. The primary specific aim of this study is to compare the effect of neuroleptic dose escalation, benzodiazepine rotation, combination therapy, and neuroleptic withdrawal on the change in Richmond Agitation Sedation Scale (RASS) over 24 hours in patients who did not experience a response to low-dose haloperidol. The second aim is to compare the effects of these treatments on (1) rescue medication use, (2) the proportion of patients in the target RASS range, (3) perceived comfort by caregivers and bedside nurses, (4) delirium-related distress in caregivers and nurses, (5) achievement of the proxy comfort goal, (6) symptom expression, (7) delirium severity, (8) adverse effects, and (9) quality of end-of-life care. The third aim is to identify novel predictive markers of response to haloperidol and lorazepam. After obtaining surrogate consent, we will administer the study medications under a titration scheme and monitor the participants closely until discharge. This study is highly innovative because (1) multiple previously untested treatment strategies are studied, (2) the outcome measures (e.g., proxy comfort goals) are novel, (3) biomarkers are included as potential predictors of treatment response, (4) the patient population (i.e., short survival) is unique, and (5) the study setting (i.e., the APCU) is distinctive. Successful completion of this definitive study will identify the optimal strategy to reduce agitation, improve patient comfort, and palliate delirium-related distress; provide timely data to address the ongoing debate regarding the proper use of haloperidol and lorazepam in delirium; inform novel strategies to monitor patients with delirium; and stimulate further studies to identify better strategies to palliate persistent agitation and improve patients' quality of life.

项目概要 谵妄是癌症患者中最常见、最令人痛苦的神经精神综合征。它有一个负数 对症状评估、患者与临床医生沟通、决策和生存的影响。大约 尽管服用低剂量药物，但 50% 的多动或混合性谵妄患者仍会出现躁动 氟哌啶醇，这会让患者和护理人员特别痛苦。抗精神病药剂量递增， 苯二氮卓类药物轮换、联合治疗和精神安定药物戒断可能会提供良好的控制 搅动。然而，还没有完成谵妄试验来直接比较这些选择；这样的试验 迫切需要改善患有这种破坏性综合症的患者的生活质量。 我们的长期目标是开发基于证据的疗法来缓解癌症患者的谵妄。 拟议的研究是一项高影响力、四组、多中心、双盲、双模拟、随机对照的研究 比较抗精神病药剂量递增、苯二氮卓类药物轮换、联合治疗和 抗精神病药停药治疗急性癌症患者持续性躁动性谵妄 姑息治疗病房 (APCU)。我们假设苯二氮卓类药物轮换和联合治疗 对躁动性谵妄特别有效。本研究的主要具体目的是比较以下方法的效果： 抗精神病药物剂量递增、苯二氮卓类药物轮换、联合治疗以及抗精神病药物停药 没有经历过激动镇静量表 (RASS) 的患者在 24 小时内的变化 对低剂量氟哌啶醇的反应。第二个目的是比较这些治疗方法对 (1) 救援的效果 药物使用情况，(2) 处于目标 RASS 范围内的患者比例，(3) 护理人员感知的舒适度 和床边护士，(4) 护理人员和护士与谵妄相关的痛苦，(5) 代理的实现 舒适目标，(6) 症状表现，(7) 谵妄严重程度，(8) 不良反应，以及 (9) 临终质量 关心。第三个目标是确定氟哌啶醇和劳拉西泮反应的新预测标记。后 获得代理人同意后，我们将根据滴定方案管理研究药物并监测 参与者密切关注直至出院。 这项研究具有高度创新性，因为（1）研究了多种先前未经测试的治疗策略， (2) 结果测量（例如替代舒适目标）是新颖的，(3) 生物标志物被列为潜在的 治疗反应的预测因素，(4) 患者群体（即短生存）是独特的，以及 (5) 研究 设置（即 APCU）是独特的。成功完成这项最终研究将确定最佳的 减少躁动、提高患者舒适度并减轻谵妄相关痛苦的策略；提供及时的数据 解决关于在谵妄中正确使用氟哌啶醇和劳拉西泮的持续争论；告知小说 监测谵妄患者的策略；并刺激进一步研究以确定更好的缓解策略 持续的躁动，改善患者的生活质量。