Strategies for Persistent Agitated Delirium in Palliative Care

项目摘要 谵妄是癌症患者最常见和最痛苦的神经精神综合征。有负面 对症状评估、患者-临床医生沟通、决策和生存的影响。约 50%的多动或混合性谵妄患者尽管接受了低剂量治疗， 氟哌啶醇，这对患者和护理人员来说可能特别令人痛苦。精神抑制剂剂量递增， 苯二氮卓类药物轮换、联合治疗和停药可能对抑郁症提供良好的控制。 激动然而，还没有完成谵妄试验来直接比较这些选择;这些试验 迫切需要改善这种毁灭性综合征患者的生活质量。 我们的长期目标是发展以证据为基础的治疗，以减轻癌症患者的谵妄。 拟定研究是一项高影响、4组、多中心、双盲、双模拟、随机对照研究 一项比较抗精神病药物剂量递增、苯二氮卓类药物轮换、联合治疗和 停药治疗癌症急性发作期患者持续激越性谵妄 姑息治疗单位（APCU）。我们假设苯二氮卓类药物轮换和联合治疗是 尤其是对激动性谵妄有效。本研究的主要目的是比较 抗精神病药物剂量递增、苯二氮卓类药物轮换、联合治疗和抗精神病药物停药 在未发生焦虑的患者中，24小时内里士满躁动镇静量表（RASS）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）抢救 药物使用，（2）目标RASS范围内的患者比例，（3）护理人员的舒适感 和床边护士，（4）照顾者和护士的谵妄相关的痛苦，（5）代理的实现 舒适目标，（6）症状表达，（7）谵妄严重程度，（8）不良反应，（9）生命终末期质量 在乎第三个目的是确定新的预测标记物的反应氟哌啶醇和劳拉西泮。后 在获得代理同意后，我们将根据滴定方案给予研究药物，并监测 参与者直到出院。 这项研究是高度创新的，因为（1）研究了多种以前未经测试的治疗策略， (2)结果测量（例如，代理舒适度目标）是新的，（3）生物标志物作为潜在的 治疗反应的预测因子，（4）患者群体（即，短期生存）是独一无二的，（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、改善患者舒适度和减轻谵妄相关痛苦的策略;提供及时的数据 为了解决正在进行的关于在谵妄中正确使用氟哌啶醇和劳拉西泮的争论;告知小说 监测谵妄患者的策略;并刺激进一步的研究，以确定更好的策略，以减轻 持续激越，提高患者生活质量。

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.