Strategies for Persistent Agitated Delirium in Palliative Care

项目总结 妄想症是癌症患者中最常见和最令人痛苦的神经精神综合征。它有一个负面的 对症状评估、患者与临床医生沟通、决策和生存的影响。大致 50%的患有多动症或混合性妄想的患者尽管服用了低剂量的药物，但仍会持续出现躁动。 氟哌啶醇，这可能是特别痛苦的患者和照顾者。抗精神病药的剂量增加， 苯二氮卓类药物的轮换、联合治疗和停用抗精神病药物可提供良好的控制 激动不安。然而，尚未完成任何精神错乱试验来直接比较这些选项；此类试验 迫切需要改善这种毁灭性综合症患者的生活质量。 我们的长期目标是开发以证据为基础的疗法来缓解癌症患者的精神错乱。 本研究为高影响、四臂、多中心、双盲、双模拟、随机对照研究 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 停用抗精神病药治疗癌症患者急性期持续性躁动妄想 姑息治疗病房(APCU)。我们假设苯二氮卓类药物的轮换和联合治疗 对焦虑性精神错乱特别有效。这项研究的主要具体目的是比较 抗精神病药物剂量递增、苯二氮卓类药物轮换、联合治疗和停药 24小时内里士满激越镇静评分(RASS)的变化 对小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，(2)在目标RASS范围内的患者的比例，(3)照顾者感受到的舒适度 和床边护士，(4)照顾者和护士中与精神错乱相关的痛苦，(5)代理人的成就 舒适目标，(6)症状表现，(7)精神错乱严重程度，(8)不良反应，和(9)临终质量 关心。第三个目标是确定对氟哌啶醇和劳拉西潘反应的新的预测标记物。之后 获得代孕人同意后，我们将根据滴定计划给予研究药物，并监测 参赛者严阵以待，直至出院。 这项研究具有很高的创新性，因为(1)研究了多种以前未经测试的治疗策略， (2)结果指标(例如，替代舒适度目标)是新颖的；(3)生物标记物是潜在的 治疗反应的预测因素，(4)患者群体(即，短期存活)是唯一的，以及(5)研究 设置(即，APCU)是独特的。成功完成这项权威性研究将确定最佳 减少焦虑、改善患者舒适度和缓解与精神错乱相关的痛苦的策略；提供及时的数据 解决有关氟哌啶醇和劳拉西潘在精神错乱中的正确使用的持续辩论；告知小说 监测精神错乱患者的策略；并鼓励进一步研究，以确定更好的缓解策略 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.