Effect of Lorazepam With Haloperidol vs Haloperidol Alone on Agitated Delirium in Patients With Advanced Cancer Receiving Palliative Care: A Randomized Clinical Trial.
Effect of Lorazepam With Haloperidol vs Haloperidol Alone on Agitated Delirium in Patients With Advanced Cancer Receiving Palliative Care: A Randomized Clinical Trial.
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DOI：
10.1001/jama.2017.11468
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发表时间：
2017-09-19
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影响因子：
--
通讯作者：
Bruera E
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作者：
Hui D;Frisbee-Hume S;Wilson A;Dibaj SS;Nguyen T;De La Cruz M;Walker P;Zhukovsky DS;Delgado-Guay M;Vidal M;Epner D;Reddy A;Tanco K;Williams J;Hall S;Liu D;Hess K;Amin S;Breitbart W;Bruera E
在生命的最后几天使用苯二氮卓类药物来控制谵妄中的躁动是有争议的。比较劳拉西泮与安慰剂作为氟哌啶醇辅助治疗晚期癌症谵妄患者持续躁动的效果。2014年2月11日至2016年6月30日，在德克萨斯州MD安德森癌症中心的急性姑息治疗单元进行了一项单中心、双盲、平行组、随机临床试验，纳入了93例晚期癌症和躁动性谵妄患者，尽管他们计划使用氟哌啶醇，但数据收集于2016年10月完成。在躁动发作时，除氟哌啶醇（2mg）外，静脉滴注劳拉西泮（3mg） （n = 47）或安慰剂（n = 43）。主要终点是治疗后8小时Richmond激动镇静量表（RASS）评分的变化（范围从- 5[无法唤醒]到4[非常激动或好斗]）。次要终点是抢救性抗精神病药的使用、谵妄回忆、舒适度（护理人员和护士的感知）、沟通能力、谵妄严重程度、不良反应、出院结局和总生存率。在90例随机患者（平均年龄62岁，女性42例[47%]）中，58例（64%）接受了研究药物治疗，52例（90%）完成了试验。劳拉西泮+氟哌啶醇组在8小时时RASS评分的降低（- 4.1分）显著高于安慰剂+氟哌啶醇组（- 2.3分）（平均差值为- 1.9分[95% CI， - 2.8至- 0.9];P < .001）。劳拉西泮+氟哌啶醇组比安慰剂+氟哌啶醇组（4.0 mg）需要更少的中位数救救性抗精神病药（2.0 mg）（中位数差为- 1.0 mg [95% CI, - 2.0至0]；P = 0.009），并且盲法护理人员和护士都认为劳拉西泮+氟哌啶醇组比安慰剂+氟哌啶醇组更舒适(护理人员：劳拉西泮+氟哌啶醇组为84%，安慰剂+氟哌啶醇组为37%；平均差为47% [95% CI， 14%至73%]，P = 0.009；护士：劳拉西泮+氟哌啶醇组77% vs安慰剂+氟哌啶醇组30%；平均差异为47% [95% CI， 17% ~ 71%], P = 0.005)。在谵妄相关的痛苦和生存率方面，两组间无显著差异。最常见的不良反应是运动功能减退（劳拉西泮+氟哌啶醇组3例（19%），安慰剂+氟哌啶醇组4例（27%））。在这项针对晚期癌症患者躁动性谵妄住院患者的初步试验中，氟哌啶醇加劳拉西泮比氟哌啶醇单独加氟哌啶醇在8小时内显著更大程度地减少躁动。需要进一步的研究来评估其普遍性和不良影响。clinicaltrials.gov识别码：NCT01949662
The use of benzodiazepines to control agitation in delirium in the last days of life is controversial. To compare the effect of lorazepam vs placebo as an adjuvant to haloperidol for persistent agitation in patients with delirium in the setting of advanced cancer. Single-center, double-blind, parallel-group, randomized clinical trial conducted at an acute palliative care unit at MD Anderson Cancer Center, Texas, enrolling 93 patients with advanced cancer and agitated delirium despite scheduled haloperidol from February 11, 2014, to June 30, 2016, with data collection completed in October 2016. Lorazepam (3 mg) intravenously (n = 47) or placebo (n = 43) in addition to haloperidol (2 mg) intravenously upon the onset of an agitation episode. The primary outcome was change in Richmond Agitation-Sedation Scale (RASS) score (range, −5 [unarousable] to 4 [very agitated or combative]) from baseline to 8 hours after treatment administration. Secondary end points were rescue neuroleptic use, delirium recall, comfort (perceived by caregivers and nurses), communication capacity, delirium severity, adverse effects, discharge outcomes, and overall survival. Among 90 randomized patients (mean age, 62 years; women, 42 [47%]), 58 (64%) received the study medication and 52 (90%) completed the trial. Lorazepam + haloperidol resulted in a significantly greater reduction of RASS score at 8 hours (−4.1 points) than placebo + haloperidol (−2.3 points) (mean difference, −1.9 points [95% CI, −2.8 to −0.9]; P < .001). The lorazepam + haloperidol group required less median rescue neuroleptics (2.0 mg) than the placebo + haloperidol group (4.0 mg) (median difference, −1.0 mg [95% CI, −2.0 to 0]; P = .009) and was perceived to be more comfortable by both blinded caregivers and nurses (caregivers: 84% for the lorazepam + haloperidol group vs 37% for the placebo + haloperidol group; mean difference, 47% [95% CI, 14% to 73%], P = .007; nurses: 77% for the lorazepam + haloperidol group vs 30% for the placebo + haloperidol group; mean difference, 47% [95% CI, 17% to 71%], P = .005). No significant between-group differences were found in delirium-related distress and survival. The most common adverse effect was hypokinesia (3 patients in the lorazepam + haloperidol group [19%] and 4 patients in the placebo + haloperidol group [27%]). In this preliminary trial of hospitalized patients with agitated delirium in the setting of advanced cancer, the addition of lorazepam to haloperidol compared with haloperidol alone resulted in a significantly greater reduction in agitation at 8 hours. Further research is needed to assess generalizability and adverse effects. clinicaltrials.gov Identifier: NCT01949662
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8.8
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