When patients with advanced cancer near the end of their life, it is important for physicians, nurses, and other health care personnel to respect and dignify the dying process of the patient. This requires a shift in focus from medical intervention to personalization of care to meet the subjective needs of patients and families, including coordination of care, symptom management, communication, and education; emotional and spiritual support; and support of patients’ social relationships and decision making.1 Pain, dyspnea, and hyperactive (ie, agitated) delirium are often experienced by dying patients and witnessed by caregivers. In a study, for example, 51% of 236 patients in palliative care units toward the end of their life had the distressing symptoms of hyperactive delirium.2 Limited evidence is available to guide the clinician in managing these symptoms. Although administration of psychoactive medications can sedate patients and reduce outward symptoms of hyperactive delirium, these drugs do so at the cost of precious time that dying patients and families have to communicate with each other, and they also have important adverse effects. In this issue of JAMA, the study by Hui et al3 provides critical evidence to help guide management of patients with hyperactive delirium in the last few days of life, a very difficult population to study. The investigators enrolled 90 patients with advanced malignancies and delirium who were admitted to an acute palliative care unit, and had at least 1 episode of hyperactive delirium within the previous 24 hours. All patients were then treated with an increased baseline regimen of scheduled haloperidol and were randomized in a blinded manner to receive additional haloperidol + lorazepam or haloperidol + placebo, if they had a recurrence of their hyperactive delirium. Of the 90 patients enrolled, 58 patients were randomized and received study medications for hyperactive delirium (delirium with a mean Richmond Agitation-Sedation Scale [RASS] score of 1.6; denoting apprehensive movement, frequent nonpurposeful movement, or both). Patients receiving haloperidol + lorazepam had a greater reduction of their RASS score over 8 hours than the haloperidol + placebo group (−4 in the haloperidol + lorazepam group vs −2.3 in the haloperidol + placebo group), and most of this decrease in the RASS score was observed in the first 30 minutes. Patients in the haloperidol + lorazepam group had fewer subsequent hyperactive delirium episodes (28% in the haloperidol + lorazepam group vs 76% in the haloperidol + placebo group) and less need for rescue antipsychotic medications. Caregivers and bedside nurses perceived that these patients appeared more comfortable. Although, on the surface, this study may seem to provide evidence to support treating every dying patient who demonstrates hyperactive delirium with a combination of haloperidol + lorazepam, clinicians taking care of these patients need to consider some important caveats. The combination of haloperidol + lorazepam did not treat delirium, but rather masked hyperactive delirium symptoms by sedating the patients and, more likely, converting those patients to hypoactive (ie, apathy, inattention, or lethargy) delirium. This may explain why patients in the haloperidol + lorazepam group had greater severity of delirium (evidenced by Memorial Delirium Assessment Scale [MDAS] scores ≥2 points higher) than the haloperidol + placebo group, despite fewer episodes of hyperactivity. However, the precise effects experienced by patients with hypoactive delirium are unknown because of the limitations of the MDAS in palliative care patients with low Karnofsky Performance Scale Index scores.4 Caregivers and nurses did “perceive” that the patients were more comfortable, yet given the distressing descriptions from some patients of what it is like to experience hypoactive delirium,5 these findings may reveal more about the desire to treat the distress experienced by caregivers and the health care team than actually being a patient-centered intervention. In the study by Hui et al, the mean RASS score among patients treated with haloperidol + lorazepam was −2 or −3 (minimally responsive to verbal stimulus) compared with 0 to −1 (awake and alert, or drowsy) in the haloperidol + placebo group; thus, fewer patients in the haloperidol + lorazepam group would have been able to communicate with their families during their dying hours, which, according to many dying patients, is an unfavorable outcome. Moreover, even though more patients in the haloperidol + placebo group had a RASS score of 1 (hyperactivity) or more in the ensuing 8 hours, the mean RASS score was 0 to −1 in this group, suggesting that these hyperactivity episodes were perhaps mild restlessness (RASS score, 1) and not dangerous or distressing agitation that would have put the patient at risk for causing injury to self or others. Furthermore, among the 32 of the 90 enrolled patients who were not randomized, 27 (84%) never had another hyperactive delirium episode, suggesting that, for many patients, these episodes were mild, self-limiting, or amenable to nonpharmacological (environmental or biopsychosocial) interventions or treatment of the underlying cause. The findings reported in the study by Hui et al pertain to patients in palliative care units near the end of life who are experiencing hyperactive delirium, and the findings should not be considered generalizable to the patients in, for example, the Related article page 1047 Opinion

中文翻译：

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在生命的最后几天人性化治疗过度活跃的谵妄

当晚期癌症患者接近生命的尽头时，医生、护士和其他卫生保健人员必须尊重和尊重患者的临终过程。这需要将重点从医疗干预转向个性化护理，以满足患者和家庭的主观需求，包括护理协调、症状管理、沟通和教育；情感和精神支持；和支持患者的社会关系和决策。1 疼痛、呼吸困难和过度活跃（即激动）谵妄通常由垂死的患者经历并由护理人员见证。例如，在一项研究中，临终前在姑息治疗病房的 236 名患者中有 51% 有过度活跃的谵妄的令人痛苦的症状。2 指导临床医生管理这些症状的证据有限。尽管服用精神活性药物可以使患者镇静并减轻过度活跃的谵妄的外在症状，但这些药物的这样做是以牺牲患者和家属必须相互沟通的宝贵时间为代价的，并且它们也有重要的副作用。在本期 JAMA 中，Hui 等人 3 的研究提供了重要证据，以帮助指导生命最后几天的过度活跃谵妄患者的管理，这是一个非常难以研究的人群。研究人员招募了 90 名患有晚期恶性肿瘤和谵妄的患者，这些患者被送入急性姑息治疗病房，并且在过去的 24 小时内至少发生过 1 次活动过度的谵妄。然后，所有患者都接受了增加的氟哌啶醇基线方案治疗，并以盲法随机分配接受额外的氟哌啶醇 + 劳拉西泮或氟哌啶醇 + 安慰剂，如果他们的过度活跃谵妄复发。在纳入的 90 名患者中，58 名患者被随机分配并接受研究药物治疗过度活跃的谵妄（谵妄，平均里士满躁动镇静量表 [RASS] 评分为 1.6；表示恐惧运动、频繁的无目的运动，或两者兼有）。与氟哌啶醇 + 安慰剂组相比，接受氟哌啶醇 + 劳拉西泮的患者在 8 小时内的 RASS 评分下降幅度更大（氟哌啶醇 + 劳拉西泮组为 -4，而氟哌啶醇 + 安慰剂组为 -2.3），并且 RASS 评分下降的大部分在前 30 分钟观察分数。氟哌啶醇 + 劳拉西泮组患者的后续过度活跃谵妄发作较少（氟哌啶醇 + 劳拉西泮组为 28%，而氟哌啶醇 + 安慰剂组为 76%）并且需要较少的抗精神病药物抢救。护理人员和床边护士认为这些患者看起来更舒服。尽管从表面上看，这项研究似乎提供了支持使用氟哌啶醇 + 劳拉西泮组合治疗每一个表现出过度活跃谵妄的垂死患者的证据，但照顾这些患者的临床医生需要考虑一些重要的警告。氟哌啶醇 + 劳拉西泮的组合不能治疗谵妄，而是通过镇静患者以及更有可能使这些患者转变为活动减退（即冷漠、注意力不集中或嗜睡）谵妄来掩盖过度活跃的谵妄症状。这可能解释了为什么氟哌啶醇 + 劳拉西泮组患者谵妄的严重程度（由纪念谵妄评估量表 [MDAS] 评分高出 ≥ 2 分证明）比氟哌啶醇 + 安慰剂组更严重，尽管多动症发作较少。然而，由于 MDAS 对 Karnofsky Performance Scale Index 评分较低的姑息治疗患者的局限性，对活动减退性谵妄患者所经历的确切影响尚不清楚。4 护理人员和护士确实“感知”到患者更舒适，但考虑到一些患者对经历活动性谵妄的痛苦描述，5 这些发现可能更多地揭示了治疗护理人员和医疗团队所经历的痛苦的愿望，而不是真正以患者为中心的干预。在 Hui 等人的研究中，氟哌啶醇 + 劳拉西泮治疗的患者的平均 RASS 评分为 -2 或 -3（对语言刺激的反应最小），而氟哌啶醇 + 的平均 RASS 评分为 0 至 -1（清醒和警觉，或昏昏欲睡）安慰剂组；因此，氟哌啶醇 + 劳拉西泮组中能够在临终时间与家人沟通的患者较少，据许多临终患者称，这是不利的结果。此外，尽管氟哌啶醇 + 安慰剂组中有更多患者在随后的 8 小时内的 RASS 评分为 1（多动）或更高，但该组的平均 RASS 评分为 0 至 -1，表明这些多动发作可能是轻微的躁动（RASS 评分，1），并且没有危险或令人痛苦的躁动，这会使患者处于对自己或他人造成伤害的风险中。此外，在未随机分组的 90 名登记患者中的 32 名中，27 名 (84%) 从未发生过另一次过度活跃的谵妄发作，这表明，对于许多患者而言，这些发作是轻微的、自限性的，或适合非药物（环境或生物心理社会）干预或治疗根本原因。Hui 等人在研究中报告的研究结果与临终关怀病房中正在经历多动性谵妄的患者有关，并且这些发现不应被视为可推广到患者，例如，相关文章第 1047 页意见 或适合非药物（环境或生物心理社会）干预或治疗根本原因。Hui 等人在研究中报告的研究结果与临终关怀病房中正在经历多动性谵妄的患者有关，并且这些发现不应被视为可推广到患者，例如，相关文章第 1047 页意见 或适合非药物（环境或生物心理社会）干预或治疗根本原因。Hui 等人在研究中报告的研究结果与临终关怀病房中正在经历多动性谵妄的患者有关，并且这些发现不应被视为可推广到患者，例如，相关文章第 1047 页意见