NEJM: 氟哌啶醇治疗ICU患者的谵妄

Abstract

Background: Haloperidol is frequently used to treat delirium in patients in the intensive care unit (ICU), but evidence of its effect is limited.氟哌啶醇常用于治疗重症监护病房 (ICU) 患者的谵妄，但其效果的证据有限。

Methods: In this multicenter, blinded, placebo-controlled trial, we randomly assigned adult patients with delirium who had been admitted to the ICU for an acute condition to receive intravenous haloperidol (2.5 mg 3 times daily plus 2.5 mg as needed up to a total maximum daily dose of 20 mg) or placebo. Haloperidol or placebo was administered in the ICU for as long as delirium continued and as needed for recurrences. The primary outcome was the number of days alive and out of the hospital at 90 days after randomization.在这项多中心、盲法、安慰剂对照试验中，我们随机分配因急性疾病入住 ICU 的谵妄成人患者接受静脉注射氟哌啶醇（2.5 mg每日3次加2.5 mg按需给药，每日最大总剂量为20 mg）或安慰剂。只要谵妄持续存在，并根据复发需要，在 ICU 给予氟哌啶醇或安慰剂。主要结局是随机化后90天时存活和出院的天数。

Results: A total of 1000 patients underwent randomization; 510 were assigned to the haloperidol group and 490 to the placebo group. Among these patients, 987 (98.7%) were included in the final analyses (501 in the haloperidol group and 486 in the placebo group). Primary outcome data were available for 963 patients (97.6%). At 90 days, the mean number of days alive and out of the hospital was 35.8 (95% confidence interval [CI], 32.9 to 38.6) in the haloperidol group and 32.9 (95% CI, 29.9 to 35.8) in the placebo group, with an adjusted mean difference of 2.9 days (95% CI, -1.2 to 7.0) (P = 0.22). Mortality at 90 days was 36.3% in the haloperidol group and 43.3% in the placebo group (adjusted absolute difference, -6.9 percentage points [95% CI, -13.0 to -0.6]). Serious adverse reactions occurred in 11 patients in the haloperidol group and in 9 patients in the placebo group.共有1000例患者接受随机化；510例分配至氟哌啶醇组，490例分配至安慰剂组。在这些患者中，987例 (98.7%) 被纳入最终分析（氟哌啶醇组501例，安慰剂组486例）。963例患者 (97.6%) 的主要结局数据可用。在90天时，氟哌啶醇组的平均出院后存活天数为35.8天（95%置信区间 [CI]，32.9-38.6），安慰剂组为32.9天 (95%CI，29.9-35.8)，校正平均差异为2.9天（95%CI，-1.2至7.0）(P = 0.22)。氟哌啶醇组90天时的死亡率为36.3%，安慰剂组为43.3%（校正的绝对差异为-6.9个百分点 [95%CI，-13.0至-0.6]）。氟哌啶醇组发生严重不良反应11例，安慰剂组9例。

Conclusions: Among patients in the ICU with delirium, treatment with haloperidol did not lead to a significantly greater number of days alive and out of the hospital at 90 days than placebo. (Funded by Innovation Fund Denmark and others; AID-ICU ClinicalTrials.gov number, NCT03392376; EudraCT number, 2017-003829-15.).在 ICU 谵妄患者中，氟哌啶醇治疗未导致90天时存活和出院天数显著多于安慰剂组。