Association Between Incident Delirium Treatment With Haloperidol and Mortality in Critically Ill Adults.
Association Between Incident Delirium Treatment With Haloperidol and Mortality in Critically Ill Adults.
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DOI：
10.1097/ccm.0000000000004976
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发表时间：
2021-08-01
影响因子：
8.8
通讯作者：
van den Boogaard M
中科院分区：
文献类型：
--
作者：
Duprey MS;Devlin JW;van der Hoeven JG;Pickkers P;Briesacher BA;Saczynski JS;Griffith JL;van den Boogaard M
尽管没有明确的证据表明氟哌啶醇有助于缓解精神错乱或提高存活率，但在重症监护病房(ICU)中，氟哌啶醇通常用于减轻精神错乱的负担及其相关症状。我们评估了氟哌啶醇用于治疗ICU偶发精神错乱及其症状和死亡率之间的关系。一项随机、双盲、安慰剂对照、预防神志不清试验的随机队列分析。14荷兰ICU在2013年7月至2016年12月期间，1495名重症成人在ICU入院时没有精神错乱，预计将在ICU停留≥2天，患者接受预防性氟哌啶醇或安慰剂最多28天，直到精神错乱发生、死亡或ICU出院。如果出现精神错乱，由临床医生酌情给予开放标签的氟哌啶醇2毫克，每日三次(每次精神错乱症状最多5毫克，每日三次)治疗。对患者进行为期28天的神志不清和昏迷评估。建立了28天和90天死亡率的时变Cox风险模型，控制了研究组、精神错乱和昏迷天数、年龄、APACHE-II评分、脓毒症、机械通气和ICU住院时间。在1495名患者中，542名(36%)在28天内出现妄想(中位数[IQR]天，伴妄想4[2-7])。共有477/542(88%)患者接受氟哌啶醇治疗(每天2.1[1.0-3.8]mg)，疗程6[3-11]天。每天服用每毫克氟哌啶醇可降低28天(HR 0.93；95%CI为0.91至0.95)和90天(HR为0.97；95%CI为0.96至0.98)的死亡率。在ICU疗程后期给予氟哌啶醇治疗对死亡的保护作用较小。通过预防研究-ARM、精神分裂症前期氟哌啶醇暴露和氟哌啶醇治疗方案的坚持，结果是稳定的。用氟哌啶醇治疗偶发性精神错乱及其症状可能与剂量依赖性的生存改善有关。未来的随机试验需要证实这些结果。
Haloperidol is commonly administered in the intensive care unit (ICU) to reduce the burden of delirium and its related symptoms despite no clear evidence showing haloperidol helps to resolve delirium or improve survival. We evaluated the association between haloperidol, when used to treat incident ICU delirium and its symptoms, and mortality. Post-hoc cohort analysis of a randomized, double-blind, placebo-controlled, delirium-prevention trial. 14 Dutch ICUs between July 2013 and December 2016 1495 critically ill adults free from delirium at ICU admission having an expected ICU stay ≥2 days Patients received preventive haloperidol or placebo for up to 28 days until delirium occurrence, death, or ICU discharge. If delirium occurred, treatment with open-label IV haloperidol 2 mg TID (up to 5 mg TID per delirium symptoms) was administered at clinician discretion. Patients were evaluated TID for delirium and coma for 28 days. Time-varying Cox hazards models were constructed for 28-day and 90-day mortality, controlling for study-arm, delirium and coma days, age, APACHE-II score, sepsis, mechanical ventilation, and ICU length of stay. Among the 1495 patients, 542 (36%) developed delirium within 28 days (median [IQR] days with delirium 4[2–7]). A total of 477/542 (88%) received treatment haloperidol (2.1 [1.0–3.8] mg daily) for 6 [3–11] days. Each milligram of treatment haloperidol administered daily was associated with decreased mortality at 28 (HR 0.93; 95% CI 0.91 to 0.95) and 90 (HR 0.97; 95% CI 0.96 to 0.98) days. Treatment haloperidol administered later in the ICU course was less protective of death. Results were stable by prevention study-arm, pre-delirium haloperidol exposure, and haloperidol treatment protocol adherence. Treatment of incident delirium and its symptoms with haloperidol may be associated with a dose-dependent improvement in survival. Future randomized trials need to confirm these results.