Department of Pharmacy and Health Systems Sciences, Bouve College of Health Sciences, Northeastern University, Boston, MA.
Department of Intensive Care, Radboud Institute for Health Science, Radboud University Medical Center, Nijmegen, The Netherlands.
Crit Care Med. 2021 Aug 1;49(8):1303-1311. doi: 10.1097/CCM.0000000000004976.
Haloperidol is commonly administered in the 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.
Fourteen Dutch ICUs between July 2013 and December 2016.
One-thousand four-hundred ninety-five critically ill adults free from delirium at ICU admission having an expected ICU stay greater than or equal to 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, Acute Physiology and Chronic Health Evaluation-II score, sepsis, mechanical ventilation, and ICU length of stay. Among the 1,495 patients, 542 (36%) developed delirium within 28 days (median [interquartile range] with delirium 4 d [2-7 d]). A total of 477 of 542 (88%) received treatment haloperidol (2.1 mg [1.0-3.8 mg] daily) for 6 days (3-11 d). Each milligram of treatment haloperidol administered daily was associated with decreased mortality at 28 days (hazard ratio, 0.93; 95% CI, 0.91-0.95) and 90 days (hazard ratio, 0.97; 95% CI, 0.96-0.98). Treatment haloperidol administered later in the ICU course was less protective of death. Results were stable by prevention study-arm, predelirium 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.
尽管没有明确的证据表明氟哌啶醇有助于消除谵妄或改善生存率，但在 ICU 中经常使用氟哌啶醇来减轻谵妄及其相关症状的负担。我们评估了氟哌啶醇治疗 ICU 新发谵妄及其症状与死亡率之间的关系。
一项随机、双盲、安慰剂对照的谵妄预防试验的事后队列分析。
2013 年 7 月至 2016 年 12 月期间，荷兰的 14 个 ICU。
1495 名入住 ICU 时无谵妄且预计 ICU 住院时间大于或等于 2 天的重症成年患者。
患者接受预防性氟哌啶醇或安慰剂治疗，最长 28 天，直至发生谵妄、死亡或 ICU 出院。如果发生谵妄，根据临床医生的判断，给予开放标签 IV 氟哌啶醇 2 mg tid（每个谵妄症状最多 5 mg tid）。
患者每天接受 4 次评估，评估谵妄和昏迷情况，为期 28 天。使用时间变化的 Cox 风险模型构建了 28 天和 90 天死亡率，控制了研究臂、谵妄和昏迷天数、年龄、急性生理学和慢性健康评估 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 天内发生谵妄（中位数[四分位距]有谵妄的时间为 4 d [2-7 d]）。共有 542 名（88%）中的 477 名患者接受了氟哌啶醇治疗（每天 2.1 mg [1.0-3.8 mg]），持续 6 天（3-11 d）。每天给予 1 毫克的治疗氟哌啶醇与 28 天（风险比，0.93；95%CI，0.91-0.95）和 90 天（风险比，0.97；95%CI，0.96-0.98）死亡率降低相关。在 ICU 病程中较晚开始使用氟哌啶醇治疗，对死亡的保护作用较小。按预防研究臂、谵妄前氟哌啶醇暴露和氟哌啶醇治疗方案依从性进行分层，结果均稳定。
用氟哌啶醇治疗新发谵妄及其症状可能与死亡率的剂量依赖性降低有关。需要进一步的随机试验来证实这些结果。
