Reade Michael C, O'Sullivan Kim, Bates Samantha, Goldsmith Donna, Ainslie William R S T J, Bellomo Rinaldo
Department of Intensive Care Medicine, Austin Hospital and the University of Melbourne, 145 Studley Road, Heidelberg, Victoria 3084, Australia.
Crit Care. 2009;13(3):R75. doi: 10.1186/cc7890. Epub 2009 May 19.
Agitated delirium is common in patients undergoing mechanical ventilation, and is often treated with haloperidol despite concerns about safety and efficacy. Use of conventional sedatives to control agitation can preclude extubation. Dexmedetomidine, a novel sedative and anxiolytic agent, may have particular utility in these patients. We sought to compare the efficacy of haloperidol and dexmedetomidine in facilitating extubation.
We conducted a randomised, open-label, parallel-groups pilot trial in the medical and surgical intensive care unit of a university hospital. Twenty patients undergoing mechanical ventilation in whom extubation was not possible solely because of agitated delirium were randomised to receive an infusion of either haloperidol 0.5 to 2 mg/hour or dexmedetomidine 0.2 to 0.7 microg/kg/hr, with or without loading doses of 2.5 mg haloperidol or 1 mug/kg dexmedetomidine, according to clinician preference.
Dexmedetomidine significantly shortened median time to extubation from 42.5 (IQR 23.2 to 117.8) to 19.9 (IQR 7.3 to 24) hours (P = 0.016). Dexmedetomidine significantly decreased ICU length of stay, from 6.5 (IQR 4 to 9) to 1.5 (IQR 1 to 3) days (P = 0.004) after study drug commencement. Of patients who required ongoing propofol sedation, the proportion of time propofol was required was halved in those who received dexmedetomidine (79.5% (95% CI 61.8 to 97.2%) vs. 41.2% (95% CI 0 to 88.1%) of the time intubated; P = 0.05). No patients were reintubated; three receiving haloperidol could not be successfully extubated and underwent tracheostomy. One patient prematurely discontinued haloperidol due to QTc interval prolongation.
In this preliminary pilot study, we found dexmedetomidine a promising agent for the treatment of ICU-associated delirious agitation, and we suggest this warrants further testing in a definitive double-blind multi-centre trial.
Clinicaltrials.gov NCT00505804.
躁动谵妄在接受机械通气的患者中很常见，尽管存在安全性和有效性方面的担忧，但通常使用氟哌啶醇进行治疗。使用传统镇静剂控制躁动可能会妨碍拔管。右美托咪定是一种新型镇静和抗焦虑药物，可能对这些患者具有特殊用途。我们试图比较氟哌啶醇和右美托咪定在促进拔管方面的疗效。
我们在一家大学医院的内科和外科重症监护病房进行了一项随机、开放标签、平行组的试点试验。20例因躁动谵妄而无法单独拔管的接受机械通气的患者被随机分配接受0.5至2毫克/小时的氟哌啶醇输注或0.2至0.7微克/千克/小时的右美托咪定输注，根据临床医生的偏好，可给予或不给予2.5毫克氟哌啶醇或1微克/千克右美托咪定的负荷剂量。
右美托咪定显著缩短了拔管的中位时间，从42.5（四分位间距23.2至117.8）小时缩短至19.9（四分位间距7.3至24）小时（P = 0.016）。右美托咪定显著缩短了重症监护病房的住院时间，从研究药物开始后的6.5（四分位间距4至9）天缩短至1.5（四分位间距1至3）天（P = 0.004）。在需要持续丙泊酚镇静的患者中，接受右美托咪定的患者所需丙泊酚的时间比例减半（插管期间的时间分别为79.5%（95%可信区间61.8至97.2%）和41.2%（95%可信区间0至88.1%）；P = 0.05）。没有患者再次插管；三名接受氟哌啶醇治疗的患者无法成功拔管并接受了气管切开术。一名患者因QTc间期延长而提前停用氟哌啶醇。
在这项初步试点研究中，我们发现右美托咪定是治疗与重症监护病房相关的谵妄性躁动的一种有前景的药物，我们建议这值得在一项确定性的双盲多中心试验中进一步测试。
Clinicaltrials.gov NCT00505804。
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