Burns, Trauma, and Critical Care Research Centre, University of Queensland and Joint Health Command, Australian Defence Force, Brisbane, Australia.
Austin Hospital, Melbourne, Australia.
JAMA. 2016 Apr 12;315(14):1460-8. doi: 10.1001/jama.2016.2707.
Effective therapy has not been established for patients with agitated delirium receiving mechanical ventilation.
To determine the effectiveness of dexmedetomidine when added to standard care in patients with agitated delirium receiving mechanical ventilation.
DESIGN, SETTING, AND PARTICIPANTS: The Dexmedetomidine to Lessen ICU Agitation (DahLIA) study was a double-blind, placebo-controlled, parallel-group randomized clinical trial involving 74 adult patients in whom extubation was considered inappropriate because of the severity of agitation and delirium. The study was conducted at 15 intensive care units in Australia and New Zealand from May 2011 until December 2013. Patients with advanced dementia or traumatic brain injury were excluded.
Bedside nursing staff administered dexmedetomidine (or placebo) initially at a rate of 0.5 µg/kg/h and then titrated to rates between 0 and 1.5 µg/kg/h to achieve physician-prescribed sedation goals. The study drug or placebo was continued until no longer required or up to 7 days. All other care was at the discretion of the treating physician.
Ventilator-free hours in the 7 days following randomization. There were 21 reported secondary outcomes that were defined a priori.
Of the 74 randomized patients (median age, 57 years; 18 [24%] women), 2 withdrew consent later and 1 was found to have been randomized incorrectly, leaving 39 patients in the dexmedetomidine group and 32 patients in the placebo group for analysis. Dexmedetomidine increased ventilator-free hours at 7 days compared with placebo (median, 144.8 hours vs 127.5 hours, respectively; median difference between groups, 17.0 hours [95% CI, 4.0 to 33.2 hours]; P = .01). Among the 21 a priori secondary outcomes, none were significantly worse with dexmedetomidine, and several showed statistically significant benefit, including reduced time to extubation (median, 21.9 hours vs 44.3 hours with placebo; median difference between groups, 19.5 hours [95% CI, 5.3 to 31.1 hours]; P < .001) and accelerated resolution of delirium (median, 23.3 hours vs 40.0 hours; median difference between groups, 16.0 hours [95% CI, 3.0 to 28.0 hours]; P = .01). Using hierarchical Cox modeling to adjust for imbalanced baseline characteristics, allocation to dexmedetomidine was significantly associated with earlier extubation (hazard ratio, 0.47 [95% CI, 0.27-0.82]; P = .007).
Among patients with agitated delirium receiving mechanical ventilation in the intensive care unit, the addition of dexmedetomidine to standard care compared with standard care alone (placebo) resulted in more ventilator-free hours at 7 days. The findings support the use of dexmedetomidine in patients such as these.
clinicaltrials.gov Identifier: NCT01151865.
对于接受机械通气的激越性谵妄患者，尚未确立有效的治疗方法。
确定右美托咪定在机械通气的激越性谵妄患者的标准治疗基础上的有效性。
设计、设置和参与者：Dexmedetomidine to Lessen ICU Agitation（DahLIA）研究是一项双盲、安慰剂对照、平行组随机临床试验，涉及 74 名成人患者，由于激越和谵妄的严重程度，认为拔管不合适。该研究在澳大利亚和新西兰的 15 个重症监护病房进行，于 2011 年 5 月至 2013 年 12 月进行。排除有晚期痴呆或创伤性脑损伤的患者。
床边护理人员最初以 0.5μg/kg/h 的速度给予右美托咪定（或安慰剂），然后根据需要滴定至 0 至 1.5μg/kg/h 之间的剂量，以达到医生规定的镇静目标。研究药物或安慰剂持续使用，直至不再需要或最长使用 7 天。所有其他护理均由主治医生决定。
随机分组后 7 天内的无呼吸机时间。预先定义了 21 个报告的次要结局。
在 74 名随机患者中（中位年龄 57 岁；18 [24%] 名女性），2 名患者后来撤回了同意，1 名患者被发现随机分配不正确，因此 39 名患者接受右美托咪定治疗，32 名患者接受安慰剂治疗。与安慰剂相比，右美托咪定增加了 7 天的无呼吸机时间（中位数分别为 144.8 小时和 127.5 小时，分别为 17.0 小时[95%CI，4.0 至 33.2 小时]；P = .01）。在 21 个预先确定的次要结局中，没有一个明显恶化，而且几个结局表现出统计学上的显著获益，包括减少拔管时间（中位数分别为 21.9 小时和 44.3 小时，与安慰剂相比，右美托咪定组的中位数差异为 19.5 小时[95%CI，5.3 至 31.1 小时]；P < .001）和加速谵妄的缓解（中位数分别为 23.3 小时和 40.0 小时，右美托咪定组的中位数差异为 16.0 小时[95%CI，3.0 至 28.0 小时]；P = .01）。使用分层 Cox 模型调整基线特征的不平衡，与分配到右美托咪定相比，分配到右美托咪定与更早的拔管显著相关（风险比，0.47[95%CI，0.27-0.82]；P = .007）。
在重症监护病房接受机械通气的激越性谵妄患者中，与单独接受标准治疗（安慰剂）相比，在标准治疗基础上添加右美托咪定可使 7 天的无呼吸机时间更长。这些发现支持在这些患者中使用右美托咪定。
clinicaltrials.gov 标识符：NCT01151865。
