Objectives: 

We sought to evaluate dexmedetomidine efficacy in assuring comfort and sparing conventional drugs when used for prolonged sedation (≥24 hr) in critically ill patients, by using validated clinical scores while systematically collecting drug dosages. We also evaluated the safety profile of dexmedetomidine and the risk factors associated with adverse events.

Design: 

Observational prospective study.

Setting: 

Nine tertiary-care PICUs.

Patients: 

Patients less than 18 years who received dexmedetomidine for greater than or equal to 24 hours between January 2016 and December 2017.

Interventions: 

None.

Measurements and Main Results: 

One-hundred sixty-three patients (median age, 13 mo; interquartile range, 4–71 mo) were enrolled. The main indication for dexmedetomidine use was as an adjuvant for drug-sparing (42%). Twenty-three patients (14%) received dexmedetomidine as monotherapy. Seven percent of patients received a loading dose. The median infusion duration was 108 hours (interquartile range, 60–168 hr), with dosages between 0.4 (interquartile range, 0.3–0.5) and 0.8 µg/kg/hr (interquartile range, 0.6–1.2 µg/kg/hr). At 24 hours of dexmedetomidine infusion, values of COMFORT-B Scale (n = 114), Withdrawal Assessment Tool-1 (n = 43) and Cornell Assessment of Pediatric Delirum (n = 6) were significantly decreased compared with values registered immediately pre dexmedetomidine (p < 0.001, p < 0.001, p = 0.027). Dosages/kg/hr of benzodiazepines, opioids, propofol, and ketamine were also significantly decreased (p < 0.001, p < 0.001, p = 0.001, p = 0.027). The infusion was weaned off in 85% of patients, over a median time of 36 hours (interquartile range, 12–48 hr), and abruptly discontinued in 15% of them. Thirty-seven percent of patients showed hemodynamic changes, and 9% displayed hemodynamic adverse events that required intervention (dose reduction in 79% of cases). A multivariate logistic regression model showed that a loading dose (odds ratio, 4.8; CI, 1.2–18.7) and dosages greater than 1.2 µg/kg/hr (odds ratio, 5.4; CI, 1.9–15.2) increased the odds of hemodynamic changes.

Conclusions: 

Dexmedetomidine used for prolonged sedation assures comfort, spares use of other sedation drugs, and helps to attenuate withdrawal syndrome and delirium symptoms. Adverse events are mainly hemodynamic and are reversible following dose reduction. A loading dose and higher infusion dosages are independent risk factors for hemodynamic adverse events.

中文翻译：

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右美托咪定在 PICU 中用于长期镇静的疗效和安全性：一项前瞻性多中心研究 (PROSDEX)。

目标： 

我们试图通过使用经过验证的临床评分同时系统地收集药物剂量来评估右美托咪定在用于危重病患者长时间镇静（≥24 小时）时确保舒适和节省常规药物的功效。我们还评估了右美托咪定的安全性以及与不良事件相关的风险因素。

设计： 

观察性前瞻性研究。

环境： 

九个三级护理 PICU。

患者： 

2016 年 1 月至 2017 年 12 月期间接受右美托咪定超过或等于 24 小时的18 岁以下患者。

干预： 

没有任何。

测量和主要结果： 

招募了 163 名患者（中位年龄，13 个月；四分位距，4-71 个月）。右美托咪定的主要适应症是作为节省药物的佐剂（42%）。23 名患者 (14%) 接受了右美托咪定单药治疗。7% 的患者接受了负荷剂量。中位输注持续时间为 108 小时（四分位距，60–168 小时），剂量在 0.4（四分位距，0.3–0.5）和 0.8 µg/kg/hr（四分位距，0.6–1.2 µg/kg/hr）之间。右美托咪定输注24 小时时， COMFORT -B 量表 ( n = 114)、戒断评估工具-1 ( n = 43) 和康奈尔小儿谵妄评估值 ( n= 6) 与右美托咪定前立即登记的值相比显着降低( p < 0.001, p < 0.001, p = 0.027)。苯二氮卓类药物、阿片类药物、丙泊酚和氯胺酮的剂量/kg/hr 也显着降低（p < 0.001, p < 0.001, p = 0.001, p= 0.027)。85% 的患者停止输注，中位时间为 36 小时（四分位距，12-48 小时），其中 15% 的患者突然停止输注。37% 的患者表现出血流动力学变化，9% 表现出需要干预的血流动力学不良事件（79% 的病例减少剂量）。多变量逻辑回归模型显示，负荷剂量（优势比，4.8；CI，1.2–18.7）和大于 1.2 µg/kg/hr 的剂量（优势比，5.4；CI，1.9–15.2）增加了血流动力学变化的几率.

结论： 

用于长时间镇静的右美托咪定可确保舒适，避免使用其他镇静药物，并有助于减轻戒断综合征和谵妄症状。不良事件主要是血流动力学，并且在剂量减少后是可逆的。负荷剂量和更高的输注剂量是血流动力学不良事件的独立危险因素。