Department of Anesthesiology and Pain Medicine, Kosin University Gospel Hospital, Busan, Korea.
Korean J Anesthesiol. 2012 May;62(5):405-11. doi: 10.4097/kjae.2012.62.5.405. Epub 2012 May 24.
Dexmedetomidine (DEX), a highly selective α(2)-adrenergic receptor agonist, is the newest agent introduced for sedation in intensive care unit (ICU). The sedation strategy for critically ill patients has stressed light sedation with daily awakening and assessment for neurologic, cognitive, and respiratory functions, since Society of Critical Care Medicine (SCCM) guidelines were presented in 2002. The traditional GABAergic agents, including benzodiazepines and propofol, have some limitations for safe sedatives in this setting, due to an unfavorable pharmacokinetic profile and to detrimental adverse effects (such as lorazepam associated propylene glycol intoxication and propofol infusion syndrome). DEX produces it's sedative, analgesic and cardiovascular effects through α(2) receptors on the locus ceruleus (LC). Activities of LC, the tuberomammillary nucleus (TMN) are depressed and activity of the ventrolateral preoptic nucleus (VLPO) is increased during DEX sedation, which is similar in features to normal non-REM (NREM) sleep. At the same time, perifornical orexinergic activity is maintained, which might be associated with attention. This mechanism of action produces a normal sleep-like, cooperative sedation. The characteristic feature of sedation, together with a concomitant opioid sparing effect, may decrease the length of time spent on a ventilator, length of stay in ICU, and prevalence and duration of delirium, as the evidence shown from several comparative studies. In addition, DEX has an excellent safety profile. In conclusion, DEX is considered as a promising agent optimized for sedation in ICU.
右美托咪定(DEX)是一种高选择性的α(2)-肾上腺素能受体激动剂,是重症监护病房(ICU)镇静的最新药物。自 2002 年危重病医学会(SCCM)指南提出以来,危重患者的镇静策略强调轻度镇静,每日唤醒并评估神经、认知和呼吸功能。传统的 GABA 能药物,包括苯二氮䓬类和丙泊酚,由于药代动力学特征不理想和不利的不良反应(如劳拉西泮相关的丙二醇中毒和丙泊酚输注综合征),对于这种情况下的安全镇静剂存在一些限制。DEX 通过蓝斑核(LC)上的α(2)受体产生其镇静、镇痛和心血管作用。LC 的活动,即结节乳头核(TMN)被抑制,腹外侧视前核(VLPO)的活动增加,在 DEX 镇静期间,这与正常非快速眼动(NREM)睡眠的特征相似。与此同时,穹窿周食欲素能活动得以维持,这可能与注意力有关。这种作用机制产生了一种类似于正常睡眠的、合作的镇静作用。镇静的特征,加上同时的阿片类药物节省效应,可能会减少呼吸机使用时间、ICU 住院时间以及谵妄的发生率和持续时间,这是几项比较研究的证据。此外,DEX 具有极好的安全性。总之,DEX 被认为是一种有前途的 ICU 镇静药物。