Groeben Harald, Mitzner Wayne, Brown Robert H
Department of Anesthesiology and Critical Care Medicine, University of Essen, Hufelandstrasse 55, 45122 Essen, Germany.
Anesthesiology. 2004 Feb;100(2):359-63. doi: 10.1097/00000542-200402000-00026.
Tracheal intubation can elicit reflex bronchoconstriction in patients with asthma or chronic obstructive pulmonary disease, complicating mechanical ventilation and weaning from mechanical support. In vitro studies of human and animal bronchial tissue indicate that alpha2-adrenoceptor stimulation can lead to smooth muscle relaxation and prevention of bronchoconstriction. Dexmedetomidine is a selective alpha2-adrenoceptor agonist approved for sedation in the intensive care unit. Whether dexmedetomidine can affect reflex bronchoconstriction is unknown.
After the approval of the institutional animal care and use committee, five mongrel dogs were anesthetized with thiopental, endotracheally intubated, and ventilated, and their airways were challenged with histamine. High-resolution computed tomography was used to measure airway luminal areas at baseline and after nebulized histamine. After recovery to baseline, on separate days, dexmedetomidine (0.5 microg/kg) was administered either intravenously or as an aerosol, and the histamine challenge was repeated.
At baseline, histamine constricted the airways to 66 +/- 27% (mean +/- SD) (P < 0.0001) and 59 +/- 30% (P < 0.0001) of maximum on the days dexmedetomidine was administered by intravenous and inhalational means, respectively. After recovery, intravenous administration of dexmedetomidine blocked the histamine-induced bronchoconstriction (87 +/- 30.4% of maximum, compared with histamine alone (P < 0.0001), whereas dexmedetomidine administered by inhalation showed no protective effect (45 +/- 30% of maximum; P < 0.0001 compared with histamine alone).
alpha2-Adrenoceptor stimulation with intravenous dexmedetomidine completely blocked histamine-induced bronchoconstriction in dogs. Therefore, dexmedetomidine might be beneficial to decrease airway reactivity in patients with chronic obstructive pulmonary disease or asthma, particularly during weaning from mechanical ventilation, when neurally mediated airway reflexes may be elicited.
气管插管可诱发哮喘或慢性阻塞性肺疾病患者出现反射性支气管收缩，使机械通气及机械支持撤离复杂化。对人和动物支气管组织的体外研究表明，α2-肾上腺素能受体激动可导致平滑肌松弛并预防支气管收缩。右美托咪定是一种经批准用于重症监护病房镇静的选择性α2-肾上腺素能受体激动剂。右美托咪定是否会影响反射性支气管收缩尚不清楚。
经机构动物护理和使用委员会批准后，对5只杂种犬用硫喷妥钠麻醉，气管插管并进行通气，用组胺刺激其气道。使用高分辨率计算机断层扫描测量基线时及雾化组胺后的气道管腔面积。恢复至基线后，在不同日期分别静脉注射或雾化给予右美托咪定（0.5μg/kg），并重复组胺刺激。
基线时，在右美托咪定分别通过静脉和吸入方式给药的日子里，组胺使气道收缩至最大收缩的66±27%（平均值±标准差）（P<0.0001）和59±30%（P<0.0001）。恢复后，静脉注射右美托咪定可阻断组胺诱导的支气管收缩（最大收缩的87±30.4%，与单独使用组胺相比，P<0.0001），而吸入右美托咪定未显示出保护作用（最大收缩的45±30%；与单独使用组胺相比，P<0.0001）。
静脉注射右美托咪定刺激α2-肾上腺素能受体可完全阻断犬组胺诱导的支气管收缩。因此，右美托咪定可能有助于降低慢性阻塞性肺疾病或哮喘患者的气道反应性，尤其是在机械通气撤离期间，此时可能会引发神经介导的气道反射。
