Muscarinic receptor antagonist therapy improves acute pulmonary dysfunction after smoke inhalation injury in sheep
Muscarinic receptor antagonist therapy improves acute pulmonary dysfunction after smoke inhalation injury in sheep
复制标题
DOI：
10.1097/ccm.0b013e3181f8557b
复制
发表时间：
2010-12-01
影响因子：
8.8
通讯作者：
Cox, Robert A.
中科院分区：
文献类型：
--
作者：
Jonkam, Collette;Zhu, Yong;Cox, Robert A.
目的：吸入性损伤增加了烧伤患者的发病率和死亡率。在人类和复合烟雾吸入和烧伤的绵羊模型中，支气管痉挛和急性呼吸道阻塞导致进行性肺功能不全。本研究验证了M_1和M_3受体拮抗剂噻托溴铵治疗M_1和M_3受体拮抗剂将减少气道收缩反应和急性支气管阻塞以改善肺功能的假说。设计：32只绵羊的随机前瞻性研究。地点：大型动物重症监护研究实验室。干预：研究包括六组：假手术组(n=4，仪器化非损伤)，对照组(n=6，损伤和未治疗)，以及硫托溴铵治疗组，包括损伤前和损伤后雾化吸入方案。各组均于伤前1小时雾化吸入硫托溴铵36毫克(n=6)，伤后1小时雾化吸入18毫克(n=6)、36毫克(n=6)和72毫克(n=4)。所有治疗组在24小时的研究期间每4小时增加14.4毫克。主要结果：硫托溴铵预处理显著减轻烟雾吸入和烧伤复合伤后出现的呼吸机压升高、肺功能障碍和上呼吸道阻塞。在预防肺功能不全方面，使用噻托溴铵的创伤后治疗与治疗前一样有效，尽管只有在所有治疗后情况下才有减少梗阻的趋势。结论：本研究描述了乙酰胆碱对吸入性损伤后的气道收缩和管腔阻塞反应的贡献，并确认小剂量的噻托溴铵雾化吸入是治疗严重吸入性损伤的一种潜在的有效治疗方法。(Crit Care Med 2010；38：2339-2344)
Objectives: Inhalation injury contributes to the morbidity and mortality of burn victims. In humans and in an ovine model of combined smoke inhalation and burn injury, bronchospasm and acute airway obstruction contribute to progressive pulmonary insufficiency. This study tests the hypothesis that muscarinic receptor antagonist therapy with tiotropium bromide, an M1 and M3 muscarinic receptor antagonist, will decrease the airway constrictive response and acute bronchial obstruction to improve pulmonary function compared to injured animals without treatment.Design: Randomized, prospective study involving 32 sheep.Setting: Large-animal intensive care research laboratory.Interventions: The study consisted of six groups: a sham group (n = 4, instrumented noninjured), a control group (n = 6, injured and not treated), and tiotropium bromide-treated groups, including both preinjury and postinjury nebulization protocols. Treatments for these groups included nebulization with 36 mu g of tiotropium bromide 1 hr before injury (n = 6) and postinjury nebulization protocols of 18 mu g (n = 6), 36 mu g (n = 6), and 72 mu g n = 4) administered 1 hr after injury. All treated groups received an additional 14.4 mu g every 4 hrs for the 24-hr study period.Main Results: Pretreatment with tiotropium bromide significantly attenuated the increases in ventilatory pressures, pulmonary dysfunction, and upper airway obstruction that occur after combined smoke inhalation and burn injury. Postinjury treatments with tiotropium bromide were as effective as pretreatment in preventing pulmonary insufficiency, although a trend toward decreased obstruction was present only in all post-treatment conditions. There was no improvement noted in pulmonary function in animals that received a higher dose of tiotropium bromide.Conclusions: This study describes a contribution of acetylcholine to the airway constrictive and lumenal obstructive response after inhalation injury and identifies low-dose nebulization of tiotropium bromide as a potentially efficacious therapy for burn patients with severe inhalation injury. (Crit Care Med 2010; 38:2339-2344)