丙泊酚镇静在大鼠自主呼吸和机械通气期间诱导相似的膈肌功能障碍和萎缩。

Sedation using propofol induces similar diaphragm dysfunction and atrophy during spontaneous breathing and mechanical ventilation in rats.

机构信息

From the Department of Surgical Intensive and Intermediate Care, and Department of Anesthesiology, University Hospital of the RWTH Aachen, University of Excellence, Aachen, Germany (C.S.B.); Fonds voor Wetenschappelijk Onderzoek-Flanders, Laboratory of Pneumology, Katholieke Universiteit Leuven, Leuven, Belgium (K.M.); Department of Anesthesiology, University Hospital of the RWTH Aachen, University of Excellence, Aachen, Germany (R.R., I.B., and C.B.); Laboratory of Pneumology, Katholieke Universiteit Leuven, Leuven, Belgium (D.T., N.C., and G.G.-R.); and Institute of Neuropathology and JARA, Translational Brain Medicine, Aachen; University Hospital of the RWTH Aachen, University of Excellence, Aachen, Germany (J.W.).

出版信息

Anesthesiology. 2014 Mar;120(3):665-72. doi: 10.1097/ALN.0000000000000125.

DOI:10.1097/ALN.0000000000000125

PMID:24401770

Abstract

BACKGROUND

Mechanical ventilation is crucial for patients with respiratory failure. The mechanical takeover of diaphragm function leads to diaphragm dysfunction and atrophy (ventilator-induced diaphragmatic dysfunction), with an increase in oxidative stress as a major contributor. In most patients, a sedative regimen has to be initiated to allow tube tolerance and ventilator synchrony. Clinical data imply a correlation between cumulative propofol dosage and diaphragm dysfunction, whereas laboratory investigations have revealed that propofol has some antioxidant properties. The authors hypothesized that propofol reduces markers of oxidative stress, atrophy, and contractile dysfunction in the diaphragm.

METHODS

Male Wistar rats (n = 8 per group) were subjected to either 24 h of mechanical ventilation or were undergone breathing spontaneously for 24 h under propofol sedation to test for drug effects. Another acutely sacrificed group served as controls. After sacrifice, diaphragm tissue was removed, and contractile properties, cross-sectional areas, oxidative stress, and proteolysis were examined. The gastrocnemius served as internal control.

RESULTS

Propofol did not protect against diaphragm atrophy, oxidative stress, and protease activation. The decrease in tetanic force compared with controls was similar in the spontaneous breathing group (31%) and in the ventilated group (34%), and both groups showed the same amount of muscle atrophy. The gastrocnemius muscle fibers did not show atrophy.

CONCLUSIONS

Propofol does not protect against ventilator-induced diaphragmatic dysfunction or oxidative injury. Notably, spontaneous breathing under propofol sedation resulted in the same amount of diaphragm atrophy and dysfunction although diaphragm activation per se protects against ventilator-induced diaphragmatic dysfunction. This makes a drug effect of propofol likely.

摘要

背景

机械通气对于呼吸衰竭患者至关重要。膈肌功能的机械接管会导致膈肌功能障碍和萎缩（呼吸机诱导的膈肌功能障碍），氧化应激增加是主要原因之一。在大多数患者中，必须启动镇静方案以允许耐受管和呼吸机同步。临床数据表明，累积异丙酚剂量与膈肌功能障碍之间存在相关性，而实验室研究表明异丙酚具有一些抗氧化特性。作者假设异丙酚可降低膈肌氧化应激、萎缩和收缩功能障碍的标志物。