Critical Care Medicine  |   April 2018
Dexmedetomidine Impairs Diaphragm Function and Increases Oxidative Stress but Does Not Aggravate Diaphragmatic Atrophy in Mechanically Ventilated Rats
Author Notes
  • From the Department of Anesthesiology (T.B., C.B., R.R., J.G., H.D., C.S.B.), the Department of Intensive and Intermediate Care (T.B., G.M., C.S.B.), and the Institute of Neuropathology (J.W.), Rheinisch-Westfalian Technical University Aachen, Aachen, Germany; and the Laboratory of Pneumology, Catholic University of Leuven, Leuven, Belgium (A.D., G.G.-R.).
  • Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).
    Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).×
  • G.G.-R. and C.S.B. contributed equally to this article.
    G.G.-R. and C.S.B. contributed equally to this article.×
  • Submitted for publication March 3, 2017. Accepted for publication December 7, 2017.
    Submitted for publication March 3, 2017. Accepted for publication December 7, 2017.×
  • Address correspondence to Dr. Breuer: Department of Anesthesiology, Medical Faculty, RWTH Aachen University, Pauwelsstr. 30, 52074 Aachen, Germany. tbreuer@ukaachen.de. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Critical Care Medicine / Basic Science / Critical Care / Pharmacology / Respiratory System
Critical Care Medicine   |   April 2018
Dexmedetomidine Impairs Diaphragm Function and Increases Oxidative Stress but Does Not Aggravate Diaphragmatic Atrophy in Mechanically Ventilated Rats
Anesthesiology 4 2018, Vol.128, 784-795. doi:10.1097/ALN.0000000000002081
Anesthesiology 4 2018, Vol.128, 784-795. doi:10.1097/ALN.0000000000002081
Abstract

Background: Anesthetics in ventilated patients are critical as any cofactor hampering diaphragmatic function may have a negative impact on the weaning progress and therefore on patients’ mortality. Dexmedetomidine may display antioxidant and antiproteolytic properties, but it also reduced glucose uptake by the muscle, which may impair diaphragm force production. This study tested the hypothesis that dexmedetomidine could inhibit ventilator-induced diaphragmatic dysfunction.

Methods: Twenty-four rats were separated into three groups (n = 8/group). Two groups were mechanically ventilated during either dexmedetomidine or pentobarbital exposure for 24 h, referred to as interventional groups. A third group of directly euthanized rats served as control. Force generation, fiber dimensions, proteolysis markers, protein oxidation and lipid peroxidation, calcium homeostasis markers, and glucose transporter–4 (Glut-4) translocation were measured in the diaphragm.

Results: Diaphragm force, corrected for cross-sectional area, was significantly decreased in both interventional groups compared to controls and was significantly lower with dexmedetomidine compared to pentobarbital (e.g., 100 Hz: –18%, P < 0.0001). In contrast to pentobarbital, dexmedetomidine did not lead to diaphragmatic atrophy, but it induced more protein oxidation (200% vs. 73% in pentobarbital, P = 0.0015), induced less upregulation of muscle atrophy F-box (149% vs. 374% in pentobarbital, P < 0.001) and impaired Glut-4 translocation (–73%, P < 0.0005). It activated autophagy, the calcium-dependent proteases, and caused lipid peroxidation similarly to pentobarbital.

Conclusions: Twenty-four hours of mechanical ventilation during dexmedetomidine sedation led to a worsening of ventilation-induced diaphragm dysfunction, possibly through impaired Glut-4 translocation. Although dexmedetomidine prevented diaphragmatic fiber atrophy, it did not inhibit oxidative stress and activation of the proteolytic pathways.