Der Anaesthesist

, Volume 63, Issue 1, pp 47–53 | Cite as

Ventilatorinduzierte diaphragmale Dysfunktion

Klinisch relevantes Problem
Intensivmedizin
First Online:

Zusammenfassung

Die mechanische Beatmung ist für Patienten mit respiratorischem Versagen oder im Rahmen der tiefen Sedierung lebensrettend. Während kontinuierlicher mandatorischer Beatmung ist das Diaphragma inaktiviert und unterliegt einer pathophysiologischen Kaskade, die zum Kraftverlust und zur Verringerung der Muskelfasermasse führt. Diese Prozesse sind im Gegensatz zur peripheren Skelettmuskulatur bereits nach 12 h nachweisbar und haben Einfluss auf die Beatmungsentwöhnung von Intensivpatienten – und damit auf Letalität sowie Morbidität. Studien der letzten Jahre haben tierexperimentell die pathophysiologischen Zusammenhänge untersucht und sind durch klinische Untersuchungen bestätigt worden. Diese Übersicht beschreibt die biochemischen Zusammenhänge, Einflüsse von Pharmaka und Interventionen zur Prophylaxe.

Schlüsselwörter

Mechanische Beatmung Beatmungsentwöhnung Muskelkontraktion Chronisch-obstruktive Lungenerkrankung Zytokine 

Ventilator-induced diaphragm dysfunction

Clinically relevant problem

Abstract

Mechanical ventilation is a life-saving intervention for patients with respiratory failure or during deep sedation. During continuous mandatory ventilation the diaphragm remains inactive, which activates pathophysiological cascades leading to a loss of contractile force and muscle mass (collectively referred to as ventilator-induced diaphragm dysfunction, VIDD). In contrast to peripheral skeletal muscles this process is rapid and develops after as little as 12 h and has a profound influence on weaning patients from mechanical ventilation as well as increased incidences of morbidity and mortality. In recent years, animal experiments have revealed pathophysiological mechanisms which have been confirmed in humans. One major mechanism is the mitochondrial generation of reactive oxygen species that have been shown to damage contractile proteins and facilitate protease activation. Besides atrophy due to inactivity, drug interactions can induce further muscle atrophy. Data from animal research concerning the influence of corticosteroids emphasize a dose-dependent influence on diaphragm atrophy and function although the clinical interpretation in intensive care patients (ICU) patients might be difficult. Levosimendan has also been proven to increase diaphragm contractile forces in humans which may prove to be helpful for patients experiencing difficult weaning. Additionally, antioxidant drugs that scavenge reactive oxygen species have been demonstrated to protect the diaphragm from VIDD in several animal studies. The translation of these drugs into the IUC setting might protect patients from VIDD and facilitate the weaning process.

Keywords

Mechanical ventilation Ventilator weaning Muscle contraction Chronic obstructive pulmonary disease Cytokines 
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Notes

Einhaltung ethischer Richtlinien

Interessenkonflikt. C.S. Bruells, G. Marx und R. Rossaint geben an, dass kein Interessenkonflikt besteht. Das vorliegende Manuskript enthält keine Studien an Menschen oder Tieren.

Literatur

  1. 1.
    Acute Respiratory Distress Syndrome Network (2000) Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 342:1301–1308CrossRefGoogle Scholar
  2. 2.
    Hudson MB, Smuder AJ, Nelson WB et al (2012) Both high level pressure support ventilation and controlled mechanical ventilation induce diaphragm dysfunction and atrophy. Crit Care Med 40:1254–1260PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Levine S, Nguyen T, Taylor N et al (2008) Rapid disuse atrophy of diaphragm fibers in mechanically ventilated humans. N Engl J Med 358:1327–1335PubMedCrossRefGoogle Scholar
  4. 4.
    Picard M, Jung B, Liang F et al (2012) Mitochondrial dysfunction and lipid accumulation in the human diaphragm during mechanical ventilation. Am J Respir Crit Care Med 186:1140–1149PubMedCrossRefGoogle Scholar
  5. 5.
    McClung JM, Judge AR, Talbert EE, Powers SK (2009) Calpain-1 is required for hydrogen peroxide-induced myotube atrophy. Am J Physiol Cell Physiol 296:C363–C371PubMedCrossRefGoogle Scholar
  6. 6.
    McClung JM, Kavazis AN, Deruisseau KC et al (2007) Caspase-3 regulation of diaphragm myonuclear domain during mechanical ventilation-induced atrophy. Am J Respir Crit Care Med 175:150–159PubMedCrossRefGoogle Scholar
  7. 7.
    Powers SK, Smuder AJ, Criswell DS (2011) Mechanistic links between oxidative stress and disuse muscle atrophy. Antioxid Redox Signal 15:2519–2528PubMedCrossRefGoogle Scholar
  8. 8.
    Powers SK, Hudson MB, Nelson WB et al (2011) Mitochondria-targeted antioxidants protect against mechanical ventilation-induced diaphragm weakness. Crit Care Med 39:1749–1759PubMedCrossRefGoogle Scholar
  9. 9.
    Levine S, Biswas C, Dierov J et al (2011) Increased proteolysis, myosin depletion, and atrophic AKT-FOXO signaling in human diaphragm disuse. Am J Respir Crit Care Med 183:483–490PubMedCrossRefGoogle Scholar
  10. 10.
    Hermans G, Agten A, Testelmans D et al (2010) Increased duration of mechanical ventilation is associated with decreased diaphragmatic force: a prospective observational study. Crit Care 14:R127PubMedCrossRefGoogle Scholar
  11. 11.
    Grosu HB, Lee YI, Lee J et al (2012) Diaphragm muscle thinning in patients who are mechanically ventilated. Chest 142:1455–1460PubMedCrossRefGoogle Scholar
  12. 12.
    Esteban A, Anzueto A, Frutos F et al (2002) Characteristics and outcomes in adult patients receiving mechanical ventilation: a 28-day international study. JAMA 287:345–355PubMedCrossRefGoogle Scholar
  13. 13.
    Criswell DS, Shanely RA, Betters JJ et al (2003) Cumulative effects of aging and mechanical ventilation on in vitro diaphragm function. Chest 124:2302–2308PubMedCrossRefGoogle Scholar
  14. 14.
    Levine S, Bashir MH, Clanton TL et al (2012) COPD elicits remodeling of the diaphragm and vastus lateralis muscles in humans. J Appl Physiol 114:1235–1245PubMedCrossRefGoogle Scholar
  15. 15.
    Sexton WL, Poole DC (1998) Effects of emphysema on diaphragm blood flow during exercise. J Appl Physiol 84:971–979PubMedGoogle Scholar
  16. 16.
    Poole DC, Kindig CA, Behnke BJ (2001) Effects of emphysema on diaphragm microvascular oxygen pressure. J Appl Physiol 168:1081–1086Google Scholar
  17. 17.
    Davis RT 3rd, Bruells CS, Stabley JN et al (2012) Mechanical ventilation reduces rat diaphragm blood flow and impairs oxygen delivery and uptake. Crit Care Med 40:2858–2866PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Li X, Moody MR, Engel D et al (2000) Cardiac-specific overexpression of tumor necrosis factor-alpha causes oxidative stress and contractile dysfunction in mouse diaphragm. Circulation 102:1690–1696PubMedCrossRefGoogle Scholar
  19. 19.
    Bruells CS, Smuder AJ, Reiss LK et al (2013) Negative pressure ventilation and positive pressure ventilation promote comparable levels of ventilator-induced diaphragmatic dysfunction in rats. Anesthesiology. DOI 10.1097/ALN.1090b1013e31829b33692Google Scholar
  20. 20.
    Haegens A, Schols AM, Gorissen SH et al (2012) NF-kappaB activation and polyubiquitin conjugation are required for pulmonary inflammation-induced diaphragm atrophy. Am J Physiol Lung Cell Mol Physiol 302:L103–L110PubMedCrossRefGoogle Scholar
  21. 21.
    Callahan LA, Supinski GS (2009) Sepsis-induced myopathy. Crit Care Med 37:S354–S367PubMedCrossRefGoogle Scholar
  22. 22.
    Schellekens WJ, Hees HW van, Vaneker M et al (2012) Toll-like receptor 4 signaling in ventilator-induced diaphragm atrophy. Anesthesiology 117:329–338PubMedCrossRefGoogle Scholar
  23. 23.
    Bruells CS, Maes K, Rossaint R et al (2013) Prolonged mechanical ventilation alters the expression pattern of angio-neogenetic factors in a pre-clinical rat model. PLoS One 8:e70524PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Maes K, Agten A, Smuder A et al (2010) Corticosteroid effects on ventilator-induced diaphragm dysfunction in anesthetized rats depend on the dose administered. Respir Res 11:178PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Sassoon CS, Zhu E, Pham HT et al (2008) Acute effects of high-dose methylprednisolone on diaphragm muscle function. Muscle Nerve 38:1161–1172PubMedCrossRefGoogle Scholar
  26. 26.
    Smuder AJ, Hudson MB, Nelson WB et al (2012) Nuclear factor-kappaB signaling contributes to mechanical ventilation-induced diaphragm weakness. Crit Care Med 40:927–934PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Maes K, Testelmans D, Thomas D et al (2011) High dose methylprednisolone counteracts the negative effects of rocuronium on diaphragm function. Intensive Care Med 37:1865–1872PubMedCrossRefGoogle Scholar
  28. 28.
    Testelmans D, Maes K, Wouters P et al (2007) Infusions of rocuronium and cisatracurium exert different effects on rat diaphragm function. Intensive Care Med 33:872–879PubMedCrossRefGoogle Scholar
  29. 29.
    Powers SK, Hudson MB, Nelson WB et al (2011) Mitochondria-targeted antioxidants protect against mechanical ventilation-induced diaphragm weakness. Crit Care Med 39:1749–1759PubMedCrossRefGoogle Scholar
  30. 30.
    Agten A, Maes K, Smuder A et al (2011) N-Acetylcysteine protects the rat diaphragm from the decreased contractility associated with controlled mechanical ventilation. Crit Care Med 39:777–782PubMedCrossRefGoogle Scholar
  31. 31.
    Doorduin J, Sinderby CA, Beck J et al (2012) The calcium sensitizer levosimendan improves human diaphragm function. Am J Respir Crit Care Med 185:90–95PubMedCrossRefGoogle Scholar
  32. 32.
    Bruells CS, Rossaint R (2011) Physiology of gas exchange during anaesthesia. Eur J Anaesthesiol 28:570–579PubMedCrossRefGoogle Scholar
  33. 33.
    Papazian L, Forel JM, Gacouin A et al (2010) Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med 363:1107–1116PubMedCrossRefGoogle Scholar
  34. 34.
    Gayan-Ramirez G, Testelmans D, Maes K et al (2005) Intermittent spontaneous breathing protects the rat diaphragm from mechanical ventilation effects. Crit Care Med 33:2804–2809PubMedCrossRefGoogle Scholar
  35. 35.
    Futier E, Constantin JM, Combaret L et al (2008) Pressure support ventilation attenuates ventilator-induced protein modifications in the diaphragm. Crit Care 12:R116PubMedCrossRefGoogle Scholar
  36. 36.
    Laghi F, Cattapan SE, Jubran A et al (2003) Is weaning failure caused by low-frequency fatigue of the diaphragm? Am J Respir Crit Care Med 167:120–127PubMedCrossRefGoogle Scholar
  37. 37.
    Bruells CS, Bergs I, Rossaint R et al (2012) Diaphragmatic repair after onset of ventilator induced diaphragmatic dysfunction needs longer than ventilation time. Congress of the American Thoracic Society Philadelphia May 17–22:A4834Google Scholar
  38. 38.
    Jaber S, Jung B, Sebbane M et al (2008) Alteration of the piglet diaphragm contractility in vivo and its recovery after acute hypercapnia. Anesthesiology 108:651–658PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Jung B, Sebbane M, Le Goff C et al (2013) Moderate and prolonged hypercapnic acidosis may protect against ventilator-induced diaphragmatic dysfunction in healthy piglet: an in vivo study. Crit Care 17:R15PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Klinik für Operative Intensivmedizin und Intermediate CareUniversitätsklinikum der RWTH AachenAachenDeutschland
  2. 2.Klinik für AnästhesiologieUniversitätsklinikum der RWTH AachenAachenDeutschland

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