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Weaning: Respiratory Muscles

Weaning: Respiratory Muscles. Theodoros Vassilakopoulos Department of Critical Care & Pulmonary Services University of Athens Medical School Evangelismos Hospital Athens, Greece. Balance Load / Neuromuscular Capacity. Vassilakopoulos T et al Eur Respir J 1996;9:2383-2400.

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Weaning: Respiratory Muscles

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  1. Weaning: Respiratory Muscles Theodoros Vassilakopoulos Department of Critical Care & Pulmonary Services University of Athens Medical School Evangelismos Hospital Athens, Greece

  2. Balance Load / Neuromuscular Capacity Vassilakopoulos T et al Eur Respir J 1996;9:2383-2400

  3. Imbalance Load / Neuromuscular Capacity FRC FRC+50%IC Roussos C et al, J Appl Physiol 1979;46:897-904

  4. Weaning: Imbalance Load / Neuromuscular Capacity Vassilakopoulos T et al, AJRCCM 1998; 158:378-85

  5. Imbalance Energy Supplies / Demands Vassilakopoulos T et al Eur Respir J 1996;9:2383-2400

  6. The load of the respiratory muscles is within the fatiguing zone in patients who fail to wean Vassilakopoulos T et al, AJRCCM 1998; 158:378-85

  7. TTI: What does it signify? Bellemare & Grassino J Appl Physiol 1982;53:1190-5

  8. Low Long-lasting High Short-lasting Moxham J et al J Appl Physiol 1982;53:1094-99 What is skeletal muscle fatigue?

  9. Low frequency diaphragmatic fatigue takes time to recover Laghi F et al J Appl Physiol 1995; 500:193-204

  10. Should we rest respiratory muscles to reverse fatiguein difficult weaning ?

  11. Is low frequency fatigue causing weaning failure? Magnetic Bilateral Phrenic nerve Stimulation Laghi F et al, AJRCCM 2003; 167:120-7

  12. Is low frequency fatigue causing weaning failure? Laghi F et al, AJRCCM 2003; 167:120-7

  13. At the last minute of the weaning trialTTIdi=0.26 Tlim= 13 minutes Laghi F et al, AJRCCM 2003; 167:120-7

  14. Weaning trials were terminated before the time patients were predicted to develop low frequency fatigue of the diaphragm

  15. If standard predefined criteria of weaning outcome are usedlow frequency fatigue is not present at the time weaning fails Controlled Mechanical Ventilation should not be used for fatigue reversal in difficult weaning • Vassilakopoulos T et al, Critical Care 2005;10(1):204

  16. Watson AC et al, Crit Care Med 2001;29:1325-1331 Laghi F et al, AJRCCM 2003; 167:120-7 Weaning Failure: Respiratory Muscle Weakness

  17. Weaning Failure: Respiratory muscle weaknessThink Of: • ICU-acquired paresis • Prolonged neuromuscular blockade • Critical illness myopathy & neuropathy • Acute quadraplegic myopathy • Ventilator-Induced diaphragmatic dysfunction (VIDD)

  18. ICU-acquired paresis • CRITICAL ILLNESS POLYNEUROPATHY & MYOPATHY (CIPNM) • Sepsis • Multi-organ dysfunction • Hyperglycemia • Intensive insulin therapy reduces CIPNM from 51.9% to 28.7% of patients receiving > 7 days of ICU care • Van den Berghe G et al N Engl J Med 2001;345:1359-67 • Drugs (NMB, corticosteroids) • Pure neuropathy, myopathy, neuromyopathy • Diagnosis: ENG, EMG, muscle biopsy Deem S et al Am J Respir Crit Care Med 2003;168:735-9

  19. ICU-acquired paresis (ICUAP) De Jonhge B et al, Intensive Care Med 2004;30:1117-1121

  20. Potential complication of CMV:Ventilator-Induced Diaphragmatic Dysfunction • “Loss of diaphragmatic force generating capacity that is specifically related to the use of controlled mechanical ventilation” Vassilakopoulos T et al. AJRCCM 2004;169: 336-341

  21. In Vitro Contractility Powers SK et al, J Appl Physiol 2002;92:1851-1858

  22. Is neural transmission impaired? Radell P. et al, Intensive Care Med 2002;28:358-364

  23. Contractile dysfunction resides within the diaphragmatic muscle

  24. Mechanisms of contractile dysfunction • Muscle Atrophy • Oxidative Stress • Structural Injury • Fiber Type Transformation • Remodeling

  25. Atrophy Shanely RA et al. Am J Respir Crit Care Med 2002;166: 1369-74

  26. Muscle Atrophy • Protein synthesis • Proteolysis

  27. Protein Synthesis Shanely RA et al. Am J Respir Crit Care Med 2004;170:994-9

  28. Proteolysis • Lysosomal proteases (cathepsins) • Calpains • Proteasome

  29. proteolysis Shanely RA et al. Am J Respir Crit Care Med 2002;166: 1369-74

  30. Calpains degrade proteins partially Calpains render proteins anemable to proteasome degradation Shanely RA et al. Am J Respir Crit Care Med 2002;166: 1369-74

  31. Proteasome

  32. 26S Proteasome

  33. 26S Proteasome degrades hydrophobic proteins

  34. 26S proteasome is upregulatedMuscle Atrophy Factor box- E3 ligase CON AMV CMV Sassoon C et al. Am J Respir Crit Care Med 2004;170:626-32

  35. 20S Proteasome is activated Shanely RA et al. Am J Respir Crit Care Med 2002;166: 1369-74

  36. 20S Proteasome degrades oxidized proteins

  37. Oxidative stress: time course Zergeroglu et al. J Appl Physiol 2003;95: 1116-1124

  38. Contractile proteins are targets of oxidative stress Ab against Myosin Heavy Chain Ab against Reactive Carbonyl Deriviatives Zergeroglu et al. J Appl Physiol 2003;95: 1116-1124

  39. Ultrastructural injury Lipid droplets Abnormal mitochondria Abnormal myofibrils Vacuoles Zhu E. et al, J Appl Physiol 2005;99:747-756

  40. Ultrastructural injury Control Mechanical Ventilation Diaphragm Diaphragm External Intercostal Bernard N et al Intensive Care Med 2003;29:111-118

  41. Force decline is proportional to injury Sassoon C. et al, J Appl Physiol 2002;92:2586-2595

  42. Summary: mechanisms of VIDD • Muscle Atrophy • Oxidative Stress • Structural Injury

  43. When to suspect VIDD • Patient who fails to wean • Controlled Mechanical Ventilation (CMV) • ICU-Acquired Paresis excluded • Prolonged neuromuscular blockade: • TOF • Critical Illness Polyneuropathy & Myopathy: • ENG, EMG, muscle biopsy • VIDD may coexist or aggravate ICUAP

  44. How to prevent VIDD • We do not really know! • Potential countermeasures: • Assisted modes of mechanical ventilation • Intermittent activity? • Periodic electrical stimulation? • Antioxidant administration

  45. Assist Control Ventilation Sassoon C et al. Am J Respir Crit Care Med 2004;170:626-32

  46. Antioxidants Betters J et al. Am J Respir Crit Care Med 2004;170:1179-84

  47. Antioxidants & contractility Betters J et al. Am J Respir Crit Care Med 2004;170:1179-84

  48. Antioxidants in mechanically ventilated patients * * Days 294 301 294 301 Vit E 1000 IU q8h Vit C 1000 mg q8h Nathens A et al Annals of Surgery 2002;236:814-822

  49. Antioxidant nutrients: a systematic review of trace elements and vitamins in the critically ill patient • Conclusions: Trace elements and vitamins that support antioxidant function are safe and may be associated with a reduction in mortality in critically ill patients Heyland D et al, Intensive Care Med 2005;31:327-337

  50. Conclusions • Respiratory muscles during weaning failure: • excessive load • Weakness • Weakness may be due: • ICU-acquired paresis • VIDD • Preventive measures: • Strict glucose control • Assisted modes of mechanical ventilation • Antioxidants

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