Weaning: Respiratory Muscles

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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. - PowerPoint PPT Presentation

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  • Weaning: Respiratory Muscles

    Theodoros Vassilakopoulos

    Department of Critical Care & Pulmonary Services University of Athens Medical SchoolEvangelismos HospitalAthens, Greece

  • Balance Load / Neuromuscular CapacityVassilakopoulos T et al Eur Respir J 1996;9:2383-2400

  • Vassilakopoulos T et al Eur Respir J 1996;9:2383-2400Balance Energy Supplies / Demands

  • Vassilakopoulos T et al Eur Respir J 1996;9:2383-2400Mechanical model of the ability to breathe

  • Roussos C et al, J Appl Physiol 1979;46:897-904Imbalance Load / Neuromuscular CapacityFRCFRC+50%IC

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

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

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

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

  • What is skeletal muscle fatigue?

  • Low frequency diaphragmatic fatigue takes time to recoverLaghi F et al J Appl Physiol 1995; 500:193-204

  • Should we rest respiratory muscles to reverse fatiguein difficult weaning ?

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

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

  • At the last minute of the weaning trial TTIdi=0.26Tlim= 13 minutesLaghi F et al, AJRCCM 2003; 167:120-7

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

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

  • Weaning Failure: Respiratory Muscle Weakness

  • ICU-acquired paresis Prolonged neuromuscular blockadeCritical illness myopathy & neuropathy Acute quadraplegic myopathyVentilator-Induced diaphragmatic dysfunction (VIDD)

    Weaning Failure: Respiratory muscle weaknessThink Of:

  • CRITICAL ILLNESS POLYNEUROPATHY & MYOPATHY (CIPNM)SepsisMulti-organ dysfunctionHyperglycemiaIntensive insulin therapy reduces CIPNM from 51.9% to 28.7% of patients receiving > 7 days of ICU careVan den Berghe G et al N Engl J Med 2001;345:1359-67Drugs (NMB, corticosteroids)Pure neuropathy, myopathy, neuromyopathyDiagnosis: ENG, EMG, muscle biopsy ICU-acquired paresisDeem S et al Am J Respir Crit Care Med 2003;168:735-9

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

  • Potential complication of CMV:Ventilator-Induced Diaphragmatic DysfunctionLoss of diaphragmatic force generating capacity that is specifically related to the use of controlled mechanical ventilationVassilakopoulos T et al. AJRCCM 2004;169: 336-341

  • In Vitro ContractilityPowers SK et al, J Appl Physiol 2002;92:1851-1858

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

  • Contractile dysfunction resides within the diaphragmatic muscle

  • Mechanisms of contractile dysfunctionMuscle AtrophyOxidative StressStructural InjuryFiber Type TransformationRemodeling

  • AtrophyShanely RA et al. Am J Respir Crit Care Med 2002;166: 1369-74

  • Muscle AtrophyProtein synthesis

    Proteolysis

  • Protein SynthesisShanely RA et al. Am J Respir Crit Care Med 2004;170:994-9

  • ProteolysisLysosomal proteases (cathepsins)CalpainsProteasome

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

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

  • Proteasome

  • 26S Proteasome

  • 26S Proteasome degrades hydrophobic proteins

  • 26S proteasome is upregulatedMuscle Atrophy Factor box- E3 ligaseCONAMVCMVSassoon C et al. Am J Respir Crit Care Med 2004;170:626-32

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

  • 20S Proteasome degrades oxidized proteins

  • Oxidative stress: time courseZergeroglu et al. J Appl Physiol 2003;95: 1116-1124

  • Contractile proteins are targets of oxidative stressZergeroglu et al. J Appl Physiol 2003;95: 1116-1124 Ab againstReactiveCarbonylDeriviativesAb againstMyosin Heavy Chain

  • Ultrastructural injuryZhu E. et al, J Appl Physiol 2005;99:747-756Lipid dropletsVacuolesAbnormalmitochondriaAbnormalmyofibrils

  • Ultrastructural injuryBernard N et al Intensive Care Med 2003;29:111-118ControlMechanical VentilationDiaphragmDiaphragmExternalIntercostal

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

  • Summary: mechanisms of VIDDMuscle AtrophyOxidative StressStructural Injury

  • When to suspect VIDDPatient who fails to weanControlled Mechanical Ventilation (CMV)ICU-Acquired Paresis excludedProlonged neuromuscular blockade: TOFCritical Illness Polyneuropathy & Myopathy: ENG, EMG, muscle biopsyVIDD may coexist or aggravate ICUAP

  • How to prevent VIDDWe do not really know!Potential countermeasures:Assisted modes of mechanical ventilationIntermittent activity?Periodic electrical stimulation?Antioxidant administration

  • Assist Control VentilationSassoon C et al. Am J Respir Crit Care Med 2004;170:626-32

  • AntioxidantsBetters J et al. Am J Respir Crit Care Med 2004;170:1179-84

  • Antioxidants & contractilityBetters J et al. Am J Respir Crit Care Med 2004;170:1179-84

  • Antioxidants in mechanically ventilated patients**DaysNathens A et al Annals of Surgery 2002;236:814-822Vit E 1000 IU q8hVit C 1000 mg q8h301294294301

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

  • ConclusionsRespiratory muscles during weaning failure:excessive loadWeaknessWeakness may be due:ICU-acquired paresisVIDDPreventive measures:Strict glucose controlAssisted modes of mechanical ventilationAntioxidants