Weaning: Respiratory Muscles
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Transcript of Weaning: Respiratory Muscles
Weaning: Respiratory Muscles
Theodoros Vassilakopoulos
Department of Critical Care & Pulmonary Services University of Athens Medical School
Evangelismos HospitalAthens, Greece
Balance Load / Neuromuscular CapacityBalance Load / Neuromuscular Capacity
Vassilakopoulos T et al Eur Respir J 1996;9:2383-2400
Roussos C et al, J Appl Physiol 1979;46:897-904
Imbalance Load / Neuromuscular Capacity
FRC
FRC+50%IC
Vassilakopoulos T et al, AJRCCM 1998; 158:378-85
Weaning: Imbalance Load / Neuromuscular CapacityWeaning: Imbalance Load / Neuromuscular Capacity
Vassilakopoulos T et al Eur Respir J 1996;9:2383-2400
Imbalance Energy Supplies / DemandsImbalance Energy Supplies / Demands
Vassilakopoulos T et al, AJRCCM 1998; 158:378-85
The load of the respiratory muscles is within the fatiguing zone in patients who
fail to wean
Bellemare & Grassino J Appl Physiol 1982;53:1190-5
TTI: What does it signify?
Moxham J et al J Appl Physiol 1982;53:1094-99
HighShort-lasting
LowLong-lasting
What is skeletal muscle fatigue?
Low frequency diaphragmatic fatigue takes time to recover
Laghi 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; 167:120-7
MagneticBilateral
Phrenic nerveStimulation
Laghi F et al, AJRCCM 2003; 167:120-7
Is low frequency fatigue causing weaning failure?
At the last minute of the weaning trial TTIdi=0.26
Tlim= 13 minutes
Laghi 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 fails
Controlled Mechanical Ventilation should not be used for fatigue reversal in difficult
weaning•Vassilakopoulos T et al, Critical Care 2005;10(1):204
Weaning Failure: Respiratory Muscle Weakness
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weaning COPD normals
weaningCOPDnormals
Laghi F et al, AJRCCM 2003; 167:120-7Watson AC et al, Crit Care Med 2001;29:1325-1331
►ICU-acquired paresis Prolonged neuromuscular blockade Critical illness myopathy & neuropathy Acute quadraplegic myopathy
►Ventilator-Induced diaphragmatic dysfunction (VIDD)
Weaning Failure: Respiratory muscle weaknessThink Of:
► 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
ICU-acquired paresis
Deem 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 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
In Vitro Contractility
Powers 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 dysfunction
►Muscle Atrophy►Oxidative Stress►Structural Injury►Fiber Type Transformation►Remodeling
Atrophy
Shanely RA et al. Am J Respir Crit Care Med 2002;166: 1369-74
Muscle Atrophy
►Protein synthesisProtein synthesis
► ProteolysisProteolysis
Protein Synthesis
Shanely RA et al. Am J Respir Crit Care Med 2004;170:994-9
Proteolysis
►Lysosomal proteases (cathepsins)Lysosomal proteases (cathepsins)►CalpainsCalpains►ProteasomeProteasome
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 anemable
to proteasome degradation
Proteasome
26S Proteasome
26S Proteasome degrades hydrophobic proteins
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
20S Proteasome is activated
Shanely RA et al. Am J Respir Crit Care Med 2002;166: 1369-74
20S Proteasome degrades oxidized proteins
Oxidative stress: time course
Zergeroglu et al. J Appl Physiol 2003;95: 1116-1124
Contractile proteins are targets of oxidative
stress
Zergeroglu et al. J Appl Physiol 2003;95: 1116-1124
Ab againstReactiveCarbonylDeriviatives
Ab againstMyosin Heavy Chain
Ultrastructural injury
Zhu E. et al, J Appl Physiol 2005;99:747-756
Lipid droplets
Vacuoles
Abnormalmitochondria
Abnormalmyofibrils
Ultrastructural injury
Bernard N et al Intensive Care Med 2003;29:111-118
Control Mechanical Ventilation
Diaphragm
Diaphragm
ExternalIntercostal
Sassoon C. et al, J Appl Physiol 2002;92:2586-2595
Force decline is proportional to injury
Summary: mechanisms of VIDD
►Muscle AtrophyMuscle Atrophy►Oxidative StressOxidative Stress►Structural InjuryStructural Injury
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
How to prevent VIDD
►We do not really know!►Potential countermeasures:
Assisted modes of mechanical ventilation
Intermittent activity? Periodic electrical stimulation? Antioxidant administration
Assist Control Ventilation
Sassoon C et al. Am J Respir Crit Care Med 2004;170:626-32
Antioxidants
Betters J et al. Am J Respir Crit Care Med 2004;170:1179-84
Antioxidants & contractility
Betters J et al. Am J Respir Crit Care Med 2004;170:1179-84
Antioxidants in mechanically ventilated patients
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Duration of MV ICU length of stay
Control
Antioxidants
*
*
Days
Nathens A et al Annals of Surgery 2002;236:814-822
Vit E 1000 IU q8hVit C 1000 mg q8h
301294 294 301
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
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