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

0

5

10

15

20

25

30

35

40

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

0

1

2

3

4

5

6

7

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