poly-neuropathy in critical care patients antonio anzueto md university of texas san antonio, texas
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Poly-Neuropathy in Critical Care Patients
Antonio Anzueto MD
University of Texas
San Antonio, Texas
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Poly-neuropathy in Critical Care Patients
• Definition and assessment• Effect of Mechanical Ventilation• Impact of Sepsis, systemic
inflammation and hyperglycemia• Effect on weaning
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Poly-neuropathy in Critical Care Patients
• Definition and assessment• Effect of Mechanical Ventilation• Impact of Sepsis, systemic
inflammation and hyperglycemia• Effect on weaning
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Definition Disease of peripheral nerve muscle neuromuscular junction
Acquired during ICU stay
Critical Illness Neuro-muscular Abnormalities
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Spectrum Acquired Neuromuscular Disorders
• Critical illness polyneuropathy• Neuromuscular disorders• Acute quadraplegic myopathy• Critical illness neuromuscular
abnormalities• ICU-acquired paresis• Critical illness polyneuropathy and
myopathy
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Acquired Neuromuscular Disorders
• More likely in patients hospitalized > 1 week.• Mechanically ventilated patients > 7 days
– > 50 % developed electrophysiological abnormalities
– 25 – 35 % - weakness
• Spectrum of disease:– Isolated nerve entrapment– Disuse atrophy– Severe myopathy or neuropathy
JAMA 274:1221, 1995; Crit Care Med 29:2281, 2001
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• Electrophysiological incidence: 50-100%• Clinical incidence : 25%• Combined axonal & muscular involvement• Gradual improvement of muscle function over
weeks or months
Main characteristicsof locomotor involvement
Critical Illness Neuro-muscular Abnormalities
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Acquired Neuromuscular Disorders
Lahgi and Tobin AJRCCM 168:10,2003
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MRC Score – evaluate peripheral muscle strength
Ali et al AJRCCM 2008; 178: 261
ICU acquired poly-neuropathy
Normal
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MRC Score - Outcome
Ali et al AJRCCM 2008; 178: 261
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Poly-neuropathy in Critical Care Patients
• Definition and assessment• Effect of Mechanical Ventilation• Impact of Sepsis, systemic
inflammation and hyperglycemia• Effect on weaning
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Effect of Mechanical Ventilation on RM function
• Present in a relative short period of time.
• Mechanism:– Tonic shortening of muscle secondary to
external PEEP.– Passive shortening during tidal ventilation,
• Drug effects: NMB, corticosteroids.
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Anzueto et al Crit Care Med 25:1187, 1997
Baboon model:-MV x 7 days-Sedated and paralyzed-TV 10 ml/kg-Topical antibiotics-Enteral feeding
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Transdiaphragmatic Pressure:Baboon Model
05
1015202530354045
20 40 60 100
Frequency (Hz)
Pdi
(cm
H2O
)
PrePost
Anzueto et al Crit Care Med 25:1187, 1997
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Lahgi and Tobin AJRCCM 168:10,2003
Control
3 days of MV
Effect of mechanical Ventilation
Rat diaphragm
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Disuse Atrophy - Diaphragm
Levine et al NEJM 2008; 358:1327
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Poly-neuropathy in Critical Care Patients
• Definition and assessment• Effect of Mechanical Ventilation• Impact of Sepsis, systemic
inflammation and hyperglycemia• Effect on weaning
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Acquired Neuromuscular Disorders: Frequency
• Underlying condition:– Sepsis 68. 5 %– MOF 70 %– Septic Shock 76 %– Sepsis + MOF 82 %
ICM 27:1288, 2001Chest 99:176, 1991ICM 22:849, 1996
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Effect of mechanical ventilationon septic diaphragm
Ebihara et al., AJRCCM 2002
Controls
LPS + MV
LPS
Rats, n=18LPS injection
* p<0.05 vs. Control† P<0.05 vs. LPS
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Antibody againstInducible NO
Saline
Gastrocnemius muscle – Rat injected with E. Coli endotoxin
Lahgi and Tobin AJRCCM 168:10,2003
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CIPNM – Immune activation
• Muscle biopsies from patients with CIPNM.• Infiltration by either small clustered
infiltrates or presence of isolated inflammatory cells.
• Macrophages and CD4+ lymphocytes.• Expression of adhesion molecules on the
vascular endothelium.
De Letter et al J Neuroimm 106: 206, 2000
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Imnunohistochemistry of Muscle biopsiesPositive stain for IL-10 (red) and macrophagesnear necrotic muscle
De Letter et al J Neuroimmunology 106:206, 2000
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De Letter et al J Neuroimmunology 106:206, 2000
Imnunohistochemistry of Muscle biopsiesActivated phenotype HLA-DR stainingin the vascular endothelium
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- Mechanisms:• Inflammation• Apoptosis• Thrombosis• Oxidant injury
– Hyperglycemia – toxic effects– Insulin: anti-inflammatory and neuro-protective
Critical Illness Neuro-muscular Abnormalities
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Neuromuscular Blockers
• 471 patients (9%)
• Median number of days receiving NMB was 2 (1-4) (Median P25-P75)
• NMB:– Used in patients that are younger– Patient requiring higher level of ventilatory
support
A.Esteban, A. Anzueto, et al. JAMA 2002;287:345-355
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Use of Neuromuscular Blockers - Outcome
NMB No NMB
MV (days) 10 ± 11* 5 ± 7
ICU stay (days) 16 ± 14* 11 ± 12
Mortality Risk OR 1.41, CI 1.1 – 1.82 *
* p < 0.001A.Esteban, A. Anzueto, et al. JAMA 2002;287:345-355
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Van Den Berghe et al., NEJM 2001 & Crit Care Med 2003
Intensive insulin therapy in critically ill patients
0
Mean blood glucoseduring ICU stay,
g/l
1,1
1,50 10 20 30 40 50 60 70 80
p<0.0001
% risk for abnormal ENMG
Conventional
insulin therapy n=783
Intensive insulin therapy
n=765 P value
ICU mortality 8.0 % 4.6 % < 0.04
ICU mortality, ICU stay > 5 d 20.2 % 10.6 % 0.005
Abnormal ENMG, ICU stay > 7 d 51.9 % 28.7 % < 0.001
Duration of MV, MV > 5 d 12 days 10 days 0.006
MV > 14 d 11.9 % 7.5 % 0.003
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Poly-neuropathy in Critical Care Patients
• Definition and assessment• Effect of Mechanical Ventilation• Impact of Sepsis, systemic
inflammation and hyperglycemia• Effect on weaning
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ICU – Acquired Paresis
• Prospective cohort study, mechanical ventilated patients > 7 days.
• Incidence 25 % (95 % CI, 17 – 35%)• Duration 1- 21 days• Duration of MV 1836 vrs 7.619.2 (p 0.03)• Independent predictors: female sex, number
of days with dysfunction of 2 or more organs, duration of MV, administration of corticosteroids.
De Jonghe et al JAMA 288:2859, 2002
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Moderatelocomotor
abnormalities
Severelocomotorabnormalities
21
6
10
9
16 15
Locomotor ENMG abnormal.
Diaphragm ENMG abnormal.
40 ICU patients unable to wean & neuromuscular cause suspected
31
Maher et al., Intensive Care Med 1995
Neuromuscular disordersand weaning failure
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Witt et al., Chest 1991
P=0.009
n=43, MV > 5 d
sepsis & MOF(30 with CIP)
Association of peripheral and respiratory neuromuscular involvement
29 patientswith ENMG of both
limb and respiratory muscles
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Durations of weaning, CINMA vs.ControlsProspective Cohort Studies
Duration of weaning (days)
Study Population CINMA
Diagnosis
CINMA Controls
P value
Leijten 1996 MV > 7 d N=38 ENMG 16.5 9.5 NS
Druschky 2001 MV > 4 d and Acute
stroke N=28 ENMG 5 1 0.002
De Jonghe 2004 MV 7 d N=95 Weakness 6 3 0.01
Garnacho-Montero 2005 MV > 7 d and
severe sepsis or septic shock
N=64 ENMG 15 2 <0.001
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ICU-acquiredparesis
6 d (1-22)
No paresis3 d (1-7)
Durationof MV afterawakening
1.0
.80
.60
.40
.20
0.0
03
69
1215
1821
2427
30
P = 0,01
De Jonghe et al., Intensive Care Med 2004
N=95MV 7 days& awakening
Dependent variable
Independent variables (multivariate analysis)
Duration of MV after awakening
COPD OR 2.6 (1.5 - 4.5)
ICU-acquired paresis OR 2.4 (1.4 - 4.2)
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Durationof weaning
Garnacho-Montero et al., Crit Care Med 2005
N=64MV 7 days Sepsis (severe or shock)Candidates for weaning
CINMA (CIP)15 d (1-74)
No CINMA2 d (0-29)
CINMA (n= 34)
No CINMA (n=30)
Weaning time, median 15 (1-74) 2 (0-29)
Weaning failure, n (%) 27 (79.4%) 6 (20%)
Reintubation, n (%) 14 (41.2%) 4 (13.3%)
Tracheostomy, n (%) 21 (61.8%) 4 (13.3%)
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Conclusions
Assessment of the respiratory neuromuscular involvement at the bedside is difficult
Both locomotor and respiratory neuromuscular systems are affected in patients
Sepsis and diaphragm inactivity may have a deleterious effect
Independent predictor of weaning duration and failure
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Obrigado