Poly-Neuropathy in Critical Care Patients

Antonio Anzueto MD

University of Texas

San Antonio, Texas

Poly-neuropathy in Critical Care Patients

• Definition and assessment• Effect of Mechanical Ventilation• Impact of Sepsis, systemic

inflammation and hyperglycemia• Effect on weaning

Poly-neuropathy in Critical Care Patients

• Definition and assessment• Effect of Mechanical Ventilation• Impact of Sepsis, systemic

inflammation and hyperglycemia• Effect on weaning

Definition Disease of peripheral nerve muscle neuromuscular junction

Acquired during ICU stay

Critical Illness Neuro-muscular Abnormalities

Spectrum Acquired Neuromuscular Disorders

• Critical illness polyneuropathy• Neuromuscular disorders• Acute quadraplegic myopathy• Critical illness neuromuscular

abnormalities• ICU-acquired paresis• Critical illness polyneuropathy and

myopathy

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

• 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

Acquired Neuromuscular Disorders

Lahgi and Tobin AJRCCM 168:10,2003

MRC Score – evaluate peripheral muscle strength

Ali et al AJRCCM 2008; 178: 261

ICU acquired poly-neuropathy

Normal

MRC Score - Outcome

Ali et al AJRCCM 2008; 178: 261

Poly-neuropathy in Critical Care Patients

• Definition and assessment• Effect of Mechanical Ventilation• Impact of Sepsis, systemic

inflammation and hyperglycemia• Effect on weaning

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.

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

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

Lahgi and Tobin AJRCCM 168:10,2003

Control

3 days of MV

Effect of mechanical Ventilation

Rat diaphragm

Disuse Atrophy - Diaphragm

Levine et al NEJM 2008; 358:1327

Poly-neuropathy in Critical Care Patients

• Definition and assessment• Effect of Mechanical Ventilation• Impact of Sepsis, systemic

inflammation and hyperglycemia• Effect on weaning

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

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

Antibody againstInducible NO

Saline

Gastrocnemius muscle – Rat injected with E. Coli endotoxin

Lahgi and Tobin AJRCCM 168:10,2003

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

Imnunohistochemistry of Muscle biopsiesPositive stain for IL-10 (red) and macrophagesnear necrotic muscle

De Letter et al J Neuroimmunology 106:206, 2000

De Letter et al J Neuroimmunology 106:206, 2000

Imnunohistochemistry of Muscle biopsiesActivated phenotype HLA-DR stainingin the vascular endothelium

- Mechanisms:• Inflammation• Apoptosis• Thrombosis• Oxidant injury

– Hyperglycemia – toxic effects– Insulin: anti-inflammatory and neuro-protective

Critical Illness Neuro-muscular Abnormalities

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

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

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

Poly-neuropathy in Critical Care Patients

• Definition and assessment• Effect of Mechanical Ventilation• Impact of Sepsis, systemic

inflammation and hyperglycemia• Effect on weaning

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

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

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

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

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)

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%)

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

Obrigado