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Poly-Neuropathy in Critical Care Patients

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.

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Poly-Neuropathy in Critical Care Patients

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  1. Poly-Neuropathy in Critical Care Patients Antonio Anzueto MD University of Texas San Antonio, Texas

  2. Poly-neuropathy in Critical Care Patients • Definition and assessment • Effect of Mechanical Ventilation • Impact of Sepsis, systemic inflammation and hyperglycemia • Effect on weaning

  3. Poly-neuropathy in Critical Care Patients • Definition and assessment • Effect of Mechanical Ventilation • Impact of Sepsis, systemic inflammation and hyperglycemia • Effect on weaning

  4. Critical Illness Neuro-muscular Abnormalities Definition • Disease of • peripheral nerve • muscle • neuromuscular junction • Acquired during ICU stay

  5. SpectrumAcquired Neuromuscular Disorders • Critical illness polyneuropathy • Neuromuscular disorders • Acute quadraplegic myopathy • Critical illness neuromuscular abnormalities • ICU-acquired paresis • Critical illness polyneuropathy and myopathy

  6. 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

  7. Critical Illness Neuro-muscular Abnormalities Main characteristics of locomotor involvement • Electrophysiological incidence: 50-100% • Clinical incidence : 25% • Combined axonal & muscular involvement • Gradual improvement of muscle function over weeks or months

  8. Acquired Neuromuscular Disorders Lahgi and Tobin AJRCCM 168:10,2003

  9. MRC Score – evaluate peripheral muscle strength Normal ICU acquired poly-neuropathy Ali et al AJRCCM 2008; 178: 261

  10. MRC Score - Outcome Ali et al AJRCCM 2008; 178: 261

  11. Poly-neuropathy in Critical Care Patients • Definition and assessment • Effect of Mechanical Ventilation • Impact of Sepsis, systemic inflammation and hyperglycemia • Effect on weaning

  12. 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.

  13. Baboon model: • MV x 7 days • Sedated and paralyzed • TV 10 ml/kg • Topical antibiotics • Enteral feeding Anzueto et al Crit Care Med 25:1187, 1997

  14. Transdiaphragmatic Pressure:Baboon Model Anzueto et al Crit Care Med 25:1187, 1997

  15. Effect of mechanical Ventilation Rat diaphragm 3 days of MV Control Lahgi and Tobin AJRCCM 168:10,2003

  16. Disuse Atrophy - Diaphragm Levine et al NEJM 2008; 358:1327

  17. Poly-neuropathy in Critical Care Patients • Definition and assessment • Effect of Mechanical Ventilation • Impact of Sepsis, systemic inflammation and hyperglycemia • Effect on weaning

  18. Acquired Neuromuscular Disorders: Frequency • Underlying condition: • Sepsis 68. 5 % • MOF 70 % • Septic Shock 76 % • Sepsis + MOF 82 % ICM 27:1288, 2001 Chest 99:176, 1991 ICM 22:849, 1996

  19. Effect of mechanical ventilationon septic diaphragm Controls LPS + MV Rats, n=18 LPS injection LPS * p<0.05 vs. Control † P<0.05 vs. LPS Ebihara et al., AJRCCM 2002

  20. Gastrocnemius muscle – Rat injected with E. Coli endotoxin Antibody against Inducible NO Saline Lahgi and Tobin AJRCCM 168:10,2003

  21. 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

  22. Imnunohistochemistry of Muscle biopsies Positive stain for IL-10 (red) and macrophages near necrotic muscle De Letter et al J Neuroimmunology 106:206, 2000

  23. Imnunohistochemistry of Muscle biopsies Activated phenotype HLA-DR staining in the vascular endothelium De Letter et al J Neuroimmunology 106:206, 2000

  24. Critical Illness Neuro-muscular Abnormalities - Mechanisms: • Inflammation • Apoptosis • Thrombosis • Oxidant injury • Hyperglycemia – toxic effects • Insulin: anti-inflammatory and neuro-protective

  25. 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

  26. Use of Neuromuscular Blockers - Outcome * p < 0.001 A.Esteban, A. Anzueto, et al. JAMA 2002;287:345-355

  27. Intensive insulin therapy in critically ill patients Mean blood glucose during ICU stay, g/l % risk for abnormal ENMG 1,5 50 60 70 0 10 20 30 40 80 1,1 p<0.0001 0 Van Den Berghe et al., NEJM 2001 & Crit Care Med 2003

  28. Poly-neuropathy in Critical Care Patients • Definition and assessment • Effect of Mechanical Ventilation • Impact of Sepsis, systemic inflammation and hyperglycemia • Effect on weaning

  29. ICU – Acquired Paresis • Prospective cohort study, mechanical ventilated patients > 7 days. • Incidence 25 % (95 % CI, 17 – 35%) • Duration 1- 21 days • Duration of MV 1836 vrs 7.619.2 (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

  30. 21 10 6 9 Moderate locomotor abnormalities Severe locomotor abnormalities Neuromuscular disorders and weaning failure Maher et al., Intensive Care Med 1995 40 ICU patients unable to wean & neuromuscular cause suspected 16 15 31 Locomotor ENMG abnormal. Diaphragm ENMG abnormal.

  31. Association of peripheral and respiratory neuromuscular involvement n=43, MV > 5 d sepsis & MOF (30 with CIP) 29 patients with ENMG of both limb and respiratory muscles P=0.009 Witt et al., Chest 1991

  32. Durations of weaning, CINMA vs.ControlsProspective Cohort Studies

  33. 1.0 .80 .60 .40 .20 0.0 15 21 27 9 3 6 24 0 18 30 12 Durationof MV afterawakening N=95 MV  7 days & awakening ICU-acquired paresis 6 d (1-22) P = 0,01 No paresis 3 d (1-7) De Jonghe et al., Intensive Care Med 2004

  34. Durationof weaning CINMA (CIP) 15 d (1-74) N=64 MV  7 days Sepsis (severe or shock) Candidates for weaning No CINMA 2 d (0-29) Garnacho-Montero et al., Crit Care Med 2005

  35. 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

  36. Obrigado

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