A. Vianello S.C. Fisiopatologia Respiratoria Azienda Ospedale-Università di Padova

1. PNEUMOTRIESTE 2016 Ventilatore Meccanico: come utilizzarlo nel malato neuromuscolare A. Vianello S.C. FisiopatologiaRespiratoria AziendaOspedale-UniversitàdiPadova

2. Neuromuscular disorders affecting respiratory function 1.Motor Neuron Diseases • Amyotrophic Lateral Sclerosis (ALS) • Poliomyelitis, Post-polio Syndrome • Spinal Muscular Atrophy (SMA) • Spino-bulbar Muscular Atrophy (Kennedy syndrome) 2. Peripheral Neuropathies • Guillain–Barrè syndrome (GBS), Chronic Inflammatory DemyelinatingPolyneuropathy (CIDP) • Critical illness polyneuropathy (CIP) • Hereditary motor sensory neuropathies (HMSN) 3. Disorders of Neuromuscular Junction • Myasthenia gravis (MG), Lambert-Eaton myasthenic syndrome (LEMS) • Congenital myasthenic syndromes 4. Myopathies 4.1 Acquired Myopathies • Inflammatory myopathies (polymyositis, dermatomyositis, IBM) • Critical illness myopathy (CIM) • Toxic myopathies 4.2 Hereditary Myopathies 4.2.1 Progressive Muscular Dysthrophies • Dystrophinopathies, Duchenne (DMD) and Becker (BMD) type • Facioscapulohumeral Muscular Dystrophy (FSHD) • Limb-girdle muscular dystrophies (LGMD) and distal myopathies • Myotonic Dystrophies 4.2.2Congenital Myopathies • central core diseases • myotubularmyopathy • nemalinemyopathy, myofibrillarmyopathies 4.2.3 Congenital Muscular Dystrophies • Ullrich’s CMD, merosin-deficient CMD, alpha-dystroglycanopathies • Emery-Dreyfuss muscular dystrophy, EDMD) 4.2.4 Metabolic myopaties • Mitochondrial myopathies • Glycogen Storage Diseases

3. Probability of Respiratory Failure • Inevitable: • Duchenne muscular dystrophy • Type I Spinal muscular atrophy (SMA) • Motor Neuron Disease (MND-ALS) • Frequent: • Limb girdle MD 2C,2D,2F,2I • Nemalinemyopathy • Int SMA • Acid maltase deficiency • X linked myotubularmyopathy • Ullrich congenital muscular dystrophy • Congenital myasthenia • Congenital myotonic dystrophy • Occasional: • Emery Dreifuss MD, Becker MD • Bethlemmyopathy, Minicore, central core myopathy • Uncommon: • FSH MD • Mitochondrial myopathy • Limb girdle MD 1, 2A,B,G,H, • Oculopharyngeal muscular dystrophy

4. Trajectory 1: Progressive RF A progressive, reasonably predictable RF developing over a period of months, or, in some cases, years. Course of Respiratory Failure in NMD Lung function Trajectory 2: Acute RF An unpredictable, acute, often severe RF requiring admission to hospital and intensive treatment. Lung function

5. Management of Slowly Progressive RF by Long-Term NIV

6. Thorax 1998;53:949-52

7. Improvement in patients’ symptoms after NPPV Young et al.Neurology 2007;68:198

8. HMV in Advanced Duchenne’s Muscular Dystrophy - 5 pts treated with NPPV - 5 unventilated control pts 24 month follow-up All pts treated with NPPV were still alive; four of five pts who underwent simple conservative treatment had died (mean survival: 9.7 ± 5.8 months) Chest 1994;105:445-448

9. Management trends in DMD Jeppesen, Neuromusc Dis 2003;13:804-12

10. Nocturnal mechanical ventilation for chronic hypoventilation in patients with neuromuscular and chest wall disorders. Current evidence about the therapeutic benefit of mechanical ventilation is weak, but consistent, suggesting alleviation of the symptoms of chronic hypoventilation in the short term, and in two small studies survival was prolonged.Mechanical ventilation should be offered as a therapeutic option to patients with chronic hypoventilation due to neuro-muscular diseases. Annane D et al, Cochrane Database of Systematic Reviews 2001

11. Trends in survival from muscular dystrophy in England and Wales and impact on respiratory services. Cause of death in muscular dystrophy in England and Wales 1993–1999 Calvert LD et al, Resp Med 2005;100:1058-63

13. Rapid shallow breathing ↑PaCO2 hypoventilation Inspiratory Muscle Weakness ventilation/perfusion mismatch Microatelectasis Expiratory Muscle Weakness Coughing and clearing tracheal secretion impairment atelectasis ↓ PaO2 Swallowing impairment complicated by aspirations Bulbar Muscle Weakness pneumonia Scoliosis Further deteriorations of the respiratory function Respiratory infections Malnutrition Cardiac failure Obstructive apnea Chest wall stiffness Racca F, Del Sorbo L, Mongini T, Vianello A, Ranieri VM. Minerva Anestesiologica 2010 ;76:51-62

14. Expiratory muscle weakness leading to ineffective cough and atelectasis

15. PeakCough Flow

16. Ullrich’s Congenital Muscular Dystrophy

17. PeakCough Flow • - Is directly correlated with the capacity to clear secretions from respiratory sistem. • Cut-off value of 160 L/min used to identify patients who would benefit from assisted cough techniques Bach JR et al. Chest 1997;112:1024-8

18.  ELASTIC LOAD PNEUMONIA, ATELECTASIS  RESISTIVE LOAD  AIRWAY RESISTANCE  LUNG VOLUME  LUNG COMPLIANCE MUCOUS ENCUMBRANCE

19. Physiopathology of Acute Respiratory Failure  Respiratory muscle capacity  Respiratory load Alveolar hypoventilation PaO2 andPaCO2

20. Conventional Approach to Managing ARF in Neuromuscular Disorders Facio-Scapulo-Humeral Muscular Dystrophy

21. Complications associated with intubation and invasive mechanical ventilation

22. In 60 cases intubations were performed successfully. Complications occurred in 4 cases: all were patients with neuromuscular disorders.

23. Critical issues raised by the conventional management of ARF in NMD Should NIV be considered a safer and more effective alternative to ETI as a first-line intervention? May NIV be useful in facilitating the weaning process for patients who still require intubation?

24. NIV as a first-line intervention for Acute Respiratory Failure

25. Study Design No of patients (age) Interventions Main Results Limit Vianello 2000 prospective case-control 14 patients (38,8+ 23 yrs) versus 14 historical controls E= NIPPV + CM C= MV via ETI Mortality and treatment failure significantly lower in the NPPV group Severe bulbar involvement NIPPV + MI-E Servera 2005 17 patients (48,7+ 20 yrs) Successful in averting death and ETI in 79.2% of the acute episodes Severe bulbar involvement prospective cohort study E= NIPPV + MI-E+ CPT; C= NIPPV+ CPT Vianello 2005 prospective case-control 11 patients (34,9+ 17,3 yrs) versus 16 historical controls Treatment failure was significantly lower in the experimental group Treatment failure only 6,6% Significant RR and PaCO2 improvement Number of patients needing intubation only 1 Padman 1994 Retrospective study 11 NMD patients (+ 4 cystic fibrosis patients) with acute on chronic respiratory failure (4-21 yrs) NIPPV Avoidance of ETI in all patients Retrospective study 10 patients (13-21 yrs) NIPPV + MI-E Niranjan 1998 Bach 2000 Retrospective study 11 children suffering from SMA type 1 (6–26 months) 28 distinct episodes of ARF Immediately upon extubation the patients received NIPPV + MI-E NIPPV was largely successful even in very young children with severe skeletal and bulbar muscle weakness Piastra 2006 Retrospective study 10 children (3 month-12yrs) NIPPV + CPT The treatment was successful in 8 out of 10 patients Racca F, Del Sorbo L, Mongini T, Vianello A, Ranieri VM. Respiratory management of Acute Respiratory Failure in Neuromuscular Diseases. Minerva Anestesiologica 2010 ;76:51-62

26. Non-invasive ventilatory approach to treatment of ARF in neuromuscular disorders. A comparison with endotracheal intubation. • Period of study: from 1995 to 1998 • Type of study: controlled; historically matched control patients • Patient populations: 14 consecutive patients with Neuromuscular Disorders in ARF in whom MV was mandatory • All patients were treated with NPPV as first line of treatment • Intubation or tracheostomy was provided when NPPV failed Intensive Care Med 2000;26:384-390

27. Cricothyroid Minitracheostomy

29. Group A Group B P Value Death, No 2 8 0.046 Treat. Failure, No 4 11 0.021 Time to improvement, hrs 8.4 (2.8) 2.8 (11) 0.0001 ICU stay, days 14.9 (10.7) 47.1(51.9) 0.032 Clinical Outcome of Patients: Cumulative Data

30. Non-invasive ventilatory approach to treatment of ARF in neuromuscular disorders. A comparison with endotracheal intubation. • Conclusions • The application of NIV tends to reduce mortality and treatment failure in comparison with PPV via ETI • The use of NIV combined with cricothyroid "minitracheostomy” in neuromuscular ARF could be extended to patients with ineffective cough • However, the ability to adequately protect the upper airway is crucial to the success and patient selection remains important Intensive Care Med 2000;26:384-390

31. Cough assist: mechanical in-exsufflator NIV assisted physio, ambu bag, portable suction machine Addition of cough inexsufflator: Cough PF <160l/min, poor cough

32. Mechanical Insufflation-Exsufflation improves outcomes for Neuromuscular Disease Patients with Respiratory Tract Infections Am J Phys Med Rehabil, 2005;84:83-88

33. Mechanical Insufflation-Exsufflation improves outcomes for Neuromuscular Disease Patients with Respiratory Tract Infections • Period of study: from January 2001 to March 2003 • Type of study: controlled • Patient populations: 11 consecutive neuromuscular patients with URTI and mucous encumbrance • All patients were treated with MI-E in addition to conventional CPT • Cricothyroid "mini-tracheostomy" or endotracheal intubation was considered when MI-E plus CPT could not expulse airway secretions Am J Phys Med Rehabil, 2005;84:83-88

34. Mechanical Insufflation-Exsufflation improves outcomes for Neuromuscular Disease Patients with Respiratory Tract Infections Group A: Mechanical In-Exsufflator + Chest Physical Treatment Group B: Chest Physical Treatment Am J Phys Med Rehabil, 2005;84:83-88

35. Mechanical Insufflation-Exsufflation improves outcomes for Neuromuscular Disease Patients with Respiratory Tract Infections. A step in the right direction. If both the inspiratory and expiratory muscle aids are used effectively, only advanced bulbar ALS and some SMA type 1 patients who develop ARF require intubation and trach. Am J Phys Med Rehabil, 2005;84:89-91

36. Critical issues raised by the conventional management of ARF in NMD ? • Non-Invasive Ventilation combined with Assisted Coughing Techniques can be recommended as a first-line intervention for NMD patients with ARF • The non-invasive approach should not be attempted unless upper-airway function is well preserved • Patients need to be carefully treated in a monitored environment Should NIV be considered a safer and more effective alternative to ETI as a first-line intervention?

37. NIV in the Weaning Process

39. Weaning process Treatment of ARF Assessing readiness to wean Extubation Re-intubation Suspicion SBT Admit Discharge Tobin MJ. Role and interpretation of weaning predictors. 5° International Consesus Conference in Intensive Care Medicine: Weaning from Mechanical Ventilation. Hosted by ERS, Ats, ESICM, SCCM and SRLF; Budapest April 28-29, 2005

40. 85 patients met the criteria to be included in the study. • 18 patients (21%) remained completely ventilator dependent at discharge • 8 (9,5%) patients required nocturnal ventilatory assistance.

41. 11 years-old girl intubated for ARF in acute GBS • Successful application of NIV after extubation • On the 6° day she could breath spontaneously

42. Protocol • - The patient was extubated directly to NIV on pressure control of at least 18 cm H2O or assist/control 800-1500 ml, rate 10-14/min, and maintained in ambient air; • - The NIV was provided via a combination of nasal, oro-nasal, and mouth piece interfaces; • Patients were taught to maximally expand their lungs by “air stacking” (retaining consecutive) ventilator delivered volumes. Once “air stacked”, an abdominal thrust was provided to manually assist the cough.

43. First attempt extubation success rate was 95%; • Six of 7 patients who initially failed extubation succeeded on subsequent attempts; • Only one patient underwent tracheostomy.

44. Case 1: Bilateral Pneumonia in CMD

46. Non-invasive Ventilation & Assisted Coughing Technique

47. Case 2: Acute Bronchitis in DMD

48. PCF : 80 L/min MEP: 20 cmH2O MIP: -18 cmH2O