1. Andrea Vianello Fisiopatologia e Terapia Intensiva Respiratoria Ospedale-Università di Padova Lo Pneumologo

2. Symptoms of ALS First signs and symptoms (frequently overlooked) Twitching and cramping of muscles (especially in hands and feet) Stiffness Weakness (especially in hands, arms and legs) Slurred speech Picture taken from the National Institute of Aging

3. Symptoms continued... Later signs and symptoms: Difficulty chewing and swallowing Shortness of breath Muscle weakness due to wasting away of muscles Causes muscles to become smaller Respiratory failure Paralysis Picture from the ALS Association

5. Clinical and Pulmonary Function evaluation ALS NMD Respir Care 2013;58:1433-41 Vitacca & Vianello

7. abdomen Chest wall abdomen Chest wall diaphragm abdomen diaphragm Normal subject Diaphragmatic fatigue Intercostal muscle fatigue

8. Cause of death in 302 French patients with ALS Most patients (63%) died in a medical facility The most frequently reported cause of death was: respiratory failure (77%) including: terminal respiratory insufficiency (58%) pneumonia (14%) asphyxia due to a foreign body (3%) pulmonary embolism (2%) Ten per cent of patients died from other causes: post-surgical or traumatic conditions (5%), cardiac causes (3.4%), suicide (1.3%) and sudden death of unknown origin (0.7%) The cause of death could not be determined in 13% of cases (6% inside a medical facility and 25% outside) Gil J, Funalot B, Verschueren A et al. Causes of death amongst French patients with amyotrophic lateral sclerosis: a prospective study. Eur J Neurol 2008;15:1245–51.

9. Long-Term Noninvasive Ventilation

10. What is Noninvasive Ventilation? “A form of ventilatory support that avoids airway invasion”

11. Underlying Respiratory Diseases

12. Palliative Care is an approach to care which focuses on comfort and quality of life for those affected by life-limiting/life-threatening illness. Its goal is much more than comfort in dying; palliative care is about living, through meticulous attention to control of pain and other symptoms, supporting emotional, spiritual, and cultural needs, and maximizing functional status.

13. 1.Role of O 2 therapy 2.Noninvasive ventilation 3.Role of opioids in palliation of dyspnea 4.Withdrawal of life-sustaining treatments – ventilatory support (invasive and noninvasive), oxygen Shared care

14. 1.Role of O 2 therapy 2.Noninvasive ventilation 3.Role of opioids in palliation of dyspnea 4.Withdrawal of life-sustaining treatments – ventilatory support (invasive and noninvasive), oxygen Shared care

15. Initiating and maintaining ventilatory support Setting up and supporting O 2 Educate patient, families, involved health care team Withdrawing ventilatory support Withdrawing O 2 Transport of palliative patients Nebulized meds (including lidocaine) Respiratory Therapy Palliative Care Shared Care

16. DYSPNEA Cortical influences (depression, fear, anxiety) Length – tension inappropriateness Respiratory effort Ventilatory drive Vagal reflexes Impediment to breathing Hyperinflation COPD asthma Airway obstruction Pulmonary oedema Pulmonary hypertension PaO2 PaCO2 Acidemia T4 Adapted from L. Sweer and Cl. Zwillich. 1990 Respiratory Muscle Fatigue Malnutrition Neuromuscular disease

17. Chest 2004; 126: 851–9

18. Patients’ symptoms before and after Noninvasive Ventilation.

19. Effect of Noninvasive Positive-Pressure Ventilation on Survival in Amyotrophic Lateral Sclerosis L.S. ABOUSSAN, S.U. KHAN, D.P. MEEKER, K. STELMACH, H. MITSUMOTO Ann Int Med 1997;127:450-453 Kaplan-Meier survival plots from initiation of NIV in Amyotrophic Lateral Sclerosis

20. Effect of Noninvasive Positive-Pressure Ventilation on Survival in Amyotrophic Lateral Sclerosis L.S. ABOUSSAN, S.U. KHAN, D.P. MEEKER, K. STELMACH, H. MITSUMOTO Ann Int Med 1997;127:450-453 Kaplan-Meier survival plots from initiation of NIV in ALS patients with moderate or severe bulbar symptoms Moderate bulbar symptomsSevere bulbar symptoms

21. RCT of NIV in MND Bourke SC Lancet Neurol 2006:5:140-7 Survival Qol All patients Mod bulbar weakness Severe bulbar All patients Severe bulbarMod bulbar No survival advantage in severe bulbar patients but QoL improved

22. NIV in MND/ALS: Quality of life Bourke et al Neurology 2003: Assessment pre, 1, 3, 5 month after starting NIV Generic: Improvements in GWbS (p=0.039), SF36 emotional limitation, health perception Specific: Improvements Epworth SS, SAQLI, CRDQ dyspnoea, fatigue & mastery Improvements at 1 month maintained at 5 months despite disease progression Indices of sleep-related symptoms most responsive Lyall et al Neurol 2001: NIV increased Vitality domain (SF36) by 25% for up to 15 months despite disease progression

24. Noninvasive Ventilation in ALS

26. ALS NMD PaCO 2 >45 mm Hg 88.5 93..13 Sleep-related hypoxemia 84.6 94.7.001 Sitting VC <50% 67.3 64.9.67 Symptoms (dyspnea,orthopnea) 61.5 52.6.13 MIP or MEP <60% 53.8 47.4.27 Indications to start HMV Respir Care 2013;58:1433-41

27. Tendency to gradually increase its use – eventually to 24/7; the implications of this does not seem to be commonly discussed Patient may be completely dependent on NIV, and unable to remove mask in event of machine or power failure The very patients who selected NIV rather than tracheostomy often find themselves on “life-support” with NIV, having to decide about withdrawal of ventilatory support Care setting for patients dependent on NIV need to address: -risk management around power / machine failure -ability to address symptoms in context of acute distress -ability to ensure comfort in context of withdrawal Palliative Considerations Regarding NIV in ALS

29. ? Survival and Quality of Life after tracheotomy

30. The mean time between intubation and death was 7.4 months, (median 2.8 months, range 1 week to 3.5 years)

31. The ALSFRS predicts survival in ALS patients on invasive mechanical ventilation D. Lo Coco, V. La Bella, T. Piccoli, A. Lo Coco Chest, 2007;132:64-69 Long-term survival after TIPPV according to ALSFRS score Median survival time: 48 months Median survival time: 10 months

32. Mean time between tracheostomy and death The median survival after tracheostomy was 21.1 months. The survival rate was 65% by 1 year, and 45% by 2 years 2011;26:329.e7-14

34. Emergency readmission after tracheostomy 7 (64%) 4 (36%) Bulbar pts More than one readmission/yr Less than one readmission/yr No readmission 11 (61%) 3 (17%) 8 (28%)4 (22%) TotalNon-bulbar pts 18 (62%) 3 (10%) [Personal data] -

35. Life Satisfaction Index –11 (Italian Version) The Life Satisfaction Index – 11 is a short form of LSI questionnaire providing a cumulative score acknowledged as an index of quality of life

36. Trach ALS Normal subject Mood tone 1,571,603 Zest for life 4,144,104 Congruence between desired and achieved goals 2,853,153 2011;26:329.e7-14

37. All patients informed in advance (9/11) have a positive view of the treatment! 11 ALS pts discharged on TIPPV

38. Italian multicenter survey on the last 3 months of life in 167 patients ventilated at home % Caregiver involvement

39. Place of death

40. ALS should be considered a “family disease” and requires interventions to help caregivers coping with such a challenging task.

41. Most individuals with ALS develop respiratory complications; NIV can be used to improve symptoms and health perception; however, patients may become increasingly dependent and unable to remove mask; Patients transitioned to trach can live for many years and in a number of cases are happy with their choice.

42. Which is the correct timing of starting NIV? For which patients tracheostomy should be recommended? Open questions