NIV indications for children with rare diseases

Transcription

1 NIV indications for children with rare diseases Renato Cutrera Dir. U.O.C. Broncopneumologie Département de Médecine Pédiatrique Hôpital Bambino Gesù, IRCCS, Rome, Italie R. Cutrera, cutrera@opbg.net 1

2 R. Cutrera, cutrera@opbg.net 2

3 PECULIARITA DELLE MALATTIE RARE A disease or disorder is defined as rare in Europe when it affects fewer than 1 in 2000 In the EU 30 million people affected over 6000 rare diseases existing. andrea.bartuli@opbg.net R. Cutrera, cutrera@opbg.net 3

4 80% of rare diseases have identified genetic origins others are the result of infections (bacterial or viral), allergies and environmental causes, or are degenerative and proliferative. 50% of rare diseases touch children. R. Cutrera, cutrera@opbg.net 4

5 Respiratory and Sleep & LTV Unit Pediatric Hospital Bambino Gesù Rome, italy NIV (262 patients) 21% 6% 6% 6% 3% 14% 7% 3% 24% Muscle Distrophy Miopaty Cerebral Palsy SMA Ondine/Rohhad CF severe obesity PWS neuro metabolic others 10% R. Cutrera, cutrera@opbg.net 5

6 CASE 1: GIULIA MARIA, 3 yrs old girl 3 years old girl admitted in IRCU due to chronic respiratory failure, referred from another hospital of Southern part of Italy Personal History In the last 6 months sudden and severe weight gain resulting in severe obesity, non associated to hyperfagia Occurence of divergent walleye at right eye Behaviour disorders, including uncaused fears, pavor nocturnus, problems at school Following an episode of diarrhea, occurence of sleep apneas and lost consciousness diagnosticated as viral encephalitis On-going problems: necessity of oxygen therapy Clinical presentation at visit Severe general conditions, obesity, light dyspnea and polypnea ABG: ph 7.29, PaO mmhg, PaCO mmhg

7 ROHHAD SYNDROME Rapid-onset Obesity with Hypothalamic dysfunction, Hypoventilation and Autonomic Dysregulation (ROHHAD syndrome) is a very rare disease affecting approximately only 76 cases worldwide. Patients with ROHHAD have damage to the mechanism governing proper breathing. ROHHAD syndrome is a disease that is potentially lethal and incurable Differently from CCHS, a genetic mutation is not identified yet Main symptoms: - hyperphagia and obesity by age of 10 years - (median age 3 years) - respiratory problems (hypoventilation, hypercarbia, OSAS) - thermal or other hypothalamic dysregulations - neurobehavioral disorders - tumors of neural crest origin Currently there are no official tests or treatments for ROHHAD. Many children are misdiagnosed or are never diagnosed until alveolar hypoventilation occurs.

8 Phenotypic features of ROHHAD (15 children) A, onset of hypothalamic clinical findings; B, onset of hypothalamic laboratory findings; C, onset of autonomic symptoms; D, onset of respiratory symptoms. Ize-Ludlow D et al. Pediatrics 2007; 120: e by American Academy of Pediatrics

9 PARAMETERS SaO 2 VALUES G.M 3 yrs F ROHHAD Nocturnal sleep study (O2 1L/m) Time (h.min) SaO 2 mean (%) 93 SaO 2 min (%) 74 SaO 2 <90% (%,me) 7.2 Pulse rate (mean value bpm) 82 MOHAI/h 7.4 Central Apnea Index/h 2.0 PARAMETERS CO 2 VALUES Time (h.min) 5.13 PtcCO 2 mean (mmhg) 51 PtcCO 2 max (mmhg) 57 %TST with PtcCO 2 > 50 mmhg( %) 68

10 Ventilation start PSV S/T, IPAP 16 cmh2o, EPAP 6 cmh2o, FR 20 br/min, I:E 1:2 FiO2 21% PARAMETERS CO 2 VALUES (O2) NIV Time (h.min) PtcCO 2 mean (mmhg) PtcCO 2 max (mmhg) %TST with PtcCO 2 > 50 mmhg (%) 68 5 PARAMETERS SaO 2 VALUES (O2 ) NIV Time (h.min) SaO 2 mean (%) SaO 2 min (%) SaO 2 <90% (%,me) Pulse rate (mean value bpm) MOHAI/h Central Apnea Index/h 2.0 0

11 CASE 2: ARIANNA, 12 months old, F, SMA1 12 months old infant with type 1 spinal muscular atrophy presenting with recurrent episodes of desaturation Personal History At the age of 2 months onset of progressive hypotonia, muscle weakness and delayed motor development At the age of 4 months diagnosis of Spinal Muscular Atrophy (SMA) confirmed with a DNA blood test. At the age of 5 months insertion of percutaneous endoscopic gastrostomy (PEG) under local anaesthesia (progressive difficulty in oral feeding - finishing a full meal, weight loss)

12 Spinal Muscular Atrophy (SMA) Spinal cord motor neurons disease and weakness. (1: :10.000) resulting in progressive muscular atropy Recessive autosomic inherited disease: 1/ 50 is a healthy carrier of the gene Gene SMN identified on the long arm of chromosome 5 in the region 5q13, exon 7 8 Survival Motoneurons Protein. R. Cutrera, cutrera@opbg.net

13 Spinal Muscular Atrophy (SMA) The clinical spectrum of SMA ranges from early infant death to normal adult life with only mild weakness. SMA clinically divided into: Ø Type I: is never sitting, 50% mortality at 7ms, 100% at 2-yrs of age Ø Type II: sitting position, never walk, respiratory failure in childhood Ø Type III: temporarily able to walk, With intervals of 0.1 Ø Type IV : adulthood R. Cutrera, cutrera@opbg.net 13

14 SMA type 1 Symptoms within 6 months of life Floppy, weak cry, foggy posture, tongue muscles fasciculation Eating disorders (impaired swallowing and GERD) ü Early involvement of respiratory muscles ü Paradox breathing ü Bell-shaped chest R. Cutrera, cutrera@opbg.net 14

15 SMA1 SMA2 Non sitters Sitters R. Cutrera, cutrera@opbg.net 15

16 MUSCLE WEAKNESS EFFECTS 1. Impaired swallowing and GERD 2. Chest wall deformity 3. Lung under development 4. Impaired cough resulting in poor clearance of lower airway secretions 5. Recurrent infections that exacerbate muscle weakness 6. Hypoventilation (sleep awake) and Sleep Disordered Breathing R. Cutrera, cutrera@opbg.net 16

17 CHEST WALL DEFORMITY NORMAL SMA Bell-shaped chest R. Cutrera, cutrera@opbg.net 17

18 Impaired Cough (expiratory muscles weakness) Impaired clearance of secretions Stasis of thick secretions Acute and chronic infectious complications A. Simonds Neuromuscular Disorders 14 (2004)56-69 R. Cutrera, cutrera@opbg.net 18

19 Atelectasis Ø segmental Ø lobar Ø micro Decreased lung volumes Increased work of breathing Progressive alteration of ventilation perfusion ratio Hypoxemia Infections R. Cutrera, cutrera@opbg.net 19

20 Cough Assist Device Mimics the physiological cough: gradually applying at the airways a positive pressure and immediately after a negative pressure. Removes deep lung secretions Reduces the recurrence of respiratory infections and pulmonary atelectasis IN EX SUFFLATOR EMERSON COUGH ASSIST (Mini) Pegaso DIMA COUGH ASSIST Philips E70 COUGH ASSIST Nippy B&D R. Cutrera, cutrera@opbg.net 20

21 Hypoventilation and SBD Individuals tend to progress to daytime respiratory failure via a sequence of recurrent chest infections, nocturnal oxygen desaturation, nocturnal hypoventilation, and then daytime hypercarbia. Baseline assessment and longitudinal monitoring can identify those at risk for sleep-disordered breathing and ineffective clearance of secretions. Ventilatory support should be added at night if sleep-disordered breathing is present and cough assistance provided if cough efficiency is reduced. R. Cutrera, cutrera@opbg.net 21

22 Consensus Statement for Standard of Care in Spinal Muscular Atrophy Chang CH et al. J Child Neurol : 1027 R. Cutrera, cutrera@opbg.net 22

23 Assisted ventilation is used in children with NMW for the following reasons: Ø To treat the symptoms of nocturnal hypoventilation. Ø To treat the symptoms of daytime hypoventilation. Ø To reduce the frequency of hospital admission for chest infections. Ø To prevent chest wall deformity in young children with the expectation of improved long-term outcome. Ø To prolong life. ASSISTED VENTILATION R. Cutrera, cutrera@opbg.net 23

24 Sleep disordered breathing in spinal muscular atrophy Uwe Mellies et al. Neuromuscular Disorders 14 (2004) R. Cutrera, cutrera@opbg.net 24

25 Sleep-disordered breathing in spinal muscular atrophy types 1 and 2 Chiarini Testa MB, Pavone M, Bertini E, Petrone A, Pagani M, Cutrera R Am J Phys Med Rehabil 2005;84: R. Cutrera, cutrera@opbg.net 25

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28 CASE 2: ARIANNA, 12 months old, F, SMA1 BASELINE SLEEP STUDY Parameters Values Total Sleep Time (TST: hrs) 6.7 Mean SpO2 (%) 96.2 SpO2 nadir (%) 87 SpO2 < 90% (%TST) 0.1 DI (N des/hrs) 2.3 AHI (N apneas- hypopneas/hrs) 1.8 Mean tcpco 2 (mmhg) 46.9 Peak tcpco 2 (mmhg) 56 tcpco 2 > 50 mmhg (%TST) 32

29 Treatment Options suggested to parents of children with SMA type 1 1. Let the Nature take its course : Home discharge without mechanical ventilation but with support for feeding and treatment for pain and dyspnoea and education to prevent and treat acute respiratory deterioration + MI-E 2. Home discharge with 1 + low span mechanical IPPV + MI-E 3. Home discharge with 1 +High span IPPV MI-E 4. Tracheal ventilation

30 Non Invasive Ventilation Sleep Study CASE 2: ARIANNA, 12 months old, F, SMA1 Parameters Values Total Sleep Time (TST: hrs) 6.1 Mean SpO2 (%) 97.8 SpO2 nadir (%) 90 SpO2 < 90% (%TST) 0.0 DI (N des/hrs) 0.7 AHI (N apneas- hypopneas/hrs) 0.2 Mean tcpco 2 (mmhg) 42.4 Peak tcpco 2 (mmhg) 49 tcpco 2 > 50 mmhg (%TST) 0

31 CASE 2: ARIANNA, 12 months old, F, SMA1 DISCHARGE PLANE Mechanical assisted cough The use of a mechanical insufflator/exsufflator via a face mask increases peak cough flow and aids airway clearance Other techniques such as breath stacking with bag, mask and one-way valve and manually assisted coughs can be very useful in older children who are able to understand commands but are not applicable to infants with severe type 1 SMA Oxygen - Home SpO2 monitoring Low-flow home oxygen should be considered for symptom relief in case of acute cyanotic attacks. However, practitioners should be aware that oxygen may mask worsening hypoventilation in the presence of hypercapnia by reducing respiratory drive. Non-invasive ventilation (NIV) Non-invasive ventilation delivered via a mask attached with straps to the child's face interface as bi-level cycling between a higher and lower positive pressure to the follows setting ( PSV S/T, IPAP 16 cmh20, EPAP 4 cmh 2 O, Back up rate 25 breath/ min) In this case the use of NIV can have a beneficial impact on chest shape, reducing the development of pectus excavatum Enteral feeding Nex visit, scheduled in one month.

32 CASE 2: ARIANNA, 12 months old, F, SMA1 after 20 days Respiratory exacerbation Emergency Department In the last two days : fever Increased secretions recurrent Hypoxemia below 80% SaO2, despite management reccomandations Clinical presentation: Instable clinic conditions Counscious Pale Profuse sweating Continuous NIV with marked patient/ ventilator asynchrony Oxygen supplementation ( FiO2 40%) Sp02 87% - 90% ABG: ph 7.31; pco mmhg Chest X Ray: left lung consolidation

33 CASE 2: ARIANNA, 12 months old, F, SMA1 Pediatric Intensive Care Unit Mechanical Invasive Ventilation (SIMV/PSV FiO2 0,35) Airway clearance Antibiotic iv therapy Progressive clinical and chest X ray findings improvement ABG: ph 7.4; pco2 43 mmhg Sa02 96% No more oxygen supplementation need Long term mechanical venxlaxon what is the best ventilatory option if the child become 24 hours a day dependent on mechanical ventilation?

34 CASE 2: ARIANNA, 12 months old, F, SMA1 Clinical History: Relevant points After two unsuccessful extubations Tracheostomy was performed as the only long term ventilatory option Setting: PACV IPAP 16 cmh2o, EPAP 4 cmh2o, 35 breath/min, I/E 1/2, trigger 8, VT 50 ml.

35 R. Cutrera, cutrera@opbg.net 35

36 Spinal Muscular Atrophy Type 1: Management and Outcomes Bach JR, Baird S, Plosky D, Navado J, Weaver B Pediatric Pulmonology 34:16 22 (2002) R. Cutrera, cutrera@opbg.net 36

37 A retrospective chart review of 194 SMA 1 (103 males, 91 females) patients outcomes has been carried out: 1. letting nature take its course (NT) 121 (62.3%), 2. tracheostomy and invasive mechanical ventilation (TV) 42 (21.7%) 3. continuous noninvasive respiratory muscles aid (NRA) including non invasive ventilation (NIV) and mechanical assisted cough (MAC) 42 (21.7%) R. Cutrera, cutrera@opbg.net 37

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39 When professionals assess the resulting life for the child and family, they sometimes fear it will result in unreasonably excessive care. The aim of this article is to present an analysis of ethical arguments that could support or oppose the provision of invasive ventilation in this population. This examination is particularly relevant as France is one of the few countries performing tracheotomies and mechanical ventilation for this condition. NIV is ineffective and contraindicated in infants who have severe bulbar weakness, usually present in babies with severe type 1 SMA The consensus of expert opinion is that once the diagnosis has been confirmed invasive ventilation is not appropriate for infants with severe type 1 SMA. R. Cutrera, cutrera@opbg.net 39

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41 SMA1-69 pts ( ) - 69 pts (31 M ; 38 F) - 53 dead (some of theme palliative NIV) - 16 alive: - 12 invasive ventilation (tracheo) - 3 in therapeutic NIV: - 1. VC, F, 2ys and 5 ms, diagnosis at 10 ms, NIV at18 ms. 2. RG, M, 23 ms, diagnosis and NIV at 4 ms 3. QR, M, 31 ms, diagnosi and NIV at 5 ms - 1 new diagnosis at 6 ms in palliative NIV Average age at diagnosis 4 months Average age at death 11.5 months Average age at tracheotomy 11.6 months R. Cutrera, cutrera@opbg.net 41

42 SMA2-55 pts ( ) - 55 pts (29 M ; 26 F) - 49 alive: 36 in therapeutic NIV 1 invasive ventilation (tracheo) 12 spontaneous breathing - 2 dead: case1 NIV at 24 mts, death at 42 mts; case2 NIV at 5yrs, death at 20 yrs - 4 lost at follow up Average age at diagnosis 17 months Average age at NIV 5 yrs R. Cutrera, cutrera@opbg.net 42

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