Title: 117th ENMC Workshop: Ventilatory Support in Congenital Neuromuscular Disorders — Congenital Myopathies, Congenital Muscular Dystrophies, Congenital Myotonic Dystrophy and SMA (II) 4–6 April 2003, Naarden, The Netherlands
Abstract: Eighteen participants from Australia, Austria, Denmark, Finland, France, Germany, The Netherlands, the UK, and the USA met in Naarden, representing a variety of disciplines with experience in the respiratory management of patients with neuromuscular disorders (NMD). The aims of the workshop were to agree upon and report minimum recommendations for the investigation and treatment of respiratory involvement in congenital muscular disorders, and to identify areas where further research is needed. The workshop specifically excluded patients with Duchenne muscular dystrophy where evidence for the need for and efficacy of the treatment of respiratory failure is better established. All participants contributed to the review and assessment of published evidence in the field, and current practice amongst the group was also compared. Despite the individual rarity of the conditions under consideration in this workshop, the accumulated experience of the group represented the care of more than 545 patients with these disorders, of whom around one-third were receiving mechanical ventilation. The first session addressed the rationale for commonly performed measurements of various aspects of respiratory function in order to generate recommendations for assessment of respiratory function in children with NMD (Appendix A). The literature on the assessment of lung function and respiratory muscle function was reviewed by Dr Laier-Groeneveld (Erfurt, Germany). Routine measurements of respiratory function include static lung volumes, flows and indices of gas exchange. If respiratory muscle weakness is suspected because of the underlying disease or abnormalities in the initial investigation, measurements may be completed by direct tests of the respiratory muscle function. In children with NMD monitoring of respiratory status is particularly important because respiratory malfunction is often progressive and a major cause of morbidity and mortality. However, data on the natural history of lung and respiratory muscle function in children with congenital NMD are scarce and some of the techniques to assess respiratory muscle function lack validation and normal values. Apart from the well-validated measurement of vital capacity (VC) and blood gas tensions the following non-invasive techniques are available to assess the respiratory muscles in children. Based on their feasibility they are of different importance in routine clinical use:•Maximum inspiratory pressure (PImax) and maximum expiratory pressure (PEmax) measured at the mouth can be obtained at approximately 6–7 years of age. Pressures increase with age and are higher in boys than in girls [1Gaultier C Zinman R Maximal static pressures in healthy children.Respir Physiol. 1983; 51: 45-61Crossref PubMed Scopus (95) Google Scholar, 2Mellies U Schultze S Schwake C Ragette R Teschler H Respiratory muscle function in 300 healthy children.Eur Respir J. 2001; 18 ([Abstract]): P827PubMed Google Scholar]. The variability of normal values and the dependence on cooperation by the child makes the assessment of the individual child difficult and requires some practice and experience with the technique.•Nasal sniff pressures (Psn) is an established test of inspiratory muscle strength in adults and has been applied to children. It is a simple and non-invasive measure, particularly of the diaphragm, and normal values for children are available [3Heijdra Y.F Dekhuijzen P.N van Herwaarden C.L Folgering H.T Differences between sniff mouth pressures and static maximal inspiratory mouth pressures.Eur Respir J. 1993; 6: 541-546PubMed Google Scholar, 4Stefanutti D Fitting J.W Sniff nasal inspiratory pressure. Reference values in Caucasian children.Am J Respir Crit Care Med. 1999; 159: 107-111Crossref PubMed Scopus (84) Google Scholar].•Mouth occlusion pressure (P0.1) is measuring the pressure generated by the inspiratory muscles during tidal breathing and allows estimation of the respiratory drive and the ratio P0.1/PImax is representing the load of respiratory muscles. It has been shown that these measures are closely correlated with angle of scoliosis, VC and gas exchange and may indicate respiratory muscle fatigue [5Gaultier C Boule M Tournier G Girard F Inspiratory force reserve of the respiratory muscles in children with chronic obstructive pulmonary disease.Am Rev Respir Dis. 1985; 131: 811-815PubMed Google Scholar, 6Mellies U Ragette R Schwake C Baethmann M Voit T Teschler H Sleep-disordered breathing and respiratory failure in acid maltase deficiency.Neurology. 2001; 57: 1290-1295Crossref PubMed Scopus (142) Google Scholar, 7Ragette R Mellies U Schwake C Voit T Teschler H Patterns and predictors of sleep disordered breathing in primary myopathies.Thorax. 2002; 57: 724-728Crossref PubMed Scopus (184) Google Scholar, 8Ramonatxo M Milic-Emili J Prefaut C Breathing pattern and load compensatory responses in young scoliotic patients.Eur Respir J. 1988; 1: 421-427PubMed Google Scholar]. The technique requires specifically trained personnel and special equipment; it may play a role in scientific questions. Normal values for children are available [2Mellies U Schultze S Schwake C Ragette R Teschler H Respiratory muscle function in 300 healthy children.Eur Respir J. 2001; 18 ([Abstract]): P827PubMed Google Scholar, 9Gaultier C Perret L Boule M Buvry A Girard F Occlusion pressure and breathing pattern in healthy children.Respir Physiol. 1981; 46: 71-80Crossref PubMed Scopus (53) Google Scholar]. There are further, more invasive or sophisticated techniques, e.g. phrenic nerve stimulation, measurement of oesophageal pressure, electromyography to assess the respiratory muscle function. However, their applications may be restricted to the research setting and have not been described in children with NMD. On the basis of data obtained from adults with various conditions including NMD the ATS/ERS Statement on respiratory muscle testing [[10]ATS/ERS Statement on respiratory muscle testing.Am J Respir Crit Care Med. 2002; 166: 518-624Crossref PubMed Scopus (1548) Google Scholar] concluded among others that:•Respiratory muscle weakness reduces VC.•Expiratory muscle weakness can increase residual capacity.•Reduction of chest wall and lung compliance, as a consequence of muscle weakness, reduces lung volumes, notably VC.•A fall in VC in the supine position, compared with when upright, suggests severe diaphragm weakness or paralysis.•Reduced maximal flows in NMD may reflect poor respiratory muscle coordination.•PaO2 and PaCO2 are affected by muscle weakness.•Respiratory muscle weakness may cause desaturations and hypercapnia during REM sleep. The ability to cough depends on VC, expiratory muscle strength and bulbar muscle function. Therefore peak cough flows (PCF) are an indirect indicator of lung and respiratory muscle function; PCF can be measured with a simple asthma peak flow meter and in adults a minimum PCF above 200 l/min can usually clear airway secretions adequately [[11]Bach J.R Amyotrophic lateral sclerosis: predictors for prolongation of life by noninvasive respiratory aids.Arch Phys Med Rehabil. 1995; 76: 828-832Abstract Full Text PDF PubMed Scopus (135) Google Scholar]. Dr Mellies (Essen, Germany) reviewed the techniques available for the detection and assessment of sleep-disordered breathing (SDB) and its significance in NMD. SDB is common in NMD [12Labanowski M Schmidt-Nowara W Guilleminault C Sleep and neuromuscular disease: frequency of sleep-disordered breathing in a neuromuscular disease clinic population.Neurology. 1996; 47: 1173-1180Crossref PubMed Scopus (145) Google Scholar, 13Van Lunteren E.K.H Kaminski H Disorders of sleep and breathing during sleep in neuromuscular disease.Sleep Breath. 1999; 3: 23-30Crossref PubMed Scopus (17) Google Scholar]. The principal cause is disease-related loss of respiratory muscle function, which in the setting of sleep-induced reduction of respiratory muscle tone and drop of central drive results in limited capacity to compensate for sleep-related drop of alveolar ventilation. SDB is particularly prevalent in REM sleep [14Becker H.F Piper A.J Flynn W.E et al.Breathing during sleep in patients with nocturnal desaturation.Am J Respir Crit Care Med. 1999; 159: 112-118Crossref PubMed Scopus (199) Google Scholar, 15Smith P.E Edwards R.H Calverley P.M Ventilation and breathing pattern during sleep in Duchenne muscular dystrophy.Chest. 1989; 96: 1346-1351Crossref PubMed Scopus (88) Google Scholar, 16White J.E Drinnan M.J Smithson A.J Griffiths C.J Gibson G.J Respiratory muscle activity and oxygenation during sleep in patients with muscle weakness.Eur Respir J. 1995; 8: 807-814PubMed Google Scholar], a period of maximal muscle atonia, and in the presence of diaphragm dysfunction [[6]Mellies U Ragette R Schwake C Baethmann M Voit T Teschler H Sleep-disordered breathing and respiratory failure in acid maltase deficiency.Neurology. 2001; 57: 1290-1295Crossref PubMed Scopus (142) Google Scholar]. It can manifest in different ways, depending on the relative contribution of upper airway or diaphragm dysfunction. Hypopneas with desaturations in REM sleep are most common, particularly in the early stages. As the disorder progresses, hypercapnic alveolar hypoventilation, first in REM, then in non-REM sleep prevails as the predominant marker of decreasing respiratory muscle force. For adults with myopathies and children with various NMD it has been shown that the degree of ventilatory restriction impacts directly on pattern and severity of SDB and that SDB-onset, nocturnal hypoventilation and respiratory failure can be reliably predicted from simple spirometry [7Ragette R Mellies U Schwake C Voit T Teschler H Patterns and predictors of sleep disordered breathing in primary myopathies.Thorax. 2002; 57: 724-728Crossref PubMed Scopus (184) Google Scholar, 17Mellies U Ragette R Schwake C Boehm H Voit T Teschler H Daytime predictors of sleep disordered breathing in children and adolescents with neuromuscular disorders.Neuromuscul Disord. 2003; 13: 123-128Abstract Full Text Full Text PDF PubMed Scopus (105) Google Scholar]. Because nocturnal hypoventilation is likely to advance to the development of cor pulmonale and daytime respiratory failure and may impact unfavourably on survival, timely recognition is important [18Consensus ConferenceClinical indications for noninvasive positive pressure ventilation in chronic respiratory failure due to restrictive lung disease, COPD, and nocturnal hypoventilation–a consensus conference report.Chest. 1999; 116: 521-534Crossref PubMed Scopus (615) Google Scholar, 19Hill N.S Eveloff S.E Carlisle C.C Goff S.G Efficacy of nocturnal nasal ventilation in patients with restrictive thoracic disease.Am Rev Respir Dis. 1992; 145: 365-371Crossref PubMed Google Scholar, 20Simonds A.K Muntoni F Heather S Fielding S Impact of nasal ventilation on survival in hypercapnic Duchenne muscular dystrophy.Thorax. 1998; 53: 949-952Crossref PubMed Scopus (327) Google Scholar, 21Simonds A.K Ward S Heather S Muntoni F Outcome of paediatric domiciliary mask ventilation in neuromuscular and skeletal disease.Eur Respir J. 2000; 16: 476-481Crossref PubMed Scopus (114) Google Scholar]. Unfortunately, SDB is rarely apparent on daytime presentation. Symptoms may be subtle and non-specific and recently it has been shown that a structured symptom questionnaire failed to predict SDB in children with advanced NMD [[16]White J.E Drinnan M.J Smithson A.J Griffiths C.J Gibson G.J Respiratory muscle activity and oxygenation during sleep in patients with muscle weakness.Eur Respir J. 1995; 8: 807-814PubMed Google Scholar]. A high index of suspicion is required and if diagnosis cannot be confirmed by simple tests such as overnight pulse oximetry additional polysomnographic evaluation may be indicated [[22]Marcus C.L Sleep-disordered breathing in children.Am J Respir Crit Care Med. 2001; 164: 16-30Crossref PubMed Scopus (464) Google Scholar]. The guidelines developed through discussion (Appendix A) were agreed as the minimum necessary to be able to predict safely the development of respiratory failure. The recommendations focus on detecting change in respiratory muscle strength, ability to cough, overnight oximetry and the presence of subtle symptoms of SDB. VC is a key investigation which should be performed regularly in all of these patients as VC below 60% expected is a good predictor of the onset of SDB and VC below 40% is a good predictor of nocturnal hypoventilation.