article 9 - Distrofia Muscular Progressiva
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article 9 - Distrofia Muscular Progressiva
Novel Methods of Ambulatory Physiologic Monitoring in Patients With Neuromuscular Disease Chris Landon Pediatrics 2009;123;S250-S252 DOI: 10.1542/peds.2008-2952L The online version of this article, along with updated information and services, is located on the World Wide Web at: http://www.pediatrics.org/cgi/content/full/123/Supplement_4/S250 PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2009 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275. Downloaded from www.pediatrics.org at BIN 8151 FMRP on May 19, 2009 SUPPLEMENT ARTICLE Novel Methods of Ambulatory Physiologic Monitoring in Patients With Neuromuscular Disease Chris Landon, MD, FAAP, FCCP, CMD Pediatric Diagnostic Center, Ventura, California Dr Landon serves on an advisory board for Hill-Rom Services Inc. ABSTRACT This is a summary of the presentation on novel methods of ambulatory physiologic monitoring in patients with neuromuscular disease, presented as part of the program on pulmonary management of pediatric patients with neuromuscular disorders at the 30th annual Carrell-Krusen Neuromuscular Symposium on February 20, 2008. Pediatrics 2009;123:S250–S252 R ECENTLY, CONSENSUS GUIDELINES were published for the respiratory care of www.pediatrics.org/cgi/doi/10.1542/ peds.2008-2952L doi:10.1542/peds.2008-2952L Abbreviations NNIV—nocturnal noninvasive ventilation MI-E—mechanical insufflator/exsufflator HFCWO— high-frequency chest wall oscillation NMD—neuromuscular disease REM—rapid eye movement patients with Duchenne muscular dystrophy and spinal muscular atrophy. These were practice-based guidelines, because the ability to generate evidence-based guidelines is limited because of the relatively rare nature of these diseases. The Accepted for publication Jan 5, 2009 respiratory care guidelines provide precise recommendations for the timing and Address correspondence to Chris Landon, MD, extent of respiratory examinations and care, from initial diagnosis through end-ofFAAP, FCCP, CMD, Pediatric Diagnostic Center, life directives. The process that produced these guidelines and the recent anesthesia 3160 Loma Vista Road, Ventura, CA 93003. E-mail: [email protected] and sedation guidelines, reviewed by Birnkrant in this conference, serves as a model PEDIATRICS (ISSN Numbers: Print, 0031-4005; for developing consensus practice parameters thataddress the multisystem involveOnline, 1098-4275). Copyright © 2009 by the ment seen for many of the muscular dystrophies.1–5 American Academy of Pediatrics In the context of continuous quality improvement, they provided an AIM stateAll tables and figures for this article appear ment and a clear guide to muscle disorders clinics of the role of pediatric pulonline at: www.pediatrics.org/content/ vol123/Supplement_4 monary evaluation and management (Table 1 www.pediatrics.org/content/vol123/ Supplement_4). The welcome shift from hospital ventilation to home ventilation, the emergence of technologic and biomedical advancements, and maximizing the benefits of therapies through appropriate timing have brought about a search for pulmonary outcome measures. Respiratory disease accounts for ⬃80% of the mortalities of patients with Duchenne muscular dystrophy. Our current measures consist of spirometry (forced vital capacity, forced expiratory volume at 1 second, oxygen saturation awake and asleep, and peak inspiratory and peak expiratory pressure) and rates of pneumonia, hospitalization, and respiratory failure.6–8 The routine evaluation of sleep has been hindered by the expense associated with technician-monitored studies geared at screening for the justification of expensive home therapies for adults with obstructive sleep apnea syndrome, lack of pediatric sleep laboratories (with the insufficiency made more difficult by the increased recommendations for evaluation of primary snoring with inadequate infrastructure in place), variability in interpretation, and inadequately developed standards of “normal.”9 Home sleep monitoring has been hindered by the frequent need for restudy, which has resulted in the denial of development of a payment structure to foster a business case for innovation.10 The reliance by private payers on Center for Medicare and Medicaid Services approval led to a reevaluation being released in March 2008, spurred by the deluge of obesity-related obstructive sleep apnea in adults with inadequate infrastructure for evaluation before initiation of home continuous positive airway pressure intervention. In the face of these developments we have sought to adapt and develop home monitoring systems to aid the clinician in assessment of sleep-disordered breathing and relief of sleep deprivation through initiation of nocturnal noninvasive ventilation (NNIV). We have also sought to assess what we have termed “awake disordered breathing” in which we can establish the epidemiology and course of disease through upright and supine ventilation strategies measured with Konno-Mead loops, 24-hour respiratory rate, 24-hour heart rate, level of activity defined with accelerometers, and relation of heart and respiratory rate to moderate-to-high levels of activity. In addition, we have studied what we have termed “life disordered breathing” associated with scoliosis surgery, gastrostomy tube placement, respiratory infection, gastroesophageal reflux, and the disappearance of adequate cough associated with suboptimal physiologic breathing patterns. We have sought to find a diagnostic and therapeutic strategy focused on prevention of progressive respiratory infection through novel methods of home monitoring, assessment of the pulmonary effects of “silent reflux” on the lungs, and assessment of the beneficial effects of mechanical methods of respiratory secretion clearance. The best available form factor, algorithms, and collection devices for the proposed applications seemed to include the Nonin wrist pulse oximeter with nVision software (Nonin Medical, Plymouth, MN) and the VivoMetrics LifeShirt (VivoMetrics, Ventura, CA), which incorporated respiratory inductive plethysmography. The advantages of respiraS250 LANDON Downloaded from www.pediatrics.org at BIN 8151 FMRP on May 19, 2009 tory inductive plethysmography are shown in Table 2 (www.pediatrics.org/content/vol123/Supplement_4). In our initial survey, the use of the mechanical insufflator/ exsufflator (MI-E), high-frequency chest wall oscillation (HFCWO), and NNIV support were assessed. Data recording used a light-weight respiratory inductive plethysmography device in the home with separate day and sleep algorithm, wrist and wireless oximeter with recording capability, and handheld spirometer. The initial participants were 5 male patients with neuromuscular disease (NMD) who were followed in a muscle disorders clinic and pediatric pulmonary center and were recruited for this pilot study. They were between 8 and 22 years of age and had been introduced to the use of HFCWO, an MI-E device, and NNIV within the previous 18 months. Patients and caretakers reported productive cough, sleep disorders, and anxiety during clinic and home visits. No patient had a tracheostomy or gastrostomy tube. The VivoLogic software (VivoMetrics) collected data with simultaneous screens allowing visual inspection of tidal volume, rib cage movement, abdominal cage movement, electrocardiogram, accelerometers for upright, supine, and lateral positioning and intensity of movement, and oxygen saturation. Figure 1 (www.pediatrics.org/content/ vol123/Supplement_4), obtained during NNIV, demonstrates poor synchronization with the ventilator; Fig 2 (www.pediatrics.org/content/vol123/Supplement_4) shows the subsequent synchrony. On the basis of these initial findings, we undertook further study to establish the utility of the LifeShirt in home sleep testing, with attention to the impact of daily use of HFCWO. As a preliminary assessment, this was a single-site study performed in the home setting. All patients resided within a 1-hour drive from the Pediatric Diagnostic Center in Ventura, California, and they resided in rural agricultural, urban, and suburban settings. The protocol was reviewed by the institutional review board of the Ventura County Medical Center. All patients gave written informed consent or assent before any study-related procedures were performed. Patients with NMD that affected the musculature of the oropharynx and the upper airway or the respiratory musculature who were aged ⱖ7 years were identified from the pediatric pulmonary clinic of the Pediatric Diagnostic Center. Patients were required to attend a clinic visit to complete the case-report form including medical history, treatments for NMD, and adverse effects of treatment. This was a single-site study. METHODS Eight patients with NMD and a history of restrictive lung disease were enrolled in a 90-day trial of HFCWO therapy. Demographic information including diagnosis, gender, age at initiation of MI-E, HFCWO, and NNIV, use of antireflux medications and/or presence of fundoplication, and need for mechanical ventilatory support were recorded (see Table 3 www.pediatrics.org/content/ vol123/Supplement_4). In addition, pulmonary function data, including the most recent spirometry results and measurements of respiratory muscle strength before the initiation of therapies (HFCWO, MI-E, and NNIV), were recorded. Data then were collected to determine the safety, tolerance, and efficacy of the LifeShirt in this patient population. Safety was assessed by noting the occurrence of pulmonary, cardiac, or gastrointestinal complications (eg, pneumothorax, pulmonary hemorrhage, cardiac dysrhythmias, nausea, or vomiting) associated with use of the device. The use of the LifeShirt was considered to be well tolerated if the patient used the device at the prescribed frequency. The patient was classified as intolerant of the device if the patient or caregiver expressed the desire to discontinue use of the LifeShirt for any reason. Patients were fitted with the wearable LifeShirt system (Fig 3 www.pediatrics.org/content/vol123/ Supplement_4), which incorporates respiratory inductance plethysmography for the noninvasive measurement of volume and timing ventilatory variables. The system also incorporates a single-channel electrocardiogram and a centrally located, 3-axis accelerometer. Data were processed and stored on a compact flash card that was housed within the recorder unit. Patients were fitted at home with a single-lead electroencephalogram (EEG) attached through a serial expansion module at baseline and 30, 60, and 90 days. The subjects slept at home wearing the 8-oz, 260-g shirt that captures ventilation, electrocardiography, pulse oxygen saturation, posture, and EEG data. Sleep studies were scored by certified sleep technicians using VivoLogic software (R and K standard criteria), and the studies underwent independent certified sleep technician reading by using a sleepscoring protocol incorporating respiratory, cardiac, and oximetry data. All studies were reviewed by the principal investigator. A registered respiratory therapist trained the patients and caregivers in the use of the LifeShirt and in HFCWO therapy with the Vest airway-clearance system (model 104; Hill-Rom, St Paul, MN). The target Vest settings included a frequency of 12 Hz and a pressure setting of 4, adjusted for patient comfort. The subject was monitored throughout the therapy. The subject and caregiver were instructed to interrupt therapy to allow the subject to cough or to clear secretions, if required, and to clear secretions through coughing or suctioning at the completion of therapy. Therapy was performed 3 times per day for 12 minutes per treatment. Clinical end points included type, frequency, and time distribution of sleep-disordered breathing events such as apneas, hypopneas, arousals, periods of oxygen desaturation, measures of sleep time, stages of sleep, accelerometry, and cardiac and respiratory data. Subjects were studied at baseline and 30, 60, and 90 days after the initiation of airway-clearance therapy with HFCWO per protocol. Evaluations were performed at 1, 2, and 3 months for pulse oximetry, spirometry, negative inspiratory flow force, and 24-hour wake and sleep continuous ambulatory physiologic monitoring. A central-lead sleep EEG was obtained and integrated with physiologic measures of rapid eye movement (REM) and non-REM sleep. PEDIATRICS Volume 123, Supplement 4, May 2009 Downloaded from www.pediatrics.org at BIN 8151 FMRP on May 19, 2009 S251 RESULTS Subject 5 was withdrawn after 60 days because of reluctance to follow the measurement and intervention protocol, and subject 8 withdrew after 30 days because of anxiety. Both subjects had excessive sweating at night, which led to difficulties in maintaining the EEG leads. Each individual served as his or her own control. Median respiratory rate over 24 hours improved by 10% within 1 month, and improvement was sustained at the 3-month exit evaluation. Sleep latency and sleeporganization parameters of slow-wave sleep, low delta, theta, and alpha activity, showed continuous improvement over the 90-day trial. One patient had an aspiration-related pneumonia during the 90-day study, with a return to improvement from baseline after resolution of the pulmonary exacerbation. CONCLUSIONS It is my hope that, with a source of funding for home sleep testing, the expanded data set available to the NMD clinician will become part of the standard of care in assessing epidemiology, progression of disease, and the impact of current and new therapies. A proposed outline for assessment and intervention is shown in Table 4 (www.pediatrics.org/content/vol123/Supplement_4). REFERENCES 1. Finder JD, Birnkrant D, Carl J, et al. Respiratory care of the patient with Duchenne muscular dystrophy: an ATS consensus statement. Am J Respir Crit Care Med. 2004;170(4):456 – 465 S252 LANDON 2. Birnkrant D, Panitch HB, Benditt JO, et al. American College of Chest Physicians consensus statement on the respiratory and related management of patients with Duchenne muscular dystrophy undergoing anesthesia or sedation. Chest. 2007;132(6): 1977–1986 3. Wang CH, Finkel RS, Bertini ES, et al. Consensus statement for standard of care in spinal muscular atrophy. J Child Neurol. 2007;22(8):1027–1047 4. Gozal D. Pulmonary manifestations of neuromuscular disease with special reference to Duchenne muscular dystrophy and spinal muscular atrophy. Pediatr Pulmonol. 2000;29(2): 141–150 5. Birnkrant DJ. The assessment and management of the respiratory complications of pediatric neuromuscular diseases. Clin Pediatr (Phila). 2002;41(5):301–308 6. Phillips MF, Quinlivan RC, Edwards RH, Calverley PM. Changes in spirometry over time as a prognostic marker in patients with Duchenne muscular dystrophy. Am J Respir Crit Care Med. 2001;164(12):2191–2194 7. Hukins CA, Hillman DR. Daytime predictors of sleep hypoventilation in Duchenne muscular dystrophy. Am J Respir Crit Care Med. 2000;161(1):166 –170 8. Phillips MF, Smith PE, Carroll N, Edwards RH, Calverley PM. Nocturnal oxygenation and prognosis in Duchenne muscular dystrophy. Am J Respir Crit Care Med. 1999;160(1):198 –202 9. Redline S, Budhiraja R, Kapur V, et al. The scoring of respiratory events in sleep: reliability and validity. J Clin Sleep Med. 2007;3(2):169 –200 10. Flemons WW, Littner MR, Rowley JA, et al. Home diagnosis of sleep apnea: a systematic review of the literature—an evidence review cosponsored by the American Academy of Sleep Medicine, the American College of Chest Physicians, and the American Thoracic Society. Chest. 2003;124(4):1543–1579 Downloaded from www.pediatrics.org at BIN 8151 FMRP on May 19, 2009 TABLE 1 AIM Statements All muscle disorder clinic patients will have an annual examination by a pediatric pulmonologist by the age of 4–5 y or by the age at which walking ceases, whichever comes first. When the forced vital capacity is ⬍1 L, survival time is ⬍5 years, and more intensive social support for the patient and caregivers will be made available. When the FEV1 is ⬍20%, daytime ventilation support will be evaluated. When the FEV1 is ⬍40%, a sleep study for consideration for nocturnal ventilation will be performed. When cough peak expiratory flow rate is ⬍160, airway clearance support, particularly with respiratory infection, will be provided, with evaluation of MI-E and/or HFCWO A daytime low SaO2 reflects airway disease; asthma, gastroesophageal reflux disease, MI-E, and HFCWO will be considered. The nighttime SaO2 will be assessed annually, and when reduced, a sleep study will be performed. Daytime SaO2 is poorly predictive of nighttime SaO2. MIP/MEP ⬍ 60 cm H2O airway clearance FEV1 indicates forced expiratory volume at 1 second; SaO2, arterial oxygen saturation. E10 LANDON TABLE 2 Respiratory Monitoring: Advantages of Inductive Plethysmography Over Impedance Pneumography Feature Inductance Impedance Detects obstructive and mixed apneas Detects central apneas Measures changes in tidal volume Detects hypopneas Means to detect a breath from a calibrated waveform, thereby not counting smaller deflections from motion artifacts as breaths Provides accurate breath rates Displays breath waveforms that have equivalent shapes to waveforms from spirometers and pneumotachographs connected to airway Can be calibrated to volume equivalency from spirometer, pneumotachograph, or fixed-volume chamber Used with heart rate for time-series respiratory sinus arrhythmia measure Accurate timing of breath waveforms Assesses thoracoabdominal coordination Wakefulness and sleep-staging capabilities Detects all elements of the sequence of respiratory muscle fatigue and dysfunction Digital data-stream output Breath amplitude not susceptible to postural alterations Random, unexplained variability of breath waveforms in terms of polarity shape and amplitude do not occur Cardiogenic artifacts do not distort respiratory waveforms Electric current not passed through body Analog signal outputs Yes Yes Yes Yes Yes No Yes No No No Yes Yes No No Yes No Yes No Yes Yes Yes Yes No No No No Yes Yes No No Yes No Yes No Yes Yes No Yes Downloaded from www.pediatrics.org at BIN 8151 FMRP on May 19, 2009 FIGURE 1 Poor patient synchrony between rib cage and abdominal effort despite NNIV, resulting in small tidal volumes. FIGURE 2 Synchrony between rib cage and abdominal effort with noninvasively assisted ventilation, resulting in improved tidal volumes. PEDIATRICS Volume 123, Supplement 4, May 2009 Downloaded from www.pediatrics.org at BIN 8151 FMRP on May 19, 2009 E11 TABLE 3 Characteristics of the Subjects Subject Diagnosis Age, Gender History of Wheelchair MI-E NNIV y Pneumonia Found 1. RG 2. EC 3. RN 4. PN 5. FD 6. JP 7. HE 8. AM Myopathy Myopathy DMD DMD SMA type 2 DMD DMD Myopathy 20 12 22 25 15 22 14 12 Female Male Male Male Male Male Male Female No Yes Yes Yes Yes Yes No Yes Yes Yes Yes Yes Yes Yes Yes Yes No Yes Yes Yes No Yes No Yes No No Yes Yes No Yes No Yes DMD indicates Duchenne muscular dystrophy; SMA, spinal muscular atrophy. FIGURE 3 A patient wearing the LifeShirt apparatus (photographed for publication with permission). TABLE 4 A New Model for Assessment and Intervention for Patients With NMDs Natural History Normal breathing Inspiratory, expiratory, bulbar muscle weakness REM-related sleep-disordered breathing, ineffective cough, reduced peak cough flows Non-REM– and REM-related sleep-disordered breathing, swallow dysfunction, chest infections Daytime ventilatory failure Death a Assessment Intervention Physical examination Baseline and serial LifeShirt evaluation for introduction of biologicals Home pulmonary function with pulmonary screener, cough peak flow, respiratory muscle strength, airway-clearance education, and diagnosis with LifeShirt Chest radiograph, home sleep study with LifeShirt, adjusting settings for airway clearance and effect with LifeShirt Swallow-function evaluation with LifeShirt assessment of gastroesophageal reflux disease and/or laryngeal reflux disease with Restech Dx-pHa effectiveness of NNIV Prednisone in Duchenne muscular dystrophy, biologicals Airway clearance with cough assistance NNIV NNIV or continuous noninvasive ventilation Dx-pH Measurement System (Restech, San Diego, CA) E12 LANDON Downloaded from www.pediatrics.org at BIN 8151 FMRP on May 19, 2009 Novel Methods of Ambulatory Physiologic Monitoring in Patients With Neuromuscular Disease Chris Landon Pediatrics 2009;123;S250-S252 DOI: 10.1542/peds.2008-2952L Updated Information & Services including high-resolution figures, can be found at: http://www.pediatrics.org/cgi/content/full/123/Supplement_4/S2 50 References This article cites 10 articles, 6 of which you can access for free at: http://www.pediatrics.org/cgi/content/full/123/Supplement_4/S2 50#BIBL Subspecialty Collections This article, along with others on similar topics, appears in the following collection(s): Respiratory Tract http://www.pediatrics.org/cgi/collection/respiratory_tract Permissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://www.pediatrics.org/misc/Permissions.shtml Reprints Information about ordering reprints can be found online: http://www.pediatrics.org/misc/reprints.shtml Downloaded from www.pediatrics.org at BIN 8151 FMRP on May 19, 2009