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