Noninvasiveventilationin Amyotrophiclateral Sclerosis: Jessica A. Cooksey,, Amen Sergew

N o n i n v a s i v e Ve n t i l a t i o n i n
A m y o t ro p h i c L a t e r a l
S c l e ros i s
Jessica A. Cooksey, MDa, Amen Sergew, MDb,*
KEYWORDS
Amyotrophic lateral sclerosis Noninvasive ventilation Bulbar ALS
Noninvasive positive pressure ventilation
KEY POINTS
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease involving upper and
lower motor neurons.
Progressive weakness involving the respiratory muscles leads to respiratory failure and death.
Home noninvasive ventilation (NIV) improves survival and quality of life, especially in those with
intact bulbar function.
Following NIV initiation, it is important to monitor symptomatic response and surrogates for gas ex-
change, such as nocturnal oximetry and remote monitoring of home NIV. Additionally, when avail-
able, transcutaneous CO2 monitoring and sleep studies can be considered in patients with
persistent issues.
INTRODUCTION of which muscles are affected first, the pattern of

onset is an important prognostic indicator. Pa-
Amyotrophic lateral sclerosis (ALS) is a devas- tients with bulbar weakness at the time of symp-
tating neurodegenerative disease that affects up- tom onset have been reported to have shorter
per and lower motor neurons, leading to median survival times.2,3 Other predictors of
progressive weakness and, ultimately, paralysis poorer prognosis include older age at onset and
of skeletal muscles. Onset of weakness in ALS more rapid rate of decline in pulmonary function.2,3
can occur first in the limbs, bulbar muscles (mus- Currently, there are a few interventions that have
cles that coordinate speech, mastication, and the potential to improve outcomes in ALS. Rilu-
swallowing) or, much less commonly, in the respi- zole, which inhibits glutaminergic neurotransmis-
ratory muscles. Irrespective of the initial distribu- sion, has been shown to prolong survival by
tion of affected muscles, weakness progresses about 3 months.4,5 Edaravone, a free radical scav-
to involve the diaphragms, leading first to disrup- enger, confers modest improvements in functional
ted sleep, then respiratory insufficiency, and ulti- outcomes in selected patients but has not been
mately respiratory failure and death. Respiratory shown to affect mortality.6–8 Home noninvasive
failure is the leading cause of death in ALS, ac- ventilation (NIV), which is interchangeably called
counting for more than 80% of mortality seen in noninvasive positive pressure ventilation, has
the disease.1 There is currently no cure for ALS, been shown to improve survival and quality of
and in the absence of treatment, the median time life, although a survival benefit has been inconsis-
from symptom onset to death is 3 years.2 Although tently reported in patients with significant bulbar
the ultimate outcome of ALS is similar regardless dysfunction.9
sleep.theclinics.com
a
Northwestern University, 1475 East Belvidere Road, Suite 185, Grayslake, IL 60030, USA; b Division of Pulmo-
nary, Critical Care and Sleep Medicine, Section of Critical Care Medicine, Department of Medicine, National
Jewish Health, 1400 Jackson Street, B140, Denver, CO 80207, USA
* Corresponding author.
E-mail address: sergewa@njhealth.org
Sleep Med Clin 15 (2020) 527–538

https://doi.org/10.1016/j.jsmc.2020.08.004
1556-407X/20/Published by Elsevier Inc.
Descargado para Anonymous User (n/a) en University El Bosque de ClinicalKey.es por Elsevier en julio 28, 2022. Para uso personal
exclusivamente. No se permiten otros usos sin autorización. Copyright ©2022. Elsevier Inc. Todos los derechos reservados.
528 Cooksey & Sergew
IMPACT OF NONINVASIVE VENTILATION ON severe bulbar dysfunction, improving NIV adher-

AMYOTROPHIC LATERAL SCLEROSIS ence may not improve survival. Other observa-
Benefits of Noninvasive Ventilation on tional series have reported a survival benefit of
Survival and Quality of Life NIV in patients with bulbar dysfunction, although
it has been reported to be more modest in patients
Several observational studies have demonstrated
without bulbar dysfunction.16,17 A single retro-
that NIV confers mortality and quality of life bene-
spective cohort study reported better survival in
fits in ALS.10–17 In the only randomized, controlled
patients with bulbar-onset disease than those
trial of NIV in ALS published to date, this finding
with limb-onset disease.18
was confirmed. Bourke and colleagues9 random-
ized patients with ALS to NIV or standard care Other Benefits of Noninvasive Ventilation:
when they developed orthopnea with maximum Sleep Quality, Oxygenation, Ventilation, Lung
inspiratory pressure less than 60 cm H2O, symp- Function, and Energy Expenditure
tomatic hypercapnia (defined as an Epworth
Sleepiness Scale score of 10 or higher), or morning NIV has also been shown to have other important
headache accompanied by hypercapnia on an impacts in ALS. It improves not just subjective
arterial blood gas. Among all patients, median sur- measures of sleep-related quality of life, but also
vival was 48 days longer among those treated with objective polysomnographic measures of sleep
NIV than in those who received standard care. This quality.19,20 It has been shown to increase the
benefit was driven by patients with relatively intact time spent in rapid eye movement sleep and
bulbar function. No mortality benefit was seen in slow wave sleep, and to reduce the microarousal
patients with severe bulbar dysfunction. Among index.19,20 Nocturnal oxygenation and transcuta-
those with preserved bulbar function, treatment neous carbon dioxide are also improved with
with NIV led to a 205-day improvement in median NIV.19–21 As with mortality and quality of life mea-
survival. Quality of life, sleep-related quality of life, sures, objective improvements in sleep quality,
and the duration of time during which quality of life nocturnal oxygenation, and ventilation have been
remained at least 75% of baseline were signifi- disproportionately described in patients without
cantly higher in the group treated with NIV. This significant bulbar dysfunction. In addition to
suggests that patients with preserved bulbar func- improving subjective measures of dyspnea, NIV
tion lived longer and did so with reasonably pre- has been shown in two studies to slow the rate
served quality of life. These quality of life of decline in vital capacity.10,15 In a study that
differences were greater in patients with preserved used indirect calorimetry to measure energy
bulbar function, although patients with severe expenditure, NIV was shown to reduce resting en-
bulbar dysfunction did show a benefit on mea- ergy expenditure.22 This suggests that NIV has the
sures of dyspnea and sleep-related quality of life. potential to slow the weight loss that typifies ALS
Patterns of use of positive airway pressure (PAP) and portends a poor prognosis.23
were different among patients with preserved
bulbar function versus those with severe bulbar INDICATIONS FOR NONINVASIVE
dysfunction. Mean NIV use among patients with VENTILATION IN AMYOTROPHIC LATERAL
preserved bulbar function was 9.3 hours per day, SCLEROSIS
whereas among those with severe bulbar dysfunc- Society Guidelines
tion, mean use was 3.8 hours per day. Overall, par-
Drawing on much of the evidence detailed previ-
ticipants randomized to NIV received bilevel PAP
ously, the current American Academy of
with a mean inspiratory PAP (IPAP) of 15 cm H2O
Neurology guidelines on the care of the patient
pressure and mean expiratory PAP (EPAP) of
with ALS recommend considering the initiation of
4 cm H2O pressure. Patients with preserved bulbar
NIV in patients with respiratory insufficiency to
function tolerated pressures that were 23% higher
prolong survival, slow the rate of forced vital ca-
than those tolerated by patients with severe bulbar
pacity (FVC) decline, and enhance quality of life.24
dysfunction. This study could not answer defini-
The issue of when in the course of disease to
tively whether a survival benefit was not seen
initiate NIV is an evolving one. In the early studies
among patients with severe bulbar dysfunction
of NIV in ALS, NIV was typically started in symp-
because they were less tolerant of PAP or because
tomatic patients with advanced neuromuscular
PAP does not confer a survival advantage in this
weakness. For example, in Bourke and col-
subgroup of patients. It was noted, however, that
leagues,9 patients had to have orthopnea with an
hours of PAP use did not correlate with improved
maximum inspiratory pressure less than 60 cm
survival among patients with severe bulbar
H2O or symptomatic daytime hypercapnia. Cur-
dysfunction, suggesting that for patients with
rent Medicare guidelines on the timing of initiation
Noninvasive Ventilation in ALS 529
of NIV in neuromuscular disease largely reflect this deliver a back-up respiratory rate is left to the
inclination, although there is mounting evidence judgment of the prescribing clinician in the current
that waiting for symptomatic respiratory insuffi- CMS RAD guidelines. It should be noted that
ciency and development of the frank gas ex- different criteria apply for other sleep-related
change abnormalities that characterize advanced hypoventilatory disorders, such as obesity hypo-
neuromuscular disease is not optimal, and pa- ventilation syndrome (discussed in Roop Kaw
tients may benefit from earlier initiation of NIV. In and Marta Kaminska’s article, “Obesity
contrast to current practice in the United States, Hypoventilation: Traditional Versus Nontraditional
the European Federation of Neuroscience guide- Populations,” in this issue) and hypercapnic
lines recommend considering initiation of NIV chronic obstructive pulmonary disease (discussed
earlier in disease, when the FVC falls less than in Jeremy E. Orr and colleagues’ article,
80% predicted.25 “Management of Chronic Respiratory Failure in
Chronic Obstructive Pulmonary Disease: High-
Centers for Medicare and Medicaid Services Intensity and Low-Intensity Ventilation,” in this
Guidelines issue). The CMS RAD guidelines apply to devices
that are able to deliver NIV with or without a back-
The current Centers for Medicare and Medicaid
up respiratory rate, but which do not have internal
Services (CMS) clinical indications for the use of
batteries or the ability for the patient to readily
respiratory-assist device therapy (RAD) in neuro-
switch between different modes of ventilation,
muscular disease arise from a consensus confer-
such as nighttime bilevel PAP via a mask and day-
ence report published in 1999 by the National
time mouthpiece ventilation. Devices with an inter-
Association for Medical Direction of Respiratory
nal battery and with the ability to provide different
Care.26 These guidelines were drafted in response
modes of ventilation for daytime and nighttime are
to rising rates of use and consequent rising costs
classified as home mechanical ventilators and are
associated with provision of NIV for a variety of
regulated slightly differently by CMS.27
disorders, in the absence of clear guidelines to
Although the one available randomized
direct appropriate use. These consensus guide-
controlled trial of NIV in ALS and most observa-
lines recommend that “appropriate symptoms
tional data suggest that NIV is not as well tolerated
attributable to nocturnal hypoventilation should
and the benefits more modest in bulbar ALS than in
first be identified” in patients with neuromuscular
nonbulbar ALS, the CMS RAD guidelines do not
disease.26 In terms of specific clinical criteria, the
make a distinction between bulbar and nonbulbar
current CMS RAD guidelines largely reflect the Na-
disease. Nor should the clinician necessarily make
tional Association for Medical Direction of Respira-
a distinction in the decision to offer NIV to a patient,
tory Care consensus conference report, and
given that there is still demonstrated benefit, albeit
recommend the initiation of NIV if any of the
more modest, in those patients with significant
following criteria are met:
bulbar dysfunction. Adjustments to the NIV pre-
FVC <50% predicted scription, however, may be advisable in patients
Maximum inspiratory pressure <60 cm H2O with significant bulbar dysfunction, given that in
pressure or sniff nasal pressure <40 cm H2O most published series, patients with bulbar
pressure dysfunction have been noted to tolerate lower pres-
Arterial blood gas (performed while awake) sures than patients without bulbar dysfunction.
with PaCO2 45 mm Hg
Nocturnal oxyhemoglobin saturation 88% EARLY SCREENING AND INITIATION OF
for 5 minutes (with a minimum recording NONINVASIVE VENTILATION
time of 2 hours on the patient’s prescribed
Initial reports of NIV in ALS examined primarily pa-
fraction of inspired oxygen)
tients with advanced disease and gas exchange
The CMS RAD criteria further require that the abnormalities. Subsequent studies have demon-
clinician document the following: strated that outcomes may be improved with pro-
vision of NIV earlier in the disease. Limited data
The presence of neuromuscular disease suggest that NIV adherence remains reasonable
Chronic obstructive pulmonary disease does with early initiation of NIV.
not contribute significantly to the patient’s
pulmonary limitation Impact of Early Initiation of Noninvasive
Ventilation on Survival
For neuromuscular disease, the decision to use
a machine that is only able to deliver a sponta- Several studies have reported an added survival
neous mode of ventilation or a machine able to benefit when NIV is initiated before FVC falls less
than 50% predicted.17,28–30 In a retrospective cohort “Noninvasive Ventilator Devices and Modes,” in
study of 474 patients, Khamankar and colleagues17 this issue. Home NIV is typically delivered via a sin-
reported an overall survival benefit of NIV in bulbar gle limb mask interface, with a vented mask that
and nonbulbar ALS, although the impact was allows for CO2 escape connected to a machine
smaller in patients with bulbar dysfunction. In that that is able to provide separately adjustable IPAP
cohort, improved survival correlated with earlier initi- and EPAP settings. The most straightforward of
ation of NIV (FVC 80% predicted), and with these is fixed bilevel PAP, in which the EPAP level
increased hours of nightly use of NIV and concomi- is set to maintain upper airway patency (eg, in the
tant use of a cough-assist device for airway clear- case of concomitant ALS and obstructive sleep
ance. Median survival among patients who started apnea) and the IPAP is set to provide pressure
NIV when FVC was less than 50% predicted was support to maintain an adequate tidal volume
20.3 months, whereas among patients who started (VT). Fixed bilevel PAP is available in spontaneous
NIV when FVC was greater than or equal to 80% pre- (S) mode (no backup respiratory rate), sponta-
dicted, median survival was 25.36 months. Another neous/timed (ST) mode (backup respiratory rate
retrospective cohort study examined early available, activated only if patient’s respiratory
(FVC <80% predicted) versus very early rate falls lower than set backup rate), and timed
(FVC 80% predicted) initiation of NIV, and reported (T) mode (breaths delivered at a set rate, indepen-
a 4-month survival benefit with initiation of NIV with dent of patient triggering). The timed mode (T) is
FVC greater than or equal to 80% predicted.29 infrequently used, because it is not designed for
patient-device synchrony.33 For patients with
Impact of Early Initiation of Noninvasive ALS, a backup respiratory rate is recommended.34
Ventilation on Forced Vital Capacity
In a pilot, randomized, sham-controlled clinical Volume-Assured Pressure Support
trial, Jacobs and colleagues31 randomized pa- Volume-assured pressure support (VAPS) is a
tients with FVC greater than 50% predicted to mode of bilevel PAP in which the IPAP and there-
either bilevel PAP set at IPAP of 8 cm H2O pres- fore the pressure support is adjusted automatically
sure and EPAP of 4 cm H2O pressure (without titra- to achieve a target level of ventilation. The clinician
tion) or sham. In the sham group, participants sets a target VT (average VAPS, Respironics, Mur-
received continuous PAP 4 cm H2O pressure via rysville, PA), or a target alveolar ventilation (VA)
a nasal mask with an enlarged exhalation port (intelligent VAPS, ResMed, San Diego, CA) based
that effectively reduced the measured delivered on the patient’s ideal body weight. The device al-
pressure to less than 1 cm H2O. Participants in gorithms calculate an average VT or VA over
the sham group were converted to active NIV several breaths, and adjust the pressure support
when they developed symptoms of respiratory accordingly within a range determined by the clini-
insufficiency or their FVC fell less than 50% pre- cian, to achieve the target VT or VA. The theoretic
dicted. At the time of study enrollment, median advantage of these modalities in the setting of pro-
FVC was 76.5% predicted in the active NIV group gressive neuromuscular weakness is that the de-
and 79.5% predicted in the sham group. This pilot vice automatically increases the pressure
study was powered primarily to look at NIV adher- support over time as patients inevitably weaken
ence, not survival or respiratory function, but did and require more support to maintain adequate
find that the rate of decline in FVC was slower in VT. This has the potential to be particularly advan-
the group treated with early NIV.31 tageous for patients who are not able to travel to
clinic for frequent reassessment of the adequacy
Impact of Early Initiation of Noninvasive of their settings, either for reasons of distance or
Ventilation on Adherence physical disability.
A retrospective cohort study reported no differ- Some devices that are capable of providing
ence in NIV adherence rates with initiation of NIV VAPS modes of ventilation must be set with a fixed
when FVC was less than 80% versus when FVC EPAP. In the absence of upper airway obstruction,
greater than 80% predicted.32 patients with ALS generally benefit from minimal
EPAP (eg, EPAP 4 cm H2O pressure), to help mini-
mize work of breathing.33 Patients with issues with
MODES OF NONINVASIVE VENTILATION IN
upper airway patency may benefit from increased
AMYOTROPHIC LATERAL SCLEROSIS
EPAP, and EPAP requirements may vary
Fixed Bilevel Positive Airway Pressure
throughout the night or from night to night. In this
Home NIV modes and devices are discussed in case, there are some machines that can provide
depth in Gaurav Singh and Michelle Cao’s article, automatically adjusting EPAP levels, which detect
airflow limitation and adjust EPAP accordingly with In an excellent review on the initiation of NIV for
a goal of maintaining upper airway patency. sleep-related hypoventilation disorders, Selim and
colleagues33 provide suggested initial settings,
Evidence for Particular Modes of Noninvasive summarized in Table 1. Additionally, Gaurav Singh
Ventilation and Michelle Cao’s article, “Noninvasive Ventilator
Devices and Modes”; and Philip Choi and col-
In a randomized crossover trial of VAPS (iVAPS,
leagues’ article, “Noninvasive Ventilation
ResMed) versus standard pressure support for pa-
Downloads and Monitoring,” in this issue discuss
tients with hypoventilation, slightly lower pressure
noninvasive ventilator devices and modes, and
support (8.3 cm H2O pressure vs 10.0 cm H2O
long-term follow-up of NIV (downloads and
pressure) was required with VAPS to achieve
troubleshooting).
similar nocturnal oxygenation and transcutaneous
For Respironics respiratory-assist devices (eg,
CO2 (TCO2), with no differences in sleep quality
DreamStation) and home ventilator (Trilogy),
and slightly better adherence to VAPS (5 hours
VAPS is considered add-on software. The mode
40 minutes vs 4 hours 20 minutes).35 In a retrospec-
of NIV must first be selected33:
tive review of VAPS versus pressure support, fewer
patients achieved their target VT with pressure sup- Spontaneous (S)
port, and the rapid shallow breathing index (respira- Spontaneous timed (ST): mandatory Ti deliv-
tory rate/VT) was higher with pressure support, ered only with timed breaths and not with
suggesting increased work of breathing.36 spontaneous breaths
Timed (T): mandatory Ti delivered with all
Patient-Device Synchrony breaths and is not used because it is not de-
In addition to selecting the mode of ventilation, cli- signed for patient-device synchrony
nicians have the option to adjust features of the Pressure control (PC): mandatory Ti delivered
pressure waveform, such as inspiratory time (Ti), with spontaneous and timed breaths
rise time, trigger sensitivity, and cycle sensitivity Patients with ALS should typically receive PC
to optimize synchrony between the patient and AVAPS or PC ST, because it ensures that they
the machine.33 This is particularly important in receive consistent, adequate Ti with all breaths.
ALS, because progressive diaphragmatic weak- For the ResMed respiratory assist device (Air-
ness can make it difficult for patients to trigger Curve 10 ST, AirCurve 10 ST-A) and home venti-
and cycle, and longer Ti can help optimize gas ex- lator (Astral), the devices are set in iVAPS without
change. Selection of these settings should be per- first setting an additional mode. In this mode, Ti
formed by an experienced clinician and/or is delivered with spontaneous and timed breaths.
respiratory therapist, and should be guided by pa-
tient comfort. In general, patients with ALS benefit
Noninvasive Ventilation During Wakefulness/
from a high trigger sensitivity, low cycle sensitivity,
Daytime Ventilation
slow rise time, and long Ti.33 Appropriate mask
fitting for comfort and to minimize unintentional When patients with ALS develop dyspnea during
mask leak is also essential. wakefulness, it is appropriate to transition to a
ventilator with an internal battery. These devices
Noninvasive Ventilation: Summary and are portable, allowing patients to safely and
Suggested Initial Settings comfortably travel outside the home with ventila-
Irrespective of the mode of NIV selected, particular tory support. Daytime support is provided via a
attention should be paid to the following: mask using a bilevel PAP or VAPS mode. It can
also be delivered using mouthpiece ventilation in
Ensuring an adequate VT, with a target of a volume- or pressure-controlled mode.33 Devices
8 mL/kg ideal body weight with internal batteries are generally capable of
Provision of a backup respiratory rate and providing multiple programs (eg, nighttime bilevel
high trigger sensitivity to ensure adequate PAP via a mask and daytime volume-controlled
minute ventilation and maximize patient- ventilation via a mouthpiece).
device synchrony
Conversion to a device with an internal battery NONINVASIVE VENTILATION FAILURE:
and the ability to provide mouthpiece ventila- CAUSES AND SUGGESTED SOLUTIONS
tion at the point at which the patient requires
respiratory support during wakefulness Adherence to NIV has been shown to correlate
Appropriate follow-up and monitoring to assess with improved mortality in ALS.10,12 Several au-
adherence and adequacy of gas exchange thors have reported that severe bulbar dysfunction
532
Table 1
Suggested NIV settings and titration for patients with ALS
Impact on respiratory mechanics Y Muscle capacity

[ Chest wall resistance
Target tidal volume (mL) Target tidal volume 8 mL/kg ideal body weight
IPAP (cm H2O) Intermediate IPAP (or best tolerated)
Adjust IPAP to a PS for tidal volume goal in BPAP-ST
Allow IPAP min at a higher baseline
Set IPAP max higher than the 90%/95% delivered value (for
AVAPS or iVAPS, to allow for automatic increase in IPAP with
further weakening)
EPAP (cm H2O) Low EPAP to reduce work of breathing and improve triggering
Respiratory rate (bpm) Adjust to goal minute ventilation based on ABG, TcCO2, or both
Respironics: use fixed RR, not autoset, to avoid mimicking a
high RR, low VT pattern (thereby increasing work of
breathing)
ResMed: use “intelligent” backup rate, backup shifts between
two-thirds of the set rate during spontaneous breaths, and
the set rate during periods of apnea
Trigger sensitivity High trigger sensitivity to support a weak respiratory muscle
effort
Respironics: flow trigger at 1–3 L/min; do not use autotrak
function because it is not validated in neuromuscular
weakness
ResMed: trigger high or very high
Rise time Default or slow rise time
Respironics: 3 (300 ms)–6 (600 ms)
ResMed: 500–900 ms
Patients with significant bulbar dysfunction are likely to need a
slower rise time; those with minimal bulbar symptoms benefit
from faster rise time
Ti (ms) Long Ti or long Ti minimum to maximize tidal volume and gas
exchange ([I:E)
Ti/Ttot 50%
Respironics: Ti applies to mandatory (timed) breaths only in
fixed or adjusting bilevel PAP mode; in pressure control
mode, Ti applies to mandatory (timed) and spontaneous
breaths ResMed: Ti applies to mandatory (timed) and
spontaneous breaths
Cycle sensitivity Default or low cycle sensitivity (late cycle) to provide a longer
inhalation time (maximize tidal volume and gas exchange by
high I:E)
Respironics: manual at 10%–15% of peak flow; do not use
autotrak function because it is not validated in
neuromuscular weakness
ResMed: cycle low or very low
Titration Adjust PS (BPAP-ST), expiratory tidal volume (AVAPS), or Va
(iVAPS) based on ABG (pH, PaCO2), TcCO2, overnight oximetry,
serum bicarbonate, work of breathing, patient comfort, or a
combination
Patients with significant bulbar dysfunction may be less tolerant
of higher pressures (and therefore less tolerant of higher VT or
Va if VAPS mode is selected)
Abbreviations: ABG, arterial blood gas; ALS, Amyotrophic lateral sclerosis; AVAPS, Average Volume Assured Pressure Sup-
port; Va, alveolar ventilation; BPAP-ST (bilevel positive airway pressure - spontaneous/timed mode); BPAP, bilevel PAP;
IPAP, inspiratory positive airway pressure; iVAPS, intelligent volume-assured pressure support; I:E inspiratory:expiratory;
Ti: inspiratory time; NIV, non-invasive ventilation; PS, pressure support; PaCO2, partial pressure of carbon dioxide in arte-
rial blood; RR, respiratory rate; TcCO2, transcutaneous carbon dioxide; VT, tidal volume.
Adapted from Selim BJ, Wolfe L, Coleman JM, 3rd, Dewan NA. Initiation of Noninvasive Ventilation for Sleep Related
Hypoventilation Disorders: Advanced Modes and Devices. Chest. 2018;153(1):251-65; with permission.
is a risk factor for NIV failure.10,11,16,37–39 Predic- Suggested Solutions: Improved Airway
tors of NIV failure in bulbar patients include the Clearance and Bulbar Symptoms
severity of bulbar function and the degree of
For severe bulbar patients, consider delaying NIV
nocturnal hypoxemia.16 Failure was noted in one
initiation until airway clearance and sialorrhea
study of mostly patients with bulbar ALS to be
have been addressed. Mechanical insufflation/
linked to upper airways obstruction, which was a
exsufflation initiation can improve airway clear-
marker of poor prognosis.40 Additionally, bulbar
ance. In patients with refractory sialorrhea, severe
patients can have more difficulty with leak from
laryngospasm, and recurrent infections, invasive
nasal masks because of incomplete mouth
ventilation is considered. Baclofen or dextrome-
closure, especially during sleep.
thorphan/quinidine (Nuedexta) do not improve
Factors that can lead to NIV intolerance include
the respiratory components of the Revised ALS
sialorrhea with associated drooling, choking, and
Functional Rating Scale but do improve the bulbar
aspiration and viscous bronchial secretions, which
component significantly48 and may be useful
can lead to recurrent infections.16,38,41 Frontotem-
adjunct therapies at the time of initiation of NIV.
poral dementia has been shown to decrease sur-
Consider low pressures, such as an IPAP 6 to 8
vival in patients with ALS and also leads to NIV
cm H2O and an EPAP of 3 to 5 cm H2O in bulbar
noncompliance in patients with ALS with bulbar
patients at the time of NIV initiation.9,44 Following
and limb-onset.42
NIV initiation, bulbar patients need close follow-
Spasticity is a common feature of ALS.43
up with careful attention to mask fit and airway
Although large muscle spasms are a more
clearance.
frequently described characteristic of ALS, laryng-
ospasm has also been described.44–46 Daytime
episodes of laryngospasm are distressing for pa- LONG-TERM MONITORING OF NONINVASIVE
tients and caregivers, and nighttime episodes VENTILATION IN AMYOTROPHIC LATERAL
can contribute to poor tolerance of NIV, particu- SCLEROSIS
larly in patients with significant bulbar dysfunction.
Once NIV has been initiated in a patient with ALS,
Several authors have described the use of low-
follow-up can include an evaluation of symptom-
dose benzodiazepines as needed for
atic response and assessment of objective
laryngospasm.44,46
improvement in gas exchange. A detailed discus-
sion of long-term monitoring of home NIV appears
Suggested Solutions: Communication
in Philip Choi and colleagues’ article, “Noninvasive
Factors that can impact NIV success include Ventilation Downloads and Monitoring,” in this
improved communication regarding the goals of issue. Briefly, this is accomplished with nocturnal
NIV. At the time of NIV initiation, patients’ and their oximetry, remote monitoring of home NIV, TCO2
caregivers’ understanding of the benefits of NIV in monitoring, and sleep studies. Our recommenda-
ALS can lead to improved adherence.41 tions in regards to long-term monitoring of NIV
are summarized in Fig. 1.
Suggested Solutions: Inpatient Initiation of
Noninvasive Ventilation Nocturnal Oximetry
In-patient initiation of NIV, either overnight in- Nocturnal oximetry is a widely available modality
laboratory titration or with multiple days in the hos- that is useful for long-term monitoring of NIV.
pital with close involvement of respiratory thera- Ventilatory asynchrony can occur during sleep
pists, has been shown to improve tolerance. In and can result in nocturnal hypoxemia despite
one study, this entailed a prolonged hospitalization minimal symptoms.49 Optimization of nocturnal
with a mean of 12 days to reach normalization of oxygenation with NIV has also been shown to
nocturnal oximetry and arterial blood gas.47 Unfor- correlate with improved mortality.50 Nocturnal ox-
tunately, this is not feasible in some health care imetry can evaluate for not only the presence and
systems because of reimbursement issues. In extent of desaturation, but also the patterns of
that case, home setup or a PAP nap titration desaturation, which may also hint at the cause of
(which entails a PAP titration during a brief daytime ventilatory asynchrony.51 For example, intermit-
clinic visit or daytime visit to the sleep laboratory) tent desaturations (ie, an elevated oxygen desatu-
are the alternatives. When initiating NIV in the ration index) can suggest upper airway obstruction
outpatient setting, factors linked with the improve- and are generally caused by oropharyngeal
ment of NIV tolerance include discussion of poten- collapse similar to obstructive sleep apnea. These
tial obstacles at the time of initiation and providing can often be resolved with increased EPAP.52 In a
in-home support for patients.41 retrospective observational study, Gonzalez-
Fig. 1. Recommendations for the initiation and long-term monitoring of non-invasive ventilation in ALS. PAP,
positive airway pressure; RR, respiratory rate; TV, tidal volume.
Bermejo and colleagues50 reported on the use of machine and a cloud-based data storage system
nocturnal oximetry to ascertain the effectiveness maintained by the device manufacturers. Various
of home NIV. In this study, nocturnal oximetry factors are important to monitor ventilation ade-
with home sleep study, spirometry, and arterial quacy, such as the exhaled VT, respiratory rate,
blood gas were evaluated in the first month then leak, and the percent of patient triggering
every 3 months for the first year following initiation breaths.51,52 The downloaded data also document
of NIV. Group 1 had “corrected ventilation” adherence and patterns of use. Additionally, eval-
defined as tolerating NIV, nocturnal oximetry less uation of the flow and pressure curve tracings can
than 90% for less than 5% of the time, and help identify some causes of asynchrony and
improved symptoms and blood gases in the first where adjustments should be made to the settings
month. Group 2 did not meet these criteria in the or device.53 Adjustments are made remotely and
first month. Following this, adjustments were on RAD machines. For regulatory reasons, adjust-
made to optimize NIV use at month 1 and then ments cannot be made remotely on home ventila-
every 3 months thereafter. The only significant dif- tors, such as the ResMed Astral or Respironics
ference between the two groups was the nocturnal Trilogy. For those devices, remote downloads
oximetry results in the first month. The 12-month are obtained, but adjustments must be made in
survival was 75% in the group 1 patients, whereas person.
for group 2 patients, it was 43%. This difference A research group in Portugal demonstrated the
was noted despite similar improvements in day- benefits of remote monitoring. The control group
time symptoms and daytime blood gas results.50 was 20 patients with ALS that had a clinic visit 2
Group 2 patients who underwent adjustment of to 3 weeks after initiation of NIV then every
their NIV settings at months 1 and 3, resulting in 3 months thereafter. Another 20 patients were
appropriate ventilation in month 6, had no signifi- assigned to the treatment group and had a modem
cant mortality difference at 12 months when that allowed for data transmission weekly or when-
compared with group 1. If adequate ventilation ever patients reported difficulties. Based on these
was not achieved by month 6 in group 2, mortality data, NIV parameters could be adjusted remotely.
was higher than in group 1. Taken together, these Both groups were followed from the time of NIV
findings highlight the importance of frequent initiation to 3 years or death. The remote moni-
assessment of nocturnal oxygenation with toring group had fewer office visits and emergency
nocturnal oximetry, especially in the first 6 months room or in-hospital admissions. In this group, there
following initiation of NIV. was also a trend toward a survival benefit
(P 5 .13).47
Remote Monitoring
Transcutaneous CO2 Monitoring
Remote monitoring of NIV devices has also
advanced the care of patients on home NIV. TCO2 monitoring has been shown to correlate well
Remote access provides data downloads of NIV with blood gas analysis.54 Although it does not
machines without an in-person visit, via an internal provide a detailed evaluation of a patient’s acid
or external modem associated with the patient’s base balance, it can help delineate between
hypoxia caused by ventilation/perfusion mismatch settings). The patients who underwent PSG titra-
and that caused by hypoventilation. This is useful tion had a lower incidence of ventilator asyn-
especially in younger patients with intact cardio- chrony. Adherence improved in patients with
vascular systems where desaturation is less likely poor adherence before PSG (defined as
during hypoventilation. TCO2 monitoring can also use <4 hours per day during the acclimatization
help identify NIV-induced hyperventilation, which period). There was a mean increase in NIV use
can lead to central apneas and glottic closures.51 by 95 min/d in the group who had a PSG and a
Despite these benefits, TCO2 is less used than decrease in use of 23 minutes in the sham group
nocturnal oximetry because of cost and limited (P 5 .01).58
availability.
Respiratory Polygraphy (Home Sleep Testing)
Polysomnography Respiratory polygraphy (home sleep testing) may
present a more cost-effective and less time
There are significant variations among centers on consuming alternative to PSG. Polygraphy ex-
the use of polysomnography (PSG) for NIV initia- cludes the use of electroencephalogram, electro-
tion and titration in ALS and no guidelines exist oculogram, and chin electromyogram, which are
that address this subject. PSGs have been shown used in PSGs for sleep-wake differentiation and
to help in the initiation and titration of NIV, leading the analysis of sleep architecture. One study eval-
to improvement of oxygen saturation, hypercap- uated patients with ALS with polygraphy and
nia, and apnea-hypopnea-index. This results in found that it was useful in patients with FVC
improved daytime sleepiness, depression, and greater than 75% because it helped to detect
quality of life.19,20,55,56 nocturnal hypoventilation, resulting in earlier initia-
Patients with ALS can have fragmented sleep tion of NIV.59 Polygraphy, similar to PSG (but not
because of arousals related to limited ability to nocturnal oximetry), provides the ability to identify
change positions and pain. One group of re- issues with upper airway patency. If impaired up-
searchers conducted a split-night PSG on all of per airway patency is identified, adjustments are
their patients with ALS and found that almost half made to improve compliance and ventilation.60
had incomplete testing mainly because of poor Overall, PSG or polygraphy can be considered
sleep efficiency and absence of rapid eye move- in patients who have persistent symptoms and
ment sleep.57 In preparing for a PSG in patients other causes of NIV failure. Given the significant
with ALS, taking measures to address ALS- cost, limitation of resources, and the burden on
specific concerns may improve the success rate patients and their families associated with these
and usefulness in PSGs. tests, identifying the appropriate patients for
Measures to create comfort for this patient pop- PSG and polygraphy is important.
ulation may include a Hoyer lift, a call bell that is
easily accessible, other aids to address pain and SUMMARY
positioning during sleep, and allowing bed part-
ners or caretakers to also spend the night. Sialor- ALS is a progressive neurodegenerative disease
rhea can also impact sleep and a suction machine that affects upper and lower motor neurons and
for these patients is helpful. An experienced and has limited treatment options. Ultimately, the
attentive staff can increase the success of a involvement of the diaphragm leads to respiratory
PSG. An in-depth discussion of how to tailor a failure and NIV is the main intervention used for the
sleep laboratory for various neuromuscular dis- management of this. NIV can improve survival,
eases is provided in Justin A. Fiala and John M. quality of life, and dyspnea symptoms. Bulbar pa-
Coleman III’s article, “Tailoring the Sleep tients have more difficulty with NIV tolerance and
Laboratory for Chronic Respiratory Failure,” in therefore with adherence. Even with better adher-
this issue. ence, the benefits of NIV are less robust in bulbar
One single-centered study evaluated the use of patients as compared with those with limb-onset
PSG on treatment-naive patients of which 88% ALS. Fixed or adjusting bilevel PAP is used for
had neuromuscular weakness.58 All of the patients NIV. Once initiated, close monitoring with
initially had a daytime titration with a PAP nap in a nocturnal oximetry, remote downloads from the
modified sleep laboratory using a protocol that home NIV machine, measurement of serum bicar-
took a minimum of 4 hours. This was followed by bonate, and TCO2 monitoring should be conduct-
2 to 3 weeks of acclimatization with patients using ed, especially in bulbar patients. Adjusting the
NIV in their homes. After this period, patients various settings on the machine (eg, IPAP, EPAP,
returned for a full night PSG titration or a sham Ti, rise time, trigger sensitivity, and cycle sensi-
titration (where no adjustments were made to tivity) can help improve synchrony, adherence,
and efficacy with regard to symptoms and gas ex- 10. Bourke SC, Bullock RE, Williams TL, et al. Noninva-
change. PSG and respiratory polygraphy have the sive ventilation in ALS: indications and effect on
potential to identify asynchrony and, in the case of quality of life. Neurology 2003;61(2):171–7.
PSG, to make real-time adjustment to settings to 11. Aboussouan LS, Khan SU, Meeker DP, et al. Effect of
improve synchrony, thereby improving NIV suc- noninvasive positive-pressure ventilation on survival
cess. These are rarely done because of cost and in amyotrophic lateral sclerosis. Ann Intern Med
inconvenience for patients and their caregivers. 1997;127(6):450–3.
During later disease, transitioning to a home venti- 12. Kleopa KA, Sherman M, Neal B, et al. Bipap im-
lator with an internal battery is imperative for safety proves survival and rate of pulmonary function
and portability. decline in patients with ALS. J Neurol Sci 1999;
164(1):82–8.
13. Pinto AC, Evangelista T, Carvalho M, et al. Respira-
DISCLOSURE tory assistance with a non-invasive ventilator (Bipap)
in MND/ALS patients: survival rates in a controlled
The authors have no disclosures or conflicts of
trial. J Neurol Sci 1995;129(Suppl):19–26.
interest.
14. Hirose T, Kimura F, Tani H, et al. Clinical characteris-
tics of long-term survival with noninvasive ventilation
and factors affecting the transition to invasive venti-
REFERENCES
lation in amyotrophic lateral sclerosis. Muscle Nerve
1. Gordon PH, Corcia P, Lacomblez L, et al. Defining 2018;58(6):770–6.
survival as an outcome measure in amyotrophic 15. Leonardis L, Dolenc Groselj L, Vidmar G. Factors
lateral sclerosis. Arch Neurol 2009;66(6):758–61. related to respiration influencing survival and respi-
2. Haverkamp LJ, Appel V, Appel SH. Natural history of ratory function in patients with amyotrophic lateral
amyotrophic lateral sclerosis in a database popula- sclerosis: a retrospective study. Eur J Neurol 2012;
tion. Validation of a scoring system and a model 19(12):1518–24.
for survival prediction. Brain 1995;118(Pt 3):707–19. 16. Sancho J, Martinez D, Bures E, et al. Bulbar impair-
3. Ringel SP, Murphy JR, Alderson MK, et al. The natu- ment score and survival of stable amyotrophic
ral history of amyotrophic lateral sclerosis. lateral sclerosis patients after noninvasive ventilation
Neurology 1993;43(7):1316–22. initiation. ERJ Open Res 2018;4(2). https://doi.org/
4. Bensimon G, Lacomblez L, Meininger V. A controlled 10.1183/23120541.00159-2017.
trial of riluzole in amyotrophic lateral sclerosis. ALS/ 17. Khamankar N, Coan G, Weaver B, et al. Associative
Riluzole Study Group. N Engl J Med 1994;330(9): increases in amyotrophic lateral sclerosis survival
585–91. duration with non-invasive ventilation initiation and
5. Lacomblez L, Bensimon G, Leigh PN, et al. Dose- usage protocols. Front Neurol 2018;9:578.
ranging study of riluzole in amyotrophic lateral scle- 18. Berlowitz DJ, Howard ME, Fiore JF Jr, et al. Identi-
rosis. Amyotrophic Lateral Sclerosis/Riluzole Study fying who will benefit from non-invasive ventilation
Group II. Lancet 1996;347(9013):1425–31. in amyotrophic lateral sclerosis/motor neurone dis-
6. Abe K, Itoyama Y, Sobue G, et al. Confirmatory ease in a clinical cohort. J Neurol Neurosurg Psychi-
double-blind, parallel-group, placebo-controlled atry 2016;87(3):280–6.
study of efficacy and safety of edaravone (MCI- 19. Boentert M, Brenscheidt I, Glatz C, et al. Effects of
186) in amyotrophic lateral sclerosis patients. Amyo- non-invasive ventilation on objective sleep and
troph Lateral Scler Frontotemporal Degener 2014; nocturnal respiration in patients with amyotrophic
15(7–8):610–7. lateral sclerosis. J Neurol 2015;262(9):2073–82.
7. Yoshino H, Kimura A. Investigation of the therapeutic 20. Vrijsen B, Buyse B, Belge C, et al. Noninvasive venti-
effects of edaravone, a free radical scavenger, on lation improves sleep in amyotrophic lateral scle-
amyotrophic lateral sclerosis (phase II study). Amyo- rosis: a prospective polysomnographic study.
troph Lateral Scler 2006;7(4):241–5. J Clin Sleep Med 2015;11(5):559–66.
8. Writing G, Edaravone ALSSG. Safety and efficacy of 21. Katzberg HD, Selegiman A, Guion L, et al. Effects of
edaravone in well defined patients with amyotrophic noninvasive ventilation on sleep outcomes in amyo-
lateral sclerosis: a randomised, double-blind, pla- trophic lateral sclerosis. J Clin Sleep Med 2013;9(4):
cebo-controlled trial. Lancet Neurol 2017;16(7): 345–51.
505–12. 22. Georges M, Morelot-Panzini C, Similowski T, et al.
9. Bourke SC, Tomlinson M, Williams TL, et al. Effects Noninvasive ventilation reduces energy expenditure
of non-invasive ventilation on survival and quality in amyotrophic lateral sclerosis. BMC Pulm Med
of life in patients with amyotrophic lateral sclerosis: 2014;14:17.
a randomised controlled trial. Lancet Neurol 2006; 23. Shimizu T, Nagaoka U, Nakayama Y, et al. Reduction
5(2):140–7. rate of body mass index predicts prognosis for
survival in amyotrophic lateral sclerosis: a multi- 35. Kelly JL, Jaye J, Pickersgill RE, et al. Randomized
center study in Japan. Amyotroph Lateral Scler trial of ’intelligent’ autotitrating ventilation versus
2012;13(4):363–6. standard pressure support non-invasive ventilation:
24. Miller RG, Jackson CE, Kasarskis EJ, et al. Quality impact on adherence and physiological outcomes.
Standards Subcommittee of the American Academy Respirology 2014;19(4):596–603.
of N Neurology. Practice parameter update: the care 36. Nicholson TT, Smith SB, Siddique T, et al. Respira-
of the patient with amyotrophic lateral sclerosis: tory pattern and tidal volumes differ for pressure
drug, nutritional, and respiratory therapies (an support and volume-assured pressure support in
evidence-based review): report of the Quality Stan- amyotrophic lateral sclerosis. Ann Am Thorac Soc
dards Subcommittee of the American Academy of 2017;14(7):1139–46.
Neurology. Neurology 2009;73(15):1218–26. 37. Servera E, Sancho J, Banuls P, et al. Bulbar impair-
25. EFNS Task Force on Diagnosis and Management of ment score predicts noninvasive volume-cycled
Amyotrophic Lateral Sclerosis:, Andersen PM, ventilation failure during an acute lower respiratory
Abrahams S, Borasio GD, et al. EFNS guidelines tract infection in ALS. J Neurol Sci 2015;358(1–2):
on the clinical management of amyotrophic lateral 87–91.
sclerosis (MALS): revised report of an EFNS task 38. Vandenberghe N, Vallet AE, Petitjean T, et al.
force. Eur J Neurol 2012;19(3):360–75. Absence of airway secretion accumulation predicts
26. Clinical indications for noninvasive positive pressure tolerance of noninvasive ventilation in subjects with
ventilation in chronic respiratory failure due to amyotrophic lateral sclerosis. Respir Care 2013;
restrictive lung disease, COPD, and nocturnal hypo- 58(9):1424–32.
ventilation: a consensus conference report. Chest 39. Gruis KL, Brown DL, Schoennemann A, et al. Predic-
1999;116(2):521–34. tors of noninvasive ventilation tolerance in patients
27. Sahni A, Wolfe L. Sleep strategies: noninvasive with amyotrophic lateral sclerosis. Muscle Nerve
ventilation: redefining insurance guidelines. 2019. 2005;32(6):808–11.
American College of Chest Physicians web site. 40. Georges M, Attali V, Golmard JL, et al. Reduced sur-
Available at: https://wwwmdedgecom/chestphysician/ vival in patients with ALS with upper airway obstruc-
article/206771/sleep-medicine/noninvasive-ventilation- tive events on non-invasive ventilation. J Neurol
redefining-insurance-guidelines. Accessed March 6, Neurosurg Psychiatry 2016;87(10):1045–50.
2020. 41. Baxter SK, Baird WO, Thompson S, et al. The initi-
28. Lechtzin N, Scott Y, Busse AM, et al. Early use of ation of non-invasive ventilation for patients with
non-invasive ventilation prolongs survival in subjects motor neuron disease: patient and carer percep-
with ALS. Amyotroph Lateral Scler 2007;8(3):185–8. tions of obstacles and outcomes. Amyotroph
29. Vitacca M, Montini A, Lunetta C, et al. Impact of an Lateral Scler Frontotemporal Degener 2013;14(2):
early respiratory care programme with non-invasive 105–10.
ventilation adaptation in patients with amyotrophic 42. Olney RK, Murphy J, Forshew D, et al. The effects of
lateral sclerosis. Eur J Neurol 2018;25(3):556-e33. executive and behavioral dysfunction on the course
30. Carratu P, Spicuzza L, Cassano A, et al. Early treat- of ALS. Neurology 2005;65(11):1774–7.
ment with noninvasive positive pressure ventilation 43. Hobson EV, McDermott CJ. Supportive and symp-
prolongs survival in amyotrophic lateral sclerosis pa- tomatic management of amyotrophic lateral scle-
tients with nocturnal respiratory insufficiency. Orpha- rosis. Nat Rev Neurol 2016;12(9):526–38.
net J Rare Dis 2009;4:10. 44. Jackson CE, McVey AL, Rudnicki S, et al. Symptom
31. Jacobs TL, Brown DL, Baek J, et al. Trial of early management and end-of-life care in amyotrophic
noninvasive ventilation for ALS: a pilot placebo- lateral sclerosis. Neurol Clin 2015;33(4):889–908.
controlled study. Neurology 2016;87(18):1878–83. 45. Braun AT, Caballero-Eraso C, Lechtzin N. Amyotro-
32. Vitacca M, Banfi P, Montini A, et al. Does timing of initi- phic lateral sclerosis and the respiratory system.
ation influence acceptance and adherence to NIV in Clin Chest Med 2018;39(2):391–400. https://doi.
patients with ALS? Pulmonology 2020;26(1):45–8. org/10.1016/j.ccm.2018.01.003.
33. Selim BJ, Wolfe L, Coleman JM 3rd, et al. Initiation of 46. van der Graaff MM, Grolman W, Westermann EJ,
noninvasive ventilation for sleep related hypoventila- et al. Vocal cord dysfunction in amyotrophic lateral
tion disorders: advanced modes and devices. Chest sclerosis: four cases and a review of the literature.
2018;153(1):251–65. Arch Neurol 2009;66(11):1329–33.
34. McKim DA, Road J, Avendano M, et al, Canadian 47. Volanti P, Cibella F, Sarva M, et al. Predictors of non-
Thoracic Society Home Mechanical Ventilation Com- invasive ventilation tolerance in amyotrophic lateral
mittee. Home mechanical ventilation: a Canadian sclerosis. J Neurol Sci 2011;303(1–2):114–8.
Thoracic Society clinical practice guideline. Can Re- 48. Smith R, Pioro E, Myers K, et al. Enhanced bulbar
spir J 2011;18(4):197–215. function in amyotrophic lateral sclerosis: the
Nuedexta treatment trial. Neurotherapeutics 2017; amyotrophic lateral sclerosis: a validation study.
14(3):762–72. Amyotroph Lateral Scler 2012;13(6):528–32.
49. Fanfulla F, Taurino AE, Lupo ND, et al. Effect of sleep 55. Butz M, Wollinsky KH, Wiedemuth-Catrinescu U,
on patient/ventilator asynchrony in patients under- et al. Longitudinal effects of noninvasive positive-
going chronic non-invasive mechanical ventilation. pressure ventilation in patients with amyotrophic
Respir Med 2007;101(8):1702–7. lateral sclerosis. Am J Phys Med Rehabil 2003;
50. Gonzalez-Bermejo J, Morelot-Panzini C, Arnol N, 82(8):597–604.
et al. Prognostic value of efficiently correcting 56. Mustfa N, Walsh E, Bryant V, et al. The effect of
nocturnal desaturations after one month of non- noninvasive ventilation on ALS patients and their
invasive ventilation in amyotrophic lateral sclerosis: caregivers. Neurology 2006;66(8):1211–7.
a retrospective monocentre observational cohort 57. Loewen AH, Korngut L, Rimmer K, et al. Limitations
study. Amyotroph Lateral Scler Frontotemporal De- of split-night polysomnography for the diagnosis of
gener 2013;14(5–6):373–9. nocturnal hypoventilation and titration of non-
51. Janssens JP, Borel JC, Pepin JL, et al. Nocturnal invasive positive pressure ventilation in amyotrophic
monitoring of home non-invasive ventilation: the lateral sclerosis. Amyotroph Lateral Scler Frontotem-
contribution of simple tools such as pulse oximetry, poral Degener 2014;15(7–8):494–8.
capnography, built-in ventilator software and auto- 58. Hannan LM, Rautela L, Berlowitz DJ, et al. Rando-
nomic markers of sleep fragmentation. Thorax mised controlled trial of polysomnographic titration
2011;66(5):438–45. of noninvasive ventilation. Eur Respir J 2019;53(5).
52. Rabec C, Georges M, Kabeya NK, et al. Evaluating https://doi.org/10.1183/13993003.02118-2018.
noninvasive ventilation using a monitoring system 59. Prell T, Ringer TM, Wullenkord K, et al. Assessment
coupled to a ventilator: a bench-to-bedside study. of pulmonary function in amyotrophic lateral scle-
Eur Respir J 2009;34(4):902–13. rosis: when can polygraphy help evaluate the need
53. Rabec C, Rodenstein D, Leger P, et al. Ventilator for non-invasive ventilation? J Neurol Neurosurg
modes and settings during non-invasive ventilation: Psychiatry 2016;87(9):1022–6.
effects on respiratory events and implications for 60. Gonzalez-Bermejo J, Perrin C, Janssens JP, et al.
their identification. Thorax 2011;66(2):170–8. Proposal for a systematic analysis of polygraphy or
54. Rafiq MK, Bradburn M, Proctor AR, et al. Using polysomnography for identifying and scoring
transcutaneous carbon dioxide monitor (TOSCA abnormal events occurring during non-invasive
500) to detect respiratory failure in patients with ventilation. Thorax 2012;67(6):546–52.

Noninvasiveventilationin Amyotrophiclateral Sclerosis: Jessica A. Cooksey,, Amen Sergew

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Noninvasiveventilationin Amyotrophiclateral Sclerosis: Jessica A. Cooksey,, Amen Sergew

Uploaded by

Copyright:

Available Formats

N o n i n v a s i v e Ve n t i l a t i o n i n

INTRODUCTION of which muscles are affected first, the pattern of

Sleep Med Clin 15 (2020) 527–538

IMPACT OF NONINVASIVE VENTILATION ON severe bulbar dysfunction, improving NIV adher-

Impact on respiratory mechanics Y Muscle capacity

You might also like