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Symptoms and signs of hypoventilation
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Box 1. Definitions of nocturnal hypoventilation
• S
<90% for ≥10% of the total recording time
aO
2
• Peak P
• P
tcCO
• Peak P
• P
tcCO
(10 mmHg), in comparison to an awake supine value >6.7 kPa (50 mmHg) for
>6.5 kPa (49 mmHg)
tcCO
2
>6.5 kPa (49 mmHg) for ≥10% of the total recording time
2
>7.3 kPa (55 mmHg)
tcCO
2
>7.3 kPa (55 mmHg) for ≥10 min or increase in P
2
of ≥1.3 kPa
tcCO
2
≥10 min
resistance, inhibition of intercostal and upper airway muscle activity and decrease in
arousal responses that occur during sleep. These normal physiological changes are
present particularly during REM sleep, which is why hypoventilation is exacerbated
and will appear first in this sleep stage. It is important to note that if an individual does
not experience REM sleep during a sleep study, the degree of hypoventilation is likely
to be underestimated.
Symptoms of nocturnal hypoventilation
Typical features include morning headaches, impaired sleep quality, daytime
sleepiness/fatigue and orthopnoea due to diaphragm impairment. However,
symptoms may be more nonspecific and subtle and include anorexia at breakfast,
concentration problems during the day, nightmares/frequent dreams, nocturia and
failure to thrive. The first occurrence of these symptoms may occur during a chest
infection or upon recovery from a general anaesthetic.
Timing of onset of hypoventilation and identifying high-risk patients
In patients with neuromuscular and chest wall disease, nocturnal hypoventilation is
unlikely to occur before vital capacity (VC) is <60% predicted. High-risk patients with
inherited neuromuscular disease are those with spinal muscular atrophy (SMA) type 1
and 2; Duchenne muscular dystrophy (DMD) where the average age of onset is in late
teens and those with sarcoglycanopathies; and myopathies. An algorithm illustrating
the progression to nocturnal hypoventilation and appropriate clinical assessment
and investigations in inherited neuromuscular disorders is shown in figure 1. New
disease-modifying therapies in genetic neuromuscular disorders such as nusinersen
and risdiplam in SMA, and gene therapy in many disorders, may delay the onset of
alveolar hypoventilation, or reduce the tendency to develop the condition.
In MND/ALS patients, referral for respiratory assessment should be made at the time
of diagnosis and most guidelines suggest investigation for nocturnal hypoventilation
if VC is <70% and/or symptoms are present. It is important to note that in MND/
ALS patients with progressive disease, significant nocturnal hypoventilation may
occur in the presence of normal or near-normal daytime P
congenital central hypoventilation syndrome or other central drive disorders such as
myotonic dystrophy may experience minimal or no symptoms of nocturnal or daytime
hypoventilation.
Patients with high cervical spinal cord, brainstem and bilateral phrenic nerve lesions are
at risk, as are scoliotic patients with early-onset, high cervicodorsal curves, a thoracic
curvature >70° and VC <50% pred. Hypoventilation is unlikely in COPD patients until
274
. Individuals with
aCO
2
ERS Handbook: Respiratory Sleep Medicine
Symptoms and signs of hypoventilation
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Respiratory clinical algorithm
Inspiratory, expiratory or bulbar muscle weakness,
Clinical assessment
scoliosis, chest wall abnormality
REM-related
SDB
FVC <60% pred
NREM and REM
SDB
FVC <40% pred
Ineective cough
Cough peak
flow <270 L·min
Swallowing dysfunction
Chest infections
Daytime ventilatory
failure
FVC <20% pred
Intervention
Physical examination, pulmonary
function, cough peak flow,
respiratory muscle strength, chest
radiography, sleep study, swallow
assessment
Prevention: influenza,
pneumococcal vaccination,
palivizumab
Intervention: physiotherapy,
cough-assist devices
Consider: glycopyrrolate,
–1
hypertonic saline, bronchodilator
if evidence of asthma
NIV, combination
with cough assist,
percutaneous
gastrostomy feeding
Tracheostomy-IPPV
Figure 1. Clinical assessment of suspected hypoventilation. IPPV: intermittent positive-pressure
ventilation.
VC is <30% pred, but may be exacerbated by coexistent OSA (known as OSA–COPD
overlap syndrome), additional lung pathology or when receiving supplemental oxygen
therapy. In all patients with nocturnal hypoventilation, oxygen therapy or sedation/
opiate analgesia may worsen hypercapnia, and weight gain or coexistent obesity may
exacerbate hypoventilation and/or OSA. Careful arterial blood gas monitoring should
be carried out to establish whether assisted ventilation is required.
Raised serum bicarbonate level has been used as a marker for OHS. The American
Thoracic Society clinical practice guideline and National Institute for Health and
Care Excellence (NICE) guideline on OHS suggest that a serum bicarbonate value
<28 mmol·L−1 can rule out OHS in those at mild-to-moderate risk. A raised serum
bicarbonate level has also been used to screen for nocturnal hypoventilation in DMD
patients, but may be an unreliable guide in some situations, due to diuretic use and
conditions such as diabetes and hypertension.
Signs and clinical features/investigations
During hypoventilation, shallow breathing can be observed, and oen, frequent
transient awakenings and restlessness. A sleep study is indicated in patients with
symptoms of hypoventilation, those at high risk and individuals fulfilling criteria
as indicated in clinical guidelines. While detailed PSG may be required in a limited
number of cases to identify additional sleep disorders or solve problems when the
diagnosis or response to treatment is unclear, in most patients respiratory polygraphy
(PG) including S
normal oximetry trace overnight in a patient who has slept well is likely to exclude
and carbon dioxide (CO2) measurement is sucient. Although a
aO
2
275ERS Handbook: Respiratory Sleep Medicine
Symptoms and signs of hypoventilation
P
S
P
100
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80
%
60
2
aO
40
20
0
200
150
100
mmHg
2
CO
50
0
25
20
mmHg
2
10
tcCO
0
22:00 1:00
Pulse
Pulse
4:00
Time
Figure 2. An example of nocturnal hypoventilation from a sleep study using oximetry and P
Note the dips in S
hypoventilation.
moderate or severe hypoventilation, P
oximetry measurement are increasingly used to establish the extent of hypercapnia
and the small increases in P
aO
2
. Heart rate also increases during episodes of
tcCO
2
monitoring devices which combine
tcCO
2
tcCO
.
2
and nocturnal desaturation, and titrate the response to NIV therapy. Most units aim
for a peak P
value overnight of <6.5 kPa (<49 mmHg).
tcCO
2
An example of mild nocturnal hypoventilation during PG is shown in figure 2.
Further reading
• Birnkrant DJ, et al. (2022). Cardiorespiratory management of Duchenne muscular dystrophy:
emerging therapies, neuromuscular genetics, and new clinical challenges. Lancet Respir Med;
10: 403–420.
• Finkel RS, et al. (2018). Diagnosis and management of spinal muscular atrophy. Part 2:
pulmonary and acute care; medications, supplements and immunizations; other organ
systems; and ethics. Neuromuscul Disord; 28: 197–207.
• Georges M, et al. (2022). Proposals from a French expert panel for respiratory care in ALS
patients. Respir Med Res; 81: 100901.
• Hukins CA, et al. (2000). Daytime predictors of sleep hypoventilation in Duchenne muscular
dystrophy. Am J Respir Crit Care Med; 161: 166–170.
• Hull J, et al. (2012). British Thoracic Society guideline for respiratory management of children
with neuromuscular weakness. Thorax; 67: Suppl. 1, i1–i40.
• Kushida CA, et al. (2005). Practice parameters for the indications for polysomnography and
related procedures: an update for 2005. Sleep; 28: 499–521.
• Mokhlesi B, et al. (2019). Evaluation and management of obesity hypoventilation syndrome.
An ocial American Thoracic Society Clinical Practice guideline. Am J Respir Crit Care Med;
200: e6–e24.
276
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Symptoms and signs of hypoventilation
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• National Institute for Health and Care Excellence (NICE) (2016). Motor neurone disease:
assessment and management. NICE Guideline [NG42]. www.nice.org.uk/guidance/ng42
Date last updated: 23 July 2019.
• National Institute for Health and Care Excellence (NICE) (2021). Obstructive sleep apnoea/
hypopnoea syndrome and obesity hypoventilation syndrome in over 16s. NICE Guideline
[NG202]. www.nice.org.uk/guidance/ng202 Date last updated: 20 August 2019.
• Ogna A, et al. (2016). Prognostic value of initial assessment of residual hypoventilation using
nocturnal capnography in mechanically ventilated neuromuscular patients: a 5-year follow-up
study. Front Med; 3: 40.
• Orlikowski D, et al. (2017). Prognostic value of nocturnal hypoventilation in neuromuscular
patients. Neuromuscul Disord; 27: 326–330.
277ERS Handbook: Respiratory Sleep Medicine
Peri-operative assessment
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and management of
pregnancy
Anita K. Simonds
Decision-making
Patients with hypoventilation syndromes require surgery for reasons due to their
condition, such as scoliosis correction, tendon lengthening surgery or bariatric surgery
for OHS, and for acute or elective interventions related to intercurrent illnesses, such
as appendicectomy or surgery for bowel obstruction or limb fracture. Where possible
in adults and children, surgery should be planned electively by a multidisciplinary
team (MDT) including pulmonologist, anaesthetist, surgeon, intensive care unit (ICU)/
high-dependency unit (HDU) team, physiotherapist and specialist nurse practitioner.
Other team members will be vital according to the intervention, e.g. dietitian, speech
and language therapist and stoma team for gastrostomy and colostomy, or if a
significant post-operative ICU stay is anticipated. The key questions are: Is the surgical
procedure necessary? What is the risk? How can that risk be minimised by optimal
management by the MDT? The risk of carrying out the procedure should be set against
the risks of not performing the intervention, and carefully discussed with the patient.
This requires full mental capacity on behalf of the patient (or proxy) to ensure they
understand and can balance these risks.
Management is discussed in this chapter with reference to patients with neuromuscular
conditions and chest wall disease, such as scoliosis. Modifications for those with other
conditions causing hypoventilation are also considered.
Pre-operative assessment
Firstly, there should be a general assessment of wellbeing: can the condition and
its management be optimised? Smoking cessation advice should be given where
appropriate. Measurements of pulmonary function with pulmonary function tests,
peak cough flow and arterial blood gas tensions are indicated, together with cardiac
assessment by electrocardiogram (ECG) and echocardiogram. Broadly, a vital
Key points
• Management of surgical interventions and pregnancy in patients with
hypoventilation requires multidisciplinary team involvement.
• Many interventions can now be safely carried out with careful assessment and
use of respiratory support, which would not have been feasible previously.
• Individualised assessment and care plans are crucial.
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Peri-operative assessment and management of pregnancy
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capacity of <50% predicted is associated with medium risk and a vital capacity of
<30% predicted is associated with high risk. Similarly, moderate or severe cardiac
insuciency and pulmonary hypertension (PH), or rapidly progressive underlying
disease, are high risk factors. Overall risk will depend on these considerations, and
the magnitude of the surgery. Risk prediction guides may help, but these are more
helpful in homogeneous groups of patients, and as neuromuscular conditions are
extremely heterogeneous and COPD patients with respiratory insuciency may have
varying comorbidities, a personalised risk assessment and proactive risk management
approach by the MDT is sensible.
A low threshold for carrying out respiratory polygraphy (PG) for those with symptoms
or vital capacity <70% predicted is advisable. NIV should be started prior to
surgery for those with nocturnal hypoventilation, and overnight arterial blood gas
tensions corrected. For patients with peak cough flow <270 L·min−1, review by the
physiotherapy team and familiarisation with cough assist devices such as mechanical
in-exsuation (MI-E) are helpful.
Anaesthetic and surgical considerations
A previous anaesthetic history and knowledge of allergies is important. Depolarising
agents such as suxamethonium can cause skeletal muscle breakdown, resulting in
raised potassium and creatinine levels, while low muscle glycogen reserves can lead
to hypoglycaemia in the post-operative period in neuromuscular patients. Individuals
with conditions such as centronuclear myopathy associated with ryanodine receptor
gene mutations are at high risk of malignant hyperpyrexia, which can be lethal, and
rhabdomyolysis can occur in children and adults with Duchenne muscular dystrophy
and other neuromuscular disorders, even with inhalational/halogenated anaesthetic
agents. Intravenous agents are therefore usually preferred, although intravenous
access may be problematic. Fluid balance is particularly critical in patients with
cardiac involvement. For all these reasons, an anaesthetic and surgical team familiar
with these conditions and their complications is vital.
Post-operative management
Any patient at risk of nocturnal hypoventilation or using NIV should be managed
post-operatively in an HDU or ICU. Extubation onto NIV is helpful in moderate- and
high-risk patients, unless there are contraindications to this. Criteria for extubation
are peripheral oxygen saturation >93% on air, minimal secretions, able to use NIV,
and alert and responsive. Pain management should be optimised, but sensitivity to
opiates or sedatives is likely and ventilatory support settings and duration of ventilatory
support should be adjusted accordingly. Availability of an experienced physiotherapy
team is vital to manage airway secretions with MI-E, and begin early rehabilitation to
avoid deconditioning. As a result of low bodyweight, analgesia may be miscalculated,
and inadvertent overdose of paracetamol has been reported.
Surgery in other conditions
For patients with congenital central hypoventilation syndrome (CCHS), lung disease
(cystic fibrosis, bronchiectasis, COPD) and OHS, similar principles hold. CCHS patients
may be peculiarly sensitive to opiates and sedatives, and have other autonomic
complications such as abnormal heart rate and BP and pain and temperature control.
There is guidance on the ecacy of weight reduction procedures and bariatric surgery
for OHS. Practical planning is needed to provide adequately sized beds and operating
theatre and scanning facilities, and to manage comorbidities such as diabetes
mellitus, metabolic syndromes, hypertension and cardiac disease in OHS patients.
279ERS Handbook: Respiratory Sleep Medicine
Peri-operative assessment and management of pregnancy
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Pregnancy feasibility and assessment in patients with hypoventilation
Several decades ago, pregnancy was not considered to be feasible in those with
inherited or acquired neuromuscular or chest wall conditions if vital capacity was
<1.5 L. The use of comprehensive clinical management and NIV has now widened
feasibility to those with much more significantly reduced lung capacity, with favourable
maternal and fetal outcomes.
A pre-pregnancy joint clinic combining the expertise of genetic, medical, anaesthetic,
obstetric and paediatric teams is ideal, so that risks and likely outcomes can be
discussed.
Contraindications to pregnancy are PH, moderate or severe cardiac failure, other
severe organ insuciency, poor control of arterial blood gas tensions and rapidly
progressive underlying disease. Genetic counselling and screening are vital. As per
perioperative assessment, patients should undergo cardiorespiratory review with
ECG, echocardiogram, pulmonary function tests and respiratory PG. If mild nocturnal
hypoventilation is demonstrated, the introduction of NIV is recommended. There
is no absolute minimum level of vital capacity for successful outcomes, but values
<800 mL are associated with high risk, in the experience of most teams. If NIV is being
used, optimal control of oxygenation and carbon dioxide tension (P
support should be attained, aiming for normal diurnal and nocturnal arterial blood
) on ventilatory
CO
2
gas tensions. In some conditions, such as spinal muscular atrophy, expiratory muscle
weakness may exceed inspiratory muscle weakness. Provision of a cough-assist
device should be considered in patients with a peak cough flow <270 L·min−1, as
growth of the fetus, impacting on diaphragm function, can impair cough ecacy as
the pregnancy progresses.
Physiological, anaesthetic and surgical considerations in pregnancy
Normal pregnancy is associated with a 40–50% increase in V′E, resulting in a fall in
steady-state P
load. Most scoliotic curves do not worsen during pregnancy if they are stable pre-
, and a 20–40% increase in cardiac output adding to cardiorespiratory
aCO
2
pregnancy. There are reports of progression of muscle weakness in myotonic
dystrophy, but in stable or slowly progressive conditions there is no clear evidence
Table 1. Management during pregnancy in patients with hypoventilation
First trimester
Early review by MDT
Discuss anaesthetic and delivery options
Consider teratogenicity of current medication, and thromboprophylaxis in wheelchair
users
Schedule sleep study to assess respiratory progress
Consider familarisation with NIV and MI-E if not previously used according to
pulmonary function
Second trimester
Regular MDT review
Growth assessment and fetal anomaly scan
Management of gastro-oesophageal reflux
Third trimester
Ventilation and cough-assist review: virtual consultations may be helpful
Plan for elective admission for delivery
Caution with magnesium sulfate use if patient has pre-eclampsia
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Peri-operative assessment and management of pregnancy
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of underlying disease progression in pregnancy. However, this may be dicult to
separate from the eects of increased load on the respiratory system, until postpartum measurements can be carried out. More recently, there have been reports of
successful pregnancies in patients with motor neurone disease/amyotrophic lateral
sclerosis, although outcomes are variable and need to be carefully and realistically
discussed with patients.
Cervical scoliosis or fusion and jaw contractures may make mouth opening and
intubation challenging. Thoracic spinal fusion or instrumentation may make spinal or
epidural anaesthetic dicult or impossible.
Management throughout pregnancy is outlined in table 1.
Labour and post-delivery management
In high-risk pregnancy, delivery at 36 weeks by Caesarean section is usually recommended.
Vaginal delivery is contraindicated in patients with cardiac decompensation. Postoperative care on an HDU or ICU with extubation onto NIV and oximetry and P
CO
monitoring should be carried out according to the advice herein on post-operative
patients. A longer than average inpatient stay may be required to enable the individual to
get back to more usual NIV use, and to be supported by midwives.
Further reading
• Apkon SD, et al. (2018). Orthopedic and surgical management of the patient with Duchenne
muscular dystrophy. Pediactrics; 142: Suppl. 2, S82–S89.
• Carron M, et al. (2020). Perioperative care of the obese patient. Br J Surg; 107: e39–e55.
• Gupta, H, et al. (2011). Development and validation of a risk calculator predicting postoperative
respiratory failure. Chest; 140: 1207–1215.
• Johnson NE, et al. (2015). The impact of pregnancy on myotonic dystrophy: a registry-based
study. J Neuromuscul Dis; 2: 447–452.
• Kynes JM, et al. (2018). Multidisciplinary perioperative care for children with neuromuscular
disorders. Children; 5: 126.
• Lamy F, et al. (2021). Survey on patients’ organisations’ knowledge and position paper on
screening for inherited neuromuscular diseases in Europe. Orphanet J Rare Dis; 16: 75.
• Norwood F, et al. (2012). 179th ENMC international workshop: pregnancy in women with
neuromuscular disorders. Neuromuscul Disord; 22: 183–190.
• Randerath W, et al. (2021). European Respiratory Society guideline on non-CPAP therapies for
obstructive sleep apnoea. Eur Respir Rev; 30: 210200.
• Soma-Pillay P, et al. (2016). Physiological changes in pregnancy. Cardiovasc J Afr; 27: 89–94.
• Stenberg E, et al. (2022). Guidelines for perioperative care in bariatric surgery: Enhanced
Recovery Aer Surgery (ERAS) Society recommendations: a 2021 update. World J Surg; 46:
729–751.
2
281ERS Handbook: Respiratory Sleep Medicine
Noninvasive ventilation
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Marieke L. Duiverman, Renzo Boersma and Peter J. Wijkstra
NIV versus invasive ventilation
Long-term mechanical ventilation to treat hypoventilation syndromes was first
introduced between 1950 and 1960 to sustain life in patients aected by the
poliomyelitis epidemic. During the following decades, chronic home mechanical
ventilation expanded rapidly and was implemented for multiple other conditions.
Long-term mechanical ventilation can be delivered via a tracheal cannula (invasive
mechanical ventilation) or noninvasively via negative or positive pressure ventilation.
Nowadays, most patients on home mechanical ventilation are treated with NIV. Longterm invasive mechanical ventilation via tracheostomy is more rare, although there
are large dierences in its use depending on the underlying diseases and in dierent
regions/countries.
Invasive mechanical ventilation is most frequently oered in patients with severe
airway pathology, in whom the airway problems require ‘stenting’ of the airways, or
in patients with diseases in whom extended continuous need for ventilatory support
or insolvable sputum problems limit the use of NIV. Also, inability to use a facial mask
may necessitate a tracheostomy. However, with the invention of dierent masks and
modes (mouthpiece ventilation or nasal prongs) and the development of cough assist
techniques (mechanical in- and exsuation), many patients can stay on NIV for a long
time or even until they die, or can be extubated aer acute episodes of respiratory
failure back to NIV. Also, tracheostomy invasive ventilation is not always anatomically
Key points
• NIV is the preferred modality for long-term home mechanical ventilation.
• Dierent underlying conditions require dierent approaches to setting
the ventilator.
• Monitoring of long-term NIV requires a detailed and repeated history, a
detailed look at ventilator data and monitoring of gas exchange.
• For monitoring of long-term NIV, telemonitoring is gaining importance, but
further research is needed to investigate when and how to act upon data.
• Adherence to long-term NIV is crucial for treatment success and depends on
patient, caregiver and therapy-related factors.
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Noninvasive ventilation
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possible, as it includes risks such as tracheal bleeding, has consequences for the care
system of the patient, and may not always result in satisfying quality of life. Thus,
deciding to switch to tracheostomy invasive ventilation should be considered and
discussed carefully, preferably in advance.
Modes of positive pressure ventilation
Compared to invasive mechanical ventilation, NIV has two unique characteristics that
need be considered when setting a ventilator. First, there will always be unintentional
leaks; the mask cannot be fixed hermetically to the patient’s face, and both external
and internal leaks (for example to the oesophagus) may occur. Second, resistance of
the upper airways needs to be managed. Therefore, in NIV, increasing pressure or
volume does not necessarily result in increased eective alveolar ventilation, as it may
induce airway obstruction.
Aer the rise of NIV in the 1980s, volume-targeted ventilation (VTV) was the
predominant mode. With VTV, a pre-set tidal volume is given, with a fixed flow–time
profile, leading to a fluctuating inspiratory pressure depending on airway resistance
and the compliance of the respiratory system. However, as each breath is delivered
with the same predetermined flow–time profile and as the area under this curve
represents the volume delivered, if there are leaks the flow will not change and this
will lead to a decrease in airway pressure and delivered volume. Also, VTV might not
accommodate changing conditions: as the volume is fixed, it does not compensate for
leakage and changes in airway resistance and compliance of the respiratory system.
Overall, patients might find VTV less comfortable.
Since the beginning of the 21st century, pressure-targeted ventilation (PTV) has
become more common, during which an airflow is delivered to meet a predefined
airway pressure. Figure 1 indicates the dierences between VTV and PTV. The actual
tidal volume delivered in PTV depends on the pre-set inspiratory pressure, patient
eort, resistance and compliance of the respiratory system, and inspiratory time. A big
advantage of PTV is that it usually compensates well for leaks.
In recent years, the enormous rise in chronic ventilation has led to a boost in
development of new modes, such as modes that auto-titrate EPAP, hybrid modes that
combine the advantages of volume- and pressure-targeted modes (volume-assured
pressure support (VAPS) modes) or modes that target mechanical derangements (such
as the expiratory flow limitation machines). It is important to realise that dierent
manufacturers have created dierent names and algorithms for the same principles;
however, their dierences will have an impact on the practicalities of how to titrate
the modes.
With VAPS ventilation, pressure-controlled modes have been developed that ensure
the average level of a predetermined tidal volume. The modes work by first getting
feedback from the ventilator on the delivered volume, then adjusting pressure in order
to reach the pre-set tidal volume over a certain time frame. This time should be short
enough to prevent hypoventilation and long enough not to disturb sleep. Theoretically,
these modes should adapt and react to changes in pulmonary impedance, providing
eective and comfortable ventilation. These modes can also be combined with
automatic titration of EPAP (AVAPS-AE or iVAPS-autoEPAP) to maintain upper airway
patency. Despite these theoretical benefits, randomised controlled trials have not
shown clear benefits of VAPS modes.
Automatic modes might be attractive for remote initiation of NIV, as the machine
automatically adjusts to changing conditions. However, a recently published
283ERS Handbook: Respiratory Sleep Medicine
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