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Chapter 32. NIV in type 2 (hypercapnic) acute respiratory failure
Shaden O. Qasrawi, MBBS, MRCP, Ahmed S. BaHammam, MD, FACP
University Sleep Disorders Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia and
the Strategic Technologies Program of the National Plan for Sciences and Technology and Innovation in
the Kingdom of Saudi Arabia.
CORRESPONDING AUTHOR:
PROF. AHMED S. BAHAMMAM
Professor of Medicine
Director, Sleep Disorders Center, College of Medicine, King Saud University
Box 225503, Riyadh 11324, Saudi Arabia
Telephone: 966-1-467-1521
Fax: 966-1-467-2558
E-mail: ashammam2@gmail.com
ashammam@ksu.edu.sa
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Abbreviations
ABG Arterial Blood Gas
AECOPD Acute Exacerbation of Chronic Obstructive Pulmonary Disease
AHRF Acute Hypercapnic Respiratory Failure
APACHE II Acute Physiology and Chronic Health Evaluation II
BPAP Bilevel Positive Airway Pressure
bpm Breath per minuteCF Cystic Fibrosis
COPD Chronic Obstructive Pulmonary Disease
CPAP Continuous Positive Airway Pressure
ECG Electrocardiogram
EPAP Expiratory Positive AirwayPressure
HDU High Dependency Unit
ICU Intensive Care Unit
IMV Invasive Mechanical Ventilation
IPAP Inspiratory Positive AirwayPressure
FFM Full Face Mask
NMD Neuro Muscular Diseases
NIV Non-Invasive Ventilation
OHS Obesity Hypoventilation Syndrome
OSA Obstructive Sleep Apnea
PaCO2 Arterial partial pressure of carbon dioxide
PE Pulmonary Embolism
RCT Randomized Controlled Trials
VtPS Volume targeted pressure support
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Abstract
Noninvasive ventilation (NIV) refers to providing ventilatory support without the use of invasive
artificial airway. The use of NIV has markedly increased recently and is currently
regarded essential in the management of acute respiratory failure and in
particular acute hypercapnic respiratory failure (AHRF).
AHRF could complicate many respiratory disorders including chronic obstructive pulmonary
disease, asthma, cystic fibrosis, bronchiectasis, neuromuscular and chest wall diseases,
including morbid obesity, kyphoscoliosis and obesity hypoventilation syndrome. The use of NIV
in such conditions helps to prevent further deterioration and avert the need for IMV, and by
this cuts down on hospital stay, costs and prevents IMV related complications. This chapter
discusses the use of NIV in AHRF, review its indications/ contraindications and predictors of
success or failure with special emphasis on obese patients with AHRF.
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Introduction
Noninvasive ventilation (NIV) refers to providing ventilatory support using a mask or a similar
device without the use of invasive artificial airway (endotracheal tube or tracheostomy tube).
The use of NIV has markedly increased in the recent years, and is currently considered to be
essential in the management of acute respiratory failure and in particular acute hypercapnic
respiratory failure (AHRF) (1, 2).
AHRF results from inadequate alveolar ventilation, which is needed to maintain normal arterial
oxygen and carbon dioxide levels (3). Conventionally, pH <7.35 and arterial partial pressure of
carbon dioxide (PaCO2) >6.5 kPa (>50mmHg) define acute respiratory acidemia and AHRF (3). In
general, if AHRF persists despite initial medical therapy, those values have been used as a
threshold for considering commencing NIV (3). AHRF could complicate many respiratory
disorders including chronic obstructive pulmonary disease (COPD), asthma, cystic fibrosis,
bronchiectasis, neuromuscular and chest wall diseases, including morbid obesity and
kyphoscoliosis (see Table 1) (3). This section aims to discuss AHRF in obese patients. However,
as obese patients may develop AHRF secondary to several respiratory disorders, we will cover
briefly the utility of NIV in different respiratory disorders that cause AHRF, and then will focus
on AHRF in patients with obesity hypoventilation syndrome (OHS).
Indications and contra-indications to NIV in AHRF
The indications for NIV are variable based on the underlying cause, its severity and the
associated comorbidities. Clinical manifestations that support the early use of NIV include,
moderate to severe dyspnea, tachypnea (>24 breaths per min in obstructive lung diseases, >30
per min in restrictive lung diseases) and signs suggestive of increased work of breathing
including accessory muscle use and thoraco-abdominal paradox (4). Other indications are
usually based on investigations showing impaired gas exchange reflecting acute or acute on
chronic ventilatory failure with raised PaCO2 and acidemia (5, 6).Table 2 summarizes the
indications and contraindication to NIV. Application of NIV could be difficult in patients with
severe facial deformity, fixed upper airway obstruction or facial burns (4). There is a number of
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other potential contraindications; however, most of those have been employed as exclusion
criteria in clinical trials rather than being proven to be associated with worse outcome (3, 7).
Chronic Obstructive Lung Disease (COPD)
Acute exacerbations of COPD accounts for a significant number of annual admissions worldwide
(8). Of these, many present with hypercapnia (9), which increases the risk of mortality (10, 11).
Developing AHRF in COPD is usually multifactorial with many underlying causes such as
infection, mucosal edema, bronchospasm, sputum retention, sedation, pneumothorax,
pulmonary embolism, left ventricular failure and excessive oxygen therapy. There is now strong
evidence showing that uncontrolled oxygen therapy increases acidemia and subsequently
mortality in acute exacerbations of COPD (AECOPD) (10). This oxygen-induced hypercapnia
applies with variable degree, to other causes of AHRF (3). Hence, in managing all patients at a
risk for AHRF, controlled oxygen therapy with oxygen saturation target of 88-92% is
recommended initially (3).
The use of NIV in AECOPD has increased markedly and its use is currently viewed as a part of
the standard therapy for patients who have persistent respiratory acidemia despite receiving
standard medical therapy (12, 13). The use of NIV in AECOPD has reduced the need for IMV,
thereby reducing complications and cutting hospital costs associated with IMV, in addition to
improving survival (13). Hence NIV is currently considered as a major progress in the
management of acute exacerbations of AECOPD (13).
Severe acidemia alone is not a contraindication for NIV trial in an appropriately equipped
setting where shifting the patient to IMV can be rapidly achieved. Nevertheless, the use of NIV
should not delay commencing IMV when needed (3).The treating team should keep in mind
other possible causes of AHRF that may coexist with COPD such as obstructive sleep apnea
(OSA) and OHS (3, 14). Obese patients with COPD may have coexisting sleep disordered
breathing, which is called overlap syndrome. For patients with overlap syndrome, NIV should
aim to correct both hypoventilation and upper airway obstruction.
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An improvement in physiological parameters such as pH and respiratory rate within 1-2 hr of
initiating treatment is usually a predictor of success of NIV, whereas worsening of those
parameters is predictive of failure of NIV with increased risk for intubation or mortality (3).
Table 3 shows the predictors of NIV success in patients with COPD exacerbation and AHRF (3,
15-20).
Monitoring of PaCO2 NIV serves as a useful guide in planning the withdrawal of NIV and
transcutaneous PaCO2 measurement serves as a convenient alternative to arterial or capillary
sampling (3).
Acute exacerbation of asthma
Patients with acute attack of asthma present usually with hypoxemic respiratory failure.
However, in advanced cases, patients may present with AHRF. Nevertheless, the use of NIV in
acute exacerbation of asthma remains a controversial topic, and reports of NIV use in patients
with severe acute asthma are limited. A few RCTs have explored the utility of NIV in hypoxemic
respiratory failure in patients with acute exacerbation of asthma (21). However, the existing
evidence is equivocal and limited by a small number of published trials with methodological
problems (21). Moreover, at present there is no strong evidence to support NIV use in
asthmatics with AHRF. The two studies reporting clear beneficial effect of NIV use in AHRF
asthma were retrospective studies with methodological limitations (22, 23). One of them,
included population who seem more likely a COPD than asthmatic population (24). At present,
there is limited evidence to recommend the use of NIV in patients with asthma exacerbation
and respiratory failure. Larger, prospective RCTs of properly selected patients and a good
methodological design are needed.
Non-CF bronchiectasis
Patients who suffer from non-CF bronchiectasis can present with recurrent episodes of
hypercapnic respiratory failure (3). Despite little data, there is no evidence that patients with
non-CF bronchiectasis presenting with AHRF do worse on NIV compared to those commenced
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on IMV (25). Therefore, NIV is indicated in the presence of respiratory acidemia using the same
criteria applicable in AECOPD (3). It is not unusual to find sleep disordered breathing in obese
patients with bronchiectasis (26). Such patients should be managed with NIV to improve
ventilation and eliminate the obstructive events during sleep.
Although managing and clearing excessive sputum while on NIV can be challenging, NIV could
actually assist by improving dyspnea and hence help patients to participate more effectively in
physiotherapy (27).
Extra-pulmonary restrictive lung diseases
Severe chest wall deformity and neuromuscular diseases (NMD) can markedly impair the
respiratory muscles function, and hence result in a restrictive lung function pattern
characterized by reduced vital capacity (VC), total lung capacity and functional residual
capacity, which in turn can lead to AHRF (28). Such patients will usually present with chronic
hypercapnia and acute respiratory failure that is commonly precipitated by infection (28). The
risk of hypercapnic respiratory failure increases when the VC falls below 1–1.5 L (29). Obese
patients with neuromuscular diseases are at an increased risk for sleep disordered breathing
and those with bulbar dysfunction are at a higher risk for OSA (30).There are no available RCTs
comparing NIV with IMV in the management of AHRF complicating extra-pulmonary restrictive
lung diseases, and the current recommendations are extended from the evidence available for
AECOPD management (3, 28). Generally, NIV should be tried in patients presenting with
hypercapnia without waiting for the development of acidemia, but if NIV fails, intubation
should not be delayed unless IMV is not desired for whatever valid reason. In patients with
NMD with bulbar dysfunction and communication difficulties, NIV is usually difficult. Moreover,
patients with bulbar dysfunction have an increased risk of aspiration. In general, patients with
NMD and chest wall deformities need an overnight sleep study once stable, and might require
nocturnal NIV at home (3).
Obesity hypoventilation syndrome (OHS)
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Hypercapnia in hospitalized obese patients is associated with an increase in morbidity and
mortality (31). OHS is generally underdiagnosed and undertreated (32). It is also not uncommon
for chronic hypercapnia to be discovered when obese patients who are otherwise not known to
have OHS, are assessed for emergency or elective operations. However, patients with OHS
commonly present with acute on top of chronic hypercapnic respiratory failure (33). A recent
study has shown that approximately 40% of patients with OHS present for the first time with
AHRF (34). Additionally, OHS patients admitted with AHRF have a high rate of in-hospital
mortality (18%) (35). Therefore, it is important to keep in mind the possibility of OHS as a cause
of AHRF in the morbidly obese patients.
OHS is the second most frequent indication (after COPD) for NIV treatment among hospitalized
patients with AHRF (36, 37). It is recommended to initiate NIV in all patients suspected of
having AHRF secondary to OHS, before performing sleep study, since early initiation of NIV may
obviate the need for IMV (2). Nevertheless, there is no enough evidence to provide a guidance
for the use of NIV in the treatment of both chronic hypercapnia and AHRF in obese patients (2).
The majority of patients with OHS have coexisting severe OSA (38). In general, NIV will be
needed as an emergency treatment in all patients with OHS presenting with AHRF (2). In
addition, NIV can be considered in admitted patients with raised PaCO2 and excessive daytime
sleepiness, sleep disordered breathing and/or right heart failure even when acidemia is absent
(39).
Pressure- and volume-limited ventilation have been reported in patients with AHRF; however,
we recommend initiating treatment with bi-level PAP (BPAP) ventilation as there is no evidence
indicating that other ventilatory modes are superior to BPAP (2). During NIV therapy,
observation and monitoring of the level of consciousness, vital signs, respiratory pattern,
oxygen saturation, and arterial blood gases are crucial (2, 40). As most patients with OHS have
coexisting OSA, EPAP should be increased gradually until snoring, witnessed apneas, and dips in
oxygen saturation are eliminated. IPAP should be gradually increased to ensure optimal
ventilation until an acceptable level of steady-state oxygen saturation (≥ 90%) is attained (33).
Figure 1 shows a proposed algorithm for the NIV management of OHS patients with AHRF (2).
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In patients who do not respond to BPAP mode, volume targeted pressure support (VtPS) can be
attempted (41). VtPS is a hybrid mode that combines the advantages of pressure-limited and
volume-limited modes of ventilation into one ventilation mode. Studies concerning the use of
volume targeted pressure support mode to treat OHS patients did not show clinical benefits
over those achieved with a fixed bi-level mode (41). Moreover, VtPS mode has not directly been
assessed in OHS during AHRF.
Limited studies have assessed the predictors of NIV failure in OHS patients with acute
respiratory failure. Lemyze et al. demonstrated in a prospective study (n=76), that severe
pneumonia and multiple organ failure predict early NIV failure in morbidly obese patients with
acute respiratory failure (42). The same study reported that more than half of the patients
experienced a delayed response to NIV, with persistence of hypercapnic acidemia during the
first 6 hours (42).
Once the patient is stable, it is recommended to perform a sleep study for patients with OHS to
choose the right ventilatory mode and pressure needed to eliminate the obstructive respiratory
events and hypoventilation. All patients with OHS will eventually need NIV use at home. Studies
that followed OHS patients with AHRF after discharge indicated higher mortality in patients
who refused PAP therapy (33, 40). Several studies have reported that good compliance with
domiciliary NIV results in improvement in gas exchange, daytime sleepiness, quality of life, and
number of hospitalizations in patients with OHS (43).
Conclusion
Obesity represents a global epidemic, and obese patients are at a higher risk for developing
AHRF. Practitioners should recognize that morbidly obese patients with sleep hypoventilation,
daytime hypercapnia, and pulmonary hypertension have an increased risk of AHRF. NIV is
currently an accepted therapeutic strategy in several disorders that can be complicated by
respiratory failure and in particular AHRF. The use of NIV in obese patients with AHRF helps to
prevent further deterioration and avert the need for IMV. When NIV is implemented, clear
treatment goals should be defined and a plan of care should document escalation measures in
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the event of failure of NIV. Although NIV is considered now as a great progress in managing
respiratory failure it should not delay intubation and IMV in those patients who fail to respond
to NIV or in whom NIV is not indicated.
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Table 1: Causes of Hypercapnic Respiratory Failure
Causes of hypercapnic respiratory failure
• Chronic obstructive pulmonary disease (COPD)
• Acute severe asthma
• Bronchiectasis
• Cystic Fibrosis
• Obstructive sleep apnea
• Kyphoscoliosis
• Morbid obesity
• Opioid and sedative drugs
Neuromuscular diseases (e.g. cervical cord lesions, Guillain–Barré syndrome,
myasthenia gravis, Muscular dystrophy)
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Table 2: Indications and contraindications for NIV
Indications and contraindications for NIV
INDICATIONS
Clinical manifestations
• Moderate to severe dyspnea
• Tachypnea (>24 bpm in obstructive, >30 bpm in restrictive)
• Signs of increased work of breathing (e.g. accessory muscles use and abdominal
paradox)
Gas exchange
• Acute or acute on chronic ventilatory failure ( PaCO2 >6.5, kPa, pH<7.35 )
• Hypoxemia
CONTRAINDICATIONS*
• Respiratory or cardiac arrest
• Inability to fit the mask (e.g. severe facial deformity or facial burns)
• Fixed upper airway obstruction
• Hypotensive shock
• Uncontrolled upper gastrointestinal bleeding
• Agitation /confusion
• Inability to protect the upper airway
• Swallowing impairment
• Excessive secretions not managed by secretion clearance techniques
• Multiple (i.e. two or more) organ failure
• Recent upper airway or upper gastrointestinal surgery
* Some are relative contraindications
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Table 3: Predictors for NIV success/failure in patients with COPD exacerbation and AHRF.
Predictors for NIV success/failure in AHRF in COPD
Predictors for treatment success
pH 7.25-7.35, PaCO2 > 6.5 kpa
GCS > 14
Respiratory rate 24-30/ min
Response to NIV within 1-2h
APACHE II < 29
Predictors for treatment Failure
pH <7.25
GCS ≤ 11
Respiratory rate >30/ min
Additional Pneumonia
Severe Mask leakage
Patient-ventilator asynchrony
Agitation or intolerance
Inability to clear secretions
APACHE II >29
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Figure legends:
Figure 1: A proposed algorithm for the NIV management of OHS patients with AHRF.
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