Introduction

Noninvasive ventilation (NIV) refers to ventilatory support without an endotracheal tube, usually delivered through a tightly fitting nasal, oronasal, or full-face mask. NIV is therefore a broad umbrella term that includes modalities such as CPAP and BiPAP, although these terms are often used inconsistently and interchangeably in clinical practice.

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With CPAP (continuous positive airway pressure), the patient breathes against a single continuous positive pressure level throughout the respiratory cycle. CPAP does not provide separate inspiratory pressure support. Its main effects are based on maintaining airway and alveolar patency and thereby increasing the volume of ventilated lung.

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BiPAP/bilevel NIV uses two pressure levels:

• IPAP, the higher pressure during inspiration

• EPAP, the lower pressure during expiration

 

The difference between these pressures, IPAP − EPAP, is the pressure support, which is the pressure difference that actually assists ventilation. It particularly affects tidal volume, minute ventilation, work of breathing, and carbon dioxide elimination.

BiPAP is a commonly used term for bilevel therapy, but it was originally a proprietary name used by a device manufacturer.

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Key NIV concepts

IPAP

IPAP is the higher pressure level used during inspiration.

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If EPAP remains unchanged, increasing IPAP increases pressure support. This usually increases tidal volume and improves alveolar ventilation, provided that the patient tolerates the pressure and that patient–device synchrony, mask leak, or air trapping do not worsen.

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EPAP

EPAP is the pressure level used during expiration. Functionally, it corresponds to PEEP during NIV.

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EPAP can:

• improve oxygenation

• prevent upper airway collapse

• keep small airways more open

• recruit alveoli in pulmonary edema and hypoxemic respiratory failure

• partially counterbalance auto-PEEP in patients with COPD

• facilitate detection of the patient's inspiratory effort by the ventilator.

 

However, excessively high EPAP can increase end-expiratory lung volume, worsen dynamic hyperinflation, and reduce venous return to the heart.

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Air trapping

Air trapping means that the patient does not have enough time to exhale all the inspired air before the next inspiration begins. Air enters the lungs faster than it can leave them.

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If the patient inhales 500 mL but manages to exhale only 400 mL before the next breath:

• 100 mL of additional air remains after the first breath

• more air may remain after the next breath

• end-expiratory lung volume increases.

 

In reality, the situation usually reaches a new equilibrium, but the lungs remain at a higher-than-normal operating volume.

Air trapping is harmful because it can lead to dynamic hyperinflation.

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Dynamic hyperinflation

Air trapping increases end-expiratory lung volume breath by breath.

incomplete expiration → air trapping → dynamic hyperinflation → auto-PEEP

 

The terms air trapping, dynamic hyperinflation, and auto-PEEP are sometimes used almost synonymously in clinical practice. Strictly speaking, however, air trapping is the mechanism, dynamic hyperinflation is the increase in lung volume, and auto-PEEP is the resulting positive end-expiratory pressure.

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When air trapping recurs from one breath to the next, end-expiratory lung volume increases. This is called dynamic hyperinflation.

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The risk increases when:

• respiratory rate is high

• expiratory time is short

• Vt is large

• Ti is long

• minute ventilation is increased aggressively

• bronchial obstruction is severe

• the patient has bronchospasm, mucus, or inflammation.

 

In addition to COPD and emphysema, air trapping occurs in severe asthma and other conditions associated with marked expiratory flow limitation.

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Auto-PEEP

Auto-PEEP refers to a situation in which expiration has not been completed before the next inspiration begins. Air therefore remains trapped in the lungs, end-expiratory lung volume increases, and alveolar pressure remains positive even without externally applied pressure.

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Auto-PEEP is also called intrinsic PEEP.

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The phenomenon is particularly associated with COPD and emphysema and with situations in which the respiratory rate is high, inspiratory time is too long, and expiratory time is too short.

 

The concepts involved in the same sequence describe different aspects of the phenomenon:

• air trapping: air remains trapped in the lungs

• dynamic hyperinflation: end-expiratory lung volume increases

• auto-PEEP: positive end-expiratory pressure remains in the alveoli.

 

Auto-PEEP increases the work of breathing because the patient must first reduce the pressure difference between the alveoli and airways with a stronger inspiratory effort before inspiratory flow can begin and the ventilator can detect the inspiratory effort. If auto-PEEP is, for example, 6 cmH₂O, the patient must generate at least an equivalent pressure change before inspiratory flow can begin. The patient therefore has to overcome an internal counterpressure before every inspiration.

 

Consequences may include:

• marked inspiratory effort

• delayed triggering

• untriggered inspiratory efforts

• patient–device asynchrony

• respiratory muscle fatigue.

 

At the same time, the lungs are already fuller than normal at the end of expiration. Taking the next breath resembles adding air to an almost fully inflated balloon: breathing occurs on an unfavorable portion of the pressure–volume curve, and generating an additional tidal volume requires more work.

 

Appropriately set external EPAP can partially counterbalance auto-PEEP and facilitate triggering. Excessively high EPAP, however, can increase end-expiratory lung volume and worsen dynamic hyperinflation.

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Pressure support

Pressure support = IPAP − EPAP

 

For example:

• IPAP 16 / EPAP 4 → pressure support 12 cmH₂O

• IPAP 16 / EPAP 8 → pressure support 8 cmH₂O

 

If EPAP is increased while IPAP remains unchanged, pressure support decreases. Tidal volume, minute ventilation, and CO₂ elimination may consequently decrease.

 

Increasing EPAP is therefore not "free" from a ventilation perspective. If EPAP is increased, for example, to counterbalance auto-PEEP or improve oxygenation, IPAP may also need to be increased to maintain pressure support.

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Tidal volume and minute ventilation

Vt, or tidal volume, refers to the volume of a single breath.

Vte refers to exhaled tidal volume.

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VE, or minute ventilation, refers to the volume ventilated per minute.

 

Minute ventilation is calculated as:

VE = Vt × respiratory rate

 

If Vte is 450 mL and the respiratory rate is 20/min:

VE = 0.45 L × 20/min = 9 L/min

 

A physiologically more important variable than total minute ventilation is alveolar ventilation:

VA = (Vt − dead space) × respiratory rate

 

Rapid, shallow breathing can produce a high minute ventilation even when effective alveolar ventilation and CO₂ elimination remain inadequate because much of the ventilation is directed to dead space, such as the trachea and main bronchi.

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Inspiratory time

Ti refers to the duration of the inspiratory phase.

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During NIV, the set Ti is particularly relevant during ventilator-triggered or time-cycled breaths. During patient-triggered breaths, inspiratory duration is usually determined by the patient's own breathing pattern; in other words, the patient determines Ti.

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Some devices have separate cycling settings and Ti min and Ti max limits.

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Backup rate

Backup rate refers to the respiratory rate at which the ventilator provides breaths if the patient does not trigger an adequate number of breaths spontaneously.

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The importance of the backup rate is particularly relevant in conditions such as neuromuscular disease, obesity hypoventilation, impaired level of consciousness, or situations in which the patient's spontaneous respiratory rate is unreliable.

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Triggering and cycling

Triggering refers to the point at which the ventilator detects the patient's inspiratory effort and increases the pressure from the EPAP level to the IPAP level.

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Cycling refers to the point at which the ventilator transitions from the IPAP level back to the EPAP level.

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Cycling that occurs too late may prolong inspiration and shorten expiratory time. This is particularly harmful in COPD and emphysema.

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Cycling that occurs too early, on the other hand, may provide insufficient inspiratory support, for example in neuromuscular or restrictive respiratory failure.

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Physiological goal of NIV

The goal of NIV is not merely to produce numbers on the ventilator display that appear favorable. The goal is to improve the patient's work of breathing, gas exchange, and hemodynamics.

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A favorable response to NIV is usually indicated by:

• decreased respiratory rate

• reduced use of accessory respiratory muscles

• relief of dyspnea

• improved patient–device synchrony

• improvement of SpO₂ into the target range

• increase or normalization of pH

• decrease or stabilization of PaCO₂

• maintenance of adequate blood pressure and level of consciousness

• sufficient time for expiration.

 

The same IPAP, EPAP, Vt, or VE settings cannot be applied to every patient. Appropriate support depends on factors including:

• mechanism of respiratory failure

• airway resistance

• lung compliance

• respiratory drive

• the patient's own respiratory muscle activity

• mask leak

• level of consciousness

• hemodynamic status

• concomitant cardiac disease

• patient–device synchrony.

 

Physiology of dyspnea

Dyspnea generally occurs when the ventilation demanded by the respiratory center does not match the ventilation that the respiratory system is able to produce.

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The brain increases respiratory drive, but the lungs, chest wall, or respiratory muscles are unable to meet this demand as expected. This is called neuromechanical dissociation. Causes may include airway obstruction, reduced lung compliance, dynamic hyperinflation, restricted chest wall movement, or respiratory muscle weakness and fatigue. The patient therefore has to increase respiratory effort, but airflow or tidal volume does not increase proportionally.

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Hypercapnia strongly increases activity of the respiratory center. An increase in CO₂ and the resulting increase in acidity create a need to breathe more. If ventilation does not increase accordingly, the typical sensation of air hunger develops.

 

Hypoxemia increases respiratory drive through peripheral chemoreceptors, but mild or moderate hypoxemia may cause surprisingly little dyspnea. The sensation usually becomes more pronounced as hypoxemia becomes more severe.

 

Dyspnea in cardiogenic pulmonary edema

The fundamental cause of cardiogenic pulmonary edema is increased left-sided cardiac filling pressure. The pressure is transmitted from the left atrium to the pulmonary veins and pulmonary capillaries, causing fluid to move first into the pulmonary interstitium and ultimately into the alveoli.

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Several simultaneous mechanisms contribute to dyspnea.

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Lung compliance decreases. Interstitial and alveolar fluid increase the stiffness of lung tissue, meaning that a greater pressure difference is required to expand the lungs. The patient must generate a stronger inspiratory effort and a more negative change in pleural pressure to achieve the same tidal volume. The work of breathing increases, and breathing often becomes rapid and shallow.

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Gas exchange deteriorates. Fluid-filled alveoli remain perfused but are poorly ventilated or not ventilated at all. This results in ventilation–perfusion mismatch and intrapulmonary shunting, which primarily impair oxygenation. Hypoxemia increases respiratory drive, work of breathing, and the sensation of air hunger. CO₂ elimination may initially be maintained through increased minute ventilation, but in severe respiratory failure or when the respiratory muscles become fatigued, alveolar ventilation also deteriorates and PaCO₂ begins to rise.

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Pulmonary receptors are activated. Increased pressure and fluid in the pulmonary interstitium stimulate vagal C fibers. This promotes rapid, shallow breathing.

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The airways may narrow. The bronchial mucosa may become edematous, and reduced lung volumes may narrow the small airways. This is sometimes referred to as cardiac asthma.

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The sympathetic response increases. Hypoxemia, elevated filling pressures, and the sensation of suffocation cause tachycardia, sweating, agitation, and anxiety.

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The supine position can worsen symptoms because venous return and pulmonary blood volume increase while lung volumes decrease.

 

Dyspnea in COPD exacerbation

During a COPD exacerbation, airway inflammation, mucus production, bronchospasm, and mucosal edema increase. Expiratory airflow becomes even more limited.

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The key mechanism of dyspnea is an acute worsening of expiratory flow limitation and the resulting dynamic hyperinflation.

The patient begins to breathe more rapidly even though expiration takes longer than normal. The next inspiration begins before the previous expiration has been completed:

air trapping → dynamic hyperinflation → auto-PEEP

 

The lungs become progressively fuller even though the patient feels unable to get enough air.

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If, for example, 8 cmH₂O of auto-PEEP, or positive pressure, remains in the alveoli, the patient must first generate a sufficiently negative pleural pressure through inspiratory effort to overcome this pressure before inspiratory flow can begin. Auto-PEEP therefore creates an inspiratory threshold load.

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Hyperinflation pushes the diaphragm downward and flattens it. A shortened and flattened diaphragm generates pressure less efficiently even when the respiratory center signals it to work forcefully.

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The patient's experience may be: "I am trying to breathe more, but my breathing does not increase."

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V/Q mismatch can cause hypoxemia. Increased dead space, respiratory muscle fatigue, and inadequate alveolar ventilation can increase PaCO₂ and decrease pH. Hypoxemia and, in particular, hypercapnia and acidosis increase respiratory drive.

Breathing is often rapid, expiration is prolonged, and the accessory respiratory muscles are active.

 

Dyspnea in stable emphysema

In stable emphysema, dyspnea is usually chronic and becomes more pronounced during exertion.

Destruction of the alveolar walls and of the attachments that help keep small airways open reduces the elastic recoil of the lungs. Small airways therefore collapse easily during expiration.

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Consequences include:

• static hyperinflation at rest

• reduced inspiratory capacity

• flattened diaphragm

• reduced mechanical efficiency of the respiratory muscles.

 

During exertion, CO₂ production and ventilatory demand increase. The patient breathes more rapidly, expiratory time shortens, and dynamic hyperinflation increases. End-expiratory lung volume rises and inspiratory capacity decreases. Eventually, inspiration begins from an already very high lung volume, leaving little room for Vt to increase.

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Destruction of the alveolar surface and pulmonary capillary bed also reduces the surface area available for diffusion. V/Q mismatch and exertional hypoxemia may increase respiratory drive, but in many patients with emphysema, dyspnea is explained more by hyperinflation and respiratory mechanics than by oxygen saturation measured at rest.

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In simplified terms:

• in pulmonary edema, the patient cannot obtain sufficient oxygen because the lungs are fluid-filled and stiff

• during a COPD exacerbation, air does not have enough time to leave the lungs

• in stable emphysema, the lungs are chronically overinflated, leaving too little room for the next inspiration.

 

CPAP and NIV in cardiogenic pulmonary edema

Effects on the lungs

In alveolar pulmonary edema, the alveoli are partially filled with fluid and may also collapse.

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Fluid impairs surfactant function, increases lung stiffness, and increases the weight of the surrounding tissue. Normal end-expiratory pressure may therefore be insufficient to keep the alveoli open.

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Alveolar collapse causes shunting and V/Q mismatch. Some blood passes through the lungs without normal gas exchange.

CPAP and NIV help keep small airways and alveoli open, particularly at end-expiration. When alveoli are recruited:

• the surface area available for gas exchange increases

• functional residual capacity increases

• oxygenation improves

• the patient does not have to reopen the same alveoli with every breath

• the mechanical properties of the lungs improve

• respiratory muscle work decreases.

 

Bilevel NIV additionally provides inspiratory support through the IPAP–EPAP pressure difference. The ventilator performs part of the work required for ventilation on behalf of the patient.

 

Hemodynamic effects

Positive intrathoracic pressure reduces left ventricular transmural pressure.

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During forceful spontaneous inspiration, intrathoracic pressure becomes negative.

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For example:

Pressure inside the LV 120 mmHg − intrathoracic pressure −10 mmHg = transmural pressure 130 mmHg

 

When CPAP, PEEP, or NIV increases intrathoracic pressure:

Pressure inside the LV 120 mmHg − intrathoracic pressure +5 mmHg = transmural pressure 115 mmHg

 

The pressure difference across the left ventricular wall, wall stress, and the work required for pumping decrease. Subendocardial perfusion may also improve.

 

Positive pressure may simultaneously reduce venous return, and therefore preload. This may be beneficial in pulmonary edema associated with elevated left-sided filling pressures.

 

However, reduced preload can cause hemodynamic instability, particularly in:

• hypovolemia

• cardiogenic shock

• severe right ventricular failure

• severe aortic stenosis

• situations in which cardiac output is strongly preload-dependent.

 

Indications for CPAP or Bilevel NIV

CPAP or bilevel NIV should be considered when cardiogenic pulmonary edema is associated with acute respiratory failure, such as:

• respiratory rate >25/min

• clearly increased work of breathing

• use of accessory respiratory muscles

• SpO₂ <90%

• PaO₂ <60 mmHg

• hypoxemia that does not rapidly improve with conventional supplemental oxygen

• severe dyspnea and acidosis, for example pH <7.35

• hypercapnia

• signs of respiratory muscle fatigue or exhaustion.

 

NIV does not need to be used routinely in every mild episode of acute heart failure. If respiratory failure is mild and the patient improves rapidly with low-flow supplemental oxygen, oxygen via nasal cannula may be sufficient.

 

In a hypoxemic patient with clear respiratory distress, positive-pressure therapy should be started early rather than waiting several hours for a possible response to diuretic treatment.

 

Choosing Between CPAP and Bilevel NIV

CPAP is often suitable for "pure" hypertensive or left-sided pulmonary edema when the patient has adequate spontaneous ventilation.

 

Bilevel NIV is more appropriate when the patient also has:

• hypercapnia

• acidemia

• COPD

• obesity hypoventilation

• markedly increased respiratory muscle work

• an inadequate response to CPAP.

 

According to the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure, oxygen therapy is recommended when SpO₂ is <90% or PaO₂ is <60 mmHg. Noninvasive positive-pressure ventilation should be considered in patients with respiratory distress, a respiratory rate >25/min, and SpO₂ <90%. Treatment should be initiated as early as possible to reduce respiratory distress and the need for intubation.

 

According to NICE, NIV is not used routinely in all cases of acute heart failure and cardiogenic pulmonary edema, but NIV should be initiated without delay when the patient has cardiogenic pulmonary edema with severe dyspnea and acidemia or when the response to medical treatment is inadequate.

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Initial CPAP and Bilevel NIV Settings

CPAP can be initiated, for example, at 5–8 cmH₂O or 6 cmH₂O and titrated according to the clinical response and blood pressure to 8–12 cmH₂O.

 

A commonly effective level is approximately 10 cmH₂O.

 

In many protocols, the upper end of the routine range is 12 cmH₂O. Some protocols use levels of up to approximately 15 cmH₂O.

 

If the patient requires a CPAP/EPAP level >12–15 cmH₂O, the mechanism of respiratory failure, hemodynamic status, and need for intubation should be reassessed.

 

Bilevel NIV can be initiated, for example, at:

• IPAP 10–15 cmH₂O

• EPAP 4–8 cmH₂O.

 

A common initial example is:

• IPAP 12 cmH₂O

• EPAP 6 cmH₂O

• backup rate 12/min.

 

A practical target range may be:

• IPAP approximately 15–20 cmH₂O

• EPAP approximately 5–10 cmH₂O.

 

In isolated pulmonary edema, increasing IPAP beyond 20–25 cmH₂O is generally not the primary solution. Concomitant COPD, obesity hypoventilation, pneumonia, significant hypercapnia, or NIV failure should then be considered.

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Oxygen saturation targets

A usual SpO₂ target is approximately 92–96%.

 

If the patient has COPD or another risk factor for hypercapnia, the target is generally 88–92%, unless an individualized target has been specified.

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Monitoring and Assessment of Response

After NIV is initiated, the following should be reassessed within 5–15 minutes:

• respiratory rate

• SpO₂

• heart rate

• blood pressure

• work of breathing

• patient cooperation

• level of consciousness

• patient–device synchrony

• mask leak.

 

Blood gases are usually reassessed after approximately 30–60 minutes. A clear trend toward improvement should be evident within 1–2 hours at the latest.

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More detailed titration of tidal volume, minute ventilation, mask leak, air trapping, and NIV settings is discussed in a separate article.