High-Frequency Oscillatory Ventilation: Balancing Pressure Amplitude, Mean

Airway Pressure, and Frequency to Optimize Gas Exchange and Prevent Airway
Collapse
Abstract
High-Frequency Oscillatory Ventilation (HFOV) is a specialized mode of mechanical ventilation designed to enhance gas
exchange in patients with severe respiratory distress. HFOV operates by oscillating around a set mean airway pressure (MAP)
with a superimposed pressure amplitude (ΔP). While HFOV offers significant benefits in terms of alveolar recruitment and
oxygenation, it also poses a risk for expiratory flow limitation and air trapping, especially when the pressure amplitude is set too
high relative to the mean airway pressure. This paper explores the physiological mechanisms and mathematical rationale behind
this phenomenon, emphasizing the importance of careful pressure setting to prevent small airway collapse. The discussion
includes the impact of frequency settings on pressure transmission and the balance needed to optimize partial pressure of
carbon dioxide (pCO₂) levels, providing a comprehensive guide for clinicians to effectively manage HFOV parameters.

Introduction
High-Frequency Oscillatory Ventilation (HFOV) represents an advanced ventilatory strategy used to manage patients with severe
respiratory failure, such as those with Acute Respiratory Distress Syndrome (ARDS). HFOV maintains alveolar recruitment by
providing continuous positive airway pressure with rapid, small tidal volumes superimposed on this baseline pressure. The
unique oscillatory nature of HFOV requires careful balancing of pressure settings to avoid complications such as expiratory flow
limitation and air trapping.

One of the critical challenges in HFOV is setting the pressure amplitude (ΔP) appropriately. Excessively high ΔP can lead to
significant negative pressures during the expiratory phase, increasing the risk of small airway collapse and subsequent air
trapping. This phenomenon is exacerbated if the pressure amplitude exceeds twice the mean airway pressure, resulting in
expiratory pressures falling below the critical closing pressure (P_closure) of the small airways. Additionally, the frequency of
oscillations plays a crucial role in pressure transmission and CO₂ clearance, with lower frequencies transmitting pressure more
effectively but posing different risks than higher frequencies. This paper aims to explain the underlying physiology and provide a
mathematical framework to guide the safe setting of pressure parameters in HFOV.

Key Factors Contributing to Expiratory Flow Limitation and Air Trapping in HFOV

1. Active Control of Both Inspiratory and Expiratory Phases: In HFOV, both inspiratory and expiratory phases are actively
controlled by the oscillator. The ventilator generates positive pressures during inspiration and negative pressures during
expiration. High amplitude oscillations can lead to significant negative pressures during expiration, which may cause small
airways to collapse if these pressures exceed the airway's ability to remain open.

2. High Amplitude Oscillations: High pressure amplitude (ΔP) results in large pressure swings within the oscillatory cycle.
While high amplitude can improve alveolar recruitment and gas exchange, it also increases the risk of generating excessive
negative pressures during expiration. When these negative pressures are too large, they can cause airway collapse, leading
to expiratory flow limitation and air trapping.

3. Mean Airway Pressure (MAP): MAP is maintained to keep the alveoli open and prevent collapse. It serves a stenting
function that is crucial during the expiratory phase to keep small airways open. However, if the amplitude of oscillations is
too high relative to MAP, the minimum pressure during the cycle can drop below the critical closing pressure of the small
airways, leading to collapse.

4. Airway Resistance: Increased airway resistance (e.g., due to bronchospasm, secretions, or airway edema) can lead to
expiratory flow limitation. High resistance can make it more difficult for air to be expelled from the lungs, contributing to air
trapping.

Mathematical and Physiological Evidence

Condition for Airway Stability: To prevent airway collapse, the minimum pressure during the oscillatory cycle (P_min) must
remain above the critical closing pressure (P_closure):
 ΔP
Pmin = Pmean −
​ ​
2
​

For the airways to remain open:

ΔP
Pmean − ​
2
​
≥ Pclosure ​

Critical Amplitude Calculation:

Given:
Pmean = 12 cm H2 O
​ ​

Assuming:
Pclosure = 5 cm H2 O
​ ​

Using the generalized equation for maximum allowable pressure amplitude:

2×(Pmean ​−Pclosure ​)
ΔP = TF
​

Assuming a transmission factor (TF) of 0.7:

2×(12−5)
ΔP = 0.7 ​

14
ΔP = 0.7 ​

ΔP = 20 cm H2 O ​

This calculation shows that with a transmission factor of 0.7, the maximum allowable pressure amplitude (ΔP) should not exceed
20 cm H₂O to prevent airway collapse.

Impact of High Amplitude

If the pressure amplitude exceeds this value, the minimum pressure during the expiratory phase will drop below the critical
closing pressure, leading to airway collapse:

Pmin = Pmean − ΔP
​
2
​ ​

Pmin < 5 cm H2 O
​ ​

For example, if ΔP = 24 cm H₂O:

24 ​
Pmin = 12 −
​
2
= 12 − 12 = 0 cm H2 O ​

This zero pressure is below the critical closing pressure, resulting in significant airway collapse and air trapping.

Frequency Setting and Its Effects

Pressure Transmission: The effectiveness of pressure transmission in HFOV is influenced by the frequency of oscillations. The
transmission factor (TF) describes the fraction of ventilator-generated pressure amplitude that reaches the alveoli. This factor is
influenced by frequency, with lower frequencies generally having a higher transmission factor than higher frequencies.

ΔPalveoli = TF × ΔPvent
​ ​

Lower Frequency (e.g., 3-5 Hz): Lower frequencies allow more time for pressure waves to travel through the airways, resulting in
better pressure transmission. This can improve CO₂ removal due to larger tidal volumes but also poses a risk of over-distension if
not carefully managed. Because of the more effective pressure transmission, lower frequencies generally require a lower pressure
amplitude to prevent small airway collapse.

Transmission Factor (TF): Typically higher (e.g., 0.7-0.8)

Higher Frequency (e.g., 10-15 Hz): Higher frequencies result in shorter inspiratory and expiratory times, reducing the pressure
transmission to distal airways. This can decrease the risk of over-distension but may impair CO₂ clearance, although air trapping
is not typically a significant issue in HFOV due to the small tidal volumes used.
Transmission Factor (TF): Typically lower (e.g., 0.5-0.6)

Adjustment of Frequency, Mean Airway Pressure, Pressure Amplitude, and Air Trapping on pCO₂
The partial pressure of carbon dioxide (pCO₂) in the blood is a critical parameter reflecting the effectiveness of ventilation. In
HFOV, pCO₂ levels are influenced by the frequency setting, mean airway pressure, pressure amplitude, and the extent of air
trapping.

Frequency Setting:

Lower Frequency: Enhances tidal volume and CO₂ removal but must be balanced against the risk of over-distension and
small airway collapse. Lower frequencies require careful adjustment of pressure amplitude to ensure that airway pressures
do not become excessively negative during expiration.
Higher Frequency: Reduces tidal volume and can impair CO₂ removal, potentially leading to hypercapnia. Higher
frequencies help reduce the risk of over-distension, with minimal risk of air trapping due to the small tidal volumes used.

Mean Airway Pressure (MAP):

Higher MAP: Improves alveolar recruitment and oxygenation but can lead to over-distension if too high. Higher MAP can
also help stent small airways open, reducing the risk of airway collapse.
Lower MAP: Reduces the risk of over-distension but may cause alveolar collapse and impaired oxygenation.

Pressure Amplitude (ΔP):

Higher ΔP: Increases tidal volume and CO₂ clearance but can cause airway collapse and air trapping if too high. The
appropriate ΔP must be carefully determined relative to the frequency setting and MAP to avoid adverse effects.
Lower ΔP: Reduces the risk of airway collapse but can impair tidal volume and CO₂ clearance, potentially leading to
hypercapnia.

Air Trapping: In HFOV, air trapping can occur due to small airway collapse when the negative pressures during expiration exceed
the critical closing pressure. Monitoring for air trapping and adjusting ΔP or frequency can mitigate this risk.

Practical Example
Given:
Pmean = 12 cm H2 O
​ ​

Assume:
Pclosure = 5 cm H2 O
​ ​

Using the generalized equation for maximum allowable pressure amplitude with a transmission factor (TF) of 0.7:

= 2×(PmeanTF−Pclosure )
​ ​

ΔP ​

ΔP = 2×(12−5)
0.7
​

14
ΔP = 0.7 ​

ΔP = 20 cm H2 O ​

This calculation shows that with a transmission factor of 0.7, the maximum allowable pressure amplitude (ΔP) should not exceed
20 cm H₂O to prevent airway collapse.

Adjustments:

Lower Frequency (e.g., 5 Hz): Set ΔP lower than 20 cm H₂O, such as 18-19 cm H₂O, to maximize pressure transmission and
CO₂ clearance without causing airway collapse due to effective pressure transmission.
Higher Frequency (e.g., 10 Hz): Set ΔP to around 20 cm H₂O to maintain adequate ventilation, considering that higher
frequencies have lower transmission factors and pose minimal risk of air trapping.
Specific Considerations for Term and Preterm Infants

Preterm Infants:
Surfactant Therapy: Often required to improve lung compliance and function.
Fragile Lungs: More susceptible to injury; therefore, gentle ventilation strategies are crucial.
Higher Frequencies: Typically, higher frequencies (10-15 Hz) are used to minimize tidal volumes and reduce the risk of
volutrauma. High frequencies also help in maintaining adequate ventilation despite the small lung volumes.
Lower ΔP: Due to their fragile lungs, a lower ΔP might be needed compared to term newborns to prevent lung injury.
Frequent Monitoring: Regular blood gas analysis and chest X-rays to monitor lung condition and adjust ventilator settings
accordingly.

Term Newborns:
Underlying Conditions: Conditions such as meconium aspiration, PPHN, or congenital diaphragmatic hernia need specific
adjustments in HFOV settings.
Higher Compliance: Generally better compliance but still requires careful management to avoid overdistension and lung
injury.
Lower Frequencies: Lower frequencies (8-12 Hz) can be used as their lung volumes and compliance are relatively better.
Adjusted ΔP: Tailored ΔP settings to manage specific conditions and ensure adequate ventilation without causing
overdistension.

Air Trapping in HFOV: Dynamic Hyperinflation vs. Small Airway Collapse

Dynamic Hyperinflation in HFOV: While true dynamic hyperinflation, as seen in conventional ventilation, is less common in
HFOV due to the rapid, small-volume oscillations and the usually longer expiratory times relative to the oscillatory cycle, some
degree of air trapping can still occur if the settings are not optimized. However, HFOV is generally designed to minimize this risk
by maintaining a high mean airway pressure and utilizing very small tidal volumes.

Key Factors in HFOV:

Oscillatory Frequency: Higher frequencies can potentially shorten the effective time for gas to be expelled, but the tidal
volumes are so small that significant hyperinflation is less likely compared to conventional modes.
Airway Resistance: Conditions like severe bronchospasm or high airway resistance could contribute to air trapping even in
HFOV.

Management:

Adjusting Frequency: Lower frequencies can provide slightly longer expiratory times if needed.
Monitoring Airway Pressures: Ensuring that mean airway pressure and amplitude are optimized to prevent excessive
negative pressures during expiration.

Small Airway Collapse in HFOV: The more common issue in HFOV related to air trapping is small airway collapse due to
excessive negative pressures during the expiratory phase.

Mechanism: When the pressure amplitude (ΔP) is too high, the negative pressure generated during expiration can cause small
airways to collapse if it drops below the critical closing pressure (P_closure).

Characteristics:

Sudden Airway Closure: This prevents effective emptying of alveolar air, leading to air trapping and potential atelectasis.
Ventilation-Perfusion Mismatch: Reduced effective alveolar ventilation leads to impaired gas exchange.

Management:
 Optimizing MAP: Maintaining sufficient mean airway pressure to stent the airways open.
Adjusting ΔP: Ensuring the pressure amplitude is not excessive to avoid generating harmful negative pressures during
expiration.

Conclusion
In HFOV, while the risk of dynamic hyperinflation as seen in conventional ventilation is low due to the nature of oscillatory
ventilation, air trapping can still occur primarily through the mechanism of small airway collapse. Proper management of
pressure settings, including mean airway pressure and pressure amplitude, is crucial to prevent small airway collapse and ensure
effective ventilation. Ensuring that the pressure amplitude (ΔP) does not exceed a safe threshold relative to the mean airway
pressure (MAP) is essential to maintain airway patency and prevent small airway collapse. Clinicians must carefully monitor and
adjust HFOV parameters, including frequency, mean airway pressure, and pressure amplitude, to balance effective ventilation
with the risk of adverse effects, optimizing patient outcomes in severe respiratory failure. Regular monitoring and adjustments
are crucial to leveraging the benefits of HFOV while minimizing its risks, particularly in maintaining effective CO₂ clearance and
preventing airway collapse.

Appendix: Deriving a General Equation for Maximum Allowable Pressure Amplitude (ΔP)
To derive a general equation for the maximum allowable pressure amplitude (ΔP) for any given transmission factor (TF), mean
airway pressure (MAP = X), and closing pressure (P_closing), we can generalize the approach used previously.

Given:

Mean Airway Pressure (MAP) = X

Closing Pressure (P_closing)
Transmission Factor (TF)

The relationship is:

ΔP
ΔPalveoli = TF ×
​
2
​

And the desired minimum Plow is: ​

Plow = X − ΔPalveoli
​ ​

To avoid small airway collapse:

ΔP
Pclosing = X − (TF ×
​
2
)
​

Rearranging to solve for ΔP:

Pclosing = X − (0.5 × TF × ΔP )
​

0.5 × TF × ΔP = X − Pclosing ​

2×(X−Pclosing ) ​

ΔP = TF
​

Therefore, the general equation for solving the maximum allowable pressure amplitude (ΔP) given any transmission factor (TF),
mean airway pressure (X), and closing pressure (P_closing) is:

2×(X−Pclosing ​)
ΔP = TF
​

This equation allows you to calculate the maximum allowable pressure amplitude for any transmission factor, mean airway
pressure, and closing pressure.