Understanding the Collapse of Lungs

with Shorter Time Constants and How

APRV Prevents It
Abstract
The management of restrictive lung diseases, such as respiratory
distress syndrome (RDS) in neonates, poses significant challenges
due to the propensity for alveolar collapse. This paper explores the
relationship between lung time constants and the tendency for
collapse, providing mathematical proof to illustrate why lungs with
shorter time constants are more prone to collapse. Additionally, it
examines how Airway Pressure Release Ventilation (APRV) can
prevent lung collapse by maintaining higher mean airway pressures
and allowing spontaneous breathing. We delve into the use of the
peak expiratory flow rate termination point (T-PEFR) to optimize the
duration of the low-pressure phase (TLow) in APRV, ensuring
adequate end-expiratory lung volume (EELV) and preventing
derecruitment. The mathematical relationships between time
constants, T-PEFR, and alveolar volume dynamics are analyzed to
provide a comprehensive understanding of these concepts.

Introduction
Restrictive lung diseases, such as respiratory distress syndrome
(RDS) in neonates, are characterized by reduced lung compliance
and increased susceptibility to alveolar collapse. Effective
ventilation strategies are crucial for managing these conditions and
preventing further lung injury. Traditional ventilation methods often
struggle to maintain alveolar stability, leading to frequent episodes of
collapse and derecruitment.

Airway Pressure Release Ventilation (APRV) is a mode of mechanical

ventilation that has shown promise in managing restrictive lung
diseases by maintaining higher mean airway pressures and allowing
spontaneous breathing. A critical aspect of optimizing APRV involves
determining the appropriate duration of the low-pressure phase
(TLow) to prevent alveolar collapse while ensuring effective CO2
removal.

This paper aims to:

1. Explain why lungs with shorter time constants tend to

collapse more readily compared to lungs with longer time
constants, using mathematical proof.
2. Discuss how APRV can prevent lung collapse in restrictive
lung disease, supported by a mathematical model of
alveolar volume dynamics.
3. Illustrate the use of the peak expiratory flow rate termination
point (T-PEFR) to determine the appropriate TLow in APRV,
ensuring adequate end-expiratory lung volume (EELV) and
preventing derecruitment.

Understanding the Collapse of Lungs with

Shorter Time Constants

Time Constant and Lung Dynamics

The time constant (τ) in respiratory physiology is given by the product

of resistance (R) and compliance (C):

τ = R×C

• Resistance (R): Resistance to airflow within the airways.

• Compliance (C): The ability of the lung tissue to expand and
contract.

Exponential Model of Lung Emptying

The volume of air (V) in the lungs during exhalation can be modeled
exponentially, where the rate of change of volume over time is
proportional to the volume itself:

V(t) = V0 × e−t/τ
where:

• V(t) is the volume at time t.

• V0 is the initial volume at the start of exhalation.
• τ is the time constant.

Comparing Lungs with Different Time Constants

Let's consider two scenarios:

1. Normal Lungs: Longer time constant (τ1)

2. Restrictive Lungs: Shorter time constant (τ2)

Assume τ1 > τ2.

For any given time t, the volumes can be expressed as:

Vnormal(t) = V0 × e−t/τ 1

Vrestrictive(t) = V0 × e−t/τ 2

Since τ1 > τ2, it follows that:

e−t/τ1 > e−t/τ2

Therefore, for the same initial volume V0:

Vnormal(t) > Vrestrictive(t)

This inequality indicates that at any given time t, the volume

remaining in the restrictive lungs (with a shorter time constant) is
less than that in normal lungs (with a longer time constant).

Implications for Lung Collapse

1. Rapid Emptying: With a shorter time constant, the restrictive

lungs empty more rapidly. The rapid decrease in volume
 means that there is less air left in the alveoli to keep them
open, increasing the risk of collapse.
2. Reduced Alveolar Stability: The faster rate of volume
decrease in restrictive lungs causes a more pronounced
reduction in airway pressure, leading to alveolar instability
and collapse.
3. Less Time for Gas Exchange: Shorter time constants mean
less time for effective gas exchange during the respiratory
cycle, leading to inadequate ventilation of the alveoli,
contributing to their collapse.

Mathematical Proof: Lung Collapse

Consider the derivative of the volume with respect to time (dV/dt) to

understand the rate of volume change:

For normal lungs:

dVnormal/dt = −V0/τ1 × e−t/τ 1

For restrictive lungs:

dVrestrictive/dt = −V0/τ2 × e−t/τ 2

Since τ1 > τ2, the magnitude of dV/dt for restrictive lungs is greater
than for normal lungs, indicating a faster rate of emptying:

∣ dVrestrictive/dt ∣ > ∣ dVnormal/dt ∣

This faster rate of volume change leads to a quicker decrease in lung

volume, promoting alveolar collapse in restrictive lung disease.

How APRV Prevents Lung Collapse in Restrictive

Lung Disease
Airway Pressure Release Ventilation (APRV) is designed to improve
alveolar recruitment and prevent collapse by maintaining higher
mean airway pressures and allowing spontaneous breathing. This is
particularly beneficial in restrictive lung disease, where the lungs are
more prone to collapse due to reduced compliance and shorter time
constants.

Principles of APRV

APRV operates by cycling between two levels of continuous positive

airway pressure (CPAP):

1. PHigh: A high pressure level maintained for a prolonged time

(THigh).
2. PLow: A lower pressure level maintained for a shorter time
(TLow).

The key is that the PHigh is held for a longer duration to promote
alveolar recruitment and stability, while the brief PLow allows for
partial exhalation and CO2 removal.

Mathematical Model: Alveolar Volume During APRV

PHigh Phase:

During PHigh, the alveolar volume (V) increases as the lung is held at
a high pressure for a prolonged period:

VPHigh(t) = V0 + ΔVrecruitment × (1 − e−t/τ )

PHigh

where:

• V0 is the baseline alveolar volume.

• ΔVrecruitment is the additional volume due to alveolar
recruitment.
• τPHigh is the time constant during the high-pressure phase.

PLow Phase:

During PLow, the alveolar volume decreases but is prevented from

fully collapsing by the high baseline pressure:
VPLow(t) = VPHigh, end × e−t/τ
PLow

where:

• VPHigh, end is the alveolar volume at the end of PHigh.

• τPLow is the time constant during the low-pressure phase.

Preventing Collapse with APRV

1. Prolonged PHigh:

By maintaining a high pressure for a longer duration (THigh), APRV

ensures that the alveoli have sufficient time to recruit and stabilize.
The prolonged high pressure helps to counteract the tendency of the
alveoli to collapse, especially in restrictive lung disease where the
compliance is low and the alveoli empty quickly.

THigh ≫ τPHigh

This relationship ensures that the alveoli remain open long enough to
achieve adequate recruitment.

2. Brief PLow:

The brief low-pressure phase (TLow) in APRV is designed to allow

partial exhalation while preventing alveolar collapse. Because TLow
is short compared to the time constant τPLow, the alveoli do not have
enough time to empty completely:

TLow ≪ τPLow

This brief period minimizes the volume loss, maintaining sufficient

alveolar volume to prevent collapse.

Mathematical Proof of Alveolar Stability in APRV

Consider the volume change during the PHigh and PLow phases:
During PHigh:

dVPHigh/dt = ΔVrecruitment/τPHigh × e−t/τ PHigh

During PLow:

dVPLow/dt = −VPHigh, end/τPLow × e−t/τ PLow

By ensuring THigh is significantly longer than τPHigh and TLow is

significantly shorter than τPLow, APRV maintains a positive alveolar
volume:

VPHigh(t) ≈ V0 + ΔVrecruitment

VPLow(t) ≈ VPHigh, end × e−TLow/τPLow

Given TLow ≪ τPLow, the volume loss during PLow is minimal:

VPlow(t) ≈ VPhigh, end

Thus, the alveoli remain partially inflated throughout the ventilatory

cycle, preventing collapse.

Using T-PEFR to Determine the Appropriate TLow in APRV

Key Concepts

1. End-Expiratory Lung Volume (EELV) / End-Release Lung

Volume (ERLV):

• EELV is the lung volume at the end of expiration.

• ERLV is the lung volume at the end of the release
phase in APRV.

2. Expiratory Flow Pattern:

 • The pattern of gas flow during expiration provides
insights into lung mechanics and the effectiveness
of ventilation settings.

3. PLow and TLow:

• PLow is the lower pressure setting during the

release phase. Setting PLow to zero allows end-
expiratory/release lung volume to be controlled
solely by time.
• TLow is the duration of the release phase, which is
critical for trapping enough gas to maintain end-
expiratory pressure (PEEP).

Titrating TLow Using T-PEFR

1. Control of Lung Volume:

• The end-release lung volume can be adjusted and

continually assessed by monitoring the expiratory
flow pattern. The expiratory gas flow results from
the inspiratory lung volume, the recoil or drive
pressure of the lung, and downstream resistance
(artificial airway, circuit, and PEEP valve).

2. Artificial Airway Resistance:

• The inherent resistance of the artificial airway

behaves as a flow resistor/limiter. When coupled
with a brief release time, it can effectively trap gas
volume to maintain end-release or expiratory
pressure (PEEP).
• During passive expiration in patients with diseased
lungs, expiratory time constants are significantly
increased due to the flow-dependent resistance of
the artificial airway.

3. Flow-Dependent Resistance:
 • Because the artificial airway produces a nonlinear,
flow-dependent resistive load, the highest flow
resistance occurs at the initial portion of the
release phase.
• TLow or the release phase should be terminated at
the T-PEFR (peak expiratory flow rate termination
point) rapidly before the flow-dependent expiratory
load is dissipated, resulting in maintained end-
expiratory volume and pressure.

4. Residual Pressure and Volume:

• The residual pressure and volume in the lung during

the brief release phase typically yield end-release
or end-expiratory pressure greater than the PLow
set at the machine’s PEEP valve.
• Commercially available ventilators with tube
compensation algorithms often provide inadequate
expiratory compensation when PEEP is reduced to
atmospheric pressure. Adding a negative pressure
source to briefly lower the end-expiratory pressure
to subatmospheric is required to fully compensate
for the expiratory resistance imposed by the
artificial airway.

5. Impact of PLow Settings:

• Using a PLow greater than 0 cm H2O delays PEFR,

while a PLow of 0 cm H2O accelerates PEFR,
concluding the release phase earlier and enabling
the PHigh phase to resume earlier in the cycle.
• A greater percent of the cycle time at THigh
increases the potential for recruitment, maintains
lung volume, limits derecruitment, and induces
spontaneous breathing.

Mathematical Proof Using Time Constants

Lung Volume and Time Constant Relationship

V(t) = V0 × e−t/τ

where:

• V(t) is the lung volume at time t.

• V0 is the initial lung volume.
• τ is the time constant (τ=R×C).

Expiratory Flow Rate: The flow rate F(t) at any time t is given by:

F(t) = −dV(t)/dt = V0/τ × e−t/τ

Determining T-PEFR

The peak expiratory flow rate (PEFR) occurs at t=0 and can be
expressed as:

PEFR = V0/τ

The T-PEFR, the time at which the expiratory flow rate has decreased
to a specific percentage of PEFR (typically 50-75%), is determined
by:

F(TPEFR) = PEFR × (0.5 to 0.75)

Let’s consider 75% of PEFR for simplicity:

V0/τ × e−T /τ
PEFR
= 0.75 × V0/τ

Solving for TPEFR:

e−T /τ
PEFR
= 0.75

Taking the natural logarithm of both sides:

−TPEFR/τ = ln(0.75)

TPEFR = −τ × ln(0.75)
TPEFR ≈ 0.287 × τ

This shows that T-PEFR is approximately 0.287 times the time

constant of the lung.

Adjusting TLow Based on T-PEFR

To maintain appropriate end-expiratory lung volume and prevent

collapse, TLow should be set to terminate the release phase at or
slightly before T-PEFR:

TLow ≤ TPEFR ≈ 0.287 × τ

By setting TLow in this manner, the lung volume at the end of the
release phase is maintained, preserving EELV and preventing
derecruitment. This approach ensures that the rapid phase of
expiratory flow is terminated before significant volume loss occurs,
thereby maintaining alveolar stability and preventing collapse.

Interpreting Expiratory Flow Patterns and

Adjustments Based on Lung Mechanics

Expiratory Flow Pattern

The expiratory flow pattern demonstrates normal deceleration at 45°

as airways empty sequentially. The release time is adjusted to
regulate T-PEFR to 50% to 75% of PEFR. The flow/time beyond the T-
PEFR correlates with ERLV (EELV). The angle of deceleration (ADEC)
can suggest alterations in lung mechanics, such as restrictive
conditions (ADEC <45°) or obstructive conditions (ADEC >45°).

Mathematical Proof Using Time Constants

Flow-Time Beyond T-PEFR and ERLV (EELV)

After T-PEFR, the flow continues to decay exponentially:

F(t) = F0 × e−t/τ
The volume of air exhaled beyond T-PEFR can be integrated over time
from TPEFR to the end of the expiration:

VERLV = ∫∞T F0 × e−t/τ dt

PEFR

VERLV = F0 × [−τ × e−t/τ]∞ T PEFR

Evaluating the integral:

VERLV = F0 × τ × e−T /τ
PEFR

Since TPEFR ≈ 0.287 × τ:

VERLV = F0 × τ × e−0.287

VERLV ≈ F0 × τ × 0.75

Thus, the end-release lung volume (ERLV) or end-expiratory lung

volume (EELV) is directly proportional to the initial PEFR and the time
constant.

Adjustments Based on Lung Mechanics

Restrictive Conditions (ADEC < 45°):

• Reduced compliance (C) leads to a shorter time constant

(τ).
• Lower T-PEFR indicates a rapid decline in flow rate.
• Adjust TLow to match the shorter T-PEFR, preventing airway
closure and maintaining higher ERLV.

Obstructive Conditions (ADEC > 45°):

• Increased resistance (R) leads to a longer time constant (τ).

• Higher T-PEFR indicates a slower decline in flow rate.
• Adjust TLow to accommodate the longer T-PEFR, ensuring
effective gas exchange and avoiding air trapping.
Normal Conditions (ADEC ≈ 45°):

• Balance between resistance and compliance.

• TLow is set to T-PEFR at 50% to 75% of PEFR, maintaining
optimal lung volume and preventing derecruitment.

Conclusion
By understanding the mathematical relationship between the time
constant, T-PEFR, and the expiratory flow pattern, clinicians can
optimize TLow settings in APRV to maintain appropriate lung
volumes and pressures. This approach leverages physiological
principles to enhance patient outcomes, particularly in restrictive
lung diseases.

References
1. Habashi, N. M. (2005). "Other approaches to open-lung
ventilation: airway pressure release ventilation." Critical
Care Medicine, 33(3 Suppl), S228-S240.
2. Kollisch-Singule, M. et al. (2014). "The mechanism of how
airway pressure release ventilation works." Critical Care,
18(6), 592.
3. Nieman, G. et al. (2017). "A physiologic approach to
mechanical ventilation." Critical Care Clinics, 33(1), 15-30.
4. West, J. B. (2012). "Respiratory Physiology: The Essentials."
Lippincott Williams & Wilkins.
5. Amato, M. B. P. et al. (1998). "Effect of a protective-
ventilation strategy on mortality in the acute respiratory
distress syndrome." New England Journal of Medicine,
338(6), 347-354.
6. Hedenstierna, G., & Edmark, L. (2012). "The effects of
anesthesia and muscle paralysis on the respiratory system."
Intensive Care Medicine, 38(5), 848-861.