Review

Airway Pressure Release Ventilation: What Do We Know?

Ehab G Daoud MD, Hany L Farag MD, and Robert L Chatburn MHHS RRT-NPS FAARC

Introduction
Terminology
APRV Versus BIPAP
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APRV Versus Conventional Ventilation

APRV Versus Other Non-Conventional Ventilation
APRV Settings
P High/P Low
T High/T Low
Settings Adjuncts
Pressure Support and Automatic Tube Compensation
Synchronization
APRV and Weaning
Advantages of APRV
Spontaneous Ventilation
Long Inflation Time
Lung-Protective Benefits
APRV and Mortality
Disadvantages of APRV
Spontaneous Breathing
Work of Breathing
Tidal Volume and Minute Ventilation
Present and Future
Conclusions

Airway pressure release ventilation (APRV) is inverse ratio, pressure controlled, intermittent man-
datory ventilation with unrestricted spontaneous breathing. It is based on the principle of open lung
approach. It has many purported advantages over conventional ventilation, including alveolar
recruitment, improved oxygenation, preservation of spontaneous breathing, improved hemodynam-
ics, and potential lung-protective effects. It has many claimed disadvantages related to risks of
volutrauma, increased work of breathing, and increased energy expenditure related to spontaneous
breathing. APRV is used mainly as a rescue therapy for the difficult to oxygenate patients with
acute respiratory distress syndrome (ARDS). There is confusion regarding this mode of ventilation,
due to the different terminology used in the literature. APRV settings include the “P high,” “T high,”
“P low,” and “T low”. Physicians and respiratory therapists should be aware of the different ways
and the rationales for setting these variables on the ventilators. Also, they should be familiar with
the differences between APRV, biphasic positive airway pressure (BIPAP), and other conventional
and nonconventional modes of ventilation. There is no solid proof that APRV improves mortality;
however, there are ongoing studies that may reveal further information about this mode of venti-
lation. This paper reviews the different methods proposed for APRV settings, and summarizes the
different studies comparing APRV and BIPAP, and the potential benefits and pitfalls for APRV.
Key words: airway pressure release ventilation; biphasic positive airway pressure; ARDS/ALI; ventilator-
induced lung injury; acute respiratory failure. [Respir Care 2012;57(2):282–292. © 2012 Daedalus En-
terprises]

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 AIRWAY PRESSURE RELEASE VENTILATION: WHAT DO WE KNOW?

Introduction

Airway pressure release ventilation (APRV) was first

described and introduced to clinical practice over 20 years
ago.1 It became commercially available in the mid-1990s.2
It is a mode of mechanical ventilation that is best de-
scribed as a partial ventilatory support,3,4 and is based on
the open lung concept.5,6 The primary goals of this mode
were to provide both safety and comfort: safety in that
adequate or superior ventilatory support is provided with-
out dangerously high applied pressures, thus minimizing
the risk of ventilator-induced lung injury (VILI), and with-
out depressing hemodynamics, while comfort in that un-
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restricted spontaneous breathing would be allowed, which

is a feature unavailable in conventional ventilatory modes,
thus minimizing patient-ventilator asynchrony. Despite its
theoretically attractive advantages over other conventional
modes of ventilation, and its availability in most of the
new commercially available ventilators, APRV is still not Fig. 1. A: Pressure (green) and volume (black)/time curve in airway
pressure release ventilation (APRV). Shown in the figure: 2 full
used routinely in clinical practice in North America. APRV mandatory breaths (not triggered by muscle effort), and 2 full spon-
is used more frequently in Europe.7 APRV is still mostly taneous breaths (triggered by muscle effort, in blue) on the top of
thought of as an alternative rescue mode for the difficult to the mandatory ones. Muscle pressure (blue): the long arrow rep-
oxygenate patient with acute lung injury (ALI) and acute resents the T high, and the short one represents the T low of the
respiratory distress syndrome (ARDS).8 mandatory breath. B: Flow (black) and volume (green)/time curve
in APRV. T high is the start of the inspiratory flow to the start of
expiratory flow, T low is the start of expiratory flow to the begin-
Terminology ning of the next inspiratory flow. The 2 red intersecting lines are at
50% of the peak expiratory flow.
APRV is classified as pressure controlled intermittent
mandatory ventilation, and is typically applied using in-
verse inspiratory-expiratory (I:E) ratios.9 As such, there the terms they use when describing various modes of ven-
are both mandatory breaths (ie, machine-triggered and ma- tilation.11 This issue has been studied by Rose and Hawk-
chine-cycled), as well as spontaneous breaths (ie, patient- ins,11 in an attempt to identify the definitional criteria of
triggered and patient-cycled) (Fig. 1). The mandatory both APRV and biphasic positive airway pressure (BIPAP)
breaths applied by APRV are time-triggered, pressure-tar- modes. They concluded: “Ambiguity exists in the criteria
geted, time-cycled breaths (depending on the ventilator, that distinguish APRV and BIPAP.” The other source of
trigger and cycle events may be synchronized with patient confusion arises from the ventilator manufacturers’ choice
breathing signals). Spontaneous breaths can occur both of terminology. Different names have been coined for the
during and between mandatory breaths. Because APRV same mode, such as BiLevel (Covidien), APRV (Dräger),
has historically been viewed as alternating levels of CPAP, Bi-Vent (Maquet), BiPhasic (CareFusion), and DuoPAP
the amplitude of the time-triggered mandatory breath is (Hamilton).
called “P high” instead of inspiratory pressure, and the
duration is called “T high” instead of inspiratory time. APRV Versus BIPAP
Similarly, the expiratory pressure is called “P low” and the
expiratory time (release time) is called “T low.”1,8,10 Both modes clearly have the same general pattern of
The confusion regarding this mode of ventilation arises airway pressures as intermittent mandatory ventilation, with
from the different terminology used in the literature, as time-triggered, pressure-targeted, and time-cycled manda-
authors seldom provide adequately explicit definitions for tory breaths according to the preset values of T high and
T low (Fig. 2). Both modes allow unrestricted spontaneous
breathing both during and between mandatory breaths, but
The authors are affiliated with the Respiratory Institute, The Cleveland there is more time for them to occur during mandatory
Clinic, Cleveland, Ohio. breaths with APRV. APRV typically uses extreme inverse
The authors have disclosed no conflicts of interest.
I:E ratios, while BIPAP usually does not.11 Also APRV
usually keeps the duration of the T low at ⱕ1.5 seconds,
DOI: 10.4187/respcare.01238 while there is no restriction on the T low in BIPAP.4,8,12

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 AIRWAY PRESSURE RELEASE VENTILATION: WHAT DO WE KNOW?

ized 30 trauma patients to either APRV or pressure con-

trolled continuous mandatory ventilation (PC-CMV); they
have shown that the APRV group had shorter ventilator
days (15 vs 21) and ICU days (23 vs 30). According to
the authors, those findings were explained by the improve-
ment in hemodynamics and the less sedation and no par-
alytic agents used in the APRV group. This study is weak-
ened by the small number of patients (15 in each group),
Fig. 2. Comparison of airway pressure release ventilation (APRV) by the fact that only 20% of the APRV group had ARDS,
(blue curve) and biphasic positive airway pressure (BIPAP) (black compared to 74% in the PC-CMV group, and by the fact
curve). Compared to APRV, BIPAP uses shorter T high, longer
T low, and usually higher P low. Despite the differences between
that the 2 groups had different sedation protocols. A recent
their settings, mathematically both can achieve the same mean retrospective study23 with a small number of patients, com-
airway pressure (red line) and same tidal volume (green curve). pared APRV to volume controlled intermittent mandatory
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Blue curves represent APRV, black curves represent BIPAP. ventilation (VC-IMV); beside improved oxygenation, it
showed a trend to lower mortality in the APRV group, but
did not reach statistical significance. A larger international
A recent review of 50 published studies of both modes11 retrospective study7 using propensity score to compare both
showed that 78% of the studies described APRV, while APRV and BIPAP to conventional ventilation confirmed
22% described BIPAP. Extreme inverse I:E (⬎ 2:1) was the significantly improved oxygenation with both modes,
used in 46% of the studies describing APRV. None of the but failed to show any mortality benefits.
studies describing BIPAP used an I:E ⬎ 2:1. Twenty-one A recent study24 in 63 adult trauma patients requiring
percent of the APRV studies used I:E of 1:1 to 2:1, com- mechanical ventilation for greater than 72 hours showed
pared to 9% of studies describing BIPAP. Thirty-one per- that APRV has a similar safety profile as the low tidal
cent of the APRV studies used I:E of 1:1, compared to volume ventilation. APRV patients tended to have increased
64% of the BIPAP studies. Finally, only 5% of the APRV ventilator days (10.49 ⫾ 7.23 d vs 8.00 ⫾ 4.01 d), ICU
studies used I:E less than 1:1, compared to 27% of the stay (16.47 ⫾ 12.83 d vs 14.18 ⫾ 13.26 d), and ventilator-
BIPAP studies. The mean reported inspiratory time (T high) associated pneumonia (VAP) (1.00 ⫾ 0.86 vs 0.56 ⫾ 0.67).
was 3.4 seconds for APRV, compared to 2.4 seconds for This may be explained by the significant initial worse
BIPAP. Conversely, the mean reported expiratory time physiologic derangement demonstrated by Acute Physiol-
(T low) was nearly 3 times longer in the BIPAP studies, ogy and Chronic Health Evaluation II (APACHE II) scores
compared to APRV (3.4 s and 1.3 s, respectively). The in the APRV group (20.5 ⫾ 5.35 vs 16.9 ⫾ 7.17).
mean P high used in the APRV studies was 6 cm H2O
higher, but not statistically significant, compared to the APRV Versus Other Non-Conventional Ventilation
BIPAP studies.
Surprisingly, despite the difference in P high and T high APRV shares some similar features with other non-con-
settings, the mean P low was similar in both APRV and ventional modes of ventilation (eg, inverse ratio venti-
BIPAP, at 5.5 cm H2O.13 lation, and high-frequency oscillatory ventilation
Interestingly those 2 modes have never been compared [HFOV]).25–27 These modes attempt to improve oxygen-
head to head in an animal or human trial to determine if ation by increasing the mean Paw. Inverse ratio ventilation,
one is superior to the other. In a bench study using a lung either with volume or pressure control, increases the mean
simulator to compare both modes, with equivalent settings Paw through increasing the inspiratory time with I-E ratio
in an ARDS lung model, we found that APRV supplied more than 1:1. This causes patient discomfort, and heavy
higher mean airway pressure (Paw) but lower minute ven- sedation or muscle paralytics may be required.26,27 HFOV
tilation (V̇E) than BIPAP.14 also uses the open lung approach by applying very low
tidal volume (potentially less than the anatomic dead space),
APRV Versus Conventional Ventilation using high-frequency oscillations around a high mean Paw.25
Heavy sedation and muscular blockers are usually required
Several studies15–22 have compared APRV to conven- during HFOV in adults, due to the inability of the only
tional mechanical ventilation in humans with ALI/ARDS, commercially available device (in the United States) to
but most of them are weakened by the small number of accommodate spontaneous breathing adequately.28 A de-
patients and by being short-term observations studies. Con- tailed description of those modes is beyond the scope of
sistently, most of them have shown improvement in oxy- this review.
genation, but none of them has shown mortality benefits Table 1 highlights some of the differences between con-
in the APRV group. Putensen and colleagues18 random- ventional ventilation (volume or pressure control), inverse

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Table 1. Comparison of Conventional Ventilation, Inverse Ratio Ventilation, Biphasic Positive Airway Pressure, Airway Pressure Release
Ventilation, and High-Frequency Oscillatory Ventilation

Conventional Inverse Ratio

BIPAP APRV HFOV
Ventilation Ventilation

I:E ratio 1:4–1:1 ⬎ 1:1 1:4–1:1 ⬎ 2:1 1:2–1:3

Mean Paw Less Increased Increased Much Increased Much Increased
Spontaneous breathing Triggers a breath Triggers a breath Allowed at any time Allowed at any time Usually suppressed intentionally
of the respiratory of the respiratory (can cause drop in mean Paw)
cycle cycle
Heavy sedation and May be required Usually required Not required Not required Usually required
Paralytics
Auto-PEEP Less common Common Less common Very common Very common

BIPAP ⫽ biphasic positive airway pressure

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APRV ⫽ airway pressure release ventilation

HFOV ⫽ high-frequency oscillatory ventilation
I:E ratio ⫽ inspiratory-expiratory ratio
Paw ⫽ airway pressure

ratio ventilation (volume or pressure), BIPAP, APRV, and P High/P Low

HFOV.
Some authors4,12,18,34 recommended constructing a pa-
APRV Settings tient pressure-volume curve, and subsequently setting the
P high below the upper inflection point (UIP), and the
P low above the lower inflection point (LIP) of the in-
As with any ventilation strategy in ARDS, the goal spiratory limb of the curve to avoid VILI. This method
should be to ventilate the lung on the steep portion of the theoretically makes the most physiologic sense and has
pressure-volume curve, where mean lung volume and pres- been studied extensively in conventional mechanical ven-
sures are adequate for oxygenation and ventilation, and the tilation.35 However, clinicians are faced with the technical
tidal volume lies between the lower and upper inflection difficulties of obtaining a clear curve, and patients often
points.6 This strategy has been found to improve lung have to be heavily sedated or paralyzed to obtain a passive
compliance, venous admixture, and PaO2 in ARDS, on one breath.36 Moreover there is controversy in the literature
hand, and to protect the lung by avoiding either collapse regarding the benefits of this method in determining the
during expiration (atelectrauma) or stretch injury during optimal PEEP,37 as well as how to interpret the pressure-
inspiration (volutrauma, barotrauma), both of which con- volume curves (ie, using the inspiratory38 or expiratory
tribute to VILI.29 –31 limb39 or the hysteresis of the curve40,41). New ventilators
There has been no consensus in the literature in regard (eg, Hamilton G5 and Dräger Infinity) have integrated
to setting APRV parameters, which continues to be a co- software tools that facilitate this task.
Other authors2,10,42 recommended setting the P high ac-
nundrum in clinical practice.32 We will discuss the various
cording to the plateau pressure of the volume controlled
methods described and recommended in the literature for
mode or the peak Paw of the pressure controlled mode. The
setting the P high/P low and the T high/T low, with their
general suggestion is to limit the P high to 30 –35 cm H2O,
advantages and disadvantages. Of note, the most studied
while setting the P low at zero cm H2O in conjunction with
but the most difficult parameters to set were the P low and setting a very short T low. The short T low creates inten-
T low.33 There are generally 2 schools of thought, one tional gas trapping (auto-PEEP) to maintain end-expira-
advocating a short T low with a P low of zero cm H2O to tory lung volume. This method takes into consideration
prolong the inflation:deflation ratio and create auto-PEEP, avoiding excessive inflating pressures, but caution has to
while the other school is to use longer T low to eliminate be exercised, taking into account that the resultant tidal
the auto-PEEP and use a higher P low to avoid alveolar volume might be highly variable and may be higher than
collapse. There are very few data to support either school the accepted standard of care (ie, 6 – 8 mL/kg)43 due to
of thought.8,32 In theory and mathematically (see Fig. 2) the contribution of the patient’s spontaneous inspiratory
both strategies may be equivalent. In this review we will effort. The disadvantages of setting the P low empirically
not make any recommendations on how to set the param- at zero cm H2O and depending on generating auto-PEEP
eters, as there are no solid data to support them. to avoid lung collapse are that tidal volume cannot be

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controlled independently of end-expiratory lung volume

(as with conventional ventilation) and that even small
changes in lung mechanics cause large changes in both
variables. Auto-PEEP may be highly variable and an un-
reliable way of avoiding alveolar collapse in contrast to
applied PEEP.8,44,45
Other authors1 have set the P high and P low according
to oxygenation and ventilation parameters. This method is
totally empirical and discouraged, as it does not take into
account lung volumes or pressures.
Newer research46 has looked into titrating the P low to
achieve a protective tidal volume of 4 – 6 mL/kg, in com-
Fig. 3. Lung simulator diagram of airway pressure release ventila-
pliance with the ARDS Network recommendations.43 This tion (APRV): volume (yellow), lung pressure (white), and flow
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method is difficult to achieve in the spontaneously breath- (orange)/time curve. Time constant (TC) was known and the T low
ing patient, as the effects on the tidal volume during the was set to more than 4 TCs. The blue vertical lines represent each
releases will be variable. TC. Intrinsic PEEP at each TC would be equal to the point inter-
secting with the pressure curve, or can be calculated as the end-
expiratory lung volume divided by respiratory compliance. Notice
T High/T Low that at each TC the flow curve did not decay to 36.2% from its
previous value, as expected per the mathematical model.
Most authors focus on the setting of T low and leave
T high as a function of the overall desired frequency of
mandatory breaths (usually 8 –12 breaths/min). constant, then the expected auto-PEEP is about 11 cm H2O,
Some authors2,10 have advocated setting the T low ac- 4 cm H2O at 2 time constants, 1.5 cm H2O at 3 time
cording to the expiratory flow curve decay to achieve about constants, and so on theoretically till infinity if no breath
50% of peak expiratory flow as a way to achieve auto- follows. Usually 4 –5 times the expiratory time constant is
PEEP and avoid lung collapse. This method attempts to needed to eliminate auto-PEEP.31,36 Unfortunately, such
create an expected average amount of auto-PEEP. The estimation has been shown to be very inaccurate, probably
problem with that method is that the amount of auto-PEEP due to the fact that the model does not account for the
generated is highly variable and depends on the set P high effect on the time constant of the mechanical properties of
(assuming P low ⫽ 0 cm H2O), respiratory system elas- the expiratory limb of different ventilators45 (Fig. 5). Cau-
tance, and resistance, all of which change frequently dur- tion has to be exercised, as the time constant changes
ing mechanical ventilation. More importantly, this is a frequently during mechanical ventilation and a guaranteed
difficult task to achieve at the bedside8,32 and the actual alveolar pressure may not be maintained.8 Another con-
level of auto-PEEP is also difficult to measure with most cern is that even with very short T low, alveolar derecruit-
ventilators (Fig. 3). New technology might help facilitate ment may occur.47 Nevertheless, in a neonatal sheep model
setting T low by allowing the trigger for mandatory breaths of ARDS, Martin and Wetzel48 found that release times of
to be set as a percentage of the peak expiratory flow, a 2–3 time constants maintained adequate oxygenation and
feature available on the Dräger Infinity ventilator (Auto ventilation. Another study, by Neumann and colleagues,49
Release feature). has shown that T low less than 1.5 seconds has resulted in
Others have advocated setting the T low according to lower tidal volumes, but the V̇E was maintained, with the
the expiratory time constant (␶) of the respiratory sys- parallel increase of spontaneous respiratory rate.
tem.10,31 The time constant is calculated as the product of Some authors2,10 have published guidelines for the ini-
the static respiratory compliance and resistance, both of tial settings of APRV, and they recommended a T low
which are easily obtained at the bedside. This method range of 0.2– 0.8 seconds. Setting the T low as high as
allows a theoretical estimate of the amount of auto-PEEP 0.8 seconds in ARDS, whose time constant is usually very
generated (Fig. 4). Pressure, volume, and flow all decay short, may cause alveolar collapse and derecruitment, which
according to the same time constant (assuming a simple, might be dangerous, especially if the P low used is
single-compartment model of the respiratory system). Dur- zero cm H2O.
ing each time constant, each variable changes by 63.2%. Earlier studies1 have used empirical settings of T low
Thus, for example, after one time constant, alveolar pres- directly and T high indirectly (by the frequency of releases
sure is 36.8% of its initial value; after 2 time constants it or mandatory breaths) to achieve certain oxygenation and
is 13.5%, after 3 time constants it is 5%, and after 4 time ventilation end points. Again, this is discouraged, as it
constants it is 1.8%. Therefore, if the P high is 30 cm H2O, does not take into account the resultant tidal volume and
P low is 0 cm H2O, and the T low is set at one time risk of stretch damage to the lungs.2,30

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Fig. 4. Illustration of the values of the inspiratory and expiratory volume, pressure, and flow in relation to the time constant theory. Each
1 time constant, the volume, pressure and flow change by 63.2% from their previous value.

airway resistance. Experts2,8,10 have expressed their con-

cerns about those adjuncts because the additional elevation
of applied pressures may significantly raise the transpul-
monary pressure above safe levels, contributing to VILI
when the assist is delivered during the P high. Addition-
ally, that support may eliminate the transient drop in trans-
pulmonary pressure created by unassisted spontaneous
breaths and thus obviate their putative beneficial effects.

Synchronization

Some ventilator manufacturers have incorporated a syn-

chronization interface for switching from P high to P low,
and vice versa, according to the patient’s spontaneous
breaths, to avoid patient-ventilator asynchrony. Usually a
Fig. 5. Expected and measured intrinsic PEEP using the time con- synchronization window of 0.25– 0.3 seconds is used for
stant method. (Adapted from Reference 45.) both triggering and cycling of the mandatory breaths. The
benefits from such a strategy have not been reported.8,50
Others46 have looked at titrating the T low to achieve
certain predefined protective tidal volume. Conceptually, APRV and Weaning
this method tries to accomplish a protective lung strategy.
Unfortunately, the tidal volume will vary with patients’ Some authors10,33 have described a “drop and stretch
efforts, and changes in lung mechanics. method” of weaning APRV; they gradually reduced the
level of P high (“drop”) and reduced the number of re-
Settings Adjuncts leases by increasing the T high (“stretch”) until the mode
is converted to CPAP as a method of spontaneous breath-
Pressure Support and Automatic Tube Compensation ing trial before extubation. A study by Rathgeber and col-
leagues51 compared duration of weaning between BIPAP,
Most of current commercially available ventilators have VC-IMV, and volume controlled continuous mandatory
incorporated the addition of pressure support (PS) and ventilation (VC-CMV) in postoperative cardiac patients,
automatic tube compensation (ATC) to augment the pa- and reported a small yet significant reduction in time on
tient’s spontaneous breaths or to overcome the artificial mechanical ventilation. To our knowledge there are no

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published studies comparing APRV to conventional wean- dation leads to depression of cough reflex and increased
ing methods like pressure support ventilation (PSV) or risk of aspiration of pharyngeal secretions.59 Unrestricted
T-tube, or to newer closed loop ventilation methods such spontaneous breathing allows the patient to cough during
as ATC, proportional assist ventilation (PAV), adaptive mandatory breaths, contributing to secretion clearance and
support ventilation (ASV), or Smart Care. possibly reducing the risk of VAP, which can translate to
the potential for decreasing the duration of ventilation.10 A
Advantages of APRV recent study has shown that APRV reduces the risk of
VAP in trauma patients with pulmonary contusion.60
APRV is considered an “open lung approach,” a con- The increase in cardiac output related to spontaneous
cept of maximizing and maintaining alveolar recruitment breathing is due to the decrease of pleural pressure and
throughout the ventilatory cycle by potentially ventilating increase of abdominal pressure. Thus, blood is shifted from
the lung on the steep portion of the pressure-volume curve, abdominal viscera to inferior vena cava, where the venous
thus avoiding over-distention on inspiration and alveolar return to the heart is increased.15,61,62 Suppression of spon-
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collapse on exhalation.6,10,30 Its major advantages over other taneous breathing during conventional ventilation can com-
modes of conventional ventilation are the preservation of promise cardiovascular function by decreasing venous re-
spontaneous unassisted ventilation throughout the entire turn and thus the cardiac output. Studies in medical and
ventilatory cycle, maintenance of relatively long inflation trauma patients comparing APRV to conventional venti-
time, and potential lung-protective benefits. lation have shown increased cardiac index and oxygen
delivery in patients on APRV.17,42 However, other studies
Spontaneous Ventilation have shown no significant difference in hemodynamics
between APRV and conventional ventilation.16,63 Some
Spontaneous breathing, accounting for 10 –30% of V̇E animal studies have shown increased regional blood flow
during APRV, leads to improved ventilation-perfusion and increased perfusion to cerebral, renal, hepatic, and
matching, decreased intrapulmonary shunt, and decreased splanchnic circulation while on APRV.64 – 67 Some studies
dead space, through improvement of transpulmonary pres- indicate that APRV does not compromise circulatory func-
sure in the juxtadiaphragmatic lung regions, with alveolar tion and tissue oxygenation, whereas conventional venti-
recruitment, and without raising peak Paw.52–55 This is in lation can impair cardiovascular function significantly.65,67
contrast with conventional ventilation, which leads to al-
teration of normal ventilation distribution and atelectasis Long Inflation Time
in dependent lung areas.53,56 Furthermore, regular sponta-
neous breathing maintains diaphragmatic muscle condi- The benefit of a prolonged inflation time can be appre-
tion. Putensen and colleagues18 have documented the ben- ciated when we consider the uneven distribution of lung
efits of spontaneous breathing during APRV, which has pathology in ALI/ARDS. The main causes of hypoxemia
increased the respiratory-system compliance, PaO2, cardiac in ALI/ARDS are shunting due to alveolar collapse and
index, and oxygen delivery, compared to patients who reduction in functional residual capacity.16,68 –70
were paralyzed during mechanical ventilation. Lung units with reduced compliance have short time
Froese and colleagues57 showed that about 60% of the constants, thus inflating and deflating rapidly. Lung units
diaphragmatic movements occur in the most dependent with normal compliance have relatively long time con-
regions of the lungs during spontaneous breathing in su- stants, thus inflating and deflating slowly.31,36 A prolonged
pine patients, in contrast to 10% movement in paralyzed T high is presumed to achieve the treatment goal of alve-
patients on mechanical ventilation. A surprising finding olar recruitment because it allows time for slow lung units
was that, despite the spontaneous breathing, the WOB and in a non-homogenous lung field to inflate. Furthermore,
oxygen consumption on APRV were not affected.49,58 longer inflation times promote collateral ventilation
Another major benefit of spontaneous breathing during through the channels of Martin, the pores of Kohn, and the
APRV is the resulting improved patient comfort. Patients canals of Lambert.71–73 Thus, the longer the inflation time,
have the ability to maintain their spontaneous tidal vol- the greater the lung areas potentially available for gas
umes with an unrestricted flow pattern. The patient has the exchange. The higher mean Paw created with T high and
ability to adjust their spontaneous ventilation in relation to short T low settings presumably results in higher mean
their metabolic needs,5 which translates in better synchrony lung volumes. To attain the same mean Paw with conven-
with the ventilator, improving comfort, leading to a re- tional volume controlled ventilation requires either larger
duced need for sedation. Studies have reported up to 70% tidal volume with the higher risk of volutrauma,31,43 pro-
reduction in the use of neuromuscular blocking agents longed inspiratory time as in inverse ratio ventilation that
(NMBAs) and 40% reduction in sedation requirements, usually requires high levels of sedation along with the risk
compared to conventional ventilation.15–17 The use of se- of hemodynamic compromise and auto-PEEP,74 increased

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respiratory rate with the risk of VILI secondary to cyclical was a small, uncontrolled study and done using conven-
alveolar opening and collapsing,29 or the addition of higher tional ventilation. Uyar and colleagues81 studied energy
levels of PEEP. Such strategy had been a matter of debate expenditure between APRV and PSV in a crossover study
for a long time. Three recent trials75–77 have documented in patients without substantial lung disease and found no
improved oxygenation with higher PEEP, but no survival significant differences between both modes. In an animal
advantages, compared to lower PEEP levels. model, the perfusion of the diaphragm, external intercos-
Longer inflation times allow a greater probability of tals and expiratory muscles increased by 2,500%, 900%,
spontaneous breaths during T high. Animal and human and 300% during spontaneous breathing, respectively.82
studies with ALI have shown that allowing spontaneous The increased perfusion of respiratory muscle may drive
breathing improved ventilation-perfusion matching by a systemic perfusion and oxygen delivery away from vital
marked decrease of intrapulmonary shunt.49,53 organs, which can be deleterious, especially in shock states.
The long inflation time allows using lower peak Paw, It is well known that hypoperfusion of the gastrointestinal
and hence tidal volumes, to maintain mean Paw. Studies in tract facilitates translocation of bacteria into the systemic
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patients with ALI/ARDS have shown that APRV allowed circulation.83

a 17% reduction in peak Paw, compared with conventional
volume controlled ventilation adjusted to deliver a com- Work of Breathing
parable or lower ventilatory support.78
The timing of spontaneous breathing during the APRV
Lung-Protective Benefits cycle can have significant effect on the amount of work of
breathing (WOB). Breaths that occur at the P low or dur-
The potential lung-protective benefit of APRV depends ing the pressure-release transition from the P high to P low
on judicious selection of settings to ensure ventilation on have higher WOB.84 Additionally, those breaths may cre-
the advantageous portion of the pressure-volume curve. A ate the most discomfort and asynchrony, as Paw would be
small study of 19 patients by Patel and colleagues22 com- decreasing and gas flow would be escaping the circuit just
paring APRV to low tidal volume (ARDSNet) ventilation as the patient was trying to inspire.32 This might be an
in ALI showed comparable safety and outcomes using argument in favor of synchronizing mandatory breath cy-
both strategies. Moreover the long inflation time results in cling with a spontaneous expiration during T high. On the
less frequent inflation and deflation, which can contribute other hand, spontaneous breaths occurring during the P high
to shear stress on the alveoli.29 A recent animal study should have the least amount of WOB, unless an excessive
showed that APRV decreases bronchoalveolar lavage fluid level of pressure is used, causing lung over-distention that
high-mobility group box-1 levels and lung water, com- paradoxically increases the elastic WOB.84
pared to low tidal volume ventilation, signifying a de- The breathing efforts may increase the transcapillary
creased risk for VILI.79 However the relationship between pressure gradient, thus enhancing pulmonary edema for-
APRV and VILI is more theoretical and has not been well mation.85 The impact of spontaneous breathing on pulmo-
studied or documented.31,32 nary edema formation during APRV is potentially depen-
dent upon the P high level and the I-E ratio employed.
APRV and Mortality However, APRV is not the only mode of ventilation as-
sociated with substantial respiratory efforts. Vigorous in-
No reported studies have shown improved mortality with spiratory efforts usually occur during conventional volume
APRV use.7,18,19,22 One small retrospective study23 of 58 or pressure control modes, especially with lung-protective
patients has shown a trend toward mortality benefit: 31% ventilation, to meet the metabolic demands.86 Thus, these
in the APRV group, compared to 59% in the SIMV group modes may accentuate pulmonary edema formation too.79
(P value of .05). Other limitations of APRV are related to the V̇E. APRV
relies on the small number of respiratory cycles to create
Disadvantages of APRV the high inflation time and the higher mean Paw. However,
this limited number of cycles per minute has to create the
Spontaneous Breathing baseline V̇E. This means that a substantial amount of V̇E
(occasionally up to 70% of the V̇E demand) may be abruptly
APRV is a mode of ventilation that has its own limita- shifted to the patient. This could result in an acute rise in
tions. There are some worries regarding the spontaneous PaCO2 level and a marked increase in respiratory drive and
breathing during APRV. Field and colleagues80 reported WOB.84 Thus, the potential options to decrease WOB while
that spontaneous breathing efforts can result in increased maintaining V̇E are to decrease the time ratios (T high:
oxygen consumption by the respiratory muscles, which T low), or to increase the cycle frequency or to increase
may exceed 25% of total body oxygen consumption. This the mandatory breath volumes. Decreasing the time ra-

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 AIRWAY PRESSURE RELEASE VENTILATION: WHAT DO WE KNOW?

tios14,17,78 usually maintains both the mandatory V̇E and kept this mode in the shadows as a primary ventilatory
the lung-protective ventilation. On the other hand, the high mode, and it is only thought of as a rescue therapy for the
inflation time and oxygenation can be potentially sacri- difficult to oxygenate patient. More work and well orga-
ficed. In some studies the cycle ratio reached 1:1.78 nized studies seem prudent for the continued use and the
acceptance of APRV in day-to-day clinical practice.
Tidal Volume and Minute Ventilation
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