Airway pressure release ventilation (APRV) is inverse ratio, pressure controlled, intermittent

mandatory 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 hemodynamics, 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 ventilation. 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.

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 described 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 without
dangerously high applied pressures, thus minimizing the risk of ventilator-induced lung injury
(VILI), and without depressing hemodynamics, while comfort in that unrestricted
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 used routinely in clinical
practice in North America. APRV is used more frequently in Europe. 7 APRV is still mostly
thought of as an alternative rescue mode for the difficult to oxygenate patient with acute lung
injury (ALI) and acute respiratory distress syndrome (ARDS).8

Terminology

APRV is classified as pressure controlled intermittent mandatory ventilation, and is typically

applied using inverse inspiratory-expiratory (I:E) ratios. 9 As such, there are both mandatory
breaths (ie, machine-triggered and machine-cycled), as well as spontaneous breaths (ie,
patient-triggered and patient-cycled) (Fig. 1). The mandatory breaths applied by APRV are
time-triggered, pressure-targeted, time-cycled breaths (depending on the ventilator, trigger
and cycle events may be synchronized with patient breathing signals). Spontaneous breaths
can occur both during and between mandatory breaths. Because APRV has historically been
viewed as alternating levels of CPAP, the amplitude of the time-triggered mandatory breath
is called “P high” instead of inspiratory pressure, and the duration is called “T high” instead of
 inspiratory time. Similarly, the expiratory pressure is called “P low” and the expiratory time
(release time) is called “T low.”1,8,10

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Fig. 1.
A: Pressure (green) and volume (black)/time curve in airway pressure release ventilation (APRV).
Shown in the figure: 2 full mandatory breaths (not triggered by muscle effort), and 2 full spontaneous
breaths (triggered by muscle effort, in blue) on the top of the mandatory ones. Muscle pressure (blue):
the long arrow represents the T high, and the short one represents the T low of the 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 beginning of the next
inspiratory flow. The 2 red intersecting lines are at 50% of the peak expiratory flow.
The confusion regarding this mode of ventilation arises from the different terminology used in
the literature, as authors seldom provide adequately explicit definitions for the terms they use
when describing various modes of ventilation.11 This issue has been studied by Rose and
Hawkins,11 in an attempt to identify the definitional criteria of both APRV and biphasic
positive airway pressure (BIPAP) modes. They concluded: “Ambiguity exists in the criteria
that distinguish APRV and BIPAP.” The other source of confusion arises from the ventilator
manufacturers' choice of terminology. Different names have been coined for the same mode,
such as BiLevel (Covidien), APRV (Dräger), Bi-Vent (Maquet), BiPhasic (CareFusion), and
DuoPAP (Hamilton).

APRV Versus BIPAP

 Both modes clearly have the same general pattern of airway pressures as intermittent
mandatory ventilation, with time-triggered, pressure-targeted, and time-cycled mandatory
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 there is
more time for them to occur during mandatory breaths with APRV. APRV typically uses
extreme inverse I:E ratios, while BIPAP usually does not. 11 Also APRV usually keeps the
duration of the T low at ≤1.5 seconds, while there is no restriction on the T low in BIPAP. 4,8,12

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Fig. 2.
Comparison of airway pressure release ventilation (APRV) (blue curve) and biphasic positive airway
pressure (BIPAP) (black curve). Compared to APRV, BIPAP uses shorter T high, longer T low, and
usually higher P low. Despite the differences between their settings, mathematically both can achieve
the same mean airway pressure (red line) and same tidal volume (green curve). Blue curves represent
APRV, black curves represent BIPAP.
A recent review of 50 published studies of both modes 11 showed that 78% of the studies
described APRV, while 22% described BIPAP. Extreme inverse I:E (> 2:1) was used in 46%
of the studies describing APRV. None of the studies describing BIPAP used an I:E > 2:1.
Twenty-one percent of the APRV studies used I:E of 1:1 to 2:1, compared to 9% of studies
describing BIPAP. Thirty-one percent of the APRV studies used I:E of 1:1, compared to 64%
of the BIPAP studies. Finally, only 5% of the APRV studies used I:E less than 1:1, compared
to 27% of the BIPAP studies. The mean reported inspiratory time (T high) was 3.4 seconds
for APRV, compared to 2.4 seconds for BIPAP. Conversely, the mean reported expiratory
time (T low) was nearly 3 times longer in the BIPAP studies, compared to APRV (3.4 s and
1.3 s, respectively). The mean P high used in the APRV studies was 6 cm H 2O higher, but
not statistically significant, compared to the BIPAP studies.
Surprisingly, despite the difference in P high and T high settings, the mean P low was similar
in both APRV and BIPAP, at 5.5 cm H2O.13
Interestingly those 2 modes have never been compared head to head in an animal or human
trial to determine if one is superior to the other. In a bench study using a lung simulator to
compare both modes, with equivalent settings in an ARDS lung model, we found that APRV
supplied higher mean airway pressure (Paw) but lower minute ventilation (V̇E) than BIPAP.14

APRV Versus Conventional Ventilation

Several studies15–22 have compared APRV to conventional mechanical ventilation in humans

with ALI/ARDS, but most of them are weakened by the small number of patients and by
 being short-term observations studies. Consistently, most of them have shown improvement
in oxygenation, but none of them has shown mortality benefits in the APRV group. Putensen
and colleagues18 randomized 30 trauma patients to either APRV or pressure controlled
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 improvement in hemodynamics and the less sedation and no
paralytic agents used in the APRV group. This study is weakened by the small number of
patients (15 in each group), by the fact that only 20% of the APRV group had ARDS,
compared to 74% in the PC-CMV group, and by the fact that the 2 groups had different
sedation protocols. A recent retrospective study 23 with a small number of patients, compared
APRV to volume controlled intermittent mandatory 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 retrospective study 7 using propensity score to
compare both APRV and BIPAP to conventional ventilation confirmed the significantly
improved oxygenation with both modes, but failed to show any mortality benefits.
A recent study24 in 63 adult trauma patients requiring mechanical ventilation for greater than
72 hours showed that APRV has a similar safety profile as the low tidal volume ventilation.
APRV patients tended to have increased ventilator days (10.49 ± 7.23 d vs 8.00 ± 4.01 d),
ICU stay (16.47 ± 12.83 d vs 14.18 ± 13.26 d), and ventilator-associated pneumonia (VAP)
(1.00 ± 0.86 vs 0.56 ± 0.67). This may be explained by the significant initial worse
physiologic derangement demonstrated by Acute Physiology and Chronic Health Evaluation
II (APACHE II) scores in the APRV group (20.5 ± 5.35 vs 16.9 ± 7.17).

APRV Versus Other Non-Conventional Ventilation

APRV shares some similar features with other non-conventional modes of ventilation (eg,
inverse ratio ventilation, and high-frequency oscillatory ventilation [HFOV]). 25–27 These
modes attempt to improve oxygenation by increasing the mean Paw. Inverse ratio ventilation,
either with volume or pressure control, increases the mean Paw through increasing the
inspiratory time with I-E ratio more than 1:1. This causes patient discomfort, and heavy
sedation or muscle paralytics may be required. 26,27 HFOV also uses the open lung approach
by applying very low tidal volume (potentially less than the anatomic dead space), using
high-frequency oscillations around a high mean Paw.25 Heavy sedation and muscular blockers
are usually required during HFOV in adults, due to the inability of the only commercially
available device (in the United States) to accommodate spontaneous breathing
adequately.28 A detailed description of those modes is beyond the scope of this review.
Table 1 highlights some of the differences between conventional ventilation (volume or
pressure control), inverse ratio ventilation (volume or pressure), BIPAP, APRV, and HFOV.
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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

APRV Settings
As with any ventilation strategy in ARDS, the goal should be to ventilate the lung on the
steep portion of the pressure-volume curve, where mean lung volume and pressures are
adequate for oxygenation and ventilation, and the tidal volume lies between the lower and
upper inflection points.6 This strategy has been found to improve lung compliance, venous
admixture, and PaO  in ARDS, on one hand, and to protect the lung by avoiding either collapse
2

during expiration (atelectrauma) or stretch injury during inspiration (volutrauma, barotrauma),

both of which contribute to VILI.29–31
There has been no consensus in the literature in regard to setting APRV parameters, which
continues to be a conundrum in clinical practice.32 We will discuss the various methods
described and recommended in the literature for setting the P high/P low and the T high/T
low, with their advantages and disadvantages. Of note, the most studied but the most difficult
parameters to set were the P low and T low.33 There are generally 2 schools of thought, one
advocating a short T low with a P low of zero cm H2O to prolong the inflation:deflation ratio
and create auto-PEEP, while the other school is to use longer T low to eliminate the auto-
PEEP and use a higher P low to avoid alveolar collapse. There are very few data to support
either school of thought.8,32 In theory and mathematically (see Fig. 2) both strategies may be
equivalent. In this review we will not make any recommendations on how to set the
parameters, as there are no solid data to support them.

P High/P Low

Some authors4,12,18,34 recommended constructing a patient 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 inspiratory limb of the curve to avoid VILI. This method
theoretically makes the most physiologic sense and has been studied extensively in
conventional mechanical ventilation. 35 However, clinicians are faced with the technical
difficulties of obtaining a clear curve, and patients often have to be heavily sedated or
paralyzed to obtain a passive breath. 36 Moreover there is controversy in the literature
regarding the benefits of this method in determining the optimal PEEP,37 as well as how to
interpret the pressure-volume curves (ie, using the inspiratory 38 or expiratory limb39 or the
hysteresis of the curve40,41). New ventilators (eg, Hamilton G5 and Dräger Infinity) have
integrated software tools that facilitate this task.
Other authors2,10,42 recommended setting the P high according to the plateau pressure of the
volume controlled mode or the peak Paw of the pressure controlled mode. The general
suggestion is to limit the P high to 30–35 cm H2O, while setting the P low at zero cm H2O in
conjunction with setting a very short T low. The short T low creates intentional gas trapping
(auto-PEEP) to maintain end-expiratory lung volume. This method takes into consideration
avoiding excessive inflating pressures, but caution has to be exercised, taking into account
that the resultant tidal volume might be highly variable and may be higher than the accepted
standard of care (ie, 6–8 mL/kg)43 due to the contribution of the patient's spontaneous
inspiratory effort. The disadvantages of setting the P low empirically at zero cm H 2O and
depending on generating auto-PEEP to avoid lung collapse are that tidal volume cannot be
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 unreliable 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 compliance with the ARDS Network recommendations. 43 This method is
difficult to achieve in the spontaneously breathing patient, as the effects on the tidal volume
during the releases will be variable.
T High/T Low

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).

Some authors2,10 have advocated setting the T low according to the expiratory flow curve
decay to achieve about 50% of peak expiratory flow as a way to achieve auto-PEEP and
avoid lung collapse. This method attempts to create an expected average amount of auto-
PEEP. The problem with that method is that the amount of auto-PEEP generated is highly
variable and depends on the set P high (assuming P low = 0 cm H2O), respiratory system
elastance, and resistance, all of which change frequently during mechanical ventilation. More
importantly, this is a difficult task to achieve at the bedside 8,32 and the actual level of auto-
PEEP is also difficult to measure with most ventilators (Fig. 3). New technology might help
facilitate setting T low by allowing the trigger for mandatory breaths to be set as a
percentage of the peak expiratory flow, a feature available on the Dräger Infinity ventilator
(Auto Release feature).

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Fig. 3.
Lung simulator diagram of airway pressure release ventilation (APRV): volume (yellow), lung
pressure (white), and flow (orange)/time curve. Time constant (TC) was known and the T low was set
to more than 4 TCs. The blue vertical lines represent each TC. Intrinsic PEEP at each TC would be
equal to the point intersecting with the pressure curve, or can be calculated as the end-expiratory lung
volume divided by respiratory compliance. Notice that at each TC the flow curve did not decay to
36.2% from its previous value, as expected per the mathematical model.
Others have advocated setting the T low according to the expiratory time constant (τ) of the
respiratory system.10,31 The time constant is calculated as the product of the static respiratory
compliance and resistance, both of which are easily obtained at the bedside. This method
allows a theoretical estimate of the amount of auto-PEEP generated (Fig. 4). Pressure,
volume, and flow all decay according to the same time constant (assuming a simple, single-
compartment model of the respiratory system). During each time constant, each variable
changes by 63.2%. Thus, for example, after one time constant, alveolar pressure is 36.8% of
its initial value; after 2 time constants it is 13.5%, after 3 time constants it is 5%, and after 4
time constants it is 1.8%. Therefore, if the P high is 30 cm H2O, P low is 0 cm H2O, and the T
low is set at one time constant, then the expected auto-PEEP is about 11 cm H 2O, 4 cm H2O
at 2 time constants, 1.5 cm H2O at 3 time constants, and so on theoretically till infinity if no
breath follows. Usually 4–5 times the expiratory time constant is needed to eliminate auto-
PEEP.31,36 Unfortunately, such estimation has been shown to be very inaccurate, probably
due to the fact that the model does not account for the effect on the time constant of the
mechanical properties of the expiratory limb of different ventilators 45 (Fig. 5). Caution has to
be exercised, as the time constant changes frequently during mechanical ventilation and a
guaranteed alveolar pressure may not be maintained. 8 Another concern is that even with
very short T low, alveolar derecruitment may occur.47 Nevertheless, in a neonatal sheep
model of ARDS, Martin and Wetzel48 found that release times of 2–3 time constants
maintained adequate oxygenation and ventilation. Another study, by Neumann and
colleagues,49 has shown that T low less than 1.5 seconds has resulted in lower tidal
volumes, but the V̇E was maintained, with the parallel increase of spontaneous respiratory
rate.

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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.
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Fig. 5.
Expected and measured intrinsic PEEP using the time constant method. (Adapted from Reference 45.)
Some authors2,10 have published guidelines for the initial settings of APRV, and they
recommended a T low range of 0.2–0.8 seconds. Setting the T low as high as 0.8 seconds in
ARDS, whose time constant is usually very short, may cause alveolar collapse and
derecruitment, which might be dangerous, especially if the P low used is zero cm H 2O.
Earlier studies1 have used empirical settings of T low directly and T high indirectly (by the
frequency of releases or mandatory breaths) to achieve certain oxygenation and ventilation
end points. Again, this is discouraged, as it does not take into account the resultant tidal
volume and risk of stretch damage to the lungs.2,30
Others46 have looked at titrating the T low to achieve certain predefined protective tidal
volume. Conceptually, this method tries to accomplish a protective lung strategy.
Unfortunately, the tidal volume will vary with patients' efforts, and changes in lung
mechanics.

Settings Adjuncts

Pressure Support and Automatic Tube Compensation

Most of current commercially available ventilators have incorporated the addition of pressure
support (PS) and automatic tube compensation (ATC) to augment the patient's spontaneous
breaths or to overcome the artificial airway resistance. Experts 2,8,10 have expressed their
concerns about those adjuncts because the additional elevation of applied pressures may
significantly raise the transpulmonary pressure above safe levels, contributing to VILI when
the assist is delivered during the P high. Additionally, that support may eliminate the transient
 drop in transpulmonary pressure created by unassisted spontaneous breaths and thus
obviate their putative beneficial effects.

Synchronization

Some ventilator manufacturers have incorporated a synchronization 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 synchronization window of 0.25–0.3 seconds
is used for both triggering and cycling of the mandatory breaths. The benefits from such a
strategy have not been reported.8,50

APRV and Weaning

Some authors10,33 have described a “drop and stretch method” of weaning APRV; they
gradually reduced the level of P high (“drop”) and reduced the number of releases by
increasing the T high (“stretch”) until the mode is converted to CPAP as a method of
spontaneous breathing trial before extubation. A study by Rathgeber and
colleagues51 compared duration of weaning between BIPAP, VC-IMV, and volume controlled
continuous mandatory ventilation (VC-CMV) in postoperative cardiac patients, and reported
a small yet significant reduction in time on mechanical ventilation. To our knowledge there
are no published studies comparing APRV to conventional weaning methods like pressure
support ventilation (PSV) or T-tube, or to newer closed loop ventilation methods such as
ATC, proportional assist ventilation (PAV), adaptive support ventilation (ASV), or Smart
Care.

Advantages of APRV

APRV is considered an “open lung approach,” a concept of maximizing and maintaining

alveolar recruitment throughout the ventilatory cycle by potentially ventilating the lung on the
steep portion of the pressure-volume curve, thus avoiding over-distention on inspiration and
alveolar collapse on exhalation. 6,10,30 Its major advantages over other modes of conventional
ventilation are the preservation of spontaneous unassisted ventilation throughout the entire
ventilatory cycle, maintenance of relatively long inflation time, and potential lung-protective
benefits.

Spontaneous Ventilation

Spontaneous breathing, accounting for 10–30% of V̇E during APRV, leads to improved

ventilation-perfusion matching, decreased intrapulmonary shunt, and decreased dead space,
through improvement of transpulmonary pressure in the juxtadiaphragmatic lung regions,
with alveolar recruitment, and without raising peak Paw.52–55 This is in contrast with
conventional ventilation, which leads to alteration of normal ventilation distribution and
atelectasis in dependent lung areas.53,56 Furthermore, regular spontaneous breathing
maintains diaphragmatic muscle condition. Putensen and colleagues 18 have documented the
benefits of spontaneous breathing during APRV, which has increased the respiratory-system
compliance, PaO , cardiac index, and oxygen delivery, compared to patients who were
2

paralyzed during mechanical ventilation.

Froese and colleagues57 showed that about 60% of the diaphragmatic movements occur in
the most dependent regions of the lungs during spontaneous breathing in supine patients, in
contrast to 10% movement in paralyzed patients on mechanical ventilation. A surprising
finding was that, despite the spontaneous breathing, the WOB and oxygen consumption on
APRV were not affected.49,58
Another major benefit of spontaneous breathing during APRV is the resulting improved
patient comfort. Patients have the ability to maintain their spontaneous tidal volumes with an
unrestricted flow pattern. The patient has the ability to adjust their spontaneous ventilation in
relation to their metabolic needs,5 which translates in better synchrony with the ventilator,
improving comfort, leading to a reduced need for sedation. Studies have reported up to 70%
reduction in the use of neuromuscular blocking agents (NMBAs) and 40% reduction in
sedation requirements, compared to conventional ventilation. 15–17 The use of sedation leads
to depression of cough reflex and increased risk of aspiration of pharyngeal
secretions.59 Unrestricted spontaneous breathing allows the patient to cough during
mandatory breaths, contributing to secretion clearance and possibly reducing the risk of
VAP, which can translate to the potential for decreasing the duration of ventilation. 10 A recent
study has shown that APRV reduces the risk of VAP in trauma patients with pulmonary
contusion.60
The increase in cardiac output related to spontaneous breathing is due to the decrease of
pleural pressure and increase of abdominal pressure. Thus, blood is shifted from abdominal
viscera to inferior vena cava, where the venous return to the heart is
increased.15,61,62 Suppression of spontaneous breathing during conventional ventilation can
compromise cardiovascular function by decreasing venous return and thus the cardiac
output. Studies in medical and trauma patients comparing APRV to conventional ventilation
have shown increased cardiac index and oxygen delivery in patients on APRV. 17,42 However,
other studies have shown no significant difference in hemodynamics between APRV and
conventional ventilation.16,63 Some animal studies have shown increased regional blood flow
and increased perfusion to cerebral, renal, hepatic, and splanchnic circulation while on
APRV.64–67 Some studies indicate that APRV does not compromise circulatory function and
tissue oxygenation, whereas conventional ventilation can impair cardiovascular function
significantly.65,67

Long Inflation Time

The benefit of a prolonged inflation time can be appreciated when we consider the uneven
distribution of lung pathology in ALI/ARDS. The main causes of hypoxemia in ALI/ARDS are
shunting due to alveolar collapse and reduction in functional residual capacity. 16,68–70
Lung units with reduced compliance have short time constants, thus inflating and deflating
rapidly. Lung units with normal compliance have relatively long time constants, thus inflating
and deflating slowly.31,36 A prolonged T high is presumed to achieve the treatment goal of
alveolar recruitment because it allows time for slow lung units in a non-homogenous lung
field to inflate. Furthermore, longer inflation times promote collateral ventilation through the
channels of Martin, the pores of Kohn, and the canals of Lambert. 71–73 Thus, the longer the
inflation time, the greater the lung areas potentially available for gas exchange. The higher
mean Paw created with T high and short T low settings presumably results in higher mean
lung volumes. To attain the same mean Paw with conventional volume controlled ventilation
requires either larger tidal volume with the higher risk of volutrauma, 31,43 prolonged
inspiratory time as in inverse ratio ventilation that usually requires high levels of sedation
along with the risk of hemodynamic compromise and auto-PEEP,74 increased respiratory
rate with the risk of VILI secondary to cyclical alveolar opening and collapsing, 29 or the
addition of higher levels of PEEP. Such strategy had been a matter of debate for a long time.
Three recent trials75–77 have documented improved oxygenation with higher PEEP, but no
survival advantages, compared to lower PEEP levels.
 Longer inflation times allow a greater probability of spontaneous breaths during T high.
Animal and human studies with ALI have shown that allowing spontaneous breathing
improved ventilation-perfusion matching by a marked decrease of intrapulmonary shunt. 49,53
The long inflation time allows using lower peak Paw, and hence tidal volumes, to maintain
mean Paw. Studies in patients with ALI/ARDS have shown that APRV allowed a 17%
reduction in peak Paw, compared with conventional volume controlled ventilation adjusted to
deliver a comparable or lower ventilatory support. 78

Lung-Protective Benefits

The potential lung-protective benefit of APRV depends on judicious selection of settings to

ensure ventilation on the advantageous portion of the pressure-volume curve. A small study
of 19 patients by Patel and colleagues 22 comparing APRV to low tidal volume (ARDSNet)
ventilation in ALI showed comparable safety and outcomes using both strategies. Moreover
the long inflation time results in less frequent inflation and deflation, which can contribute to
shear stress on the alveoli.29 A recent animal study showed that APRV decreases
bronchoalveolar lavage fluid high-mobility group box-1 levels and lung water, compared to
low tidal volume ventilation, signifying a decreased risk for VILI. 79 However the relationship
between APRV and VILI is more theoretical and has not been well studied or
documented.31,32

APRV and Mortality

No reported studies have shown improved mortality with APRV use.7,18,19,22 One small
retrospective study23 of 58 patients has shown a trend toward mortality benefit: 31% in the
APRV group, compared to 59% in the SIMV group (P value of .05).

Disadvantages of APRV

Spontaneous Breathing

APRV is a mode of ventilation that has its own limitations. There are some worries regarding
the spontaneous breathing during APRV. Field and colleagues 80 reported that spontaneous
breathing efforts can result in increased oxygen consumption by the respiratory muscles,
which may exceed 25% of total body oxygen consumption. This was a small, uncontrolled
study and done using conventional ventilation. Uyar and colleagues 81 studied energy
expenditure between APRV and PSV in a crossover study in patients without substantial
lung disease and found no significant differences between both modes. In an animal model,
the perfusion of the diaphragm, external intercostals and expiratory muscles increased by
2,500%, 900%, and 300% during spontaneous breathing, respectively. 82 The increased
perfusion of respiratory muscle may drive systemic perfusion and oxygen delivery away from
vital organs, which can be deleterious, especially in shock states. It is well known that
hypoperfusion of the gastrointestinal tract facilitates translocation of bacteria into the
systemic circulation.83

Work of Breathing

The timing of spontaneous breathing during the APRV cycle can have significant effect on
the amount of work of breathing (WOB). Breaths that occur at the P low or during the
 pressure-release transition from the P high to P low have higher WOB. 84 Additionally, those
breaths may create the most discomfort and asynchrony, as Paw would be decreasing and
gas flow would be escaping the circuit just as the patient was trying to inspire. 32 This might
be an argument in favor of synchronizing mandatory breath cycling with a spontaneous
expiration during T high. On the other hand, spontaneous breaths occurring during the P
high should have the least amount of WOB, unless an excessive level of pressure is used,
causing lung over-distention that paradoxically increases the elastic WOB. 84
The breathing efforts may increase the transcapillary pressure gradient, thus enhancing
pulmonary edema formation.85 The impact of spontaneous breathing on pulmonary edema
formation during APRV is potentially dependent upon the P high level and the I-E ratio
employed. However, APRV is not the only mode of ventilation associated with substantial
respiratory efforts. Vigorous inspiratory efforts usually occur during conventional volume or
pressure control modes, especially with lung-protective ventilation, to meet the metabolic
demands.86 Thus, these modes may accentuate pulmonary edema formation too. 79 Other
limitations of APRV are related to the V̇E. APRV relies on the small number of respiratory
cycles to create the high inflation time and the higher mean Paw. However, this limited number
of cycles per minute has to create the baseline V̇E. This means that a substantial amount of
V̇E (occasionally up to 70% of the V̇E demand) may be abruptly shifted to the patient. This
could result in an acute rise in PaCO  level and a marked increase in respiratory drive and
2

WOB.84 Thus, the potential options to decrease WOB while maintaining V̇E are to decrease
the time ratios (T high: T low), or to increase the cycle frequency or to increase the
mandatory breath volumes. Decreasing the time ratios 14,17,78 usually maintains both the
mandatory V̇E and the lung-protective ventilation. On the other hand, the high inflation time
and oxygenation can be potentially sacrificed. In some studies the cycle ratio reached 1:1. 78

Tidal Volume and Minute Ventilation

APRV, as a form of pressure controlled ventilation, carries the risk of volume changes with
alteration in lung mechanics and the changes in the patient's spontaneous inspiratory effort,
which may cause large tidal volume and transpulmonary pressure swings, potentially
contributing to volutrauma.30,32 Larger release volumes could maintain V̇E, and this would
produce a more satisfying breath while lessening the power demands on the respiratory
muscles. In some APRV studies the measured exhaled volumes were 9 mL/kg of measured
body weight.19,78 We have personally observed exhaled volumes considerably larger than
this. Large exhaled volumes imply potentially large end-inspiratory volumes that might
obviate the desired lung-protective strategies, with potential increase in VILI and possibly
mortality.86 Thus, the theory that the superimposition of spontaneous tidal volumes on the
top of the mandatory breath may increase the likelihood of stretch-related injury is in
question.32,84
There is a concern that patients with left ventricular dysfunction may not benefit from the
augmentation of venous return and the increase in afterload occurring with the decrease in
intrathoracic pressures.55 There is also the theoretical concern for using APRV in patients
with COPD who require prolonged exhalation time, though there are no conclusive
data.8,10 The limited research and experience with this form of ventilation can be a potential
problem in certain facilities, though this mode is now integrated on most new commercially
used ventilators.

Present and Future

 The lack of proven mortality reduction has been a factor in the slow adoption of this mode,
but there is an increasing interest. There are ongoing studies registered in the National
Institutes of Health (clinicaltrials.gov), mostly comparing APRV to low tidal volume ventilation
as a lung-protective strategy, which hopefully may shed more light on this mode and answer
some of the needed questions.

Conclusions

Despite increasing evidence of improving oxygenation, hemodynamics, patient comfort, and

safety, there are still a lot of unanswered questions regarding this unconventional mode of
ventilation. In the United States the lack of proof that APRV in ALI/ARDS improves mortality
has kept this mode in the shadows as a primary ventilatory mode, and it is only thought of as
a rescue therapy for the difficult to oxygenate patient. More work and well organized studies
seem prudent for the continued use and the acceptance of APRV in day-to-day clinical
practice.

Footnotes

 The authors have disclosed no conflicts of interest.

 © 2012 by Daedalus Enterprises Inc.

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