REVIEW

CME EDUCATIONAL OBJECTIVE: Readers will be able to explain what some of the new ventilator modes do
CREDIT and their theoretical and actual benefits

EDUARDO MIRELES-CABODEVILA, MD ENRIQUE DIAZ-GUZMAN, MD GUSTAVO A. HERESI, MD ROBERT L. CHATBURN, BS, RRT-NPS*
Department of Pulmonary and Critical Care Medicine, Respiratory Institute, Respiratory Institute, Respiratory Institute, Respiratory Therapy Section,
University of Arkansas for Medical Sciences, Cleveland Clinic Cleveland Clinic Cleveland Clinic
Little Rock, AR

Alternative modes of mechanical

ventilation: A review for the hospitalist
■ ■ABSTRACT
T echnologic advances and computer-
ized control of mechanical ventilators
have made it possible to deliver ventilatory
Newer ventilators can be set to modes other than the
pressure-control and volume-control modes of older ma- assistance in new modes. Driving these in-
chines. In this paper, the authors review several of these novations is the desire to prevent ventilator-
alternative modes (adaptive pressure control, adap- induced lung injury, improve patient comfort,
and liberate the patient from mechanical ven-
tive support ventilation, proportional assist ventilation,
tilation as soon as possible.
airway pressure-release ventilation, biphasic positive We call these innovations “alternative”
airway pressure, and high-frequency oscillatory ventila- modes to differentiate them from the plain
tion), explaining how they work and contrasting their volume-control and pressure-control modes.
theoretical benefits and the actual evidence of benefit. Some clinicians rarely use these new modes,
but in some medical centers they have become
■ ■KEY POINTS the most common ones used, or are being used
The alternative modes of ventilation were developed unknowingly (the operator misunderstands
the mode name). The information we provide
to prevent lung injury and asynchrony, promote better
on these modes of ventilation is by no means
oxygenation and faster weaning, and be easier to use. an endorsement of their use, but rather a tool
However, evidence of their benefit is scant. to help the clinician understand their physi-
ologic, theoretical, and clinical effects.
Until now, we have lacked a standard nomenclature for We focused on two goals:
mechanical ventilation, leading to confusion. • Explain what the mode does
• Briefly review the theoretical benefits and
Regardless of the mode used, the goals are to avoid the actual evidence supporting these alter-
native modes of ventilation.
lung injury, keep the patient comfortable, and wean the
patient from mechanical ventilation as soon as possible.
■■ STANDARD NOMENCLATURE NEEDED
Abbreviations used in this article
APC—adaptive pressure control Since its invention, mechanical ventilation
APRV—airway pressure-release ventilation has been plagued by multiple names being used
ASV—adaptive support ventilation
CPAP—continuous positive airway pressure
to describe the same things. For example, vol-
Fio2—fraction of inspired oxygen ume-control ventilation is also called volume-
HFOV—high-frequency oscillatory ventilation cycled ventilation, assist-control ventilation,
PAV—proportional assist ventilation
PEEP—positive end-expiratory pressure
volume-limited ventilation, and controlled
PSV—pressure support ventilation mechanical ventilation. Similarly, multiple
abbreviations are used, each depending on the
*
Mr. Chatburn has disclosed that he has received fees from Cardinal Health for serving on brand of ventilator, and new acronyms have
advisory committees or review panels and from Strategic Dynamics Inc for consulting.
been added in recent years as new modes have
doi:10.3949/ccjm.76a.08043 been developed. The vast number of names
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 MECHANICAL VENTILATION

Volume control Tidal volume

set by operator
Volume

Flow Patient
effort
Pressure control Inspiratory pressure
set by operator
Airway
pressure

No respiratory Small respiratory Larger respiratory

effort effort effort

FIGURE 1. Volume control (top) and pressure control (bottom) are modes of continuous mandatory
ventilation. Each mode is depicted as patient effort increases. Notice that the mode’s control variable
(volume or pressure) remains constant as patient effort increases. Contrast these findings with those
in FIGURE 2.

and modes can confuse even the most sea- ends (cycles) it.
soned critical care physician. Therefore, a volume-controlled breath is
Efforts to establish a common nomencla- triggered by the patient or by the machine,
The mode ture are under way.1 limited by flow, and cycled by volume (FIGURE
name can be 1). A pressure-controlled breath is triggered by
■■ WHAT IS A MODE? the patient or the machine, limited by pres-
misleading sure, and cycled by time or flow (FIGURE 1).
A mode of mechanical ventilation has three
essential components: The breath sequence
• The control variable There are three possible breath sequences:
• The breath sequence • Continuous mandatory ventilation, in
• The targeting scheme. which all breaths are controlled by the
Similar modes may require more detailed machine (but can be triggered by the pa-
descriptions to distinguish them, but the basic tient)
function can be explained by these three com- • Intermittent mandatory ventilation, in
ponents. which the patient can take spontaneous
breaths between mandatory breaths
The control variable • Continuous spontaneous ventilation, in
In general, inspiration is an active process, which all breaths are spontaneous (TABLE 1).
driven by the patient’s effort, the ventilator, or
both, while expiration is passive. For simplic- The targeting scheme
ity, in this article a mechanical breath means The targeting or feedback scheme refers to
the inspiratory phase of the breath. the ventilator settings and programming that
The machine can only control the volume dictate its response to the patient’s lung com-
(and flow) or the pressure given. The breaths pliance, lung resistance, and respiratory effort.
can be further described on the basis of what The regulation can be as simple as controlling
triggers the breath, what limits it (the maxi- the pressure in pressure-control mode, or it
mum value of a control variable), and what can be based on a complicated algorithm.
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 MIRELES-CABODEVILA AND COLLEAGUES

TABLE 1
Mechanical breath terminology
Mechanical breath description
Control variable—the mechanical breath goal, ie, a set pressure or a set volume
Trigger variable—that which starts inspiration, ie, the patient (generating changes in pressure or flow)
or a set rate (time between breaths)
Limit variable—the maximum value during inspiration
Cycle variable—that which ends inspiration

Breath sequence
Continuous mandatory ventilation—all breaths are controlled by the ventilator, so usually they have the
same characteristics regardless of the trigger (patient or set rate); no spontaneous breaths are allowed
Intermittent mandatory ventilation—a set number of mechanical breaths is delivered regardless of the
trigger (patient initiation or set rate); spontaneous breaths are allowed between or during mandatory
breaths
Continuous spontaneous ventilation—all breaths are spontaneous with or without assistance

Type of control or targeting scheme a

Set point—the ventilator delivers and maintains a set goal, and this goal is constant (eg, in pressure
control, the set point is pressure, which will remain constant throughout the breath); to a degree, all modes
have some set-point control scheme
Servo—the ventilator adjusts its output to a given patient variable (ie, in proportional assist ventilation,
the inspiratory flow follows and amplifies the patient’s own flow pattern)
Adaptive—the ventilator adjusts a set point to maintain a different operator-selected set point (ie, in A mode
pressure-regulated volume control, the inspiratory pressure is adjusted breath to breath to achieve a target
tidal volume) of ventilation
Optimal—the ventilator uses a mathematical model to calculate the set points to achieve a goal (ie, in is only as good
adaptive support ventilation, the pressure, respiratory rate, and tidal volume are adjusted to achieve a goal as the operator
minute ventilation)
who applies it
a
Mentioned in this review; for more information, refer to Chatburn1

In the sections that follow, we describe some goes in and out in 1 minute; the tidal volume
of the available alternative modes of mechani- × breaths per minute) in the face of changing
cal ventilation. We will explain only the tar- lung mechanics or patient effort, or both. To
geting schemes in the modes reviewed (TABLE 1, solve this problem, in 1991 the Siemens Servo
TABLE 2), but more information on other target- 300 ventilator (Siemens, Maquet Critical Care
ing schemes can be found elsewhere.1,2 We will AB, Solna, Sweden) introduced Pressure Reg-
focus on evidence generated in adult patients ulated Volume Control, a mode that delivers
receiving invasive mechanical ventilation. pressure-controlled breaths with a target tidal
volume and that is otherwise known as adap-
■■ ADAPTIVE PRESSURE CONTROL tive pressure control (APC) (FIGURE 2).

One of the concerns with pressure-control ven- Other names for adaptive pressure control
tilation is that it cannot guarantee a minimum • Pressure Regulated Volume Control (Ma-
minute ventilation (the volume of air that quet Servo-i, Rastatt, Germany)
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 MECHANICAL VENTILATION

TABLE 2

Classification of modes of ventilation

CONTROL VARIABLE BREATH SEQUENCE TARGETING SCHEME EXAMPLES of commercially available modes

Volume Continuous Set point Volume control, VC-A/C, CMV, (S)CMV,

mandatory Assist/Control
ventilation Dual CMV + pressure limited
Adaptive Adaptive flow
Intermittent Set point SIMV, VC-SIMV
mandatory
Dual SIMV + pressure limited
ventilation
Adaptive AutoMode (VC-VS), mandatory minute volume
Pressure Continuous Set point Pressure control, PC-A/C, AC PCV,
mandatory high-pressure oscillatory ventilation a
ventilation Adaptive Pressure-regulated volume control, a VC+AC a,
AMV+AutoFlow a
Intermittent Set point Airway pressure-release ventilation, a
mandatory SIMV PCV, BiLevel, a PCV+ a
ventilation Adaptive VC+SIMV, V V+SIMV APVSIMV,
SIMV+AutoFlow, Automode (PRVC-VS)
Optimal Adaptive support ventilation a
Continuous Set point Continuous positive airway pressure,
spontaneous pressure support
ventilation
Mechanical Dual Volume assured pressure support,
volume augment
breaths can be
Servo Proportional assist ventilation, a automatic
delivered only tube compensation
via pressure Adaptive Volume support
control or Intelligent SmartCare
volume control Three levels of classification of the modes of mechanical ventilation. As noted in the text, for a given combination of control vari-
able, breath sequence, and targeting scheme, several commercial mode names are described. Each commercial mode name can
have subtle differences from others in the same class; however, the main characteristics of the mode can be determined by this
classification.
a
Discussed in this paper
CMV = continuous mandatory ventilation, CSV = continuous spontaneous ventilation, IMV = intermittent mandatory ventilation,
SIMV = synchronized intermittent mandatory ventilation

• AutoFlow (Dräger Medical AG, Lübeck, What does adaptive pressure control do?
Germany) The APC mode delivers pressure-controlled
• Adaptive Pressure Ventilation (Hamilton breaths with an adaptive targeting scheme
Galileo, Hamilton Medical AG, Bonaduz, (TABLE 2).
Switzerland) In pressure-control ventilation, tidal vol-
• Volume Control+ (Puritan Bennett, Tyco umes depend on the lung’s physiologic mechan-
Healthcare; Mansfield, MA) ics (compliance and resistance) and patient
• Volume Targeted Pressure Control, Pres- effort (FIGURE 1). Therefore, the tidal volume
sure Controlled Volume Guaranteed (Eng- varies with changes in lung physiology (ie,
ström, General Electric, Madison, WI). larger or smaller tidal volumes than targeted).
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 MIRELES-CABODEVILA AND COLLEAGUES

Adaptive pressure control Target tidal volume

Volume set by operator
Airway
pressure Pressure

Flow Patient
effort
Adaptive support ventilation Target tidal volume
set by operator

No respiratory Small respiratory Larger respiratory Inspiratory pressure is

effort effort effort adjusted to maintain
a target tidal volume

FIGURE 2. A machine in adaptive pressure control mode (top) adjusts the inspiratory pressure to main-
tain a set tidal volume. Adaptive support ventilation (bottom) automatically selects the appropriate
tidal volume and frequency for mandatory breaths and the appropriate tidal volume for spontaneous
breaths on the basis of the respiratory system mechanics and the target minute ventilation.

To overcome this effect, a machine in APC This is essentially different from volume con-
mode adjusts the inspiratory pressure to deliver trol, in which flow is set by the operator and
the set minimal target tidal volume. If tidal vol- hence is fixed. Thus, if the patient effort is
ume increases, the machine decreases the in- strong enough (FIGURE 1), this leads to what is The response of
spiratory pressure, and if tidal volume decreases, called flow asynchrony, in which the patient the ventilator
the machine increases the inspiratory pressure. does not get the flow asked for in a breath.
However, if the patient effort is large enough, to the patient is
the tidal volume will increase in spite of decreas- Ventilator settings regulated in a
ing the inspiratory pressure (FIGURE 2). The adjust- in adaptive pressure control
ments to the inspiratory pressure occur after the Ventilator settings in APC are:
number of ways
tidal volume is off-target in a number of breaths. • Tidal volume
• Time spent in inspiration (inspiratory time)
Common sources of confusion • Frequency
with adaptive pressure control • Fraction of inspired oxygen (Fio2)
First, APC is not a volume-control mode. In • Positive end-expiratory pressure (PEEP).
volume control, the tidal volume does not Some ventilators also require setting the
change; in APC the tidal volume can increase speed to reach the peak pressure (also known
or decrease, and the ventilator will adjust the as slope percent or inspiratory rise time).
inflation pressure to achieve the target volume.
Thus, APC guarantees an average minimum Clinical applications
tidal volume but not a maximum tidal volume. of adaptive pressure control
Second, a characteristic of pressure con- This mode is designed to maintain a consis-
trol (and hence, APC) is that the flow of gas tent tidal volume during pressure-control
varies to maintain constant airway pressure ventilation and to promote inspiratory flow
(ie, maintain the set inspiratory pressure). synchrony. It is a means of automatically re-
This characteristic allows a patient who gen- ducing ventilatory support (ie, weaning) as
erates an inspiratory effort to receive flow as the patient’s inspiratory effort becomes stron-
demanded, which is likely more comfortable. ger, as in awakening from anesthesia.
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 MECHANICAL VENTILATION

APC may not be ideal for patients who Mandatory minute ventilation is a mode that
have an inappropriately increased respira- allows the operator to preset a target minute
tory drive (eg, in severe metabolic acidosis), ventilation, and the ventilator then supplies
since the inspiratory pressure will decrease to mandatory breaths, either volume- or pres-
maintain the targeted average tidal volume, sure-controlled, if the patient’s spontaneous
inappropriately shifting the work of breathing breaths generate a lower minute ventilation.
onto the patient. ASV automatically selects the appropri-
ate tidal volume and frequency for mandatory
Theoretical benefits breaths and the appropriate tidal volume for
of adaptive pressure control spontaneous breaths on the basis of the respi-
APC guarantees a minimum average tidal vol- ratory system mechanics and target minute
ume (unless the pressure alarm threshold is set alveolar ventilation.
too low, so that the target tidal volume is not Described in 1994 by Laubscher et al,8,9
delivered). Other theoretical benefits are flow ASV became commercially available in 1998
synchrony, less ventilator manipulation by the in Europe and in 2007 in the United States
operator, and automatic weaning of ventilator (Hamilton Galileo ventilator, Hamilton Med-
support. ical AG). This is the first commercially avail-
able ventilator that uses an “optimal” target-
Evidence of benefit ing scheme (see below).
of adaptive pressure control
Physiologic benefits. This mode has lower What does adaptive support ventilation do?
peak inspiratory pressures than does volume- ASV delivers pressure-controlled breaths us-
control ventilation,3,4 which is often reported ing an adaptive (optimal) scheme (TABLE 2).
as a positive finding. However, in volume- “Optimal,” in this context, means minimizing
control mode (the usual comparator), the the mechanical work of breathing: the ma-
peak inspiratory pressure is a manifestation of chine selects a tidal volume and frequency that
both resistance and compliance. Hence, peak the patient’s brain would presumably select if
APC adjusts inspiratory pressure is expected to be higher the patient were not connected to a ventila-
the inspira- but does not reflect actual lung-distending tor. This pattern is assumed to encourage the
pressures. It is the plateau pressure, a manifes- patient to generate spontaneous breaths.
tory pressure tation of lung compliance, that is related to The ventilator calculates the normal re-
to deliver the lung injury. quired minute ventilation based on the pa-
Patient comfort. APC may increase the tient’s ideal weight and estimated dead space
set target tidal work of breathing when using low tidal vol- volume (ie, 2.2 mL/kg). This calculation
volume ume ventilation and when there is increased represents 100% of minute ventilation. The
respiratory effort (drive).5 Interestingly, APC clinician at the bedside sets a target percent
was less comfortable than pressure support of minute ventilation that the ventilator will
ventilation in a small trial.6 support—higher than 100% if the patient has
Outcomes have not been studied.7 increased requirements due, eg, to sepsis or in-
creased dead space, or less than 100% during
Adaptive pressure control: Bottom line weaning.
APC is widely available and widely used, The ventilator initially delivers test
sometimes unknowingly (eg, if the operator breaths, in which it measures the expiratory
thinks it is volume control). It is relatively time constant for the respiratory system and
easy to use and to set; however, evidence of its then uses this along with the estimated dead
benefit is scant. space and normal minute ventilation to calcu-
late an optimal breathing frequency in terms
■■ ADAPTIVE SUPPORT VENTILATION of mechanical work.
The optimal or target tidal volume is calcu-
Adaptive support ventilation (ASV) evolved lated as the normal minute ventilation divid-
as a form of mandatory minute ventilation ed by the optimal frequency. The target tidal
implemented with adaptive pressure control. volume is achieved by the use of APC (see
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 MIRELES-CABODEVILA AND COLLEAGUES

above) (FIGURE 2). This means that the pressure fort have not been studied.
limit is automatically adjusted to achieve an Outcomes. Two trials suggest that
average delivered tidal volume equal to the ASV may decrease time on mechanical
target. The ventilator continuously monitors ventilation.14,15 However, in another trial,16
the respiratory system mechanics and adjusts compared with a standard protocol, ASV led
its settings accordingly. to fewer ventilator adjustments but achieved
The ventilator adjusts its breaths to avoid similar postsurgical weaning outcomes. The
air trapping by allowing enough time to ex- effect of this mode on the death rate has not
hale, to avoid hypoventilation by delivering been examined.17,18
tidal volume greater than the dead space, and
to avoid volutrauma by avoiding large tidal Adaptive support ventilation: Bottom line
volumes. ASV is the first commercially available mode
that automatically selects all the ventilator
Ventilator settings settings except PEEP and Fio2. These seem
in adaptive support ventilation appropriate for different clinical scenarios
Ventilator settings in ASV are: in patients with poor respiratory effort or in
• Patient height (to calculate the ideal body paralyzed patients. Evidence of the effect in
weight) actively breathing patients and on outcomes
• Sex such as length of stay or death is still lack-
• Percent of normal predicted minute ven- ing.
tilation goal
• Fio2 ■■ PROPORTIONAL ASSIST VENTILATION
• PEEP.
Patients who have normal respiratory drive
Clinical applications but who have difficulty sustaining adequate
of adaptive support ventilation spontaneous ventilation are often subjected
ASV is intended as a sole mode of ventila- to pressure support ventilation (PSV), in
tion, from initial support to weaning. which the ventilator generates a constant APC
pressure throughout inspiration regardless of is not a
Theoretical benefits the intensity of the patient’s effort.
of adaptive support ventilation In 1992, Younes and colleagues19,20 devel- volume-
In theory, ASV offers automatic selection of oped proportional assist ventilation (PAV) as controlled
ventilator settings, automatic adaptation to an alternative in which the ventilator gen-
changing patient lung mechanics, less need erates pressure in proportion to the patient’s
mode
for human manipulation of the machine, im- effort. PAV became commercially available
proved synchrony, and automatic weaning. in Europe in 1999 and was approved in the
United States in 2006, available on the Puri-
Evidence of benefit tan Bennett 840 ventilator (Puritan Bennett
of adaptive support ventilation Co, Boulder, CO). PAV has also been used for
Physiologic benefits. Ventilator settings noninvasive ventilation, but this is not avail-
are adjusted automatically. ASV selects dif- able in the United States.
ferent tidal volume-respiratory rate combina-
tions based on respiratory mechanics in passive Other names for proportional
and paralyzed patients.10–12 In actively breath- assist ventilation
ing patients, there was no difference in the Proportional Pressure Support (Dräger Medi-
ventilator settings chosen by ASV for differ- cal; not yet available in the United States).
ent clinical scenarios (and lung physiology).10
Compared with pressure-controlled intermit- What does proportional
tent mandatory ventilation, with ASV, the assist ventilation do?
inspiratory load is less and patient-ventilator This mode delivers pressure-controlled
interaction is better.13 breaths with a servo control scheme (TABLE 2).
Patient-ventilator synchrony and com- To better understand PAV, we can compare
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 MECHANICAL VENTILATION

Proportional assist ventilation

Volume Pressure

Patient Flow, pressure, and volume delivered

effort Flow
Ventilator measuring by the ventilator are adjusted
respiratory system proportionally to patient effort
characteristics
FIGURE 3. In proportional assist ventilation, the flow, pressure, and volume delivered are adjusted
proportionally to the patient’s effort.

it with PSV. With PSV, the pressure applied by ration ends, flow should stop; this param-
the ventilator rises to a preset level that is held eter tells the ventilator at what flow to end
constant (a set-point scheme) until a cycling inspiration).
criterion (a percent of the maximum inspirato- Caution when assessing the literature.
ry flow value) is reached. The inspiratory flow Earlier ventilator versions, ie, Dräger and Man-
and tidal volume are the result of the patient’s itoba (University of Manitoba, Winnipeg, MB,
inspiratory effort, the level of pressure applied, Canada), which are not available in the United
and the respiratory system mechanics. States, required the repeated calculation of the
In contrast, during PAV, the pressure applied respiratory system mechanics and the manual
is a function of patient effort: the greater the setting of flow and volume assists (amplification
inspiratory effort, the greater the increase in ap- factors) independently. To overcome this limi-
ASV selects plied pressure (servo targeting scheme) (FIGURE tation, new software automatically adjusts the
a tidal volume 3). The operator sets the percentage of support flow and volume amplification to support the
to be delivered by the ventilator. The ventila- loads imposed by the automatically measured
and frequency tor intermittently measures the compliance and values of resistance and elastance (inverse of
that the resistance of the patient’s respiratory system and compliance) of the respiratory system.21 This
the instantaneous patient-generated flow and software is included in the model (Puritan Ben-
patient’s volume, and on the basis of these it delivers a nett) available in the United States.
brain would proportional amount of inspiratory pressure.
presumably In PAV, as in PSV, all breaths are spontane- Clinical applications
ous (TABLE 1). The patient controls the timing of proportional assist ventilation
select and size of the breath. There are no preset pres- The PAV mode is indicated for maximizing
sure, flow, or volume goals, but safety limits on ventilator patient synchrony for assisted spon-
the volume and pressure delivered can be set. taneous ventilation.
PAV is contraindicated in patients with
Ventilator settings respiratory depression (bradypnea) or large air
in proportional assist ventilation leaks (eg, bronchopleural fistulas). It should
Ventilator settings in PAV are: be used with caution in patients with severe
• Airway type (endotracheal tube, trache- hyperinflation, in which the patient may still
ostomy) be exhaling but the ventilator doesn’t recog-
• Airway size (inner diameter) nize it. Another group in which PAV should
• Percentage of work supported (assist range be used with caution is those with high ven-
5%–95%) tilatory drives, in which the ventilator over-
• Tidal volume limit estimates respiratory system mechanics. This
• Pressure limit situation can lead to overassistance due to the
• Expiratory sensitivity (normally, as inspi- “runaway phenomenon,” in which the venti-
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 MIRELES-CABODEVILA AND COLLEAGUES

lator continues to provide support even if the APRV combines high constant positive airway
patient has stopped inspiration.22 pressure (improving oxygenation and promot-
ing alveolar recruitment) with intermittent
Theoretical benefits releases (causing exhalation).
of proportional assist ventilation In 1989, Baum et al31 described bipha-
In theory, PAV should reduce the work of sic positive airway pressure ventilation as a
breathing, improve synchrony, automatically mode in which spontaneous ventilation could
adapt to changing patient lung mechanics and be achieved at any point in the mechanical
effort, decrease the need for ventilator inter- ventilation cycle—inspiration or exhalation
vention and manipulation, decrease the need (FIGURE 4). The goal was to allow unrestricted
for sedation, and improve sleep. spontaneous breathing to reduce sedation and
promote weaning. These modes are conceptu-
Evidence of benefit ally the same, the main difference being that
of proportional assist ventilation the time spent in low pressure (Tlow; see be-
Physiologic benefits. PAV reduces the work low) is less than 1.5 seconds for APRV. Other-
of breathing better than PSV,21 even in the wise, they have identical characteristics, thus
face of changing respiratory mechanics or in- allowing any ventilator with the capability
creased respiratory demand (hypercapnia).23–25 of delivering APRV to deliver biphasic posi-
The hemodynamic profile is similar to that in tive airway pressure, and vice versa. Machines
PSV. Tidal volumes are variable; however, in with these modes became commercially avail-
recent reports the tidal volumes were within able in the mid 1990s.
the lung-protective range (6–8 mL/kg, plateau
pressure < 30 cm H20).26,27 Other names for biphasic positive airway
Comfort. PAV entails less patient effort pressure
and discomfort that PSV does.23,25 PAV sig- Other names for biphasic positive airway pres-
nificantly reduces asynchrony,27 which in turn sure are:
may favorably affect sleep in critically ill pa- • BiLevel (Puritan Bennett)
tients.28 • BIPAP (Dräger Europe) In PAV, the
Outcomes. The probability of spontaneous • Bi Vent (Siemens) greater the
breathing without assistance was significantly • BiPhasic (Avea, Cardinal Health, Inc,
better in critically ill patients ventilated with Dublin, OH) inspiratory
PAV than with PSV. No trial has reported the • PCV+ (Dräger Medical) effort, the
effect of PAV on deaths.27,29 • DuoPAP (Hamilton).
Caution—name confusion. In North
greater the
Proportional assist ventilation: Bottom line America, BiPAP (Respironics, Murrysville, increase in
Extensive basic research has been done with PA) and BiLevel are used to refer to noninva- applied
PAV in different forms of respiratory failure, sive modes of ventilation.
such as obstructive lung disease, acute respira- APRV has no other name. pressure
tory distress syndrome (ARDS), and chronic re-
spiratory failure. It fulfills its main goal, which is What do these modes do?
to improve patient-ventilator synchrony. Clini- These modes deliver pressure-controlled,
cal experience with PAV in the United States is time-triggered, and time-cycled breaths us-
limited, as it was only recently approved. ing a set-point targeting scheme (TABLE 2). This
means that the ventilator maintains a con-
■■ AIRWAY PRESSURE-RELEASE stant pressure (set point) even in the face of
VENTILATION AND spontaneous breaths.
BIPHASIC POSITIVE AIRWAY PRESSURE Caution—source of confusion. The term
continuous positive airway pressure (CPAP)
Airway pressure-release ventilation (APRV) is often used to describe this mode. However,
was described in 1987 by Stock et al30 as a CPAP is pressure that is applied continuously
mode for delivering ventilation in acute lung at the same level; the patient generates all
injury while avoiding high airway pressures. the work to maintain ventilation (“pressure-
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 MECHANICAL VENTILATION

Airway pressure-release ventilation

Volume
Pressure

Phigh and Thigh Plow and Tlow Thigh:Tlow = 4:1 Spontaneous breaths occur
at any point without altering
the ventilator-delivered
Biphasic positive airway pressure breaths

Phigh and Thigh Plow and Tlow Thigh:Tlow = 1:1–4

FIGURE 4. Airway pressure-release ventilation (top) and biphasic positive airway pressure (bottom)
are forms of pressure-controlled intermittent mandatory ventilation in which spontaneous breaths
can occur at any point without altering the ventilator-delivered breaths. The difference is that the
time spent in high pressure is greater in airway pressure-release ventilation.

controlled continuous spontaneous ventila- expiration ratio of 4:1. This means a patient
tion” in the current nomenclature). In APRV, spends most of the time in Phigh and Thigh, and
APRV allows the airway pressure is intermittently released exhalations are short (Tlow and Plow). In con-
spontaneous and reapplied, generating a tidal volume that trast, the biphasic mode uses conventional
supports ventilation. In other words, this is inspiration-expiration ratios (FIGURE 4).
breaths at any a pressure-controlled breath with a very pro- As with any form of pressure control, the
point in the longed inspiratory time and a short expiratory tidal volume is generated by airway pressure
time in which spontaneous ventilation is pos- rising above baseline (ie, the end-expiratory
cycle sible at any point (“pressure-controlled inter- value). Hence, to ensure an increase in minute
mittent mandatory ventilation” in the current ventilation, the mandatory breath rate must
nomenclature). be increased (ie, decreasing Thigh, Tlow, or both)
How these modes are set in the ventilator or the tidal volume must be increased (ie, in-
may also be a source of confusion. To describe creasing the difference between Phigh and Plow).
the time spent in high and low airway pres- This means that in APRV the Tlow has to hap-
sures, we use the terms Thigh and Tlow, respec- pen more often (by increasing the number of
tively. By convention, the difference between breaths) or be more prolonged (allowing more
APRV and biphasic mode is the duration of air to exhale). Because unrestricted spontane-
Tlow (< 1.5 sec for APRV). ous breaths are permitted at any point of the
Similarly, Phigh and Plow are used to describe cycle, the patient contributes to the total min-
the high and low airway pressure. To better un- ute ventilation (usually 10%–40%).
derstand this concept, you can create the same In APRV and biphasic mode, the opera-
mode in conventional pressure-control venti- tor’s set time and pressure in inspiration and
lation by thinking of the Thigh as the inspiratory expiration will be delivered regardless of the
time, the Tlow as the expiratory time, the Phigh as patient’s breathing efforts—the patient’s spon-
inspiratory pressure, and the Plow as PEEP. taneous breath does not trigger a mechanical
Hence, APRV is an extreme form of in- breath. Some ventilators have automatic ad-
verse ratio ventilation, with an inspiration-to- justments to improve the trigger synchrony.
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 MIRELES-CABODEVILA AND COLLEAGUES

Ventilator settings Patient comfort. These modes are

in APRV and biphasic mode thought to decrease the need for analgesia
These modes require the setting of two pressure and sedation,38 but a recent trial showed no
levels (Phigh and Plow) and two time durations difference with pressure-controlled intermit-
(Thigh and Tlow). One can add pressure support tent mandatory ventilation.41 Patient venti-
or automatic tube compensation to assist spon- lator synchrony and comfort have not been
taneous breaths. The difference in Tlow gener- studied.32,42
ates differences in the Thigh:Tlow ratio: APRV Outcomes. In small trials, these modes
has a short Tlow (an inspiration-expiration ra- made no difference in terms of deaths, but
tio of 4:1). Biphasic mode has a conventional they may decrease the length of mechanical
inspiration-expiration ratio of 1:1 to 1:4. ventilation.38,41,43,44

Clinical applications APRV and biphasic mode: Bottom line

APRV is used in acute lung injury and Maintaining spontaneous breathing while on
ARDS. This mode should be used with cau- mechanical ventilation has hemodynamic and
tion or not at all in patients with obstructive ventilatory benefits.
lung disease or inappropriately increased re- APRV and biphasic mode are not the same
spiratory drive.32–35 thing. APRV’s main goal is to maximize mean
Biphasic mode is intended for both venti- airway pressure and, hence, lung recruitment,
lation and weaning. In a patient who has poor whereas the main goal of the biphasic mode is
respiratory effort or who is paralyzed, bipha- synchrony.
sic is identical to pressure-control/continuous There is a plethora of ventilator settings and
mandatory ventilation. questions related to physiologic effects.33,34,36
Although these modes are widely used in
Theoretical benefits some centers, there is no evidence yet that
of APRV and biphasic mode they are superior to conventional volume- or
Multiple benefits have been ascribed to these pressure-control ventilation with low tidal vol-
modes. In theory, APRV will maximize and ume for ARDS and acute lung injury. There is Maintaining
maintain alveolar recruitment, improve oxy- no conclusive evidence that these modes im- spontaneous
genation, lower inflation pressures, and decrease prove synchrony, time to weaning, or patient
overinflation. Both APRV and biphasic, by pre- comfort. breathing while
serving spontaneous breathing, will improve on mechanical
ventilation-perfusion matching and gas diffusion, ■■ HIGH-FREQUENCY
improve the hemodynamic profile (less need for OSCILLATORY VENTILATION
ventilation has
vasopressors, higher cardiac output, reduced ven- benefits
tricular workload, improved organ perfusion), High-frequency oscillatory ventilation
and improve synchrony (decrease the work of (HFOV) was first described and patented in
breathing and the need for sedation). 1952 by Emerson and was clinically developed
in the early 1970s by Lunkenheimer.45
Evidence of benefit of APRV The goal of HFOV is to minimize lung
and biphasic mode injury; its characteristics (discussed below)
APRV and biphasic are different modes. make it useful in patients with severe ARDS.
However studies evaluating their effects are The US Food and Drug Administration ap-
combined. This is in part the result of the no- proved it for infants in 1991 and for children
menclature confusion and different practice in in 1995. The adult model has been available
different countries.36 since 1993, but it was not approved until 2001
Physiologic benefits. In studies, sponta- (SensorMedics 3100B, Cardinal Health, Inc).
neous breaths contributed to 10% to 40% of
minute ventilation,37,38 improved ventilation Other names for high-frequency
of dependent areas of the lung, improved ven- oscillatory ventilation
tilation-perfusion match and recruitment,39 While HFOV has no alternative names, the
and improved hemodynamic profile.40 following acronyms describe similar modes:
CL EVE L AND CL I NI C J O URNAL O F M E DI CI NE    V O L UM E 76  •   NUM BE R 7   J ULY   2009   427
 MECHANICAL VENTILATION

High-frequency oscillatory ventilation

Mean airway
Airway pressure pressure
amplitude (power)

Tidal volume
Frequency
FIGURE 5. High-frequency oscillatory ventilation delivers very small mandatory breaths (oscillations)
at frequencies of up to 900 breaths per minute.

• HFPPV (high-frequency positive pressure deeply sedated, since deep spontaneous

ventilation) breathing will trigger alarms and affect venti-
• HFJV (high-frequency jet ventilation) lator performance.
• HFFI (high-frequency flow interruption) To manage ventilation (CO2 clearance),
• HFPV (high-frequency percussive ventila- one or several of the following maneuvers can
tion) be done: decrease the oscillation frequency,
• HFCWO (high-frequency chest wall oscil- increase the amplitude of the oscillations, in-
lation). crease the inspiratory time, or increase bias
All of these modes require different spe- flow (while allowing an endotracheal tube cuff
cialized ventilators. leak). Oxygenation adjustments are controlled
by manipulating the mean airway pressure and
The goal What does high-frequency the Fio2.
of HFOV oscillatory ventilation do?
Conceptually, HFOV is a form of pressure- Ventilator settings
is to minimize controlled intermittent mandatory venti- in high-frequency oscillatory ventilation
lung injury, lation with a set-point control scheme. In Ventilator settings in HFOV are46:
contrast to conventional pressure-controlled • Airway pressure amplitude (delta P or
especially intermittent mandatory ventilation, in which power)
in ARDS relatively small spontaneous breaths may be • Mean airway pressure
superimposed on relatively large mandatory • Percent inspiration
breaths, HFOV superimposes very small man- • Inspiratory bias flow
datory breaths (oscillations) on top of sponta- • Fio2.
neous breaths.
HFOV can be delivered only with a spe- Clinical applications
cial ventilator. The ventilator delivers a of high-frequency oscillatory ventilation
constant flow (bias flow), while a valve cre- This mode is usually reserved for ARDS pa-
ates resistance to maintain airway pressure, tients for whom conventional ventilation is
on top of which a piston pump oscillates at failing. A recently published protocol46 sug-
frequencies of 3 to 15 Hz (160–900 breaths/ gests considering HFOV when there is oxy-
minute). This creates a constant airway pres- genation failure (Fio2 ≥ 0.7 and PEEP ≥ 14 cm
sure with small oscillations (FIGURE 5); often, H2O) or ventilation failure (pH < 7.25 with
clinicians at the bedside look for the “chest tidal volume ≥ 6 mL/kg predicted body weight
wiggle” to assess the appropriate amplitude and plateau airway pressure ≥ 30 cm H2O).
settings, although this has not been system- This mode is contraindicated when
atically studied. there is known severe airflow obstruction or
Adult patients are usually paralyzed or intracranial hypertension.
428  CLEV ELA N D C LI N I C JOURNAL OF MEDICINE   VOL UME 76  •  N UM BE R 7   J ULY   2009
 MIRELES-CABODEVILA AND COLLEAGUES

Theoretical benefits HFOV as rescue therapy for severe ARDS

of high-frequency oscillatory ventilation than with conventional mechanical ventila-
Conceptually, HFOV can provide the high- tion. Two randomized controlled trials have
est mean airway pressure paired with the low- studied HFOV vs high-tidal-volume conven-
est tidal volume of any mode. These benefits tional mechanical ventilation for early severe
might make HFOV the ideal lung-protective ARDS; HFOV was safe but made no differ-
ventilation strategy. ence in terms of deaths.42,51–54

Evidence of benefit High-frequency oscillatory ventilation:

of high-frequency oscillatory ventilation Bottom line
Physiologic benefits. Animal models have In theory, HFOV provides all the benefits of an
shown less histologic damage and lung inflam- ideal lung-protective strategy, at least for para-
mation with HFOV than with high-tidal- lyzed or deeply sedated patients. Animal stud-
volume conventional ventilation47,48 and low- ies support these concepts. In human adults,
tidal-volume conventional ventilation.49 HFOV has been shown to be safe and to pro-
Patient comfort has not been studied. vide better oxygenation but no improvement
However, current technology does impose in death rates compared with conventional
undue work of breathing in spontaneously mechanical ventilation. Currently, HFOV is
breathing patients.50 better reserved for patients with severe ARDS
Outcomes. Several retrospective case se- for whom conventional mechanical ventila-
ries have described better oxygenation with tion is failing. ■

■■ REFERENCES interactions during partial ventilatory support: a preliminary study

comparing the effects of adaptive support ventilation with synchro-
1. Chatburn RL. Classification of ventilator modes: update and pro- nized intermittent mandatory ventilation plus inspiratory pressure
posal for implementation. Respir Care 2007; 52:301–323. support. Crit Care Med 2002; 30:801–807.
2. Chatburn RL. Computer control of mechanical ventilation. Respir 14. Gruber PC, Gomersall CD, Leung P, et al. Randomized controlled trial
Care 2004; 49:507–517. comparing adaptive-support ventilation with pressure-regulated
3. Alvarez A, Subirana M, Benito S. Decelerating flow ventilation ef- volume-controlled ventilation with automode in weaning patients
fects in acute respiratory failure. J Crit Care 1998; 13:21–25. after cardiac surgery. Anesthesiology 2008; 109:81–87.
4. Guldager H, Nielsen SL, Carl P, Soerensen MB. A comparison of 15. Sulzer CF, Chiolero R, Chassot PG, et al. Adaptive support ventila-
volume control and pressure regulated volume control ventilation tion for fast tracheal extubation after cardiac surgery: a randomized
in acute respiratory failure. Crit Care 1997; 1:75–77. controlled study. Anesthesiology 2001; 95:1339–1345.
5. Kallet RH, Campbell AR, Dicker RA, Katz JA, Mackersie RC. Work of 16. Petter AH, Chiolèro RL, Cassina T, Chassot PG, Müller XM, Revelly
breathing during lung protective ventilation in patients with acute JP. Automatic “respirator/weaning” with adaptive support ventila-
lung injury and acute respiratory distress syndrome: a comparison tion: the effect on duration of endotracheal intubation and patient
between volume and pressure regulated breathing modes. Respir management. Anesth Analg 2003; 97:1743–1750.
Care 2005; 50:1623–1631. 17. Brunner JX, Iotti GA. Adaptive support ventilation (ASV). Minerva
6. Betensley AD, Khalid I, Crawford J, Pensler RA, DiGiovine B. Patient Anestesiol 2002; 68:365–368.
comfort during pressure support and volume controlled continuous 18. Campbell RS, Branson RD, Johannigman JA. Adaptive support venti-
mandatory ventilation. Respir Care 2008; 53:897–902. lation. Respir Care Clin North Am 2001; 7:425–440.
7. Branson RD, Chatburn RL. Controversies in the critical care setting. 19. Younes M. Proportional assist ventilation, a new approach to venti-
Should adaptive pressure control modes be utilized for virtually latory support. Theory. Am Rev Respir Dis 1992; 145:114–120.
all patients receiving mechanical ventilation? Respir Care 2007; 20. Younes M, Puddy A, Roberts D, et al. Proportional assist ventilation.
52:478–485. Results of an initial clinical trial. Am Rev Respir Dis 1992; 145:121–
8. Laubscher TP, Frutiger A, Fanconi S, Jutzi H, Brunner JX. Automatic 129.
selection of tidal volume, respiratory frequency and minute ventila- 21. Kondili E, Prinianakis G, Alexopoulou C, Vakouti E, Klimathianaki M,
tion in intubated ICU patients as start up procedure for closed-loop Georgopoulos D. Respiratory load compensation during mechanical
controlled ventilation. Int J Clin Monit Comput 1994; 11:19–30. ventilatio—proportional assist ventilation with load-adjustable gain
9. Laubscher TP, Heinrichs W, Weiler N, Hartmann G, Brunner JX. An factors versus pressure support. Intensive Care Med 2006; 32:692–
adaptive lung ventilation controller. IEEE Trans Biomed Eng 1994; 699.
41:51–59. 22. Kondili E, Prinianakis G, Alexopoulou C, Vakouti E, Klimathianaki
10. Arnal JM, Wysocki M, Nafati C, et al. Automatic selection of breath- M, Georgopoulos D. Effect of different levels of pressure support
ing pattern using adaptive support ventilation. Intensive Care Med and proportional assist ventilation on breathing pattern, work of
2008; 34:75–81. breathing and gas exchange in mechanically ventilated hypercap-
11. Campbell RS, Sinamban RP, Johannigman JA, et al. Clinical evalu- nic COPD patients with acute respiratory failure. Respiration 2003;
ation of a new closed loop ventilation mode: adaptive supportive 70:355–361.
ventilation (ASV). Crit Care 1999; 3(suppl 1):083. 23. Grasso S, Puntillo F, Mascia L, et al. Compensation for increase in re-
12. Belliato M, Palo A, Pasero D, Iotti GA, Mojoli F, Braschi A. Evaluation spiratory workload during mechanical ventilation. Pressure support
of adaptive support ventilation in paralysed patients and in a physi- versus proportional assist ventilation. Am J Respir Crit Care Med
cal lung model. Int J Artif Organs 2004; 27:709–716. 2000; 161:819–826.
13. Tassaux D, Dalmas E, Gratadour P, Jolliet P. Patient ventilator 24. Wrigge H, Golisch W, Zinserling J, Sydow M, Almeling G, Burchardi

CL EVE L AND CL I NI C J O URNAL O F M E DI CI NE    V O L UM E 76  •   NUM BE R 7   J ULY   2009   429

 MECHANICAL VENTILATION

H. Proportional assist versus pressure support ventilation: effects on adult respiratory distress syndrome. Crit Care 2001; 5:221–226.
breathing pattern and respiratory work of patients with chronic ob- 41. Varpula T, Valta P, Niemi R, Takkunen O, Hynynen M, Pettilä VV.
structive pulmonary disease. Intensive Care Med 1999; 25:790–798. Airway pressure release ventilation as a primary ventilatory mode in
25. Ranieri VM, Giuliani R, Mascia L, et al. Patient ventilator interaction acute respiratory distress syndrome. Acta Anaesthesiol Scand 2004;
during acute hypercapnia: pressure support vs. proportional assist 48:722–731.
ventilation. J Appl Physiol 1996; 81:426–436. 42. Siau C, Stewart TE. Current role of high frequency oscillatory
26. Kondili E, Xirouchaki N, Vaporidi K, Klimathianaki M, Georgopoulos ventilation and airway pressure release ventilation in acute lung
D. Short-term cardiorespiratory effects of proportional assist and injury and acute respiratory distress syndrome. Clin Chest Med 2008;
pressure support ventilation in patients with acute lung injury/acute 29:265–275.
respiratory distress syndrome. Anesthesiology 2006; 105:703–708. 43. Rathgeber J, Schorn B, Falk V, Kazmaier S, Spiegel T, Burchardi H.
27. Xirouchaki N, Kondili E, Vaporidi K, et al. Proportional assist ven- The influence of controlled mandatory ventilation (CMV), intermit-
tilation with load-adjustable gain factors in critically ill patients: tent mandatory ventilation (IMV) and biphasic intermittent positive
comparison with pressure support. Intensive Care Med 2008; airway pressure (BIPAP) on duration of intubation and consumption
34:2026–2034. of analgesics and sedatives. A prospective analysis in 596 patients
28. Bosma K, Ferreyra G, Ambrogio C, et al. Patient ventilator inter- following adult cardiac surgery. Eur J Anaesthesiol 1997; 14:576–
action and sleep in mechanically ventilated patients: pressure 582.
support versus proportional assist ventilation. Crit Care Med 2007; 44. Habashi NM. Other approaches to open lung ventilation: airway
35:1048–1054. pressure release ventilation. Crit Care Med 2005; 33(suppl 3):S228–
29. Sinderby C, Beck J. Proportional assist ventilation and neurally S240.
adjusted ventilatory assist—better approaches to patient ventilator 45. Hess D, Mason S, Branson R. High-frequency ventilation design and
synchrony? Clin Chest Med 2008; 29:329–342. equipment issues. Respir Care Clin North Am 2001; 7:577–598.
30. Stock MC, Downs JB, Frolicher DA. Airway pressure release ventila- 46. Fessler HE, Derdak S, Ferguson ND, et al. A protocol for high fre-
tion. Crit Care Med 1987; 15:462–466. quency oscillatory ventilation in adults: results from a roundtable
31. Baum M, Benzer H, Putensen C, Koller W, Putz G. [Biphasic positive discussion. Crit Care Med 2007; 35:1649–1654.
airway pressure (BIPAP)—a new form of augmented ventilation]. 47. Hamilton PP, Onayemi A, Smyth JA, et al. Comparison of con-
Anaesthesist 1989; 38:452–458. ventional and high-frequency ventilation: oxygenation and lung
32. Seymour CW, Frazer M, Reilly PM, Fuchs BD. Airway pressure release pathology. J Appl Physiol 1983; 55:131–138.
and biphasic intermittent positive airway pressure ventilation: are 48. Sedeek KA, Takeuchi M, Suchodolski K, et al. Open-lung protec-
they ready for prime time? J Trauma 2007; 62:1298–1308. tive ventilation with pressure control ventilation, high-frequency
33. Myers TR, MacIntyre NR. Respiratory controversies in the critical oscillation, and intratracheal pulmonary ventilation results in similar
care setting. Does airway pressure release ventilation offer impor- gas exchange, hemodynamics, and lung mechanics. Anesthesiology
tant new advantages in mechanical ventilator support? Respir Care 2003; 99:1102–1111.
2007; 52:452–458. 49. Imai Y, Nakagawa S, Ito Y, Kawano T, Slutsky AS, Miyasaka K. Com-
34. Neumann P, Golisch W, Strohmeyer A, Buscher H, Burchardi H, Sy- parison of lung protection strategies using conventional and high-
dow M. Influence of different release times on spontaneous breath- frequency oscillatory ventilation. J Appl Physiol 2001; 91:1836–1844.
ing pattern during airway pressure release ventilation. Intensive 50. van Heerde M, Roubik K, Kopelent V, Plötz FB, Markhorst DG.
Care Med 2002; 28:1742–1749. Unloading work of breathing during high-frequency oscillatory
35. Calzia E, Lindner KH, Witt S, et al. Pressure-time product and work ventilation: a bench study. Crit Care 2006; 10:R103.
of breathing during biphasic continuous positive airway pressure 51. Derdak S, Mehta S, Stewart TE, et al; Multicenter Oscillatory
and assisted spontaneous breathing. Am J Respir Crit Care Med Ventilation For Acute Respiratory Distress Syndrome Trial (MOAT)
1994; 150:904–910. Study Investigators. High-frequency oscillatory ventilation for acute
36. Rose L, Hawkins M. Airway pressure release ventilation and biphasic respiratory distress syndrome in adults: a randomized, controlled
positive airway pressure: a systematic review of definitional criteria. trial. Am J Respir Crit Care Med 2002; 166:801–808.
Intensive Care Med 2008; 34:1766–1773. 52. Bollen CW, van Well GT, Sherry T, et al. High-frequency oscillatory
37. Sydow M, Burchardi H, Ephraim E, Zielmann S, Crozier TA. Long- ventilation compared with conventional mechanical ventilation in
term effects of two different ventilatory modes on oxygenation in adult respiratory distress syndrome: a randomized controlled trial
acute lung injury. Comparison of airway pressure release ventilation [ISRCTN24242669]. Crit Care 2005; 9:R430–R439.
and volume-controlled inverse ratio ventilation. Am J Respir Crit 53. Mehta S, Granton J, MacDonald RJ, et al. High frequency oscillatory
Care Med 1994; 149:1550–1556. ventilation in adults: the Toronto experience. Chest 2004; 126:518–
38. Putensen C, Zech S, Wrigge H, et al. Long-term effects of spontane- 527.
ous breathing during ventilatory support in patients with acute 54. Chan KP, Stewart TE, Mehta S. High-frequency oscillatory ventila-
lung injury. Am J Respir Crit Care Med 2001; 164:43–49. tion for adult patients with ARDS. Chest 2007; 131:1907–1916.
39. Davis K Jr, Johnson DJ, Branson RD, Campbell RS, Johannigman JA,
Porembka D. Airway pressure release ventilation. Arch Surg 1993; ADDRESS: Eduardo Mireles-Cabodevila, MD, Department of Pulmonary
128:1348–1352. and Critical Care Medicine, University of Arkansas for Medical Sciences,
40. Kaplan LJ, Bailey H, Formosa V. Airway pressure release ventilation 4301 West Markham Street, Slot 555, Little Rock, AR 77205; e mail mire-
increases cardiac performance in patients with acute lung injury/ [email protected].

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