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EDUARDO MIRELES-CABODEVILA, MD
Department of Pulmonary and Critical Care Medicine,
University of Arkansas for Medical Sciences,
Little Rock, AR
Alternative modes of mechanical
ventilation: A review for the hospitalist
ABSTRACT
Newer ventilators can be set to modes other than the
pressure-control and volume-control modes of older ma-
chines. In this paper, the authors review several of these
alternative modes (adaptive pressure control, adap-
tive support ventilation, proportional assist ventilation,
airway pressure-release ventilation, biphasic positive
airway pressure, and high-frequency oscillatory ventila-
tion), explaining how they work and contrasting their
theoretical benefits and the actual evidence of benefit.
KEY POINTS
The alternative modes of ventilation were developed
to prevent lung injury and asynchrony, promote better
oxygenation and faster weaning, and be easier to use.
However, evidence of their benefit is scant.
Until now, we have lacked a standard nomenclature for
mechanical ventilation, leading to confusion.
Regardless of the mode used, the goals are to avoid
lung injury, keep the patient comfortable, and wean the
patient from mechanical ventilation as soon as possible.
CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 76 • NUMBER 7 JULY 2009
417
T
and computer-
ized control of mechanical ventilators
have made it possible to deliver ventilatory
assistance in new modes. Driving these in-
novations is the desire to prevent ventilator-
induced lung injury, improve patient comfort,
and liberate the patient from mechanical ven-
tilation as soon as possible.
We call these innovations “alternative”
modes to differentiate them from the plain
volume-control and pressure-control modes.
Some clinicians rarely use these new modes,
but in some medical centers they have become
the most common ones used, or are being used
unknowingly (the operator misunderstands
the mode name). The information we provide
on these modes of ventilation is by no means
an endorsement of their use, but rather a tool
to help the clinician understand their physi-
ologic, theoretical, and clinical effects.
We focused on two goals:
Explain what the mode does•
Briey review the theoretical benets and •
the actual evidence supporting these alter-
native modes of ventilation.
STANDARD NOMENCLATURE NEEDED
Since its invention, mechanical ventilation
has been plagued by multiple names being used
to describe the same things. For example, vol-
ume-control ventilation is also called volume-
cycled ventilation, assist-control ventilation,
volume-limited ventilation, and controlled
mechanical ventilation. Similarly, multiple
abbreviations are used, each depending on the
brand of ventilator, and new acronyms have
been added in recent years as new modes have
been developed. The vast number of names
REVIEW
*Mr. Chatburn has disclosed that he has received fees from Cardinal Health for serving on
advisory committees or review panels and from Strategic Dynamics Inc for consulting.
doi:10.3949/ccjm.76a.08043
ENRIQUE DIAZ-GUZMAN, MD
Respiratory Institute,
Cleveland Clinic
GUSTAVO A. HERESI, MD
Respiratory Institute,
Cleveland Clinic
ROBERT L. CHATBURN, BS, RRT-NPS*
Respiratory Institute, Respiratory Therapy Section,
Cleveland Clinic
Abbreviations used in this article
APC—adaptive pressure control
APRV—airway pressure-release ventilation
ASV—adaptive support ventilation
CPAP—continuous positive airway pressure
Fio2—fraction of inspired oxygen
HFOV—high-frequency oscillatory ventilation
PAV—proportional assist ventilation
PEEP—positive end-expiratory pressure
PSV—pressure support ventilation
EDUCATIONAL OBJECTIVE: Readers will be able to explain what some of the new ventilator modes do
and their theoretical and actual benefits
CREDIT
CME
418
CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 76 • NUMBER 7 JULY 2009
MECHANICAL VENTILATION
and modes can confuse even the most sea-
soned critical care physician.
Efforts to establish a common nomencla-
ture are under way.1
WHAT IS A MODE?
A mode of mechanical ventilation has three
essential components:
The control variable•
The breath sequence•
The targeting scheme.•
Similar modes may require more detailed
descriptions to distinguish them, but the basic
function can be explained by these three com-
ponents.
The control variable
In general, inspiration is an active process,
driven by the patient’s effort, the ventilator, or
both, while expiration is passive. For simplic-
ity, in this article a mechanical breath means
the inspiratory phase of the breath.
The machine can only control the volume
(and ow) or the pressure given. The breaths
can be further described on the basis of what
triggers the breath, what limits it (the maxi-
mum value of a control variable), and what
ends (cycles) it.
Therefore, a volume-controlled breath is
triggered by the patient or by the machine,
limited by ow, and cycled by volume (FIGURE
1). A pressure-controlled breath is triggered by
the patient or the machine, limited by pres-
sure, and cycled by time or ow (FIGURE 1).
The breath sequence
There are three possible breath sequences:
Continuous mandatory ventilation, in •
which all breaths are controlled by the
machine (but can be triggered by the pa-
tient)
Intermittent mandatory ventilation, in •
which the patient can take spontaneous
breaths between mandatory breaths
Continuous spontaneous ventilation, in •
which all breaths are spontaneous (TABLE 1).
The targeting scheme
The targeting or feedback scheme refers to
the ventilator settings and programming that
dictate its response to the patient’s lung com-
pliance, lung resistance, and respiratory effort.
The regulation can be as simple as controlling
the pressure in pressure-control mode, or it
can be based on a complicated algorithm.
The mode
name can be
misleading
Tidal volume
set by operator
Inspiratory pressure
set by operator
Airway
pressure
Patient
effort
Larger respiratory
effort
Small respiratory
effort
No respiratory
effort
Volume
Flow
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.
Volume control
Pressure control
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419
MIRELES-CABODEVILA AND COLLEAGUES
In the sections that follow, we describe some
of the available alternative modes of mechani-
cal ventilation. We will explain only the tar-
geting schemes in the modes reviewed (TABLE 1,
TABLE 2), but more information on other target-
ing schemes can be found elsewhere.1,2 We will
focus on evidence generated in adult patients
receiving invasive mechanical ventilation.
ADAPTIVE PRESSURE CONTROL
One of the concerns with pressure-control ven-
tilation is that it cannot guarantee a minimum
minute ventilation (the volume of air that
goes in and out in 1 minute; the tidal volume
× breaths per minute) in the face of changing
lung mechanics or patient effort, or both. To
solve this problem, in 1991 the Siemens Servo
300 ventilator (Siemens, Maquet Critical Care
AB, Solna, Sweden) introduced Pressure Reg-
ulated Volume Control, a mode that delivers
pressure-controlled breaths with a target tidal
volume and that is otherwise known as adap-
tive pressure control (APC) (FIGURE 2).
Other names for adaptive pressure control
Pressure Regulated Volume Control (Ma-•
quet Servo-i, Rastatt, Germany)
A mode
of ventilation
is only as good
as the operator
who applies it
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
pressure-regulated volume control, the inspiratory pressure is adjusted breath to breath to achieve a target
tidal volume)
Optimal—the ventilator uses a mathematical model to calculate the set points to achieve a goal (ie, in
adaptive support ventilation, the pressure, respiratory rate, and tidal volume are adjusted to achieve a goal
minute ventilation)
a Mentioned in this review; for more information, refer to Chatburn1
420
CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 76 • NUMBER 7 JULY 2009
MECHANICAL VENTILATION
AutoFlow (Dräger Medical AG, Lübeck, •
Germany)
Adaptive Pressure Ventilation (Hamilton •
Galileo, Hamilton Medical AG, Bonaduz,
Switzerland)
Volume Control+ (Puritan Bennett, Tyco •
Healthcare; Manseld, MA)
Volume Targeted Pressure Control, Pres-•
sure Controlled Volume Guaranteed (Eng-
ström, General Electric, Madison, WI).
What does adaptive pressure control do?
The APC mode delivers pressure-controlled
breaths with an adaptive targeting scheme
(TABLE 2).
In pressure-control ventilation, tidal vol-
umes depend on the lung’s physiologic mechan-
ics (compliance and resistance) and patient
effort (FIGURE 1). Therefore, the tidal volume
varies with changes in lung physiology (ie,
larger or smaller tidal volumes than targeted).
Mechanical
breaths can be
delivered only
via pressure
control or
volume control
TABLE 2
Classification of modes of ventilation
CONTROL VARIABLE BREATH SEQUENCE TARGETING SCHEME EXAMPLES OF COMMERCIALLY AVAILABLE MODES
Volume Continuous
mandatory
ventilation
Set point Volume control, VC-A/C, CMV, (S)CMV,
Assist/Control
Dual CMV + pressure limited
Adaptive Adaptive flow
Intermittent
mandatory
ventilation
Set point SIMV, VC-SIMV
Dual SIMV + pressure limited
Adaptive AutoMode (VC-VS), mandatory minute volume
Pressure Continuous
mandatory
ventilation
Set point Pressure control, PC-A/C, AC PCV,
high-pressure oscillatory ventilation a
Adaptive Pressure-regulated volume control, a VC+AC a,
AMV+AutoFlow a
Intermittent
mandatory
ventilation
Set point Airway pressure-release ventilation, a
SIMV PCV, BiLevel, a PCV+ a
Adaptive VC+SIMV, V V+SIMV APVSIMV,
SIMV+AutoFlow, Automode (PRVC-VS)
Optimal Adaptive support ventilation a
Continuous
spontaneous
ventilation
Set point Continuous positive airway pressure,
pressure support
Dual Volume assured pressure support,
volume augment
Servo Proportional assist ventilation, a automatic
tube compensation
Adaptive Volume support
Intelligent SmartCare
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
CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 76 • NUMBER 7 JULY 2009
421
MIRELES-CABODEVILA AND COLLEAGUES
To overcome this effect, a machine in APC
mode adjusts the inspiratory pressure to deliver
the set minimal target tidal volume. If tidal vol-
ume increases, the machine decreases the in-
spiratory pressure, and if tidal volume decreases,
the machine increases the inspiratory pressure.
However, if the patient effort is large enough,
the tidal volume will increase in spite of decreas-
ing the inspiratory pressure (FIGURE 2). The adjust-
ments to the inspiratory pressure occur after the
tidal volume is off-target in a number of breaths.
Common sources of confusion
with adaptive pressure control
First, APC is not a volume-control mode. In
volume control, the tidal volume does not
change; in APC the tidal volume can increase
or decrease, and the ventilator will adjust the
ination pressure to achieve the target volume.
Thus, APC guarantees an average minimum
tidal volume but not a maximum tidal volume.
Second, a characteristic of pressure con-
trol (and hence, APC) is that the ow of gas
varies to maintain constant airway pressure
(ie, maintain the set inspiratory pressure).
This characteristic allows a patient who gen-
erates an inspiratory effort to receive ow as
demanded, which is likely more comfortable.
This is essentially different from volume con-
trol, in which ow is set by the operator and
hence is xed. Thus, if the patient effort is
strong enough (FIGURE 1), this leads to what is
called ow asynchrony, in which the patient
does not get the ow asked for in a breath.
Ventilator settings
in adaptive pressure control
Ventilator settings in APC are:
Tidal volume•
Time spent in inspiration (inspiratory time)•
Frequency•
Fraction of inspired oxygen (Fi• 2)
Positive end-expiratory pressure (PEEP).•
Some ventilators also require setting the
speed to reach the peak pressure (also known
as slope percent or inspiratory rise time).
Clinical applications
of adaptive pressure control
This mode is designed to maintain a consis-
tent tidal volume during pressure-control
ventilation and to promote inspiratory ow
synchrony. It is a means of automatically re-
ducing ventilatory support (ie, weaning) as
the patient’s inspiratory effort becomes stron-
ger, as in awakening from anesthesia.
The response of
the ventilator
to the patient is
regulated in a
number of ways
Target tidal volume
set by operator
Target tidal volume
set by operator
Inspiratory pressure is
adjusted to maintain
a target tidal volume
Larger respiratory
effort
Small respiratory
effort
No respiratory
effort
Airway
pressure
Patient
effort
Volume
Flow
Pressure
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.
Adaptive support ventilation
Adaptive pressure control
422
CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 76 • NUMBER 7 JULY 2009
MECHANICAL VENTILATION
APC adjusts
the inspira-
tory pressure
to deliver the
set target tidal
volume
APC may not be ideal for patients who
have an inappropriately increased respira-
tory drive (eg, in severe metabolic acidosis),
since the inspiratory pressure will decrease to
maintain the targeted average tidal volume,
inappropriately shifting the work of breathing
onto the patient.
Theoretical benefits
of adaptive pressure control
APC guarantees a minimum average tidal vol-
ume (unless the pressure alarm threshold is set
too low, so that the target tidal volume is not
delivered). Other theoretical benets are ow
synchrony, less ventilator manipulation by the
operator, and automatic weaning of ventilator
support.
Evidence of benefit
of adaptive pressure control
Physiologic benets. This mode has lower
peak inspiratory pressures than does volume-
control ventilation,3,4 which is often reported
as a positive nding. However, in volume-
control mode (the usual comparator), the
peak inspiratory pressure is a manifestation of
both resistance and compliance. Hence, peak
inspiratory pressure is expected to be higher
but does not reect actual lung-distending
pressures. It is the plateau pressure, a manifes-
tation of lung compliance, that is related to
lung injury.
Patient comfort. APC may increase the
work of breathing when using low tidal vol-
ume ventilation and when there is increased
respiratory effort (drive).5 Interestingly, APC
was less comfortable than pressure support
ventilation in a small trial.6
Outcomes have not been studied.7
Adaptive pressure control: Bottom line
APC is widely available and widely used,
sometimes unknowingly (eg, if the operator
thinks it is volume control). It is relatively
easy to use and to set; however, evidence of its
benet is scant.
ADAPTIVE SUPPORT VENTILATION
Adaptive support ventilation (ASV) evolved
as a form of mandatory minute ventilation
implemented with adaptive pressure control.
Mandatory minute ventilation is a mode that
allows the operator to preset a target minute
ventilation, and the ventilator then supplies
mandatory breaths, either volume- or pres-
sure-controlled, if the patient’s spontaneous
breaths generate a lower minute ventilation.
ASV automatically selects the appropri-
ate tidal volume and frequency for mandatory
breaths and the appropriate tidal volume for
spontaneous breaths on the basis of the respi-
ratory system mechanics and target minute
alveolar ventilation.
Described in 1994 by Laubscher et al,8,9
ASV became commercially available in 1998
in Europe and in 2007 in the United States
(Hamilton Galileo ventilator, Hamilton Med-
ical AG). This is the rst commercially avail-
able ventilator that uses an “optimal” target-
ing scheme (see below).
What does adaptive support ventilation do?
ASV delivers pressure-controlled breaths us-
ing an adaptive (optimal) scheme (TABLE 2).
“Optimal,” in this context, means minimizing
the mechanical work of breathing: the ma-
chine selects a tidal volume and frequency that
the patient’s brain would presumably select if
the patient were not connected to a ventila-
tor. This pattern is assumed to encourage the
patient to generate spontaneous breaths.
The ventilator calculates the normal re-
quired minute ventilation based on the pa-
tient’s ideal weight and estimated dead space
volume (ie, 2.2 mL/kg). This calculation
represents 100% of minute ventilation. The
clinician at the bedside sets a target percent
of minute ventilation that the ventilator will
support—higher than 100% if the patient has
increased requirements due, eg, to sepsis or in-
creased dead space, or less than 100% during
weaning.
The ventilator initially delivers test
breaths, in which it measures the expiratory
time constant for the respiratory system and
then uses this along with the estimated dead
space and normal minute ventilation to calcu-
late an optimal breathing frequency in terms
of mechanical work.
The optimal or target tidal volume is calcu-
lated as the normal minute ventilation divid-
ed by the optimal frequency. The target tidal
volume is achieved by the use of APC (see
CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 76 • NUMBER 7 JULY 2009
423
MIRELES-CABODEVILA AND COLLEAGUES
above) (FIGURE 2). This means that the pressure
limit is automatically adjusted to achieve an
average delivered tidal volume equal to the
target. The ventilator continuously monitors
the respiratory system mechanics and adjusts
its settings accordingly.
The ventilator adjusts its breaths to avoid
air trapping by allowing enough time to ex-
hale, to avoid hypoventilation by delivering
tidal volume greater than the dead space, and
to avoid volutrauma by avoiding large tidal
volumes.
Ventilator settings
in adaptive support ventilation
Ventilator settings in ASV are:
Patient height (to calculate the ideal body •
weight)
Sex•
Percent of normal predicted minute ven-•
tilation goal
Fi• 2
PEEP.•
Clinical applications
of adaptive support ventilation
ASV is intended as a sole mode of ventila-
tion, from initial support to weaning.
Theoretical benefits
of adaptive support ventilation
In theory, ASV offers automatic selection of
ventilator settings, automatic adaptation to
changing patient lung mechanics, less need
for human manipulation of the machine, im-
proved synchrony, and automatic weaning.
Evidence of benefit
of adaptive support ventilation
Physiologic benets. Ventilator settings
are adjusted automatically. ASV selects dif-
ferent tidal volume-respiratory rate combina-
tions based on respiratory mechanics in passive
and paralyzed patients.10–12 In actively breath-
ing patients, there was no difference in the
ventilator settings chosen by ASV for differ-
ent clinical scenarios (and lung physiology).10
Compared with pressure-controlled intermit-
tent mandatory ventilation, with ASV, the
inspiratory load is less and patient-ventilator
interaction is better.13
Patient-ventilator synchrony and com-
fort have not been studied.
Outcomes. Two trials suggest that
ASV may decrease time on mechanical
ventilation.14,15 However, in another trial,16
compared with a standard protocol, ASV led
to fewer ventilator adjustments but achieved
similar postsurgical weaning outcomes. The
effect of this mode on the death rate has not
been examined.17,18
Adaptive support ventilation: Bottom line
ASV is the rst commercially available mode
that automatically selects all the ventilator
settings except PEEP and F2. These seem
appropriate for different clinical scenarios
in patients with poor respiratory effort or in
paralyzed patients. Evidence of the effect in
actively breathing patients and on outcomes
such as length of stay or death is still lack-
ing.
PROPORTIONAL ASSIST VENTILATION
Patients who have normal respiratory drive
but who have difculty sustaining adequate
spontaneous ventilation are often subjected
to pressure support ventilation (PSV), in
which the ventilator generates a constant
pressure throughout inspiration regardless of
the intensity of the patient’s effort.
In 1992, Younes and colleagues19,20 devel-
oped proportional assist ventilation (PAV) as
an alternative in which the ventilator gen-
erates pressure in proportion to the patient’s
effort. PAV became commercially available
in Europe in 1999 and was approved in the
United States in 2006, available on the Puri-
tan Bennett 840 ventilator (Puritan Bennett
Co, Boulder, CO). PAV has also been used for
noninvasive ventilation, but this is not avail-
able in the United States.
Other names for proportional
assist ventilation
Proportional Pressure Support (Dräger Medi-
cal; not yet available in the United States).
What does proportional
assist ventilation do?
This mode delivers pressure-controlled
breaths with a servo control scheme (TABLE 2).
To better understand PAV, we can compare
APC
is not a
volume-
controlled
mode
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CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 76 • NUMBER 7 JULY 2009
MECHANICAL VENTILATION
ASV selects
a tidal volume
and frequency
that the
patient’s
brain would
presumably
select
it with PSV. With PSV, the pressure applied by
the ventilator rises to a preset level that is held
constant (a set-point scheme) until a cycling
criterion (a percent of the maximum inspirato-
ry ow value) is reached. The inspiratory ow
and tidal volume are the result of the patient’s
inspiratory effort, the level of pressure applied,
and the respiratory system mechanics.
In contrast, during PAV, the pressure applied
is a function of patient effort: the greater the
inspiratory effort, the greater the increase in ap-
plied pressure (servo targeting scheme) (FIGURE
3). The operator sets the percentage of support
to be delivered by the ventilator. The ventila-
tor intermittently measures the compliance and
resistance of the patient’s respiratory system and
the instantaneous patient-generated ow and
volume, and on the basis of these it delivers a
proportional amount of inspiratory pressure.
In PAV, as in PSV, all breaths are spontane-
ous (TABLE 1). The patient controls the timing
and size of the breath. There are no preset pres-
sure, ow, or volume goals, but safety limits on
the volume and pressure delivered can be set.
Ventilator settings
in proportional assist ventilation
Ventilator settings in PAV are:
Airway type (endotracheal tube, trache-•
ostomy)
Airway size (inner diameter)•
Percentage of work supported (assist range •
5%–95%)
Tidal volume limit•
Pressure limit•
Expiratory sensitivity (normally, as inspi-•
ration ends, ow should stop; this param-
eter tells the ventilator at what ow to end
inspiration).
Caution when assessing the literature.
Earlier ventilator versions, ie, Dräger and Man-
itoba (University of Manitoba, Winnipeg, MB,
Canada), which are not available in the United
States, required the repeated calculation of the
respiratory system mechanics and the manual
setting of ow and volume assists (amplication
factors) independently. To overcome this limi-
tation, new software automatically adjusts the
ow and volume amplication to support the
loads imposed by the automatically measured
values of resistance and elastance (inverse of
compliance) of the respiratory system.21 This
software is included in the model (Puritan Ben-
nett) available in the United States.
Clinical applications
of proportional assist ventilation
The PAV mode is indicated for maximizing
ventilator patient synchrony for assisted spon-
taneous ventilation.
PAV is contraindicated in patients with
respiratory depression (bradypnea) or large air
leaks (eg, bronchopleural stulas). It should
be used with caution in patients with severe
hyperination, in which the patient may still
be exhaling but the ventilator doesn’t recog-
nize it. Another group in which PAV should
be used with caution is those with high ven-
tilatory drives, in which the ventilator over-
estimates respiratory system mechanics. This
situation can lead to overassistance due to the
“runaway phenomenon,” in which the venti-
Ventilator measuring
respiratory system
characteristics
Flow, pressure, and volume delivered
by the ventilator are adjusted
proportionally to patient effort
Patient
effort
Volume
Flow
Pressure
FIGURE 3. In proportional assist ventilation, the flow, pressure, and volume delivered are adjusted
proportionally to the patient’s effort.
Proportional assist ventilation
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MIRELES-CABODEVILA AND COLLEAGUES
In PAV, the
greater the
inspiratory
effort, the
greater the
increase in
applied
pressure
lator continues to provide support even if the
patient has stopped inspiration.22
Theoretical benefits
of proportional assist ventilation
In theory, PAV should reduce the work of
breathing, improve synchrony, automatically
adapt to changing patient lung mechanics and
effort, decrease the need for ventilator inter-
vention and manipulation, decrease the need
for sedation, and improve sleep.
Evidence of benefit
of proportional assist ventilation
Physiologic benets. PAV reduces the work
of breathing better than PSV,21 even in the
face of changing respiratory mechanics or in-
creased respiratory demand (hypercapnia).23–25
The hemodynamic prole is similar to that in
PSV. Tidal volumes are variable; however, in
recent reports the tidal volumes were within
the lung-protective range (6–8 mL/kg, plateau
pressure < 30 cm H20).26,27
Comfort. PAV entails less patient effort
and discomfort that PSV does.23,25 PAV sig-
nicantly reduces asynchrony,27 which in turn
may favorably affect sleep in critically ill pa-
tients.28
Outcomes. The probability of spontaneous
breathing without assistance was signicantly
better in critically ill patients ventilated with
PAV than with PSV. No trial has reported the
effect of PAV on deaths.27,29
Proportional assist ventilation: Bottom line
Extensive basic research has been done with
PAV in different forms of respiratory failure,
such as obstructive lung disease, acute respira-
tory distress syndrome (ARDS), and chronic re-
spiratory failure. It fullls its main goal, which is
to improve patient-ventilator synchrony. Clini-
cal experience with PAV in the United States is
limited, as it was only recently approved.
AIRWAY PRESSURE-RELEASE
VENTILATION AND
BIPHASIC POSITIVE AIRWAY PRESSURE
Airway pressure-release ventilation (APRV)
was described in 1987 by Stock et al30 as a
mode for delivering ventilation in acute lung
injury while avoiding high airway pressures.
APRV combines high constant positive airway
pressure (improving oxygenation and promot-
ing alveolar recruitment) with intermittent
releases (causing exhalation).
In 1989, Baum et al31 described bipha-
sic positive airway pressure ventilation as a
mode in which spontaneous ventilation could
be achieved at any point in the mechanical
ventilation cycle—inspiration or exhalation
(FIGURE 4). The goal was to allow unrestricted
spontaneous breathing to reduce sedation and
promote weaning. These modes are conceptu-
ally the same, the main difference being that
the time spent in low pressure (Tlow; see be-
low) is less than 1.5 seconds for APRV. Other-
wise, they have identical characteristics, thus
allowing any ventilator with the capability
of delivering APRV to deliver biphasic posi-
tive airway pressure, and vice versa. Machines
with these modes became commercially avail-
able in the mid 1990s.
Other names for biphasic positive airway
pressure
Other names for biphasic positive airway pres-
sure are:
BiLevel (Puritan Bennett)•
BIPAP (Dräger Europe)•
Bi Vent (Siemens)•
BiPhasic (Avea, Cardinal Health, Inc, •
Dublin, OH)
PCV+ (Dräger Medical)•
DuoPAP (Hamilton).•
Caution—name confusion. In North
America, BiPAP (Respironics, Murrysville,
PA) and BiLevel are used to refer to noninva-
sive modes of ventilation.
APRV has no other name.
What do these modes do?
These modes deliver pressure-controlled,
time-triggered, and time-cycled breaths us-
ing a set-point targeting scheme (TABLE 2). This
means that the ventilator maintains a con-
stant pressure (set point) even in the face of
spontaneous breaths.
Caution—source of confusion. The term
continuous positive airway pressure (CPAP)
is often used to describe this mode. However,
CPAP is pressure that is applied continuously
at the same level; the patient generates all
the work to maintain ventilation (“pressure-
426
CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 76 • NUMBER 7 JULY 2009
MECHANICAL VENTILATION
controlled continuous spontaneous ventila-
tion” in the current nomenclature). In APRV,
the airway pressure is intermittently released
and reapplied, generating a tidal volume that
supports ventilation. In other words, this is
a pressure-controlled breath with a very pro-
longed inspiratory time and a short expiratory
time in which spontaneous ventilation is pos-
sible at any point (“pressure-controlled inter-
mittent mandatory ventilation” in the current
nomenclature).
How these modes are set in the ventilator
may also be a source of confusion. To describe
the time spent in high and low airway pres-
sures, we use the terms Thigh and Tlow, respec-
tively. By convention, the difference between
APRV and biphasic mode is the duration of
Tlow (< 1.5 sec for APRV).
Similarly, Phigh and Plow are used to describe
the high and low airway pressure. To better un-
derstand this concept, you can create the same
mode in conventional pressure-control venti-
lation by thinking of the Thigh as the inspiratory
time, the Tlow as the expiratory time, the Phigh as
inspiratory pressure, and the Plow as PEEP.
Hence, APRV is an extreme form of in-
verse ratio ventilation, with an inspiration-to-
expiration ratio of 4:1. This means a patient
spends most of the time in Phigh and Thigh, and
exhalations are short (Tlow and Plow). In con-
trast, the biphasic mode uses conventional
inspiration-expiration ratios (FIGURE 4).
As with any form of pressure control, the
tidal volume is generated by airway pressure
rising above baseline (ie, the end-expiratory
value). Hence, to ensure an increase in minute
ventilation, the mandatory breath rate must
be increased (ie, decreasing Thigh, Tlow, or both)
or the tidal volume must be increased (ie, in-
creasing the difference between Phigh and Plow).
This means that in APRV the Tlow has to hap-
pen more often (by increasing the number of
breaths) or be more prolonged (allowing more
air to exhale). Because unrestricted spontane-
ous breaths are permitted at any point of the
cycle, the patient contributes to the total min-
ute ventilation (usually 10%–40%).
In APRV and biphasic mode, the opera-
tor’s set time and pressure in inspiration and
expiration will be delivered regardless of the
patient’s breathing efforts—the patient’s spon-
taneous breath does not trigger a mechanical
breath. Some ventilators have automatic ad-
justments to improve the trigger synchrony.
Spontaneous breaths occur
at any point without altering
the ventilator-delivered
breaths
Thigh:Tlow = 4:1Phigh and Thigh Plow and Tlow
Thigh:Tlow = 1:1–4
Phigh and Thigh Plow and Tlow
Volume
Pressure
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.
Biphasic positive airway pressure
Airway pressure-release ventilation
APRV allows
spontaneous
breaths at any
point in the
cycle
CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 76 • NUMBER 7 JULY 2009
427
MIRELES-CABODEVILA AND COLLEAGUES
Ventilator settings
in APRV and biphasic mode
These modes require the setting of two pressure
levels (Phigh and Plow) and two time durations
(Thigh and Tlow). One can add pressure support
or automatic tube compensation to assist spon-
taneous breaths. The difference in Tlow gener-
ates differences in the Thigh:Tlow ratio: APRV
has a short Tlow (an inspiration-expiration ra-
tio of 4:1). Biphasic mode has a conventional
inspiration-expiration ratio of 1:1 to 1:4.
Clinical applications
APRV is used in acute lung injury and
ARDS. This mode should be used with cau-
tion or not at all in patients with obstructive
lung disease or inappropriately increased re-
spiratory drive.32–35
Biphasic mode is intended for both venti-
lation and weaning. In a patient who has poor
respiratory effort or who is paralyzed, bipha-
sic is identical to pressure-control/continuous
mandatory ventilation.
Theoretical benefits
of APRV and biphasic mode
Multiple benets have been ascribed to these
modes. In theory, APRV will maximize and
maintain alveolar recruitment, improve oxy-
genation, lower ination pressures, and decrease
overination. Both APRV and biphasic, by pre-
serving spontaneous breathing, will improve
ventilation-perfusion matching and gas diffusion,
improve the hemodynamic prole (less need for
vasopressors, higher cardiac output, reduced ven-
tricular workload, improved organ perfusion),
and improve synchrony (decrease the work of
breathing and the need for sedation).
Evidence of benefit of APRV
and biphasic mode
APRV and biphasic are different modes.
However studies evaluating their effects are
combined. This is in part the result of the no-
menclature confusion and different practice in
different countries.36
Physiologic benets. In studies, sponta-
neous breaths contributed to 10% to 40% of
minute ventilation,37,38 improved ventilation
of dependent areas of the lung, improved ven-
tilation-perfusion match and recruitment,39
and improved hemodynamic prole.40
Patient comfort. These modes are
thought to decrease the need for analgesia
and sedation,38 but a recent trial showed no
difference with pressure-controlled intermit-
tent mandatory ventilation.41 Patient venti-
lator synchrony and comfort have not been
studied.32,42
Outcomes. In small trials, these modes
made no difference in terms of deaths, but
they may decrease the length of mechanical
ventilation.38,41,43,44
APRV and biphasic mode: Bottom line
Maintaining spontaneous breathing while on
mechanical ventilation has hemodynamic and
ventilatory benets.
APRV and biphasic mode are not the same
thing. APRV’s main goal is to maximize mean
airway pressure and, hence, lung recruitment,
whereas the main goal of the biphasic mode is
synchrony.
There is a plethora of ventilator settings and
questions related to physiologic effects.33,34,36
Although these modes are widely used in
some centers, there is no evidence yet that
they are superior to conventional volume- or
pressure-control ventilation with low tidal vol-
ume for ARDS and acute lung injury. There is
no conclusive evidence that these modes im-
prove synchrony, time to weaning, or patient
comfort.
HIGH-FREQUENCY
OSCILLATORY VENTILATION
High-frequency oscillatory ventilation
(HFOV) was rst described and patented in
1952 by Emerson and was clinically developed
in the early 1970s by Lunkenheimer.45
The goal of HFOV is to minimize lung
injury; its characteristics (discussed below)
make it useful in patients with severe ARDS.
The US Food and Drug Administration ap-
proved it for infants in 1991 and for children
in 1995. The adult model has been available
since 1993, but it was not approved until 2001
(SensorMedics 3100B, Cardinal Health, Inc).
Other names for high-frequency
oscillatory ventilation
While HFOV has no alternative names, the
following acronyms describe similar modes:
Maintaining
spontaneous
breathing while
on mechanical
ventilation has
benefits
428
CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 76 • NUMBER 7 JULY 2009
MECHANICAL VENTILATION
HFPPV (high-frequency positive pressure •
ventilation)
HFJV (high-frequency jet ventilation)•
HFFI (high-frequency ow interruption)•
HFPV (high-frequency percussive ventila-•
tion)
HFCWO (high-frequency chest wall oscil-•
lation).
All of these modes require different spe-
cialized ventilators.
What does high-frequency
oscillatory ventilation do?
Conceptually, HFOV is a form of pressure-
controlled intermittent mandatory venti-
lation with a set-point control scheme. In
contrast to conventional pressure-controlled
intermittent mandatory ventilation, in which
relatively small spontaneous breaths may be
superimposed on relatively large mandatory
breaths, HFOV superimposes very small man-
datory breaths (oscillations) on top of sponta-
neous breaths.
HFOV can be delivered only with a spe-
cial ventilator. The ventilator delivers a
constant ow (bias ow), while a valve cre-
ates resistance to maintain airway pressure,
on top of which a piston pump oscillates at
frequencies of 3 to 15 Hz (160–900 breaths/
minute). This creates a constant airway pres-
sure with small oscillations (FIGURE 5); often,
clinicians at the bedside look for the “chest
wiggle” to assess the appropriate amplitude
settings, although this has not been system-
atically studied.
Adult patients are usually paralyzed or
deeply sedated, since deep spontaneous
breathing will trigger alarms and affect venti-
lator performance.
To manage ventilation (CO2 clearance),
one or several of the following maneuvers can
be done: decrease the oscillation frequency,
increase the amplitude of the oscillations, in-
crease the inspiratory time, or increase bias
ow (while allowing an endotracheal tube cuff
leak). Oxygenation adjustments are controlled
by manipulating the mean airway pressure and
the F2.
Ventilator settings
in high-frequency oscillatory ventilation
Ventilator settings in HFOV are46:
Airway pressure amplitude (delta P or •
power)
Mean airway pressure•
Percent inspiration•
Inspiratory bias ow•
F• 2.
Clinical applications
of high-frequency oscillatory ventilation
This mode is usually reserved for ARDS pa-
tients for whom conventional ventilation is
failing. A recently published protocol46 sug-
gests considering HFOV when there is oxy-
genation failure (F2 ≥ 0.7 and PEEP ≥ 14 cm
H2O) or ventilation failure (pH < 7.25 with
tidal volume ≥ 6 mL/kg predicted body weight
and plateau airway pressure ≥ 30 cm H2O).
This mode is contraindicated when
there is known severe airow obstruction or
intracranial hypertension.
Frequency
Mean airway
pressure
Tidal volume
Airway pressure
amplitude (power)
FIGURE 5. High-frequency oscillatory ventilation delivers very small mandatory breaths (oscillations)
at frequencies of up to 900 breaths per minute.
The goal
of HFOV
is to minimize
lung injury,
especially
in ARDS
High-frequency oscillatory ventilation
CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 76 • NUMBER 7 JULY 2009
429
MIRELES-CABODEVILA AND COLLEAGUES
Theoretical benefits
of high-frequency oscillatory ventilation
Conceptually, HFOV can provide the high-
est mean airway pressure paired with the low-
est tidal volume of any mode. These benets
might make HFOV the ideal lung-protective
ventilation strategy.
Evidence of benefit
of high-frequency oscillatory ventilation
Physiologic benets. Animal models have
shown less histologic damage and lung inam-
mation with HFOV than with high-tidal-
volume conventional ventilation47,48 and low-
tidal-volume conventional ventilation.49
Patient comfort has not been studied.
However, current technology does impose
undue work of breathing in spontaneously
breathing patients.50
Outcomes. Several retrospective case se-
ries have described better oxygenation with
HFOV as rescue therapy for severe ARDS
than with conventional mechanical ventila-
tion. Two randomized controlled trials have
studied HFOV vs high-tidal-volume conven-
tional mechanical ventilation for early severe
ARDS; HFOV was safe but made no differ-
ence in terms of deaths.42,51–54
High-frequency oscillatory ventilation:
Bottom line
In theory, HFOV provides all the benets of an
ideal lung-protective strategy, at least for para-
lyzed or deeply sedated patients. Animal stud-
ies support these concepts. In human adults,
HFOV has been shown to be safe and to pro-
vide better oxygenation but no improvement
in death rates compared with conventional
mechanical ventilation. Currently, HFOV is
better reserved for patients with severe ARDS
for whom conventional mechanical ventila-
tion is failing.
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ADDRESS: Eduardo Mireles-Cabodevila, MD, Department of Pulmonary
and Critical Care Medicine, University of Arkansas for Medical Sciences,
4301 West Markham Street, Slot 555, Little Rock, AR 77205; e mail mire-
lee@uams.edu.
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