P a t i e n t - Ve n t i l a t o r

S y n c h ro n y
Kevin C. Doerschug, MD, MS, FCCP

KEYWORDS
 Mechanical ventilation  Respiratory failure  Dysychrony  Asynchrony

KEY POINTS
 Patient-ventilator asynchrony develops when a patient’s respiratory drive is not met with sufficient
output from the ventilator.
 Patient-ventilator asynchrony causes injurious ventilation and can contribute to patient self-
induced lung injury.
 Ventilator waveforms provide valuable information with which to diagnose patient-ventilator asyn-
chrony.

INTRODUCTION main determinant of respiratory drive. Indeed,

Mechanical ventilation of critically ill patients can
be delivered precisely to a patient made passive
through deep sedation or neuromuscular
blockade. However, sedation and paralysis place
patients at risk of atrophy of the diaphragm,1,2
persistent neuromuscular weakness, prolonged
ventilation,3 and death.4 In contrast, assist (or sup-
port) modes allow for patient-ventilator interac-
tions, which, if synchronized, help preserve
respiratory muscle function and generally require
less sedation. Many critically ill patients, however,
possess an elevated respiratory drive. If that drive
is not met with sufficient output from mechanical
ventilation, patient-ventilator asynchrony ensues.
ICU clinicians must be skilled in the recognition
of asynchrony, identification of its causes, and
management of the ventilator to reduce
asynchrony.
CAUSES OF ASYNCHRONY
Patient Factors Contributing to Asynchrony
Critical illness results in many perturbations known
to increase respiratory drive, and a thorough dis-
cussion of the modulation of respiratory drive is
complex and beyond the scope of this review.
increasing PaCO2 leads to increasing respiratory
effort by the patient.5 However, several patient
factors relevant to critical illness contribute to a
persistently elevated respiratory drive and
patient-ventilator asynchrony even when blood
gases are normalized. Inflammation stimulates
respiratory drive even in the absence of fever.6
Pain, metabolic acidosis, pulmonary deadspace,7
and altered chemoreceptor responses8 also alter
respiratory drive and are highly relevant to critical
illness. Importantly, providers should be careful
to not consider asynchrony as a sign of discom-
fort, as this thought process may lead to increases
in comfort measures (ie, sedation and analgesia)
rather than adjustment of the ventilator to match
an unconscious drive to breathe more.
Ventilator Factors Contributing to Asynchrony
Although respiratory drive is usually increased in
critical illness, factors of mechanical ventilation
also contribute to ventilator output that is insuffi-
cient for a patient’s respiratory drive. Lung-
protective ventilation with tidal volumes of 6 to
8 cc/kg ideal body weight improves outcomes in
patients with9 and without acute respiratory
chestmed.theclinics.com

Arterial gas content, especially partial pressure of distress syndrome (ARDS).10 However, a decrease
carbon dioxide (PaCO2), is often considered a in tidal volume increases respiratory drive11 and

Department of Internal Medicine, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City,
IA 52246, USA
E-mail address: kevin-doerschug@uiowa.edu

Clin Chest Med 43 (2022) 511–518

https://doi.org/10.1016/j.ccm.2022.05.005
0272-5231/22/Ó 2022 Published by Elsevier Inc.
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512 Doerschug
asynchrony,12 presumably mediated through lung
stretch receptor reflexes.13 Additionally, insuffi-
cient positive end-expiratory pressure (PEEP)
may increase asynchrony and lung injury.14
HARMFUL EFFECTS OF ASYNCHRONY
Asynchrony leads to several, sometimes clinically
subtle, undesired effects. At a basic level, asyn-
chrony is an increased work of breathing with the
potential for depletion of energy stores and pro-
duction of lactic acid within respiratory muscles.
Excessive work of breathing may lead to dia-
phragm dysfunction, atrophy, and an increased
risk of death.4 Asynchrony resulting in stacked
breaths before exhalation of the first breath leads
to a likely injurious tidal volume approaching
10 cc/kg.15 Excessively negative pleural pressures
create transpulmonary pressures that are not re-
flected by inspiratory pressures delivered by the
ventilator, but result in injurious tidal volumes.
However, even normal tidal volumes generated
from excessive spontaneous efforts result in
occult pendelluft, or regional overdistension, of
the already injured lung.16,17 Through these mech-
anisms, patient-ventilator asynchrony may pre-
cede patient decompensation,18 contribute to
failed liberation trials,19 result in prolonged me-
chanical ventilation,20 and contribute to patient
mortality.21
CLASSIFICATION OF ASYNCHRONY
Patient-ventilator asynchronies can be classified
by when they occur during the respiratory cycle.
Asynchronies may occur during breath initiation
(trigger asynchrony), during breath delivery (flow
asynchrony), and the transition from inspiratory
phase to expiratory phase (cycle asynchrony).
Trigger Asynchrony
Ineffective trigger asynchrony is defined as a pa-
tient inspiratory effort that does not trigger a breath
supported by the ventilator. A spontaneous breath
during mechanical ventilation is triggered when the
diaphragm decreases pleural pressure below the
trigger threshold of the ventilator, which is
measured at the airway opening. Weak inspiratory
strength (eg, neuromuscular weakness) or effort
(sedation) may not lower pleural pressure suffi-
ciently and thus fail to trigger the ventilator. Alter-
natively, intrinsic PEEP increases alveolar
pressure, and normal respiratory muscles may
fail to induce the larger drop in pleural pressure
necessary to reach the trigger threshold. Accord-
ingly, trigger asynchrony is present in nearly all pa-
tients with COPD,22 but is commonly seen in
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patients without obstructive lung disease; it can
occur in any mode. Importantly, trigger asyn-
chrony is associated with prolonged liberation
from mechanical ventilation.23 Ineffective trigger
may be recognized by a deflection of the
pressure-time curve without an accompanying in-
crease in volume. More subtly, the expiratory flow
may demonstrate an upward deflection from the
normally decaying flow pattern.(Fig. 1). It is logical
that failed triggers are often preceded by factors
that increase intrinsic PEEP such as breaths that
are relatively larger or with shorter respiratory cy-
cle and expiratory times.24
Autotriggering occurs when an assisted (not
controlled) breath is triggered and delivered by
the ventilator without patient effort, and often indi-
cates circuit leaks or hyperdynamic cardiac
impulses.25
Reverse triggering is defined as entrainment of
diaphragmatic muscles of a deeply sedated pa-
tient, whereby the patient is triggered to initiate
an assisted breath by a controlled breath delivered
by the ventilator.26
Flow Asynchrony
After a breath is triggered, the ventilator delivers a
breath to the targeted pressure or flow. Flow asyn-
chrony develops when the flow delivered by the
ventilator is inadequate for the patient’s needs,
leading to increased patient inspiratory effort.27
Most critically ill patients have elevated respiratory
drive, thus their needs for inspiratory flow may
differ significantly from healthy individuals. Flow
asynchrony is recognized by a downward deflec-
tion in the pressure-time waveforms in flow-
targeted (eg, volume-assist control, Fig. 2) and
pressure-targeted modes (Fig. 3), reflecting the
increasingly negative pleural pressure generated
by the actively breathing patient. Breath-by-
breath variations of the pressure-time waveforms
are indicative of variable patient effort and thus
signal flow asynchronies.
Cycle Asynchrony
The mechanical ventilator switches from inspira-
tion to expiration in most ventilator modes accord-
ing to a set inspiratory time. Cycle asynchrony
ensues when this machine inspiratory time does
not match the patient’s neural inspiratory time.
Observers of the flow-time curves will recognize
cycle asynchrony by the upper (less negative)
deflection in early expirations, indicating ongoing
patient inspiratory effort (Fig. 4). The most obvious
form of cycle asynchrony occurs when patient
inspiratory effort is sufficient to generate a second
stacked breath early in the expiratory phase.

Stacked breaths are common during ventilation
with lung-protective tidal volumes that require
short set inspiratory times.15 However, stacked
breaths paradoxically result in tidal volumes
approaching 10 cc/kg ideal body weight and are
likely injurious rather than protective.
Pressure support modes of ventilation do not
have a set inspiratory time, but instead terminate
breaths once flow decays below a threshold set
as a percentage of peak inspiratory flow. Airway
resistance caused by obstructive lung disease
may lead to a slower decay of inspiratory flow,
which in turn prolongs inspiration and potentially
increases tidal volume. If the inspiratory time of
the ventilator is prolonged beyond neural inspira-
tory time, the patient may initiate active exhalation
and thus have increased work or breathing.
MONITORING PATIENT-VENTILATOR
SYNCHRONY
Waveforms
Given the previously stated harms of patient-
ventilator asynchronies, providers must be able
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Patient-Ventilator Synchrony 513
Fig. 1. Trigger asynchrony. Ineffective
trigger is depicted in the pressure- (up-
per) and flow (lower)-vs-time wave-
forms. Arrows denote fluctuations in
the waveform indicating patient effort
that do not trigger a breath from the
ventilator.
to recognize asynchrony. Fortunately, asynchrony
can be detected and monitored through various
methods. Practiced clinicians habitually evaluate
not just numerical data from mechanical ventila-
tors but also scrupulously inspect ventilator graph-
ical waveforms in search of signs of asynchrony.28
This method has the advantage of being noninva-
sive, requiring no additional resources, and univer-
sally available in modern ventilators. Consistent
initial ventilator settings (eg, inspiratory flow 60 L/
min in constant flow pattern) are helpful to estab-
lish a visual normal waveform, facilitating recogni-
tion of abnormal waveforms. Importantly,
identification of patient-ventilator asynchrony via
waveform analysis can be successfully performed
by practitioners of varied professions with specific
training.29
Esophageal Manometry
Measures of respiratory effort may provide hints
toward occult asynchrony. Esophageal manom-
etry can detect increasingly negative pleural pres-
sure from diaphragmatic activity, and thus identify
Fig. 2. Flow asynchrony in volume-assist-
control mode. A pressure-time (upper)
tracing during constant-flow targeted
ventilation depicts downward deflection
from the usual scalloped curve (inset
lower left) as well as breath-to-breath
variation indicate inadequate inspiratory
flow. Note (a) that a visual estimate of
flow (middle tracing) is less than 50 L/
min (actual flow 46 L/min, not shown),
and (b) the inspiratory tidal volume is
larger than target tidal volume.
514 Doerschug

Fig. 3. Flow asynchrony in pressure-targeted modes. Passive ventilation with pressure-control mode of (left) dem-
onstrates typical pressure-time tracings (upper tracing) including a plateau at the targeted pressure and a tidal
volume deemed protective. Pressure support ventilation (right) with the same pressures as previous but with
spontaneous respirations demonstrates concavity rather than plateau of the pressure-time waveform during
inspiration, and results in larger tidal volumes that may not be protective.

when patient effort increases.30 Enthusiasm for the
use of esophageal manometry is dampened by its
cost and the need for further education in order to
interpret its data, as well as a lack of data to
demonstrate a change in clinical outcomes. Unfor-
tunately pleural pressure is not uniform throughout
the thorax, and this heterogeneity is increased
during spontaneous breathing. Thus esophageal
manometry may not accurately reflect regional
pleural pressure changes, leading to overdisten-
sion in the dependent, injured lung during sponta-
neous breathing.16
P0.1
The drop in airway pressure against a closed
airway during the initial 100 milliseconds of a spon-
taneous breath, or P0.1, accurately estimates
respiratory drive.31 Most modern ventilators pro-
vide measures of P0.1, although some estimate
this without airway occlusion; these estimated
values are reasonable estimates, as they correlate
with electrical activity of the diaphragm and
esophageal pressure-time constants.32 Elevated
P0.1 during a spontaneous breathing trial may pre-
dict failure as well as the potential for acute
decompensation.18 This noninvasive and readily
available measure of respiratory drive may provide
important clues of increased respiratory effort,
prompting further investigation for occult
asynchrony.
Expiratory Occlusion Pressure
While P0.1, measured during inspiration, estimates
respiratory drive, it does not fully represent the
Fig. 4. Cycle asynchrony. Pressure- (up-
per), flow- (middle), and volume- (lower)
time tracings all show stacked breaths, or
delivery of a second breath before the
prior breath is exhaled. Note the exhaled
tidal volume (a) of the stacked breaths is
1.6 times the target tidal volume. More
subtly, the expiratory flow tracing de-
picts an upward deflection (less expira-
tory flow, [b]) followed by a downward
deflection (more expiratory flow) repre-
senting an active attempt to inhale prior
to more passive exhalation. Both find-
ings are examples of cycle asynchrony.

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stress on the lung created by the combined effects
of mechanical ventilation and respiratory effort. In
contrast, the deflection of airway pressure during
an applied end-expiratory occlusion maneuver
(Poccl) represents the magnitude of patient effort.
Noninvasive Pocc correlates with more invasive
measures of respiratory effort from esophageal
manometry,33 and can accurately detect transpul-
monary pressures greater than 20 cm H20.34
Inspiratory Hold
The peak pressure delivered by a ventilator is the
sum of (1) PEEP, (2) the pressure to distend the
lung to a given a given tidal volume (Pelast), and (3)
the pressure to overcome the resistance of flow
(Pres). Peak pressure in a passive patient will be
higher than Pplat. Compared with a passive patient
on identical pressure-cycled ventilator settings, an
actively breathing patient will have larger transpul-
monary pressures and thus larger tidal volumes
and higher Pplat. Because of patient effort, Pres may
not be fully estimated by Ppeak, and an inspiratory
hold may reveal a Pplat that is actually higher than
Ppeak (Fig. 5).35 Accordingly, the true driving pressure
(Pplat -PEEP) may be not be protective.36 The direc-
tion and magnitude of the change in Pplat from Ppeak
during an inspiratory hold correlate with work of
breathing measured by esophageal manometry.37
Thus in pressure-cycled modes, an inspiratory hold
that reveals Pplat higher than Ppeak signifies an unmet
respiratory drive and patient-ventilator asynchrony.
MITIGATION OF ASYNCHRONY
Overdrive
As asynchrony represents a respiratory drive that
exceeds that delivered by the ventilator, increases
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Patient-Ventilator Synchrony 515
in minute ventilation via increases in tidal volume
or respiratory rate—ventilator overdrive—may
serve to both increase delivery and suppress res-
piratory drive. Overdrive decreases PaCO2, poten-
tially well below normal values, suppressing the
work of breathing.5 Overdrive does have limita-
tions, however. An increased respiratory rate risks
decreased expiratory time and the potential for dy-
namic hyperinflation (intrinsic PEEP). Increases in
tidal volume risk injurious overdistension, although
even the ARMA trial of lung-protective ventilation
allowed tidal volumes up to 8 cc/kg IBW if asyn-
chrony cannot otherwise be avoided. Certainly
additional strategies to mitigate asynchrony
should be attempted before resorting to increasing
tidal volume. Other strategies are more specific to
the type of asynchrony encountered.
Sufficient Flow
The elevated respiratory drives of most critically ill
patients demand an inspiratory flow near 60 L/min;
flows less than 50 L/min are rarely tolerated.27 The
shortened inspiratory time created by inspiratory
flow greater than 60 L/min risks cycle asynchrony.
Further increases in flow can lead to reflex tachyp-
nea.38 In flow-targeted modes, a constant flow,
rather than decelerating flow, will assure flow is
sufficient throughout inspiration, and facilitate
easier recognition of abnormal patterns, but the
choice and optimization of flow profiles remain
poorly studied.
Increased Inspiratory Time
Cycle asynchrony typically arises when the set
inspiratory time is less than that of the patient’s
neurologic inspiratory time. Increasing ventilator
Fig. 5. Occult driving pressure in pres-
sure support. Spontaneous respirations
with pressure-support (pressure-tar-
geted) mode with an inspiratory pressure
of 10 cm H2O more than PEEP of
12 cm H2O results in tidal volumes over
600 mL. The pressure-time (top) tracing
demonstrates concavity rather than con-
stant pressure during inspiration, indi-
cating flow asynchrony. An inspiratory
hold (arrow) following the third breath
reveals a plateau of 31 cm H2O. The
calculated actual driving pressure of
19 cm H2O is much higher than the set
pressure support of 10 cm H2O, and dem-
onstrates that patient-ventilator asyn-
chrony may contribute to injurious
ventilation.
516 Doerschug
set inspiratory times to approach that of the pa-
tient will therefore reduce the risk of cycle asyn-
chrony. Inserting an inspiratory pause will
increase the inspiratory time without decreasing
flow, thereby avoiding flow asynchrony. This
method reduces stacked breaths more effectively
than sedation.39
Adjust Cycle-Off During Pressure Support
When inspiratory flow in pressure support mode is
sustained longer than the patient’s neural inspira-
tory time, increasing the percent cycle-off
threshold (cycle-off at higher flow) will decrease
the delivered inspiratory time to approach that of
the patient and improve synchrony. This subse-
quently reduces tidal volume, intrinsic PEEP, and
patient inspiratory effort.40
Increase Positive End-Expiratory Pressure
Effective triggering occurs when airway opening
pressure is sufficiently lowered below PEEP. In
obstructed patients with ineffective triggering
caused by intrinsic PEEP, a higher applied PEEP
(compared with lower PEEP) reduces the needed
change in pleural pressure. Compared with low
PEEP, a higher PEEP reduces the needed change
in pleural pressure and minimizes ineffective trig-
gering in patients with obstructive lung disease.
High PEEP produces a more homogeneous distri-
bution of pleural pressures during ARDS, which re-
duces inspiratory effort, tidal volume, and lung
injury in patients.14,41
Neurally Adjusted and Proportional Assist
Ventilatory Modes
Neurally adjusted ventilatory assist (NAVA) and
proportional assist ventilation (PAV) are 2 modes
that specifically recognize patient effort and thus
improve synchrony in spontaneously breathing
patients. Neither mode sets pressure, volume,
flow, or inspiratory time. Instead, all of these vari-
ables change in response to the patient’s ventila-
tory demand. NAVA is controlled an
electromyographic electrode (placed via special-
ized nasogastric tube) and adjusts each breath ac-
cording to diaphragmatic activity. The clinician can
adjust the degree of assistance by altering the
amount of inspiratory pressure applied per millivolt
of EMG signal. NAVA decreases asynchrony,42
and duration of mechanical ventilation may not
affect survival.43
PAV measures work of breathing and adjusts
the ventilator output to unload a proportion the
work of breathing from the patient; the clinician
sets the proportion (percent) unloaded by the
ventilator. Compared with pressure support
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ventilation, PAV reduces cycle asynchrony,44,45
albeit with longer inspiratory times and potentially
larger tidal volumes.44 Data demonstrating
improved patient outcomes are lacking.
Both NAVA and PAV offer clinicians an opportu-
nity to assess patient effort with the potential to
reduce asynchrony. To this end, these modes
have been successful. The current body of evi-
dence does not demonstrate an effect of NAVA
or PAV on patient-centered outcomes, although
trials have been limited. The critical care commu-
nity awaits further data of larger trials, perhaps
including patient populations at high risk of asyn-
chrony and powered to detect these important
outcomes.
Techniques to Avoid
Over-reliance on blood gas analysis
Attempts to normalize blood gases, in particular
PaCO2, often result in a minute ventilation that is
insufficient for a critically ill patient’s elevated res-
piratory drive. Rather, pH values between 7.2 and
7.55 have little physiologic consequence and are
best tolerated by the clinician as needed to
achieve patient-ventilator synchrony.
Excessive and ineffective sedation
Many clinicians consider increasing sedation as
the first line of defense against asynchrony. How-
ever, prolonged deep sedation is associated with
increased incidence of ICU delirium and long-
term neuromuscular and cognitive symptoms.
Importantly, increasing sedative/analgesic medi-
cations is actually less effective than optimizing
ventilator settings at mitigating asynchrony.39 In
the setting of evolving drug shortages, sedation
may be less available; thus clinicians are forced
to focus on optimum ventilator management to
mitigate asynchrony. With a high risk profile and
inadequate effectiveness, it is suggested that
sedation not be the first approach to address
asynchrony regardless of drug availability.
Change of ventilator modes
Lung-protective ventilation using tidal volume
6 cc/kg ideal body weight with flow-targeted
modes may lead to more asynchrony than larger
tidal volumes. Similarly, a change to pressure sup-
port mode will likely improve synchrony but at the
expense of increasing tidal volumes that may no
longer be considered protective.39 Further, the
set pressures during pressure support ventilation
may be deceptively reassuring, as they may not
accurately represent transpulmonary pressures
during excessive spontaneous effort. Attempts to
decrease pressure support are often countered
by increased patient effort and therefore little

change in injurious tidal volume. For these rea-
sons, clinicians should search for mitigation strate-
gies while maintaining lung-protective tidal
volumes in flow-targeted ventilation.
SUMMARY
Patient-ventilator asynchrony develops when the
output from mechanical ventilation does not
match a patient’s respiratory drive. Asynchrony
contributes to increased work of breathing, dia-
phragm dysfunction, injurious overdistension of
the lung, and is associated with adverse patient
outcomes. Clinicians must be skilled at recog-
nizing patient-ventilator asynchrony through scru-
pulous analysis of ventilator graphics. Ventilator
adjustments mitigate asynchrony more effectively
than sedation.
CLINICS CARE POINTS
 Patient-ventilator asynchrony contributes to
excess work of breathing, diaphragm
dysfunction, lung injury, and mortality in crit-
ically ill patients
 With specific training, clinicians can accu-
rately identify patient-ventilator
asynchronies
 Ventilator adjustments are more effective
than sedation to decrease patient-ventilator
asynchronies
DISCLOSURE
K.C. Doerschug has no relevant conflicts to
disclose.
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