REVIEW

URRENT
C
OPINION

Monitoring patientventilator asynchrony

Martin Dres a,b,c, Nuttapol Rittayamai b,c,d, and Laurent Brochard b,c

Purpose of review
This article describes and discusses the importance of monitoring patientventilator asynchrony, and the
advantages and limitations of the specific techniques available at the bedside to evaluate it.
Recent findings
Signals provided by esophageal catheters (pressure or electromyogram) are the most reliable and accurate
instruments to detect asynchronies. Esophageal signals (providing electrical activity of the diaphragm or/
and esophageal pressure) have allowed the recent description of reverse triggering, a new kind of
asynchrony, in which mechanical insufflation repeatedly triggers diaphragmatic contractions. However,
the use of esophageal catheters is not widespread, and data on the prevalence and consequences of
asynchronies are still scarce. The development of software solutions that continuously and automatically
record breathing waveforms from the ventilator recording is emerging. Using this technology, recent data
support the fact that asynchronies are frequent and may be negatively associated with outcome.
Summary
The prevalence and consequences of asynchronies may be largely underestimated because of a frequent
lack of monitoring. Dedicated software solutions that continuously and automatically detect asynchronies
may allow both clinical research and clinical applications aimed at determining the effects of
asynchronies and minimizing their incidence among critically ill patients.
Keywords
asynchrony, diaphragm, esophageal pressure, mechanical ventilation

INTRODUCTION
Mechanical ventilation is a life supporting treatment
which unfortunately can also be associated with
complications, such as ventilator-induced lung
injury, ventilator-associated pneumonia, or ventilation-induced diaphragm dysfunction [1]. In part
to avoid ventilation-induced diaphragm dysfunction, clinicians are using partially assisted/supported
ventilation instead of fully controlled ventilation in
critically ill patients [2]. This strategy aims at avoiding
diaphragmatic atrophy by maintaining a contractile
activity of the respiratory muscles [3] but also requires
harmonious synchronization and matching with
the patients demands in terms of ventilator needs.
Asynchrony between the patient and the ventilator
occurs when there is a mismatch between the patient
and ventilator in terms of breath delivery timing. In
reality, some asynchrony is almost inevitable because
of the mechanical and electrical delays existing
within the complex patientventilator loop. For this
reason, some authors have described gross asynchronies as those where the mismatch between the breath
delivery and the patient effort is large, such as
autotriggering or missing effort. We will concentrate
on these gross asynchronies. Though some
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asynchronies can be associated with discomfort

and dyspnea and/or increased need for sedative
and paralytic agents, this is not the case for all [4]
and some may even result from deep levels of sedation [5]. Therefore, a classification based on their
mechanism appears useful. A high incidence of asynchrony is associated with prolonged mechanical
ventilation and ICU length of stay [6,7] and with
mortality [8 ]. Thus, it seems intuitively important
to enhance the detection of asynchronies and to
adapt the ventilator assistance, although we have
no direct evidence to date that reducing asynchrony
&&

a
Sorbonne Universites, UPMC Univ Paris 06, INSERM, UMRS_1158
Neurophysiologie Respiratoire Experimentale et Clinique, Paris, France,
b
Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St Michaels Hospital, cInterdepartmental Division of
Critical Care Medicine, University of Toronto, Toronto, Canada and
d
Department of Medicine, Division of Respiratory Diseases and Tuberculosis, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok,
Thailand

Correspondence to Laurent Brochard, Keenan Research Centre for

Biomedical Science, Li Ka Shing Knowledge Institute, St. Michaels
Hospital, Toronto, Canada. E-mail: BrochardL@smh.ca
Curr Opin Crit Care 2016, 22:246253
DOI:10.1097/MCC.0000000000000307
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Monitoring patient--ventilator asynchrony Dres et al.

KEY POINTS
 Asynchronies are prevalent in ICU patients and
negatively related to outcome ranging from prolonged
mechanical ventilation, prolonged ICU and hospital
stays, and increased mortality.
 Detection of asynchronies mostly relies on a mismatch
between surrogates of the patient inspiratory effort and
the ventilator cycling.
 Larger studies that use automatic and continuous
monitoring are needed to determine the exact
prevalence and related outcomes of asynchronies.

improves outcome. In the present review, we summarize the current knowledge on type and definitions of asynchronies and discuss the most
recent developments of technologies designed to
monitor them.

DEFINITIONS
Poor patientventilator interactions can often be
called phase problems which refer to matching
between the neural inspiration and expiration times
of the patient on the one hand and the ventilator
insufflation and expiration times on the other.
These asynchronies can happen when the patients
respiratory drive is relatively high as is often the case
in acute respiratory failure. In such a case, the clinician has to decide whether the high drive to breathe
and the asynchronies are caused by an insufficient
level of ventilator assistance which creates dyspnea
and unmatched needs, or whether it is intrinsic to
the patients acute disease and is best treated with
additional sedation. At the other extreme, asynchronies happen when the respiratory drive is low
because of sedation or hyperventilation. In these
cases, the clinician must identify the excess of sedation or ventilation. These are very different circumstances and different forms of disharmony. For this
reason, we will classify asynchronies based on the
circumstances of occurrence.

Low respiratory drive and excessive

ventilator assistance
Pressure support-induced apneas
During sleep, the apneic threshold for partial pressure of arterial carbon dioxide (PaCO2) rises and
lowering PaCO2 level below this threshold by excessive ventilation rapidly leads to a specific form of
patientventilator disharmony, characterized by

central apneas that negatively influence sleep

in the absence of backup ventilation. High levels
of pressure support ventilation may cause sleep disruption from periodic breathing [9]. If pressure support delivers a higher than needed alveolar minute
ventilation, hyperventilation, and hypocapnia can
occur and will inevitably be followed by apnea,
continuously causing high degrees of sleep fragmentation [10]. Avoiding excessive levels of assistance is,
therefore, very important with pressure support
ventilation, especially during sleep. The use of ventilator modes with backup ventilation such as assistcontrol mode or synchronized intermittent mandatory ventilation can prevent periodic breathing but
these approaches may have other downside effects if
they excessively rest respiratory muscles. Apneas
during pressure support ventilation may be worsened in patients with heart failure who have a
tendency to develop central apnea or abnormal
breathing pattern, since they have long circulation
time and increased chemoreceptor sensitivity [11].
The level of assistance needs to be carefully adjusted
to prevent hyperventilation during sleep in patients
with chronic heart failure.
Ineffective efforts
Excessive ventilator assistance can promote
dynamic hyperinflation that itself generates intrinsic positive end expiratory pressure, and simultaneously reduces respiratory drive. This is favored
by airway obstruction. The higher the level of pressure support, the longer the insufflation time and
the longer its termination after the end of the
patients neural inspiratory time. The patients
efforts will then arrive too early in expiration and
become insufficient to overcome intrinsic positive
end expiratory pressure and trigger the ventilator.
The result is a failure to deliver the breath following
the effort (Table 1; Fig. 1). Whatever the mode,
higher levels of assistance increase ineffective efforts
[11]. Ineffective efforts occur mostly in case of
diminished respiratory drive and are not associated
with dyspnea. For instance, deep sedation with propofol can promote ineffective effort during pressure
support ventilation [12 ].
&&

Autotriggering
Autotriggering occurs when the ventilator delivers
an assisted breath that is not initiated by the patient.
As a drop in airway pressure (Paw) or a flow signal
is used to trigger the ventilator, circuit leaks
or strong cardiac oscillations can reach the triggering threshold of the ventilator independent of
the patients effort and provoke the insufflation
of repeated extra breaths, sometimes causing
profound hyperventilation.

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Cardiopulmonary monitoring
Table 1. Main asynchronies and their description
Asynchronies

Description

Related to

Inspiratory effort

Patient inspiratory effort not followed by a ventilator-delivered pressurization

Triggering

Double triggering

Two ventilator-delivered pressurizations during one single patient inspiratory effort

Triggering

Auto triggering

Ventilator pressurization without inspiratory effort

Triggering

Reverse triggering

Entrainment

Premature cycling

Inspiratory efforts occurring near the end of each mechanical inspiration in a repetitive and
consistent manner
Duration of pressurization shorter than the duration of patient inspiratory effort

Cycling off

Delayed cycling

Duration of pressurization twice as long as patient inspiratory effort

Cycling off

Reverse triggering
Reverse triggering was first documented by
Akoumianaki and colleagues [13] who observed
repetitive decrease in esophageal pressure (Peso)
occurring regularly near the end of each mechanical
inspiration in heavily sedated patients (Fig. 2).
Inspiratory efforts were directly triggered by the
insufflations. This was observed during both
pressure and volume-controlled ventilation. This
new kind of neuro-mechanical coupling was previously reported as a phenomenon of respiratory
entrainment in animals, healthy humans, and
chronically ventilated patients, and preterm infants.
In the ICU, it could result in eccentric contractions

of respiratory muscles, in extra breaths being unrecognized (inducing double cycling) and in unreliable plateau pressures. The use of neuromuscular
blocking agents at the early phase of acute respiratory distress syndrome might avoid reverse triggering. This could have participated to the benefits
observed with neuromuscular blocking agents in
acute respiratory distress syndrome [14].

Increase in respiratory drive and/or

insufficient ventilator assistance
Despite the delivery of a breath by the ventilator,
when a patients demand is high, the inspiratory

Paw (cmH2O)
20

10

1 sec

Flow (l/sec)
1.0

1.0
EAdi (V)
10

FIGURE 1. Ineffective efforts. Tracings of Paw, flow, and EAdi demonstrate ineffective efforts in a patient ventilated with
pressure support ventilation. Missing efforts can be detected from two small negative deflections of Paw tracing and positive
deflections of flow tracing (thick arrows) corresponding with positive EAdi signals (thin arrows). EAdi, electrical activity of the
diaphragm; Paw, airway pressure.
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Monitoring patient--ventilator asynchrony Dres et al.

Paw (cmH2O)
20

10

0
1 sec

Flow (l/sec)
1.0

1.0
Peso (cmH2O)
1.0

FIGURE 2. Reverse triggering. Tracings of airway pressure (Paw), flow, and Peso in a patient with acute respiratory distress
syndrome during pressure control ventilation illustrating reverse triggering (1 : 2 entrainment; arrows). The dotted lines
represent the beginning of inspiratory efforts indicated by positive deflections of flow and negative deflections of Peso
tracings. The entrained breaths are strong enough to trigger the ventilator and the ventilator provides the assisted breaths with
the same pressure control level (arrows). Peso, esophageal pressure.

effort can continue throughout the preset ventilator

inspiratory time and remains present after ventilator
inspiratory time has finished. This corresponds to a
premature cycling resulting in increased work of
breathing [15].
Depending on the ventilator, this phenomenon
can lead to the consecutive delivery of two cycles
for only one patient effort (double triggering),
also referred to as breath stacking (Table 1; Fig. 3).
A short inspiratory time, frequently associated with
a low tidal volume setting, and a relatively high
respiratory drive will be risk factors for multiple
double triggering.

PREVALENCE
Until recently, studies assessing the prevalence of
asynchrony were limited to relatively short evaluation periods (from several minutes to 24 h). The
prevalence of asynchrony may have been underestimated. The largest existing study reported that
among 200 ventilator-dependent patients in a
weaning center, ineffective efforts were clinically
detected in 10% of study participants [16]. Among
62 ICU patients, Thille et al. [7] found that 15 (24%)
exhibited a high asynchrony index, above 10%,

defined as the ratio of the number of asynchrony

events divided by the total respiratory rate; most
of these were ineffective effort. In a recent study,
Mellott et al. [17] found that 24% of 43 758 breaths
were asynchronous; most of these were ineffective
efforts. More recently, Blanch et al. [8 ], used a
device dedicated to continuous detection of asynchronies, and found a median asynchrony index of
3.4% (interquartile range 2.05.8) during the entire
course of mechanical ventilation.
&&

IMPACT
Asynchronies may have important clinical implications in mechanically ventilated patients. Several
studies reported that ineffective efforts are associated with a longer duration of mechanical ventilation [6,7]. Others have shown that asynchronies
induce sleep disorders [18] with a direct relationship
between ineffective efforts and a decrease in the
proportion of rapid eye movement sleep [19]. In
addition, double triggering, by delivering a double
tidal volume, can promote dynamic hyperinflation
but also ventilator-induced lung injury. In the study
of Blanch et al. [8 ], the effect of asynchrony on
outcome was investigated. Among the 50 patients of

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&&

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Cardiopulmonary monitoring

Paw (cmH2O)
20

10

0
1 sec

Mechanical Ti

Flow (l/sec)
1.0

1.0

Peso (cmH2O)
10
5
0
5

Neural Ti

FIGURE 3. Premature cycling. Paw, flow, and Peso tracings in a patient ventilated with pressure support ventilation and a
high-flow cycling criteria. The second breath illustrates a premature cycling with double triggering which can be explained by
a mismatch between mechanical and neural Ti (mechanical Ti < neural Ti). The dotted line indicates the termination of the
mechanical breath but the patient continues making inspiratory effort (further decrease in Peso). As a result, Paw decreases
below the triggering threshold and then is followed by the new mechanical breath (arrow). Ti, inspiratory time; Paw, airway
pressure; Peso, esophageal pressure.

the study, six had an asynchrony index above 10%.

These patients had similar outcomes in terms of
extubation failure and tracheostomies with a trend
toward longer duration of mechanical ventilation
(16 vs. 6 days, P 0.061). More interestingly, there
was a significant relationship between an asynchrony index more than 10% and an increase in
ICU and hospital mortality even after multiple
adjustments [8 ]. Whether asynchronies increase
mortality or are just a biomarker of illness severity
and whether reducing these asynchronies will
change the outcome deserve further studies.

muscle electromyograms have been used to measure

patientventilator interactions [22]. However, these
devices are not routinely used for patient care. Thus,
clinicians mostly rely on physical examination of
the patient as well as visual inspection of waveforms
to assess for patientventilator interaction. We
have summarized below the current modalities of
detection of asynchronies.

&&

DETECTION AT THE BEDSIDE

Even if patientventilator asynchrony is very
common, studying this phenomenon remains
a challenge in daily clinical practice [20]. Accurate
assessment of patientventilator interactions
requires semi-invasive measurements of pleural
pressure and/or respiratory muscle electromyogram
[21]. Use of an esophageal balloon, which gives a
surrogate for pleural pressure, and respiratory
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Airway pressure and flow waveforms

Paw, volume, and flow waveforms are displayed in
real time on the screen of ventilators. Visual inspection of these waveforms correlates well with esophageal-balloon readings, but is not without error [16].
In partially assisted modes, ventilator waveforms
can enable the detection of ineffective effort by
showing a deflection in Paw and expiratory flow
not followed by a ventilator cycle (Fig. 1). Double
triggering can also be observed when two ventilator
insufflations are separated by a brief expiratory time
but it can be difficult to differentiate from a second
cycle caused by reverse triggering (Fig. 3). Triggering
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Monitoring patient--ventilator asynchrony Dres et al.

Table 2. Modalities of detection of asynchronies
Modalities

Advantages

Disadvantages

Ventilator waveforms

Noninvasive

Needs expertise

Easily available

No automated analysis from ventilators

Depicts diaphragm activity

Need a dedicated catheter and ventilator

Reliable

Does not detect other muscles

May miss some

Electrical activity of the diaphragm

Esophageal (and/or transdiaphragmatic)

pressure

Continuous and quantified

Needs proper placement

Can be mounted on feeding tubes

Synchrony not automatically detected

Good estimate of the inspiratory effort

Needs catheter placement and specific

monitoring

Gold standard
Software

Can be mounted on feeding tubes

Technical specificities (calibration procedure)

Continuous

Few studies

Automatic

Not yet validated

Real-time analysis

occurring synchronously with cardiogenic oscillations suggests autotriggered breaths.

There are limitations in the detection
of asynchronies from ventilator waveforms
(Table 2). First, the ability of ICU physicians, even
experts, to detect asynchrony can be poor and
does not enable a simple, reliable, and sensitive
detection of asynchronies [20]. Second, because
asynchronies can happen at any time, it is not
possible to continuously track for asynchronies.
Third, some types of asynchronies such as reverse
triggering are not easily detected by the inspection
of pressure, flow, or volume waveforms only.

Esophageal pressure
Many studies exploring asynchronies have used
esophageal catheter that provides a direct observation of the patients inspiratory effort. Monitoring Peso in this context enables detection of every
inspiratory effort, and hence understands the
interaction and synchrony between patient and
ventilator [23 ]. For instance, use of Peso has
allowed the description of reverse triggering [13].
A drop in the Peso trace was observed in deeply
sedated patients ventilated with controlled mode
[13], related to diaphragmatic contractions triggered by ventilator insufflations (Fig. 2). Without
Peso, it would have been impossible to detect such
asynchronies. Additionally, following real-time
Peso and Paw tracings enables association of every
patient inspiratory effort with every ventilator
cycle, and thus allows detection of ineffective
effort in case of drop in Peso not followed by a
ventilator breath (Fig. 1).

Electrical activity of the diaphragm

Today, the electromyogram of the diaphragm can be
relatively easily and continuously obtained through
a special catheter equipped with multiple electrodes.
The processed signal is referred to as the amplitude
of the electrical activity of the diaphragm (EAdi).
Because EAdi is a direct measure of neural respiratory drive, it can be used to detect the onset and
duration of neural inspiration and expiration. Some
investigators have used EAdi to detect asynchronies,
inspiratory effort, or neuro-mechanical coupling in
adult and pediatric settings [2427]. In the specific
context of patients receiving extracorporeal membrane oxygenation for acute respiratory distress syndrome with very low static compliance, Mauri et al.
[28] calculated an EAdi-based asynchrony index as
the number of flow, pressure, and EAdi-based asynchrony events divided by patients EAdi-based
respiratory rate. EAdi-based measurements of asynchrony, indeed, were extremely high, with premature cycling being the most represented pattern [28].

&&

Standardized and automatic dedicated

software
Most of the clinical studies assessing asynchronies
used off line breath by breath analysis. On line
assessment only was possible during short periods
(from several minutes to few hours). This raised the
interest for dedicated software designed to continuously detect asynchronies in real time. To date, few
studies reported the feasibility and results of
such technology.
An approach based on the equation of motion
using tidal volume, Paw, flow, and Peso signals on

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251

Cardiopulmonary monitoring

one hand, and estimated values of elastance and

resistance on the other, has been developed [29].
This method provides a real-time trace that reflects
respiratory muscle pressure output along with
Paw and flow [29]. Therefore, it gives a real-time
visual feedback about the instant state of patient
ventilator, and hence enables a reliable detection
of excessive trigger delay, cycling-off delay, and
ineffective efforts.
In 2012, Blanch et al. [30] validated a software
(Better Care, Better Care S.L., Sabadell, Catalonia,
Spain) designed to detect ineffective effort during
expiration. The software captures digital output
from different ventilators and associates each
acquired waveform with the parameter it represents
(flow, Paw, or tidal volume). Signals are then tagged,
converted to the specific standard, formatted,
and stored in the hospital picture archiving and
communication system for analysis. This algorithm
is able to identify ineffective effort with an area
under the receiving operating characteristics curve
of 0.96 when the gold standard is experts judgment
[30]. The authors applied this technology in 50 ICU
patients and reported findings automatically
computed from the analysis of 7027 h of mechanical
ventilation, and corresponding to 8 731 981 breaths
[8 ]. As detailed above, this method reported
original data on the real prevalence and outcome
related to asynchrony [8 ].
Other investigators have proposed automatic
detection of asynchronies. Sinderby and colleagues
[31] designed a new index of patientventilator
interaction. The EAdi and ventilator pressure
waveforms were analyzed for their timings (manually and automatically determined), and the mismatch between the two waveforms was quantified.
A new index of patientventilator interaction
(NeuroSync index), standardized and automated,
was compared to manual analysis. The authors
found that NeuroSync index produced high
test-retest and inter-rater reliability [31]. The same
technology was used in patients with chronic
obstructive pulmonary disease under noninvasive
ventilation. In this last study, there was a significant
correlation between the number of wasted efforts
and the NeuroSync index [32].
&&

&&

Research perspectives
As inspiratory efforts can be detected by looking
at the thickening of the diaphragm [33], diaphragmatic ultrasound could become an interesting
approach in the detection of asynchronies. This
requires synchronizing ventilator waveforms with
the ultrasound signal of the diaphragm breath by
breath [34]. Further studies are warranted to
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investigate the potential interest of diaphragmatic

ultrasound in this context.

CONCLUSION
Today, there is growing evidence that asynchronies
negatively correlate with clinical outcomes. This
should encourage physicians to pay more attention
to the interaction between patient and ventilator
but tools allowing an easy recognition of asynchronies are necessary. The emergence of dedicated
software solutions that provide continuous and
real-time monitoring of asynchronies represents
an exciting opportunity.
Acknowledgements
This work was supported by the Department of Critical
Care Medicine, St Michaels Hospital, Toronto, Canada.
L.B. holds the Keenan Chair in Acute Respiratory Failure
and Critical Care Medicine.
Financial support and sponsorship
M.D. was supported by the French Intensive Care Society
(bourse de mobilite 2015). The 2015 Short-Term Fellowship program of the European Respiratory Society. The
2015 Bernhard Drager Award for advanced treatment of
ARF of the European Society of Intensive Care Medicine,
the Assistance Publique Hopitaux de Paris and
the Fondation pour la Recherche Medicale (FDM
20150734498).
N.R. was receiving a grant from his home institution
in Thailand.
Conflicts of interest
M.D. gave lectures for Pulsion Medical Systems.
L.B.s research laboratory received research grantsand/or
equipment from Covidien, General Electric, Fisher Paykel, Maquet (with St Michaels Hospital), and Philips.

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