CONCISE CLINICAL REVIEW

Reverse Triggering during Controlled Ventilation

From Physiology to Clinical Management
Antenor Rodrigues1, Irene Telias1,2,3, L. Felipe Damiani4, and Laurent Brochard1,2
1
Keenan Centre for Biomedical Research, Li Ka Shing Knowledge Institute, Unity Health Toronto, Toronto, Ontario, Canada;
2
Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada; 3Division of Respirology,
Department of Medicine, University Health Network and Sinai Health System, Toronto, Ontario, Canada; and 4Departamento Ciencias
de la Salud, Carrera de Kinesiolog
ıa, Facultad de Medicina, Pontificia Universidad Cato
lica de Chile, Santiago, Chile

Abstract asynchronous efforts. Diagnosing reverse triggering might be

Reverse triggering dyssynchrony is a frequent phenomenon
recently recognized in sedated critically ill patients under
controlled ventilation. It occurs in at least 30–55% of these
patients and often occurs in the transition from fully passive to
assisted mechanical ventilation. During reverse triggering, patient
inspiratory efforts start after the passive insufflation by
mechanical breaths. The most often referred mechanism is the
entrainment of the patient’s intrinsic respiratory rhythm from the
brainstem respiratory centers to periodic mechanical insufflations
from the ventilator. However, reverse triggering might also occur
because of local reflexes without involving the respiratory rhythm
generator in the brainstem. Reverse triggering is observed during
the acute phase of the disease, when patients may be susceptible
to potential deleterious consequences of injurious or
challenging and can easily be missed. Inspection of ventilator
waveforms or more sophisticated methods, such as the electrical
activity of the diaphragm or esophageal pressure, can be used for
diagnosis. The occurrence of reverse triggering might have
clinical consequences. On the basis of physiological data, reverse
triggering might be beneficial or injurious for the diaphragm and
the lung, depending on the magnitude of the inspiratory effort.
Reverse triggering can cause breath-stacking and loss of
protective lung ventilation when triggering a second cycle. Little
is known about how to manage patients with reverse triggering;
however, available evidence can guide management on the basis
of physiological principles.
Keywords: reverse triggering; mechanical ventilation;
dyssynchrony; monitoring

Definition
Reverse triggering is a frequent and
intriguing phenomenon frequently observed
in sedated mechanically ventilated patients
under controlled ventilation, such as assist-
control ventilation with only mandatory
breaths or synchronized intermittent
ventilation with mandatory breaths. The
apparent pattern suggests that the ventilator
triggers respiratory efforts from the patient
instead of the patient triggering the
ventilator. It often occurs with regularity, the
patient being entrained by the ventilator (i.e.,
reverse triggering) (Figure 1) (1). It can have
different consequences (Table 1), such as
breath stacking and loss of protective lung
ventilation when triggering a second
mandatory breath (2–4), but it may also offer
some protective effects, such as being
protective against diaphragm disuse atrophy
(4). Recognized only recently in the ICU (1),
there is a lack of strong clinical evidence on
how to manage this asynchronous breathing
pattern.
Prevalence During Controlled
Ventilation
The prevalence of reverse triggering in
mechanically ventilated patients (i.e., the
proportion of patients within the

(Received in original form August 5, 2022; accepted in final form December 5, 2022)
Author Contributions: All authors contributed to the conception of the work. All authors contributed to drafting the manuscript or critically revised
it for important intellectual content, approved the final version of the manuscript, and took responsibility for the integrity of the data.
Correspondence and requests for reprints should be addressed to Antenor Rodrigues, Ph.D., St. Michael’s Hospital, Room 4-709,
36 Queens Street E, Toronto, M5B 1W8, Ontario, Canada. E-mail: antenor.rodrigues@unityhealth.to.
This article has an online supplement, which is accessible from this issue’s table of contents at www.atsjournals.org.
CME will be available for this article at https://shop.thoracic.org/collections/cme-moc/ethos-format-type-journal.
Am J Respir Crit Care Med Vol 207, Iss 5, pp 533–543, Mar 1, 2023
Copyright © 2023 by the American Thoracic Society
Originally Published in Press as DOI: 10.1164/rccm.202208-1477CI on December 5, 2022
Internet address: www:atsjournals:org

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Figure 1. Signals to identify reverse triggering. (A) Patient on pressure-control ventilation triggering every mechanical insufflation. (B) Patient on
pressure-control ventilation with midcycle reverse triggering at a 1:1 entrainment ratio; reverse triggering occurring after the fifth mechanical
insufflation triggered an additional mechanical insufflation before complete exhalation and caused breath stacking (horizontal black bracket).
(C) Patient on volume-control ventilation with midcycle reverse triggering at a 1:2 entrainment ratio. The gray area in B and C shows the
difference between the onset of the mechanical insufflation and the onset of the electric activity of the diaphragm (EAdi) and esophageal
pressure (Pes) activity (respectively). a: Absence of drop in the pressure at the onset of the mechanical insufflation, suggesting an absence of
effort at the onset of the mechanical insufflation. b: Absence of an increase in the EAdi signal at the onset of the mechanical insufflation,
indicating the absence of effort at the onset of the mechanical insufflation. c: Drop in the pressure–time curve during the inspiratory phase of the
mechanical ventilator because of reverse triggering-associated effort occurring during pressure-control ventilation. d: Increase in the flow–time
curve during the inspiratory phase of the mechanical ventilator because of a reverse triggering effort occurring during pressure-control
ventilation. e: Deformation of the flow–time curve during the expiratory phase of the ventilator because of a reverse triggering-associated effort

534 American Journal of Respiratory and Critical Care Medicine Volume 207 Number 5 | March 1 2023
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Table 1. Criteria Associated with Potentially Favorable or Harmful Effects of Reverse Triggering and Potential Approaches for
Management

Reverse Triggering Potential Approach for

Characteristic Ventilation Mode Potentially Favorable Effect Potentially Harmful Management

Timing: during Pressure control Mitigate diaphragm disuse *Distending Modify set inspiratory time,
inspiration atrophy. transpulmonary tidal volume, and rate.†
pressure
*Increasing tidal volume Assess for the presence
of IRR and consider
transition to
spontaneous mode.
Timing: during Volume control Mitigate diaphragm disuse *Pendelluft Modify set inspiratory time,
inspiration atrophy. tidal volume, and rate.†
*Increasing regional Assess for the presence
distension of IRR and consider
transition to
spontaneous mode.
Timing: during late Pressure or volume Postinspiratory diaphragm Pendelluft Modify set inspiratory time,
inspiration and/or control activity can reduce lung tidal volume, and rate.†
expiration collapse and improve Eccentric diaphragm Assess for the presence
oxygenation. contractions of IRR and consider
Breath stacking transition to
spontaneous mode.
Degree of effort Pressure or volume Small efforts can mitigate Large efforts can Assess/manage inspiratory
control diaphragm disuse atrophy. contribute to drive stimuli (e.g.,
diaphragm injury concentration of CO2).
Assess for the presence
of IRR and consider
transition to
spontaneous mode.
Frequency Pressure or volume Patients with a higher rate of — Assess for the presence
control reverse triggering had of IRR and consider
better oxygenation and transition to
were more likely to spontaneous mode.
progress to an assisted
mode or be extubated
within the following 24 h.

Definition of abbreviation: IRR = intrinsic respiratory rate.

*Should be increased.
†
The main concept is not to mandate a rate superior to the patient’s intrinsic rate.

population studied presenting any amount
of reverse triggered breaths during the
observed period) is influenced by the
duration of the observation, the diagnostic
method, and the ICU population (3, 5–12)
(Table 2).
Prevalence of Reverse Triggering
Dyssynchrony in Patients under
Controlled Ventilation
The overall prevalence of reverse triggering
dyssynchrony is high in sedated patients under
controlled ventilation, at least between 30% and
55% (Table 2) (5–12). Yet, these observations
may have underestimated the phenomenon,
given the short duration of the recordings.
Most of these studies were developed in
patients undergoing lung-protective ventilation,
with low tidal volumes (i.e., around 6 ml/kg

Figure 1. (Continued ). that persisted throughout the expiratory phase during both (B) pressure- and (C) volume-control ventilation. f: Variation in
the plateau pressure on the pressure–time curve of the ventilator because of a reverse triggering during volume-control ventilation. g: Positive
change in the Pes signal at the onset of a mechanical insufflation, indicating passive insufflation (note this change can be subtle or not visible
in some cases [e.g., because of cardiac artifacts]). The horizontal solid line indicates the expiratory time is equal to that set on the ventilator,
indicating the mechanical insufflation was triggered by the ventilator. The horizontal dashed line indicates that the expiratory time was shorter
than that set on the ventilator, and the mechanical insufflation was triggered by the patient’s inspiratory effort associated with reverse
triggering. The vertical dashed line indicates the onset of the EAdi activity that occurred before the onset of the mechanical insufflation,
indicating the mechanical insufflation was triggered by the patient. *Expiratory flow–time curve of the ventilator in the absence of a patient
inspiratory effort. †Plateau pressure on the pressure–time curve during volume-control ventilation in the absence of a patient inspiratory
effort. ‡Drop in the pressure–time curve of the ventilator at the onset of the mechanical insufflation, indicating a patient inspiratory effort
was present at the onset of the mechanical insufflation and triggered the mechanical insufflation. EAdi = electric activity of the diaphragm;
PAW = airway pressure.

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Table 2. Summary of the Characteristics of Studies Reporting the Prevalence of Reverse Triggering in Patients under Controlled Ventilation

Duration of Recordings
Prevalence Prevalence Each per D Recorded D
of RT of Mode of Recording, per Patient, per Patient, Method of Degree of
Study n Dyssynchrony RT Breaths Population Ventilation min n n Detecting RT Sedation

Pham, et al. 109 53% of NR Hypoxemic Pressure or 20 to 40 2 to 3 1 to 7 Visual inspection of NR

the patients respiratory failure volume C ventilator
(PF ,200 mm Hg) waveforms

Rodriguez, et al. 100 50% of Median ARDS Volume C 30 1 1 Automated algorithm RASS 25 to 24
the patients (IQR, 25% to 75%) (PF ,300 mm Hg) on the basis
4.8 (0.03 to 4.3) of ventilator
per min per patient waveforms
or 17.7%
(0.95% to 49.5%)
of the patient’s
mechanical insufflations
Su, et al. 56 30% of 4% of all mechanical ARDS (PF ,300 mm Hg) PRVC, or NR 1 1 Visual inspection NR
the patients insufflations recorded pressure C of Campbell
in all patients diagram with
Pes signals

Baedorf Kassis, 55 45% of 12.1% of all mechanical ARDS (PF ,300 mm Hg) PRVC, or 4.5 to 8.5 1 1 Visual inspection of NR
et al. the patients insufflations recorded pressure C Campbell diagram
in patients with Pes signals
presenting RT
Sklar, et al. 55 33% of NR General ICU patients Volume or 60 1 1 Automated algorithm SAS 1 to 4
the patients in the 24 h preceding pressure C on the basis of
on controlled EAdi resumption ventilator
ventilation waveforms
and EAdi signals

Mellado Artigas, 39 90% of Ranged from General ICU patients Volume or 60 1 1 Automated algorithm SAS 1 to 4
et al. the patients 0.1 to 75% of in the first 24 h of pressure C on the basis of
each patient's mechanical ventilation ventilator
mechanical waveforms
insufflations and EAdi signals
(median, 8%)
Shimatani, et al. 100 41.6% of 2.4% of all mechanical Pediatric patients SIMV PC-PS 30 1 1 Visual inspection SBS 21 to 21
the patients insufflations with ARDS of ventilator
recorded in waveforms and
all patients Pes signals

Bourenne, et al. 10* 33% of NR Moderate-to-severe Volume C 60 1 1 Visual inspection of NR

the patients ARDS PF ,150 ventilator
waveforms and
Pes signal

Definition of abbreviations: ARDS = acute respiratory distress syndrome; C = controlled ventilation; EAdi = electric activity of the diaphragm; IQR = interquartile range; NR = not
reported; Pes = esophageal pressure; PF = PaO2/FIO2 ratio; PRVC = pressure-regulated volume control; RASS = richmond agitation sedation scale; RT = reverse triggering;
SBS = state behavioral scale; SIMV PC-PS = synchronized intermittent mandatory ventilation pressure control–pressure support.
*Patients not on neuromuscular-blocking agents.
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Figure 2. Schematic representation of the potential feedback loop system associated with reverse triggering. The ventilator is set in assist
control and triggers a mandatory mechanical insufflation. The mechanical insufflation provides a stimulus (dashed black arrow) that can
stimulate one or multiple sensors located in the respiratory muscles (depicted in red color [e.g., muscle spindles]), lungs (depicted in light pink
[e.g., lung stretching receptors]), or cardiovascular system (not depicted in the figure [carotid bodies]). These sensors send feedback to the
central pattern generator (CPG) (solid red arrow). The feedback stimulates the activity of the CPG, which activates the respiratory muscles
(e.g., the diaphragm via phrenic nerve activity) to contract (red dashed arrow). The respiratory muscle contraction, therefore, starts after the onset
of the mechanical insufflation characterizing the reverse-triggered breath (solid black arrow). See text for more details. (A) Mechanical ventilator set
on controlled ventilation. (B) Brain, where the CPG and respiratory centers are located. (C) Ribcage, including the diaphragm and intercostal
muscles, lungs, and carotid bodies. (D) Mechanical ventilator showing reverse-triggered breaths. For definition of abbreviations, see Figure 1.

predicted body weight) during controlled
ventilation, and most patients were under
continuous sedation (3, 5–9).
Rate of Reverse-triggered Breaths
In patients with reverse triggering
identified, the rate of reverse-triggered
breaths varied and has been reported in
different ways. The overall rate of reverse
triggering breaths in sedated patients under
controlled ventilation can vary from 0.1%
to 75% of all patient’s mechanical
insufflations (Table 2) (3, 5, 7, 8, 12).
Studies analyzing long recording
periods (e.g., 24 hours/day) from intubation
until patients recover spontaneous breathing
might be necessary to confirm the real
prevalence. Possibly, the majority of patients
under sedation and lung-protective
controlled ventilation develop reverse
triggering at some point during the course of
mechanical ventilation.
Pathophysiological Mechanisms
The pathophysiological mechanisms
involved during reverse triggering are not
fully understood. Respiratory entrainment is
the most often referred mechanism (Figure 2).
Reflexes from the phrenic, intercostal and
vagal nerve, spine, and suprapontine
structures can contribute to reverse
triggering as part of respiratory entrainment
or independent mechanisms (1, 12–15).
Respiratory Entrainment
Respiratory entrainment refers to the
establishment of a fixed repetitive temporal
relationship between the patient’s respiratory
rhythm with external input. For example, the
respiratory rhythm can be entrained to the
rhythm of the limbs’ movements during
exercise (16, 17). Respiratory entrainment to
mechanical ventilation (1) results in the
patient’s breathing efforts following the
ventilator’s rhythm during controlled
ventilation with a regular time interval (phase
delay angle). It has been described in humans
during quiet wakefulness and sleep (18), under
anesthesia (19), and after a double lung
transplant (20). When respiratory entrainment
occurs, the patient’s rate of breathing effort
involuntary follows the rate of the external
periodic stimulus. This interaction between the
patient and the ventilator can occur with
different patterns of coupling (see later and
Video E1 in the online supplement).
Stimuli and Potential Mechanisms of
Respiratory Entrainment to Periodic
Insufflation
Central pattern generators (CPGs) are
networks of neurons underlying the
production of central commands that control
stereotyped, rhythmic motor patterns such as
breathing (21, 22). The respiratory CPG is
composed of neurons in the brainstem that
connect with respiratory regions of the
medulla and pons, exerting their motor
control mostly via phrenic motoneurons
innervating the diaphragm (21, 23). Within
the CPG, neurons in the pre-Botzinger
complex have intrinsic pacemaker properties
primarily responsible for rhythm generation.
They receive inputs from the Botzinger
complex, postinspiratory complex, and
lateral parafacial nucleus, allowing breathing
to coordinate with functions such as
speaking, singing, and swallowing (21–23).
The CPG normally receives inputs from
various sources that modulate the rate of the
respiratory center’s discharge and, ultimately,
the timing of effort (24). A potential input for
respiratory entrainment to mechanical
ventilation is the periodic oscillations of
arterial PCO2 (24). The onset of the inspiratory

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Figure 3. Assessment of intrinsic respiratory rate drive and effort in patients with reverse triggering. (A) Patient on volume-control ventilation
with midcycle reverse triggering at a 1:2 entrainment ratio and an intrinsic rate present during the occlusion. (B) Patient on volume-control
ventilation with reverse triggering without a clear ratio of entrainment and no visible intrinsic rate during the occlusion. The solid horizontal line
shows the time elapsed between the onset of two inspiratory efforts (drop in esophageal pressure) during the pause (duration of one respiratory
cycle). The patient’s intrinsic respiratory rate can thus be estimated as 12 breaths per minute (4.99 sec/60 sec). The horizontal dashed line
shows the time elapsed between the onset of two inspiratory efforts during control ventilation. Long dash dot horizontal lines show the duration
of the end-expiratory pause. Black arrows show the absence of plateau pressure, which indicates the presence of reverse triggering.
DPes = pressure swing in the esophageal pressure waveform during the end-expiratory pause; DPocc = pressure swing in the pressure–time
waveform during the end-expiratory pause; P0.1 = drop in the airway pressure time waveform during the first 100 ms of the end-expiratory
occlusion maneuver; Paw = airway pressure; Pes = esophageal pressure.

activity coincided with the time of the highest
degree of PCO2 during these periodic
oscillations (24). During controlled
ventilation, oscillations in the degree of PCO2
occur as a consequence of the ventilator’s
periodic insufflation and exhalation (25, 26).
Thus, PCO2 oscillations occurring during
controlled ventilation can induce respiratory
entrainment by phase-locking the onset of the
neural inspiratory time to the peak PCO2
degree achieved during each of these
oscillations (i.e., after the onset of the
mechanical insufflation) (24).
Lung inflation through vagal afferents
may also mediate respiratory entrainment via
the Hering-Breuer reflex (20, 27, 28). For
instance, a mechanical insufflation occurring
during the patient’s neural expiratory time
would activate vagal afferents evoking the
Hering-Breuer expiratory prolonging reflex.
Early animal models suggested vagal
afferents influencing the respiratory CPG
were important for respiratory entrainment
to occur as entrainment disappeared after
vagotomy (27). Vagal afferents facilitate
phase-locking in animals (28) and humans
during sleep (20). Later, however, it was
shown that vagal afferents are not mandatory
for respiratory entrainment to mechanical
ventilation because it has been reported in
vagotomized dogs (24) and double-lung
transplant patients (20, 29).
Stretching of intercostal muscles with rib
cage displacement and activation of the
intercostal-to-phrenic reflex is also
hypothesized to contribute to respiratory
entrainment (30, 31). During controlled
ventilation, the rib cage is periodically
displaced. Activation of intercostal muscle
spindles sends afferent signals to the CPG that
inhibit phrenic nerve activity and modify the
onset timing of the inspiratory effort (30, 31).
Stimuli from higher neural centers may
also contribute to respiratory entrainment in
critically ill patients, like periodic noise arising
from the ventilator, as happens with music.
The neural centers processing the auditory
stimuli send input to the respiratory CPG
with a specific frequency (i.e., the rhythm of
music). If the magnitude of the auditory
stimulus is stronger than that of other stimuli,
respiratory entrainment can occur (32).
Patterns of Respiratory Entrainment
During Controlled Ventilation
Respiratory entrainment can occur in a phase-
locked rhythmic pattern with the rhythm of
the mechanical insufflations at different
integral ratios (1, 13–15). It frequently occurs
in a 1:1 (one inspiratory muscle contraction
after each mechanical insufflation) or 1:2 (one
inspiratory muscle contraction after every
other mechanical insufflation) ratio (1, 13–15).
The integral ratio can be, however, modified
by factors such as incomplete exhalation,
hyperinflation, variable effort, breath stacking,
ventilator modes without a constant pattern
for breath delivery and cycling (e.g.,
synchronized intermittent mandatory
ventilation pressure control–pressure
support), or by changing the ventilator
parameters (e.g., inspiratory time, respiratory
rate, and tidal volume) (1, 12–15). All these
factors can make the apparent pattern look
irregular. Respiratory entrainment can also
occur in an apparently chaotic pattern (33)
with a lack of fixed temporal relationship with
mechanical insufflation (1, 13–15). However,
the phase-angle (see below) that expresses the
difference between patient effort compared
with the start of the mechanical insufflation
remains relatively constant across breaths,
lacking the natural variability of physiological
breathing (1).
Alternative Mechanisms (Reflex
Contraction without Entrainment of
the Respiratory CPG)
Reverse triggering has been reported in two
brain-dead patients without brainstem
function (34) and in patients with a lack
of inspiratory effort during long end-
expiratory occlusions (i.e., no intrinsic
activity from the CPG) (Figure 3). These
results suggest that reverse triggering can
also occur without entrainment of the
respiratory rhythm generator but as a
consequence of local reflexes, such as a
spinal reflex contraction of the respiratory
muscle during chest wall inflation (35).
Clinical Predisposing Factors
Predisposing factors that influence the
occurrence of reverse triggering and

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entrainment are related to characteristics of
the external stimuli (i.e., periodic insufflation
as dictated by mechanical ventilator settings)
or to patient intrinsic factors that modify
susceptibility to entrainment or facilitate the
occurrence of local reflexes (e.g., respiratory
drive, sleep stages, and sedation).
The tidal volume and respiratory rate
set on the ventilator modulate the intensity
and the characteristics of the stimulus-
inducing respiratory entrainment. Overall,
there is a range of rates within which the
respiratory rhythm can be entrained, related
to the intrinsic rate of the CPG (18, 20).
Reducing the ventilator rate can modify the
entrainment ratio or abolish reverse
triggering if the set rate falls below the
patient’s intrinsic rate and the patient starts
triggering the ventilator (8, 18, 20, 36). Set
tidal volume may also play an important role,
and most of the recent observations
described concerned patients with protective
ventilation and tidal volumes around 6 ml/kg
predicted body weight. In Damiani’s
experimental work in animals with lung
injury, reverse triggering was induced by
reducing tidal volume (4). In adult patients
with acute respiratory distress syndrome
(ARDS), reverse triggering was
independently associated with lower tidal
volumes set on the ventilator (5). Cause or
more likely a consequence, reverse triggering
was associated with larger tidal volumes in
pediatric patients with ARDS under pressure
controlled ventilation (12). In anesthetized
humans, larger tidal volumes reduce
respiratory entrainment by modifying the
onset time and duration of the triggered
breath and either changing the entrainment’s
integral rate or abolishing it (19). One
hypothesis is that greater lung insufflation
could activate the Hering-Breuer reflex,
shorten the neural inspiratory time
associated with the triggered breath or
prolong the neural expiratory time (19).
Greater lung insufflation can also change
arterial CO2, and it is possible that the high
occurrence of reverse triggering in recent
studies could be associated with more
frequent use of slightly elevated
concentrations of CO2 (37). CO2 is a classical
stimulus of the respiratory drive and
decreases susceptibility for respiratory
entrainment in animal models (38).
However, mild increases in the respiratory
drive because of increasing CO2
concentrations were not able to affect
respiratory entrainment in humans (18). In
summary, the relationship between tidal
Concise Clinical Review
volume and reverse triggering is complex as
there might be an interplay between tidal
volume and CO2 depending on the set
ventilator rate and the patient’s intrinsic
respiratory rate. In these circumstances,
particularly when patients are sedated with
opioids (see below) and have low intrinsic
respiratory rates, reverse triggering may
occur even with larger tidal volumes.
Sedation is associated with reverse
triggering. Reverse triggering is typically
found during the transition from deep
sedation to the patient resuming
spontaneous ventilation (1, 7, 8). Moreover,
specific drugs can increase the susceptibility
for reverse triggering, although this is not
fully elucidated. For instance, higher doses of
opioids but not benzodiazepines were
associated with increased susceptibility to
reverse triggering in adult patients with
ARDS (8).
Sleep can also change the susceptibility
to entrainment in healthy humans (18),
possibly because of the loss of modulation
from forebrain influences to perceived
respiratory sensations (e.g., lung inflation by
mechanical insufflation) during sleep (18).
The loss of such influences would reduce the
capacity of the respiratory CPG to modify
the respiratory rhythm and its susceptibility
to phase-locking with the rhythm of the
mechanical insufflations (18). Reverse
triggering dyssynchrony is often associated
with the transition between deep-to-light
sedation that a similar mechanism can
explain (8).
Diagnosis
General Principles
Different approaches can be used to identify
reverse triggering at the bedside, including
ventilator waveforms, displayed on most
ventilators (8), and more sophisticated
methods, such as the electric activity of the
diaphragm (EAdi) (7) and esophageal
pressure (Pes) (1, 3, 5, 9).
To classify a breath as reverse triggering,
it is necessary to first determine if the patient
or the ventilator initiated the mechanical
insufflation. Nowadays, most ventilators
indicate on their screens whether the
mechanical insufflation was triggered by the
ventilator or the patient, which facilitates
the identification process at the bedside.
To determine whether the mechanical
insufflation was triggered by the ventilator,
one can also check the following: absence of
deflection in the ventilator airway
pressure–time curve (Figures 1B and 1C); a
positive change in the Pes signal at the onset
of the mechanical insufflation (Figure 1C);
the absence of an increase in the EAdi signal
at the onset of the mechanical insufflation
(Figure 1B); and the expiratory time of the
previous breath is the expiratory time preset
on the ventilator in controlled ventilation
(Figures 1B and 1C) (1, 7, 9).
Ventilator Waveforms
During the ventilator’s expiratory time, the
patient effort can usually be detected by the
deformation of the expiratory flow–time
curve that lacks its normal exponential decay,
and a peak expiratory flow reduced
compared with breaths without reverse
triggering (Figures 1B and 1C) (1, 7–9).
During the inspiratory time of volume-
control ventilation, the airway pressure curve
shows a deformation induced by the effort. If
a short inspiratory pause is set at the end of
the ventilator’s inspiratory phase, patient
effort will cause an apparent decrease in
the plateau pressure during the pause
(Figure 1C) (1, 7–9).
During the inspiratory time of pressure-
control ventilation, there might be a subtle
drop in the airway pressure and an increase
in the flow–time curves, but often difficult to
detect (Figure 1B) (1, 7–9).
Reference Techniques: EAdi and Pes
EAdi and Pes can detect reverse triggering
(i.e., patient effort) (Figures 1B and 1C)
(7, 39). If the EAdi signal increases after the
onset of a mechanical insufflation triggered
by the ventilator, it indicates reverse
triggering (Figure 1B). Because ECG artifacts
in the EAdi signal can lead to false positives
(40), using different cutoffs for the peak EAdi
(e.g., >3 μv) may help improve accuracy (7).
An inspiratory muscle contraction will
generate a negative change in pleural
pressure and Pes (41). A negative swing in
Pes after an initial positive deflection at the
onset of a passive mechanical insufflation
triggered by the ventilator can detect reverse
triggering (Figure 1C) (1, 9). Campbell
diagrams constructed with the Pes signal
have also been used to detect reverse
triggering (3, 5).
Electrical Impedance Tomography
Reverse triggering has been described with
electrical impedance tomography giving a
secondary rise in ventilation (2).
539

Automated Techniques
Algorithms to identify reverse triggering
were developed on the basis of the criteria
described above. On the basis of only
ventilator waveforms (8, 9) or using EAdi
(7), they showed good accuracy, sensitivity,
and specificity in detecting reverse
triggering in relatively large data sets (7–9).
This highlights the feasibility of identifying
reverse triggering on the basis of signals
readily available at the bedside and the
potential for future largescale
implementation of these automated
methods in ICUs worldwide, which will
likely provide support to clinicians and for
future studies to improve reverse triggering
detection and management (7–9).
Expiratory Hold
Using an end-expiratory hold has been
suggested for differentiating patients with
reverse triggering from those with
spontaneous efforts during controlled
ventilation (42, 43). However, inspiratory
effort frequently occurs during the expiratory
hold in patients with reverse triggering
(see Figure 3) and depicts the intrinsic
respiratory rate of the patient lower than that
set in the ventilator.
Characterization of Reverse
Triggering
Phase angle. The phase-locking of the
inspiratory effort to the mechanical
insufflation is quantified by the phase angle,
which is the difference between the onset of
the mechanical insufflation and the onset of
the inspiratory effort (Figures 1A and 1B) (1):
Phase angle ð
Þ
Inspiratory effort onset time 2 mechanical insufflation onset time
5 360
,
mechanical ventilator cycle duration
in which the mechanical ventilator cycle
duration is the time elapsed between two
mandatory mechanical insufflations.
A phase angle of zero means the
simultaneous activity of the inspiratory
effort and the mechanical insufflation; a
negative phase angle means the inspiratory
effort began before the mechanical
insufflation; and a positive phase angle
means that the inspiratory effort began
after the mechanical insufflation (i.e.,
reverse triggering) (1).
In addition, the coefficient of variation
between the timing of the reverse-triggered
breaths is typically used to determine its
variability (1):
540 American Journal of Respiratory and Critical Care Medicine Volume 207 Number 5 | March 1 2023
Coefficient of variation ð%Þ
standard deviation of the phase angle
5 :
mean phase angle
It has been shown that during reverse
triggering with respiratory entrainment,
a lower coefficient of variation (e.g., less
than 15%) of its phase angle than the
normal variability of spontaneous
breathing is expected (43). Factors can
modify the entrainment ratio and may lead
to a greater coefficient of variation
(1, 12–15).
Phenotypes. Because the onset of the
reverse-triggered breath can occur either
during the inspiratory or expiratory time of
the ventilator, different phenotypes have
been suggested (3). Early reverse triggering
with early relaxation, when the maximum
effort and relaxation occur during the
ventilator inspiratory time; early reverse
triggering with late relaxation, when the
relaxation and termination of the reverse
triggering occur during the ventilator
expiratory time; midcycle reverse triggering,
when reverse triggering starts during the
ventilator inspiratory time of the ventilator,
but the maximal effort is reached during
the ventilator expiratory time; late reverse
triggering, when reverse triggering occurs
completely during the ventilator expiratory
phase; and reverse triggering leading to
double-cycling. These different phenotypes
were associated with different physiological
consequences, such as various degrees of
eccentric contraction (3).
Double breaths and breath stacking.
If strong enough, the inspiratory effort
associated with the reverse triggering can
cause the ventilator to trigger a second
mechanical insufflation, resulting in breath
stacking (Figure 1B) (1, 3, 15). It is important
to differentiate breath stacking caused by
reverse triggering from double triggering.
Double triggering is usually a consequence of
short cycling and high inspiratory drive. It
occurs when the same patient effort triggers a
first mechanical insufflation, continues after
the ventilator cycles off, and is strong enough
to trigger a second mechanical insufflation.
Managing this dyssynchrony requires
readjusting the ventilator when possible
CONCISE CLINICAL REVIEW
(e.g., increasing the tidal volume) or
reinforcing sedation to decrease respiratory
drive. As described above, it is often easy to
identify if the first mechanical insufflation is
triggered by the patient or by the ventilator
(Figure 1). When available, EAdi or Pes can
provide further information (Figure 1) (15).
Breath stacking can occur as a consequence
of reverse triggering, but the first mechanical
insufflation is triggered by the ventilator,
followed by an inspiratory effort, late and
strong enough to trigger a second
mechanical insufflation (Figure 1B) (1, 3, 15).
The differentiation between breath stacking
because of double triggering or reverse
triggering will impact the strategy for
managing ventilation and sedation. If breath
stacking occurs because of reverse triggering,
adjusting the ventilatory settings may have
little effect. The clinician may instead choose
to reduce or interrupt sedation to let the
patient control breathing frequency
(see below).
Clinical Implication of
Reverse Triggering
Reverse triggering may have various effects
on lung and diaphragm structure and
function (Table 1). Its consequences might
depend on the frequency, phenotype, and
degree of breathing effort. When reverse
triggering is observed at the bedside, a
careful assessment and interpretation should
be made.
Lung Consequences
Reverse triggering may be harmful to the
lungs because of multiple mechanisms.
Superimposing a spontaneous effort to a
ventilator breath has an additive effect on the
distending transpulmonary pressure and the
resulting tidal volume depending on the
mode. In pressure-control modes, tidal
volume is variable and is influenced by the
patient’s breathing efforts. Depending on the
phenotype, reverse triggering can increase
the average tidal volume and inspiratory
transpulmonary pressure (3). If deep and
long enough, the patient’s inspiratory effort
will persist beyond the end of the mechanical
insufflation, leading to double cycling, with
potentially the sum of two consecutive tidal
volumes. During volume-controlled
ventilation, pendelluft (i.e., inspiratory
transfer of gas from one part of the lung to
another, usually nondependent to dependent
lung [2]) may occur during reverse triggering
CONCISE CLINICAL REVIEW
without any increase in tidal volume and
could generate regional hyperinflation.
Pendelluft during reverse triggering can
induce regional overstretch in dependent
lung regions compared with that observed in
the same region during passive controlled
ventilation at the same tidal volume (2).
On the opposite, the potential lung
benefit from the (postinspiratory) expiratory
activity of the diaphragm was recently
demonstrated in a pig model of acute
hypoxemic respiratory failure (AHRF).
Diaphragmatic activity during the ventilator
expiratory phase delayed and reduced the
expiratory collapse and increased lung
aeration, compared with mechanical
ventilation with muscle paralysis and absence
of diaphragm activity (44). The diaphragm
can exert an expiratory braking effect
helping to preserve the end-expiratory lung
volume (44).
Diaphragm Consequences
Diaphragm activity during reverse triggering
often occurs during the ventilator expiratory
phase (e.g., midcycle reverse triggering),
resulting in an eccentric contraction. The
impact of diaphragm eccentric contractions
on its function and structure could go in
opposite directions and is associated with the
degree of breathing effort (4).
Reverse triggering may harm the
diaphragm when contractions repeatedly
occur during the ventilator’s expiratory
phase, concomitantly with lung volume
reduction and inspiratory muscle
lengthening in the context of excessive
breathing efforts (4). Animal models
demonstrated that the combination of
reverse triggering and high inspiratory effort
or induced eccentric contractions might be
associated with impaired diaphragm
structure and force-generating capacity
(4, 45). The potentially harmful effect of
these eccentric contractions relates to a lack
of homogeneity in sarcomeres stretching
(asymmetric lengthening), triggering a
cascade of events possibly leading to
inflammatory reaction and reactive oxygen
species production (46, 47).
Conversely, reverse triggering at low or
moderate efforts could help protecting
diaphragm function compared with passive
ventilation. Experimental data demonstrated
that reverse triggering resulting in low
breathing effort preserved diaphragm
function after 3 hours compared with passive
mechanical ventilation (4).
Concise Clinical Review
Clinical Outcomes
The impact of reverse triggering on patient-
centered outcomes is unknown.
Many breathing efforts during reverse
triggering are probably not excessive. In a
clinical study, muscular efforts (muscular
pressure) during reverse triggering had a
median (interquartile range, 25–75%) of 8.7
(5.6–9.9) cmH2O (9); the median peak EAdi
was 1.7 (0.8–4.3) μV (7); and the rate of
double-cycling was very low (,0.1–3% of
reverse-triggered breaths) (7, 8).
Evidence also supports that a positive
impact of reverse triggering in the early
phases of hypoxemic respiratory failure is
possible. In a prospective cohort study,
patients with a higher rate of reverse
triggering and low breathing effort (average
EAdi, 1.7 μV) had better oxygenation and
were more likely to progress to an assisted
mode or be extubated within the following
24 hours as compared with patients with a
low rate or no reverse-triggered breaths (7).
Moreover, reverse triggering has been
associated with reduced hospital mortality
(hazard ratio, 0.65; 95% confidence interval,
0.57–0.73), indirectly suggesting that reverse
triggering may be a marker of favorable
outcomes (8).
Possible Management
There is no direct evidence about the best
strategy to manage reverse triggering. If
reverse triggering is not associated with
potentially harmful consequences (e.g.,
double cycling, breath stacking, and/or
strong inspiratory efforts), perhaps no action
is required, and it can be used as a sign that
the patient may be close to being ready to
trigger the ventilator. If reverse triggering is
associated with these potentially harmful
consequences, modifying ventilator settings
or transitioning the patient to a spontaneous
ventilation mode should be considered.
Unfortunately, a frequent approach
clinicians adopt to manage patient–ventilator
dyssynchrony is increasing the depth of
sedation and, in some cases, paralysis with
neuromuscular blocking (48, 49). Paralysis
and sedation are associated with diaphragm
inactivity, muscle dysfunction (including the
diaphragm), longer ICU length of stay, and
potentially increased mortality (6, 50–53).
Increasing sedation to treat dyssynchronies,
including reverse triggering, is only
appropriate when dyssynchrony results in
excessive respiratory drive and effort and
after attempts to optimize ventilator settings,
metabolic derangements, and pain and
anxiety were implemented (52).
Assessing the Presence of Intrinsic
Respiratory Rate in Patients with
Reverse Triggering
Looking for the presence of intrinsic
respiratory rate in patients with reverse
triggering (Figure 3) can be the first step to
help the clinician decide whether the patient
has the potential to be transitioned to a
spontaneous mode of ventilation. A trial can
be made to transition the patient to a
spontaneous mode of ventilation and
sedation further reduced or stopped.
Changing Ventilator Settings
Reducing respiratory rate can, in some cases,
abolish reverse triggering. If the respiratory
rate is set below the patient’s intrinsic
respiratory rate, the patient can start
triggering the ventilator (8, 36). Decreasing
the rate may increase CO2, which may also
contribute to stopping the reverse triggering
process. Increasing respiratory rate seems to
have no (or a less clear) effect (8, 36). It can
be more complex if the patient has no
intrinsic respiratory rate and reverse
triggering occurs purely because of
respiratory entrainment. In this scenario,
reverse triggering is likely to occur over a
range of ventilator respiratory rates, which
can vary between patients and, for example,
be influenced by the integrity of (e.g., vagal
and/or phrenic) afferences to the CPG, the
intensity of the respiratory drive, ventilator
settings, and wakefulness and/or sleep stages
(20, 28, 38, 54).
Increasing the inspiratory time set on
the ventilator can reduce the number of
breath-stacking events in patients who are
mechanically ventilated (48). It should
be differentiated if breath stacking is caused
by reverse triggering or double triggering.
Even if breath stacking caused by reverse-
triggered breaths is abolished, reverse
triggering can still occur.
In patients with ARDS, reverse
triggering was associated with small set tidal
volumes (8). Increasing tidal volume on the
ventilator during volume-control ventilation
or increasing inspiratory time or driving
pressure during pressure-control ventilation
will induce larger tidal volumes, which may
shorten the duration of the inspiratory effort
associated with the reverse-triggered breath
and possibly mitigate breath-stacking or
strong efforts.
541
 CONCISE CLINICAL REVIEW

Assessing Breathing Effort in Patients
with Reverse Triggering
Assessing the magnitude of the effort
associated with the reverse-triggered breath
will help guide the management of reverse
triggering because the consequences to the
lungs and diaphragm are mediated by the
effort associated with the reverse-triggered
breath (2, 4).
The magnitude of the inspiratory effort
associated with the reverse-triggered breath
can be estimated during an end-expiratory
occlusion maneuver by calculating the airway
pressure swing in the pressure waveform (42,
55, 56) (Figure 3A) in patients who have an
intrinsic rate. Esophageal pressure swings can
also be used during the reverse-triggered
breath or during the end-expiratory occlusion
maneuver (Figure 3) (52, 57). There are no
reference values to determine whether a
patient’s inspiratory drive is adequate on the
basis of only EAdi signals (39, 52, 57).
Transitioning Patients to a
Spontaneous Mode of Ventilation
If the patient has an intrinsic respiratory rate
and clinically improving, a trial to transition
the patient to a spontaneous ventilation
mode (e.g., pressure support, (proportional
assist ventilation) PAV1, or (neurally
adjusted ventilatory assist) NAVA) can be
performed, ideally concomitantly to reducing
sedation. If the patient can sustain adequate
degrees of ventilation and effort, the
transition is likely beneficial, as it can
mitigate diaphragm atrophy without harmful
effects on the lungs and diaphragm (52).
However, if the patient cannot maintain
adequate degree of ventilation, lung injury is
still significant, or develops excessive
inspiratory effort, there is an increased risk of
lung and (load-induced) diaphragm injury,
and other management strategies might be
needed (58).
Reducing the sedation can also facilitate
the resumption of spontaneous breathing in
patients with reverse triggering and accelerate
the transition to a spontaneous ventilation
mode. If reverse triggering is associated with
excessive inspiratory efforts or double cycling,
which does not improve after changes in
ventilator settings and the patient cannot be
safely transitioned to a spontaneous mode of
ventilation, paralysis can be a last resource
option to mitigate possible harmful
consequences to the lungs and diaphragm.
Priorities for Research
Further work is necessary to better
characterize reverse triggering prevalence,
risk factors increasing its susceptibility, and
to elucidate when reverse triggering could be
beneficial or harmful for patients.
Prospective studies investigating the effects
of changes in ventilator settings, such as rate
and tidal volume, are necessary to support
the development of management strategies
that can be tested in randomized trials.
Studies with recordings of ventilator
waveforms 24 hours per day over multiple
consecutive days are also useful to provide a
clearer picture of the prevalence and
distribution (i.e., the presence of clusters
(59)) of reverse triggering in patients who are
mechanically ventilated. Moreover, which
factors influence the degree of effort
associated with reverse-triggered breaths is an
important question. Knowing whether the
same factors influencing the degree of effort in
patients triggering the ventilator (e.g., PCO2 )
could be useful in developing management
strategies. Finally, clinical and specifically
designed studies to assess the impact of
reverse triggering on lung and diaphragm
function and injury are also required.
Conclusions
Reverse triggering is highly prevalent in
sedated patients under mechanical ventilation
in a controlled mode. It can be either
beneficial or harmful for patients depending
on the magnitude of the effort associated with
it and its consequences on the interaction
between the patient and the ventilator. The
clinician at the bedside should be able to
perform the diagnosis, understand the
pathophysiological mechanisms and
predisposing factors associated with reverse
triggering, and use potential tools for its
management. Reverse triggering should not
be regarded as always harmful to the patient,
and in some cases, it can be interpreted as a
sign of readiness to resume spontaneous
ventilation. Careful assessment of ventilator
waveforms at the bedside can provide the
clinician with valuable information to decide
which management strategies (if any) might
be necessary. 䊏
Author disclosures are available with the
text of this article at www.atsjournals.org.

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