©
or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which may allow access COPYRIGHT 2021 EDIZIONI MINERVA MEDICA
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© 2020 EDIZIONI MINERVA MEDICA
Online version at http://www.minervamedica.it
The inscrutable signatures of patient-ventilator
asynchrony: all the light we cannot see
Department of Pediatrics, Critical Care Medicine, Albany Medical Center, Albany, NY, USA
*Corresponding author: Kathleen M. Ventre, Unit of Pediatrics, Critical Care Medicine, Albany Medical Center, Albany, NY, USA.
E-mail: ventrek@amc.edu
A t the turn of the 21st century, the ARDS
Network confirmed in a multicenter clini-
cal trial that tidal volume and plateau pressure
limitation attenuate inflammation and reduce
mortality1, 2 – adding substantially to a wealth of
evidence suggesting that the ventilator can be as
much a part of the problem as it is the solution
for patients with acute respiratory failure.3-5 Ac-
cordingly, a major focus of the lung protective
era has been the pursuit of supportive care strat-
egies that would allow critically ill patients to
be supported with the minimum effective dose
and duration of mechanical ventilation. To date,
several robust clinical trials have demonstrated
that dynamic, goal-directed sedation manage-
ment facilitates earlier liberation from the venti-
lator.6-8 This outcome is concordant with the ob-
servation that when the human body is oriented
horizontally, spontaneous breathing optimizes
diaphragmatic and respiratory system mechanics
in a manner that improves matching of ventila-
tion to perfusion and reduces the applied airway
pressures required to maintain functional re-
sidual capacity.9 Taken together, these findings
justify the now widespread practice of managing
ventilated patients in a state of greater wakeful-
ness using patient-triggered, “assisted” modes of
ventilation.
For all that evidence-based supportive care
practices for ventilated patients have contributed
toward improving outcomes over the past two
decades,10-13 there remains a growing awareness
278
Minerva Anestesiologica 2021 March;87(3):278-82
DOI: 10.23736/S0375-9393.20.15087-9
EDITORIAL
Kathleen M. VENTRE *
that optimization of patient-ventilator interac-
tions among spontaneously breathing patients
may represent the next frontier in reducing ex-
cess ventilator-associated morbidity. Patient-
ventilator asynchrony is exceedingly common; in
controlled settings it has been observed in up to
80-100% of the study population.14-16 Most com-
mon asynchrony patterns can be classified as flow
asynchronies, cycling asynchronies, and trigger
asynchronies (Table I). Flow asynchronies occur
when the ventilator flow is inadequate to meet
patient demand. Cycling asynchronies occur
when the set inspiratory time is out of synchrony
with the patient’s own “neural” inspiratory time.
Trigger asynchronies include ineffective efforts,
trigger delay, auto triggering and double trigger-
ing, a phenomenon resulting in the delivery of up
to twice the intended tidal volume. Each of these
patterns can manifest as noticeable increases in
patient work, to a degree that often prompts cli-
nicians to uptitrate patient sedation and/or the set
ventilator parameters. Such approaches can pro-
vide some short-term relief for the patient, but
over time they can potentially prolong ventilator
dependence and contribute to excess lung injury.
Published reports on the prevalence of patient
ventilator asynchronies began to proliferate as
the lung protective ventilation era was dawn-
ing. Using esophageal manometry to estimate
the timing of inspiratory muscle efforts, Fabry et
al. demonstrated significant asynchronies in 9/11
(82%) of adult patients transitioning to pressure
Minerva Anestesiologica March 2021
 ©
or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which may allow access COPYRIGHT 2021 EDIZIONI MINERVA MEDICA
cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo, or other proprietary information of the Publisher.
This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either sporadically
to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is not permitted to remove,
INSCRUTABLE SIGNATURES OF PATIENT-VENTILATOR ASYNCHRONY VENTRE
Table I.—Patient-ventilator asynchrony patterns.
Type Subtype
Trigger asynchrony Ineffective (“missed”) effortsPatient’s inspiratory effort does not trigger delivery of a ventilator
Trigger delay
Auto-triggering
Double triggering
Cycling (termination) Early cycling
asynchrony (premature breath termination) inspiratory time
Late cycling
(delayed breath termination)
Flow asynchrony
support ventilation, a median of three days af-
ter intubation.17 In seven (63%) of the patients,
≥10% of their inspiratory efforts did not trigger
a breath from the ventilator, a metric that would
come to be known in the research arena as a sig-
nificantly elevated missed efforts “asynchrony
index.” Subsequent investigators using mainly
standard ventilator waveform analysis went on to
confirm the high prevalence of patient-ventilator
asynchronies in spontaneously breathing adult
and pediatric patients, reporting all-cause asyn-
chrony indices (the proportion of ventilator cycles
demonstrating any asynchrony pattern) of ≥10%
in 24% to 80% of patients,15, 16, 18-20 occurring as
early as the first 24 hours of mechanical ventila-
tion.15 The prevalence of asynchronies tends to
depend on both patient and ventilator factors.
Higher prevalence is observed among patients
with heightened respiratory drive, airways ob-
struction (e.g. COPD), and low PaO2/FiO2 ratio,
as well as patients ventilated in assisted modes
with multiple set parameters (e.g. assist-control
mode), or those ventilated using PEEP, high lev-
els of pressure support, higher tidal volume, and
reduced tidal volume in combination with short
inspiratory time.16, 18, 21-25 The few available
studies examining the effect of patient-ventilator
asynchrony on patient outcomes have suggested
an association between asynchrony index >10%,
prolonged mechanical ventilation,15, 18, 19 pro-
longed hospitalization15 and mortality.19
To the extent that the prevalence of patient-
ventilator asynchronies is directly related to the
number of set parameters, elimination of these
events would entail allowing patients to assume
Vol. 87 - No. 3 Minerva Anestesiologica
Description
breath
Delivery of the ventilator breath is delayed relative to the timing of
the patient’s inspiratory effort
Ventilator breath is delivered in the absence of patient’s inspiratory
effort
Patient’s inspiratory effort triggers second ventilator breath before
exhalation of the initial triggered breath is complete
Set or automated inspiratory time is shorter than patient’s neural
Set or automated inspiratory time is longer than patient’s neural
inspiratory time
Set flow rate is insufficient to meet patient demand
a respiratory pattern that is in greater harmony
with their neural inclinations. Neurally adjusted
ventilatory assist (NAVA) is unique among con-
temporary modes in that it uses the onset and de-
cay of diaphragmatic electrical activity (EAdi) to
guide the initiation and termination of each venti-
lator breath, and delivers a breath proportional in
scale to the magnitude of this electrical signal26
(Figure 1).27-29 Published studies have consistent-
ly found that NAVA technology dramatically re-
duces the prevalence of asynchronies in patients
of all ages, when used in conjunction with either
an invasive30-34 or noninvasive35-37 interface.
More widespread use of this mode remains lim-
ited by the need for a specialized catheter fitted
with an electrode array to detect the EAdi, spe-
cialized ventilator software to record and process
the signal, and expertise in catheter placement
and titration of support in NAVA mode. In this
issue of Minerva Anestesiologica, Di Nardo et al.
use the transesophageal electromyogram as a di-
agnostic instrument, outside the context of NAVA
mode.38 These investigators added an EAdi trace
to traditional waveforms recorded from the ven-
tilator console, in an effort to determine whether
this information would improve pediatric in-
tensivists’ ability to diagnose patient-ventilator
asynchronies.38 They recorded digital pressure,
flow, and EAdi signals from 10 non-neonatal
patients during their first hour of ventilation in
PSV mode, where PEEP and FiO2 settings were
discretionary, PS was set to target an expiratory
tidal volume of 6-8 mL/kg actual body weight,
inspiratory rise time was set at 0.15s, inspiratory
flow trigger at 0.25 L/min, and expiratory trig-
279
 ©
or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which may allow access COPYRIGHT 2021 EDIZIONI MINERVA MEDICA
cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo, or other proprietary information of the Publisher.
This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either sporadically

to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is not permitted to remove,

VENTRE INSCRUTABLE SIGNATURES OF PATIENT-VENTILATOR ASYNCHRONY

↑ NAVA level
The work of Di Nardo et al. adds to published
Vo
lu
evidence from adult ICUs suggesting that pa-
m
e
co
nt
tient-ventilator asynchronies frequently go un-
↓ NAVA level
ro
l recognized, even in clinical settings with particu-
Ventilator pressure

Pressure control
lar expertise in ventilator management. In prior
work, Colombo et al. similarly recorded EAdi-
enhanced waveform tracings from a population
of 24 adults ventilated in PSV mode, to devel-
op an expert consensus regarding the presence
NA
VA and type of identifiable asynchrony patterns.23
Comparing this reference standard against the
Patient effort responses of 10 experienced intensivists and 10
Figure 1.—Relationship between ventilator pressure and pa- first year postgraduate trainees evaluating only
tient effort, as governed by the equation of motion for the re- the pressure and flow waveforms, the investi-
spiratory system.27-29 At a given elastic and resistive load, the
transrespiratory system pressure delivered by the ventilator gators found that each provider type accurately
is inversely related to patient effort in “volume controlled” diagnosed the asynchrony pattern with 88% and
modes of ventilation. In “pressure controlled” modes, venti- 93% specificity (P=0.10) but only 28% and 16%
lator pressure is unrelated to the magnitude of patient effort.
An essential distinction between either of these modes and sensitivity (P=0.03), respectively. The study also
NAVA mode is that in NAVA mode, ventilator pressure is confirmed the observation that clinicians have
directly related to patient effort. The curved arrow illustrates
that increasing the gain (“NAVA level”) allows the operator particular difficulty detecting auto-triggering and
to increase the intensity of mechanical support (i.e. the slope missed efforts, events whose signature on stan-
of the ventilator pressure vs. patient effort relationship) as
necessary for acute disease states and weaning the NAVA dard pressure or flow waveforms is often subtle
level reduces the intensity of support. The graphic illustrates or absent.23, 38 One of the study’s most compel-
the potential limitations of “volume controlled” modes in ling findings was that the rate of accurate asyn-
their capacity to unload respiratory muscles, and the theo-
retical advantages of NAVA in this regard. Modified from chrony detection decreased as the asynchrony
Kacmarek et al., Skorko et al., Younes et al.27-29 prevalence increased on any given trace, sug-
gesting that breathing patterns in which instances
ger at 25% of peak inspiratory flow. Data from of patient-ventilator asynchrony are not anoma-
two of the patients were excluded due to EAdi lous can easily evade human perception.
artifacts. Recordings from each of the remaining Together with studies of similar design, the
eight patients were segmented into 240 screen work of Di Nardo et al. raises the important
captures showing 15 seconds of pressure, flow, possibility that published prevalence estimates
and EAdi tracings. From the 1920 individual based on identification of asynchrony patterns
screen captures, the investigators used a consen- through expert analysis of traditional ventilator
sus process to curate a select group of six shots waveforms may underestimate the magnitude of
that demonstrated no more than one of three im- the patient-ventilator asynchrony problem. In its
portant asynchronies: double triggering, autotrig- present form, NAVA technology offers important
gering, and missed efforts. Versions of the final diagnostic and therapeutic advantages that po-
screen captures that included and excluded the sition it to play a prominent role in future mul-
EAdi signal were presented in random order to ticenter clinical trials powered to provide new
60 experienced pediatric intensivists as part of a insights into the relationship between patient-
10-minute written survey requiring them to iden- ventilator asynchrony and clinical outcomes.
tify the type of asynchrony in each figure. Results Looking further ahead, more reliable detection
of the survey indicated that inclusion of the EAdi of dysfunctional patient-ventilator interactions in
signal increased clinicians’ ability to detect auto- settings where NAVA is not feasible may depend
triggering (13% to 67% [P<0.0001]) and missed on the development and refinement of integrated
efforts (43% to 95%; P<0.0001) but did not add software packages capable of identifying asyn-
much to their ability to identify double triggering chrony patterns that would otherwise remain out-
(78% without vs. 85% with EAdi; P=0.52).38 side the limits of human apprehension.39, 40 For

280 Minerva Anestesiologica March 2021

 ©
or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other means which may allow access COPYRIGHT 2021 EDIZIONI MINERVA MEDICA
cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo, or other proprietary information of the Publisher.
This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either sporadically
to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is not permitted to remove,
INSCRUTABLE SIGNATURES OF PATIENT-VENTILATOR ASYNCHRONY VENTRE
now, addressing a potentially important modifi-
able risk factor for ventilator associated injury
may well await a day when technology can il-
luminate things currently unseen.
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cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo, or other proprietary information of the Publisher.
This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies (either sporadically

to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is not permitted. It is not permitted to remove,

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Conflicts of interest.—The author certifies that there is no conflict of interest with any financial organization regarding the material
discussed in the manuscript.
Authors’ contributions.—The author read and approved the final version of the manuscript.
Comment on: Di Nardo M, Lonero M, Staffieri F, Di Mussi R, Murgolo F, Lorusso P, et al. Can visual inspection of the electrical
activity of the diaphragm improve the detection of patient-ventilator asynchronies by pediatric critical care physicians? Minerva
Anestesiol 2021;87:319-24. DOI: 10.23736/S0375-9393.20.14543-7.
History.—Article first published online: October 15, 2020. - Manuscript accepted: September 30, 2020. - Manuscript received: July
31, 2020.
(Cite this article as: Ventre KM. The inscrutable signatures of patient-ventilator asynchrony: all the light we cannot see. Minerva
Anestesiol 2021;87:278-82. DOI: 10.23736/S0375-9393.20.15087-9)

282 Minerva Anestesiologica March 2021