Neurally adjusted ventilatory assist and proportional assist ventilation both improve patient-ventilator interaction
Schmidt et al. Critical Care
Neurally adjusted ventilatory assist and proportional assist ventilation both improve patient-ventilator interaction
Matthieu Schmidt 0 1
Jrme Cecchini 0 1
Elise Morawiec 0 1
Thomas Similowski 0 1
Alexandre Demoule 0 1
0 INSERM, UMR_S 1158 Neurophysiologie Respiratoire Experimentale et Clinique , F-75005 Paris , France
1 Sorbonne Universites, UPMC Univ Paris 06, UMR_S 1158 Neurophysiologie Respiratoire Experimentale et Clinique , F-75005 Paris , France
Introduction: The objective was to compare the impact of three assistance levels of different modes of mechanical ventilation; neurally adjusted ventilatory assist (NAVA), proportional assist ventilation (PAV), and pressure support ventilation (PSV) on major features of patient-ventilator interaction. Methods: PSV, NAVA, and PAV were set to obtain a tidal volume (VT) of 6 to 8 ml/kg (PSV100, NAVA100, and PAV100) in 16 intubated patients. Assistance was further decreased by 50% (PSV50, NAVA50, and PAV50) and then increased by 50% (PSV150, NAVA150, and PAV150) with all modes. The three modes were randomly applied. Airway flow and pressure, electrical activity of the diaphragm (EAdi), and blood gases were measured. VT, peak EAdi, coefficient of variation of VT and EAdi, and the prevalence of the main patient-ventilator asynchronies were calculated. Results: PAV and NAVA prevented the increase of VT with high levels of assistance (median 7.4 (interquartile range (IQR) 5.7 to 10.1) ml/kg and 7.4 (IQR, 5.9 to 10.5) ml/kg with PAV150 and NAVA150 versus 10.9 (IQR, 8.9 to 12.0) ml/kg with PSV150, P <0.05). EAdi was higher with PAV than with PSV at level100 and level150. The coefficient of variation of VT was higher with NAVA and PAV (19 (IQR, 14 to 31)% and 21 (IQR 16 to 29)% with NAVA100 and PAV100 versus 13 (IQR 11 to 18)% with PSV100, P <0.05). The prevalence of ineffective triggering was lower with PAV and NAVA than with PSV (P <0.05), but the prevalence of double triggering was higher with NAVA than with PAV and PSV (P <0.05). Conclusions: PAV and NAVA both prevent overdistention, improve neuromechanical coupling, restore the variability of the breathing pattern, and decrease patient-ventilator asynchrony in fairly similar ways compared with PSV. Further studies are needed to evaluate the possible clinical benefits of NAVA and PAV on clinical outcomes.
Partial ventilatory assistance minimizes adverse effects of
controlled mechanical ventilation, such as excessive
sedation and ventilator-induced diaphragm dysfunction
[1-3]. The most widely used partial ventilatory assistance
mode is pressure support ventilation (PSV) , in which
a constant preset level of pressure assists each inspiration,
regardless of the patients inspiratory effort. Mismatching
between patient demand and level of assistance is therefore
possible and can be potentially harmful: underassistance
may induce respiratory discomfort , and overassistance
may cause lung overdistention and volutrauma . Of
note, underassistance and overassistance may both
generate patient-ventilator asynchrony that is associated with
poorer clinical outcomes .
Proportional Assisted Ventilation (PAV) and Neurally
Adjusted Ventilatory Assist (NAVA) have been designed
to overcome this weakness of PSV. These two modes
adjust proportionally the amount of assistance delivered.
NAVA adjusts ventilator assistance to the electrical
activity of the diaphragm (EAdi), recorded with an
esophageal catheter . PAV adjusts ventilator assistance
to the activity of respiratory muscles estimated by an
algorithm . Previous studies have shown the potential
benefits of PAV and NAVA to prevent the risk of
overassistance [10-13], to increase the variability of the
breathing pattern [14-20], and to improve patient-ventilator
interaction and synchrony [11,12,21-26]. PAV and NAVA
have been previously compared with PSV but not with
each other. This comparison would be clinically relevant,
as these two modes have their own specific strengths
and weaknesses [9,27].
In the study reported here, we hypothesized that PAV
and NAVA improve patient-ventilator interaction in
similar ways. The aim of this study was therefore to
compare, in patients recovering from acute respiratory
failure, the respective impacts of various levels of NAVA,
PAV, and PSV on four major features of patient-ventilator
interaction: (1) breathing pattern, including prevention of
overassistance; (2) respiratory drive; (3) breathing pattern
variability, and (4) patient-ventilator synchrony.
Materials and methods
The study was conducted over a period of 3 months in a
10-bed Intensive Care Unit (ICU) in an 1,800-bed
university hospital. The protocol was approved by the
Comite de Protection des Personnes Ile de France VI.
Informed consent was obtained from patients or relatives.
Patients initially intubated and ventilated in the ICU
were eligible for inclusion in the study if (1) they had
been ventilated for acute respiratory failure via an
endotracheal tube for more than 48 hours, (2) the condition
that had required mechanical ventilation had improved
(in particular, the ability to trigger the ventilator with an
FiO2 of 50% and positive end-expiratory pressure
(PEEP) 5 cmH2O), (3) sedation had been stopped for
more than 6 hours, (4) hemodynamic stability was
achieved without vasopressor or inotropic medication.
Exclusion criteria were known or suspected phrenic
nerve dysfunction or other neuromuscular disorders that
may involve the diaphragm or impair respiratory drive.
Patients with contraindications to EAdi catheter
placement (for example, gastroesophageal varices or
obstruction, recent gastroesophageal surgery, facial surgery or
trauma, or upper gastrointestinal bleeding) were
excluded. Patients in whom the decision had been made to
withhold life-sustaining treatment were also ineligible
The conventional nasogastric tube was removed and
replaced by a 16 Fr EAdi catheter (Maquet Critical Care,
Solna, Sweden), and its position was controlled
according to the manufacturers recommendations . PSV
and NAVA were delivered by using a Servo-I ventilator
(Maquet Critical Care), and PAV+ was delivered by
using a PB840 ventilator (Covidien, Boulder, CO, USA).
Male and female patients were ventilated with an 8- and
7.5-mm internal diameter endotracheal tube, respectively.
Inspiratory pressure support level was initially titrated to
obtain a tidal volume (VT) of 6 to 8 ml/kg of predicted
ideal body weight. Flow-trigger sensitivity was set at the
lowest possible level without inducing autotriggering,
and cycling-off was set at 30% of peak inspiratory flow
(default value). This level of assistance was defined as
PSV100. Patients were then switched to NAVA, and the
corresponding NAVA level to obtain a similar VT of 6 to
8 ml/kg was determined during a 5-minute period. This
NAVA level was termed NAVA100. Patients were finally
switched to PAV, and the percentage unloading (%Assist)
was set also to obtain a similar VT of 6 to 8 ml/kg.
This %Assist corresponded to PAV100. In each of the
three modes, the assist level was further decreased by
50%, corresponding to PSV50, NAVA50, and PAV50
and then increased by 50%, corresponding to PSV150,
NAVA150, and PAV150. In the Results section, PSV100,
NAVA100, and PAV100 define a medium assistance level
also termed level100; PSV50, NAVA50, and PAV50 define a
low assistance level, also termed level50; and PSV150,
NAVA150, and PAV150 define a high assistance level also
termed level150. Of note, inspiratory pressure-support
level in PSV50 could not be lower than 7 cmH2O. A high
upper pressure limit at 45 cmH2O was set in PAV and
Positive end-expiratory pressure (PEEP) and inspired
oxygen fraction (FiO2) were maintained constant
throughout the study period at the values in use before
patient enrollment. The endotracheal tube was suctioned
before the beginning of each trial. Each patient
underwent three 30-minute trials, in each mode, consisting of
20-minute stabilization followed by 10-minute recording
stored on a computer for further analysis. The three
modes were applied in computer-generated random
order. At the end of each trial, arterial blood was
sampled for gas analysis (Radiometer ABL 330, Tacussel,
Copenhagen, Denmark) via a catheter, and dyspnea was
rated by using a visual analogue scale when possible.
Flow was measured with a heated Fleisch
pneumotachograph, dead space 51 ml (Hans Rudolph, Kansas City,
MO, USA) and airway pressure was measured by a
pressure transducer (DP 1532, Validyne, Northridge, CA,
USA) for all modes. Digital EAdi signal was converted
into an analog signal (National Instruments, Austin, TX,
USA). During all three modes of ventilation, the EAdi
waveform was simultaneously recorded with flow and
airway pressure from the respective ventilator (see
Additional file 1). All signals were digitized at a 100-Hz
sampling rate (PowerLab/4SP, ADInstruments, Castle Hill,
Australia) and recorded on a personal computer for
subsequent analysis (Chart software, ADInstruments, Castle
comparison by using the Dunn post/hoc test. The
relationships among both EAdimax and Pmax and EAdiAUC and VT
were examined by using a linear regression analysis, and
the coefficient of correlation (r2) was determined.
Differences were considered significant when the probability p of
a type I error was less than 5%.
Respiratory Parameters and Breathing Pattern
Neural respiratory rate (RR), VT, duration of pneumatic
inspiration (Ti), maximum EAdi, (EAdimax), area under
the curve of EAdi during inspiratory time (EAdiAUC,
integrated from baseline to peak), and the VT-(ml/kg)/
Eadimax ratio were calculated offline from the 10-minute
airway flow and EAdi recordings. The coefficient of
variation (standard deviation divided by the mean) for both
flow (CVVT) and EAdi-related variables (CVEAdimax) was
calculated. Maximum (Pmax) and mean inspiratory
airway pressure (Pmean) were measured and calculated from
airway pressure recordings.
Within the three modes and in all conditions,
correlations between EAdimax and Pmax and between EAdiAUC
and VT were calculated. The inspiratory trigger delay
was measured as the time difference between the
beginning of the increase in the EAdi signal and the beginning
of the ventilator inspiratory flow. The expiratory trigger
delay was measured as the time difference between
EAdimax and the end of the insufflation, as defined by a
ventilator inspiratory flow equal to zero. Using the EAdi
waveform, we quantified the three main types of
asynchronies accordingly to previously published definitions
[7,25] (see also Additional file 2): (1) ineffective efforts;
(2) auto-triggering, and (3) double triggering. Of note,
only type II double triggering, defined as one neural
inspiration triggering two breath cycles, was considered
 (see example in Additional file 3). The number
of each type of asynchrony was reported as the total
number of each event per minute. A global asynchrony
index (AI) was computed .
Statistical analysis was performed with Prism 4.01
software (GraphPad Software, San Diego, CA, USA).
Normality testing failed for all results
(KolmogorovSmirnov). Results are therefore expressed as median (25 to
75 interquartile range). Within each of the three assistance
level groups (that is, level50, level100, and level150),
Friedman ANOVA for repeated measures was performed
to compare breathing pattern, variability, prevalence of the
main asynchronies and blood gases measured with PAV,
NAVA, and PSV, respectively. Comparison between the
three modes was followed, when appropriate, by a pairwise
The study pertains to a convenience sample of 16
patients (10 males). Their main characteristics and
the precipitating factor of acute respiratory failure are
summarized in Table 1. Respective assistance levels used
for each mode are reported in Table 2. Of note, three
patients had chronic obstructive pulmonary disease
(COPD) (patients 5, 7, and 16).
Breathing pattern and electrical activity of the diaphragm
Group median values for representative breathing
pattern variables are provided in Figure 1 and Figure 2 (see
also Additional file 4). Inspiratory pressures for each
patient under all conditions are displayed in Additional file 4.
Median airway pressure was similar among level100 and
level150 groups. Within all assistance levels (level50, level100,
level150), Pmax was higher with NAVA than with PAV and
PSV (P = 0.001; Figure 1, Table 3). At level50 and level100,
VT was similar among modes. However, at a high
assistance level, VT was significantly higher with PSV150 than
with NAVA150 and PAV150 (P < 0.05). Tidal volume was
similar with NAVA and PAV regardless of the assistance
level. Inspiratory time and RR remained similar within all
modes and at each level of assistance. Of note, at level100,
and level150, EAdimax and EAdiAUC were higher in PAV
than in PSV (Figure 2; Table 3). Whereas the VT/EAdimax
ratio was similar among groups at level50, it was
higher with PSV than with PAV at level100 and level150
(P <0.0001). In addition, the VT/EAdimax ratio was
higher with PSV (P <0.0001) but did not differ between
PAV and NAVA regardless of the assistance level.
Group median values for coefficient of variation VT and
EAdimax are provided in Figure 3 (see also Additional
file 5). The coefficient of variation of VT was higher
with PAV and NAVA than with PSV at level100 and
level150 (P <0.05), whereas the coefficient of variation
of VT was similar between NAVA and PAV at each level
of assistance. Conversely, the coefficient of variation of
EAdimax did not change according to ventilator mode
and level of assistance, except at level150, where it was
lower with PAV150 than with PSV150.
Table 4 and Additional file 6 show the inspiratory and
expiratory trigger delays, the correlation between both
Table 1 Patient characteristics at enrollment
Patient no. Age (years) BMI (kg.m2) SAPS 2
Acute respiratory failure due to 7
decompensation of COPD
Acute respiratory failure due to 7
decompensation of COPD
Acute respiratory failure due to 21
decompensation of COPD
Median (IQR) 67 (6375)
0.5 (0.5-0.5) 4 (45)
M, male; F, female; BMI, body mass index; SAPS II, Simplified Acute Physiology Score II; MV, mechanical ventilation; PEEP, positive end-expiratory pressure;
IQR, interquartile range; ARDS, acute respiratory distress syndrome, COPD, chronic obstructive pulmonary disease.
VT and Pmax and EAdi, and the prevalence of
patientventilator asynchrony in each condition. Inspiratory
trigger delay was significantly lower in NAVA than in
PAV and PSV at level100 and level150, respectively.
Similarly, expiratory trigger delay was lower during
NAVA100 and NAVA150 than during PSV100 and
PSV150, respectively (Table 4). The correlation
between EAdiAUC and VT, was higher during NAVA
and PAV than during PSV (Table 4). The correlation
between EAdimax and Pmax was higher during NAVA
than during PAV and PSV (Table 4). At each level of
assistance, almost no ineffective efforts were reported
with PAV and NAVA, whereas the ineffective efforts
were detected with PSV at a higher level (P <0.05).
Inversely, although very few double-triggering events
were observed with PSV and PAV, the prevalence of
double triggering was significantly higher with NAVA
(P <0.05, Table 4). Type II double triggering was due
to ventilator cycled off when the EAdi dropped to
70% of its peak, followed by a rebound in inspiratory
flow, cause of the retriggering, when cycled off to
PEEP (see Additional file 3).
Table 2 Assistance levels in each experimental condition
Mode, assistance setting Level50 Level100
PSV, inspiratory pressure (cmH2O) 7.0 (7.0-7.2) 14.0 (11.5-15.2)
PAV, proportion of assistance (%)
The NAVA level is a proportional gain factor expressed in
cmH2O/V of EAdi. It represents the magnitude (in cmH2O)
of positive airway pressure applied per V EAdi during the
course of each inspiration.
The proportion of assistance is the percentage of work
provided by the ventilator. The rest of the work is provided
by the patient.
EAdi, electrical activity of the diaphragm; PSV, pressure support ventilation; NAVA, neurally adjusted ventilatory assist; PAV, proportional assist ventilation.
Data are provided as median (interquartile range).
Figure 1 Impact of ventilator mode and level of assistance on
mean (Pmean) and maximum airway pressure (Pmax). Pressure
support ventilation (PSV)100, neurally adjusted ventilatory assist
(NAVA)100, and proportional assist ventilation (PAV)100 are medium
levels of assistance set to obtain a tidal volume (VT) between 6 and
8 ml/kg ideal body weight. PSV50, NAVA50 and PAV50 are low levels
of assistance defined by decreasing the assistance level by 50% in
each condition. Inversely, PSV150, NAVA150, and PAV150 are defined
by increasing the assistance level by 50% in each condition. *P <0.05
with PSV; P <0.05 with NAVA. Data are expressed as median and
No autotriggering was observed in any condition.
Overall, the asynchrony index was significantly lower with
PAV50 and PAV100 than with NAVA50 and NAVA100,
respectively (P < 0.05). Of note, only two patients exhibited
an AI >10% in PSV150, mostly due to a high number of
ineffective efforts (patients 7 and 14). Dyspnea was able to
be evaluated in only two patients because of insufficient
cooperation (data not shown).
Neither the mode (PSV, NAVA, PAV) nor the level of
assistance (level50, 100, 150) influenced PaO2, PaCO2, or pH,
which remained not significantly different between all
conditions, except for PaCO2 that was higher and pH
that was lower with PAV100, than with NAVA100 (see
Additional file 7 for detailed blood gas values).
The main findings of our study are as follows: (1) PAV
and NAVA both prevented overassistance-induced
hyperinflation, in contrast with PSV; (2) PAV and NAVA
restored a comparable level of breathing-pattern variability
that was greater than the variability observed with PSV;
(3) Regardless of the level of assistance, PAV and NAVA
induced less patient-ventilator asynchrony than PSV, with
the exception of double triggering, which was more
frequent with NAVA. The similarities observed between
NAVA and PSV in terms of breathing pattern, variability,
and asynchrony are consistent with the conceptual
similarities of these two modes.
Breathing pattern and central respiratory neural output
Increasing PSV assist levels were associated with
increasing VT values, in keeping with previous data [29,30]. In
contrast, VT remained stable with NAVA and PAV,
despite increasing assist levels [12,31], suggesting that these
modes protect against overdistention. With PSV, the end
of the patients inspiratory effort does not determine
cycling-off of the ventilator. A patient may therefore
trigger a PSV breath with a small inspiratory effort, then
relax, and be passively insufflated. If this breath is given
at an excessive assist level, the insufflation may continue
while the patient has already stopped inspiring. In
contrast, with PSV, NAVA and PAV deliver an insufflation
that stops when either the output of the inspiratory
centers to the diaphragm ends, in the case of NAVA (12), or
when the inspiratory muscle activity ends, in the case of
In addition, because overdistention contributes to
downregulate the activity of respiratory control centers
(29), tidal volume is maintained constant with PAV and
NAVA but not with PSV. The robustness of this
protective biofeedback provided by proportional modes, as
opposed to PSV, is illustrated in the present study by
the marked alteration of the coupling between VT and
EAdimax (that is, higher VT /EAdi ratio) observed with
PSV at high levels of assistance (see Figure 2), which was
not observed with the two proportional modes.
Fluctuations in the resting breathing pattern of healthy
humans have been known for a long time . Breathing
pattern variability seems to originate from the activity of
central pattern generators . It is further influenced by
the loadcapacity relationship of the respiratory system:
the higher the loading, the lower the variability [19,34,35].
In the present study, the variability of VT with NAVA
and PAV was greater than with PSV at each assistance
Figure 2 Impact of ventilator mode and level of assistance on the major descriptors of breathing pattern and diaphragmatic electrical
activity (EAdi). Pressure support ventilation (PSV)100, neurally adjusted ventilatory assist (NAVA)100, and proportional assist ventilation (PAV)100 are
medium levels of assistance set to obtain a tidal volume (VT) between 6 and 8 ml/kg ideal body weight. PSV50, NAVA50 and PAV50 are low levels
of assistance defined by decreasing the assistance level by 50% in each condition. Inversely, PSV150, NAVA150, and PAV150 are defined by increasing
the assistance level by 50% in each condition. EAdimax, peak of EAdi; RR, respiratory rate; VT/Eadimax, neuromechanical coupling. *P <0.05 with PSV.
Data are expressed as median and interquartile range.
level. In contrast, the variability of EAdi was similar
between the three modes, except at high assistance level.
These data indicate that the increase in breath-to-breath
variability observed during NAVA and PAV is actually
due to unmasking of the underlying variability in
central respiratory neural output and is a direct result of
improvement of neuromechanical coupling. To our
knowledge, these data, previously described in NAVA
, have never been described with PAV. They suggest
that PAV and NAVA both improve neuromechanical
coupling in similar ways.
As previously observed, NAVA and PAV improved
patient-ventilator synchrony as compared with PSV
[12,21,22,24,25,31]. Although inspiratory trigger delays
in all modes were consistently greater than previously
reported [11,36,37], lower inspiratory and expiratory
trigger delays seemed to be more frequently noted in
NAVA. Wide variability of the delays (see Additional
file 6) and their greater values can be ascribed to
different ventilators used, varying levels of assist provided,
experimental settings themselves, and the different
etiologies of respiratory failure. It is noteworthy that, in the
present study, PAV and NAVA provided a similar benefit
on ineffective triggering. It suggests that PAV and NAVA
improve the relationship between EAdi and tidal volume
in a similar way, which in turn prevents chest
hyperinflation, a major risk factor for ineffective triggering .
Two types of double triggering have been described in
NAVA . Type I double triggering is the result of a
biphasic EAdi signal, but its significance is unknown,
which is why, strictly speaking, it cannot be considered
to be patientventilator asynchrony. With type II double
triggering, however, one neural inspiration triggers two
breaths, which was due to ventilator cycle off when the
EAdi dropped to 70% of its peak, followed by a rebound
in inspiratory flow, cause of the re/-triggering, when
cycled off to PEEP. Pneumatic trigger set to pressure
instead of flow might limit the rebound in inspiratory
flow. We therefore considered only type II double
triggering in the present study and observed that this
asynchrony was significantly more frequent with NAVA than
with PSV and PAV. The relevance of this asynchrony
and how to decrease its prevalence in NAVA need
further investigations .
The correlation between VT and EAdiAUC was much
weaker in PSV than in NAVA or PAV, whereas no
Table 3 Impact of ventilator mode and level of assistance
on the main descriptors of breathing pattern and
electrical activity of the diaphragm (EAdi)
PSV NAVA PAV
Inspiratory time (sec)
level150 1.67 (0.64-3.22) 0.83 (0.37-1.60)*
EAdimax, peak EAdi; EAdiAUC, area under the EAdi curve; Pmean; mean inspiratory
airway pressure; Pmax, maximum inspiratory airway pressure; PSV, pressure
support ventilation; PAV, proportional assist ventilation; NAVA, neurally adjusted
Level100 is a medium assistance level set to obtain a VT of 6 to 8 ml/.kg ideal
body weight. Level50 is a low assistance level defined as level100 decreased by
50%. Level150 is a high assistance level defined as level100 increased by 50%.
Data are provided as median (interquartile range).
*P <0.05 with PSV; P <0.05 with NAVA.
Figure 3 Impact of ventilator mode and level of assistance on
the coefficient of variation of tidal volume (CVVT) and maximum
electrical activity of the diaphragm (CVEAdimax). Pressure support
ventilation (PSV)100, neurally adjusted ventilatory assist (NAVA)100,
and proportional assist ventilation (PAV)100 are medium levels of
assistance set to obtain a tidal volume (VT) between 6 and 8 ml/kg
ideal body weight. PSV50, NAVA50 and PAV50 are low levels of
assistance defined by decreasing the assistance level by 50% in each
condition. Inversely, PSV150, NAVA150 and PAV150 are defined by
increasing the assistance level by 50% in each condition. *P <0.05
with PSV; P <0.05 with NAVA; Data are expressed as median and
significant difference was found between NAVA and
PAV, which demonstrates that these two modes provide
an assistance that is proportional to the central
respiratory drive. This is consistent with the recent report from
Akoumianaki et al. , showing that the correlation
between the inspiratory integral of transdiaphragmatic
pressure and the VT was weaker with NAVA than with
PAV . Interestingly, the correlation between EAdimax
and Pmax was higher in NAVA than in PAV, which may
have two distinct explanations. First, during NAVA,
EAdi and airway pressure are by definition strictly
proportional and a strong correlation between EAdimax and
Pmax is intrinsic to NAVA. Second, as opposed to NAVA
Table 4 Impact of ventilator mode and level of assistance
on patient-ventilator interaction and asynchrony indices
PSV NAVA PAV Inspiratory trigger delay (msec)
162 (109241) 157 (138289)
170 (140282) 124 (100238)
266 (140427) 164 (99278)*
156 (112191) 151 (125175)
212 (176273) 157 (140188)* 182 (116230)
255 (227541) 146 (131218)* 225 (169333)
0.02 (0.01-0.04) 0.56 (0.51-0.65)* 0.02 (0.00-0.04)
0.03 (0.01-0.08) 0.85 (0.78-0.90)* 0.04 (0.00-0.07)
0.03 (0.01-0.06) 0.64 (0.43-0.88)* 0.03 (0.02-0.08)
0.15 (0.14-0.19) 0.48 (0.40-0.57)* 0.39 (0.25-0.45)*
0.13 (0.06-0.22) 0.64 (0.60-0.79)* 0.29 (0.21-0.42)
0.02 (0.01-0.06) 0.72 (0.65-0.88)* 0.28 (0.25-0.41)*
0.00 (0.00-0.07) 0.00 (0.00-0.00)* 0.00 (0.00-0.00)*
0.03 (0.00-0.26) 0.00 (0.00-0.00)* 0.00 (0.00-0.00)*
0.27 (0.01-1.23) 0.00 (0.00-0.00)* 0.00 (0.00-0.00)*
0.00 (0.00-0.03) 0.00 (0.00-0.00) 0.00 (0.00-0.00)
0.00 (0.00-0.03) 0.00 (0.00-0.00) 0.00 (0.00-0.00)
0.00 (0.00-0.00) 0.00 (0.00-0.00) 0.00 (0.00-0.00)
0.00 (0.00-0.00) 0.42 (0.08-0.50)* 0.00 (0.00-0.00)
0.00 (0.00-0.18) 0.33 (0.10-0.92)* 0.00 (0.00-0.10)
0.00 (0.00-0.21) 0.30 (0.02-0.87)* 0.00 (0.00-0.20)
0.21 (0.00-0.65) 1.41 (0.34-2.91)* 0.13 (0.00-0.44)
0.61 (0.04-1.28) 1.73 (0.38-2.69) 0.00 (0.00-0.58)
level150 1.65 (0.58-5.77) 1.17 (0.05-3.99) 0.19 (0.00-1.12)
EAdiAUC, area under the diaphragmatic electrical activity curve; PSV, pressure
support ventilation; NAVA, neurally adjusted ventilatory assist; PAV, proportional
assist ventilation; VT, tidal volume. Level100 is a medium assistance level set to
obtain a VT of 6to 8 ml/kg ideal body weight. Level50 is a low assistance level
defined as level100 decreased by 50%. Level150 is a high assistance level defined as
level100 increased by 50%.
The number of each type of asynchrony is reported as the total number of each
event per minute. Asynchrony index is defined as the total number of asynchrony
events 100/(ventilator respiratory rate + ineffective efforts).
*P <0.05 with PSV; P <0.05 with NAVA; data are expressed as median
that delivers an assistance proportional to the only
diaphragm activity, PAV delivers an assistance that is
proportional to the whole inspiratory activity of respiratory
muscles. As a consequence, PAV integrates not only
diaphragm activity, but also the activity of
extradiaphragmatic inspiratory muscles such as scalenes or parasternal
intercostal muscles .
Limitations of the study
Our study has several limitations. First, as patients at
high risk of asynchrony (for example, difficult-to-wean
or severe COPD patients) were not specifically selected
in this study  and because we targeted a VT of 6 to
8 ml/kg in level100 , a very low incidence of
asynchrony was observed with all modes and conditions.
This study may therefore have underestimated the
benefits of NAVA and PAV [20,39,41,42], but we deliberately
decided to compare these modes in patients in the
recovery phase after acute respiratory failure encountered
in daily practice rather than in a very selected
population, with the risk of showing results that would be
transposable only to a niche population.
Second, the trials in our study were probably not
sufficiently long to allow an improvement of gas exchange.
This might explain why, despite a greater variability of
the breathing pattern in PAV and NAVA, no impact on
PaO2 was observed in contrast with previously published
Third, the choice of a resulting VT of 6 to 8 ml/kg to
match the assistance level100 with the three modes may
be questionable. Indeed, a poor correlation between VT
and PAV %Assist  as well as NAVA level  has
been reported. In addition, the high VT variability may
have jeopardized the accuracy of its setting. However,
the fact that we observed a comparable Pmean with the
three modes at assistance level100 suggests that the
patients received a comparable level of assistance.
Fourth, because we focused on patients in the recovery
phase after acute respiratory failure and because PSV50
could not be lower than 7 cmH2O, PSV100 settings could
sometimes be very close to PSV50.
Fifth, although the expiration starts at 70% of the
EAdimax in NAVA, the expiratory trigger delay was
calculated as the time difference between EAdimax and the
end of insufflation by the ventilator within the three
modes. Finally, contrary to the sequence of the
ventilatory modes tested, the sequence of the level of assistance
was not randomized. Therefore, we cannot rule out a
potential time effect.
Most of our findings are potentially clinically relevant.
Lung-protective ventilation has become a major concern
in ICU patients, even in those without acute respiratory
distress syndrome [44,45]. Preventing alveolar
overdistention and subsequent volotrauma caused by lung
hyperinflation is now a major therapeutic goal. In this
respect, NAVA and PAV provide an interesting tool to
prevent overassistance-induced hyperinflation.
Variability of breathing pattern has become a matter
of concern in ICU patients, as a recent study showed
that a higher variability of respiratory rate was
associated with better prognosis . In addition, a more
variable breathing pattern is associated with better
pulmonary function in animal models of lung injury
[47-51]. Finally, severe patient-ventilator asynchrony is
associated with longer duration of mechanical
ventilation and a greater need for tracheostomy . Of note,
patient-ventilator asynchrony may be either a cause or
a consequence of the severity of the respiratory disease
requiring mechanical ventilation. Whether optimization
of ventilatory settings, by using PAV or NAVA, can
shorten the duration of mechanical ventilation by
reducing the incidence of asynchrony, has therefore not been
In conclusion, PAV and NAVA both prevent
overdistention and improve neuromechanical coupling and
patient-ventilator asynchrony in fairly similar ways
compared with PSV. Further studies are needed to
evaluate the possible clinical benefits of NAVA and
PAV on clinical outcomes, especially in the recovery
phase of acute respiratory failure.
The variability of VT with NAVA and PAV is greater
than with PSV at each assistance level.
PAV and NAVA both restore natural variability of
The increase in breath-to-breath variability observed
during NAVA and PAV is due to unmasking of the
underlying variability in central respiratory neural
output and is a direct result of improvement of
NAVA and PAV both improve patient-ventilator
synchrony as compared with PSV, especially on
Additional file 1: Waveforms of EAdi, pressure and flow for all
three modes (PSV100, NAVA100, PAV100) in the same patient.
Additional file 2: Definitions of patient- ventilator interaction indices
and the main asynchronies collected.
Additional file 3: Example of Type II double triggering under NAVA.
Additional file 4: Inspiratory pressure (cmH2O) over PEEP for each
patient under the three modes and three assist levels.
Additional file 5: Impact of ventilator mode and assistance level on
the coefficients of variation of neural respiratory rate, tidal volume,
and peak electrical activity of the diaphragm (EAdimax).
Additional file 7: Impact of ventilator mode and level of assistance
on gas exchange.
AI: Asynchrony index; CV: coefficient of variation; CVEAdimax: coefficient
of variation of EAdimax; EAdi: electrical activity of the diaphragm;
EAdimax: maximum electrical activity of the diaphragm; EAdiAUC: integrated
EAdi activity; IQR: interquartile range; NAVA: neurally adjusted ventilatory
assist; PAV: proportional assisted ventilation; PEEP: positive end-expiratory
pressure; Pmax: peak airway pressure; PSV: pressure support ventilation;
RR: respiratory rate; Ti: inspiratory time; VT: tidal volume.
The Association pour le Dveloppement et l'Organisation de la Recherche en
Pneumologie, a nonprofit structure that supports the research activities of the
Service de Pneumologie et Ranimation Mdicale, Groupe Hospitalier
Piti-Salptrire, has received an unrestricted research grant from Maquet
France SA, Orlans, France (2009), and Covidien, Dublin, Ireland (2013), to
support pathophysiological research studies on NAVA and PAV, respectively.
A. Demoule is the principal investigator of a study on NAVA, has been a
consultant for Covidien, and has given lectures for Covidien and Maquet. The
others authors have no conflict of interest.
MS conceived the study and contributed to the data collection, analysis,
statistics, and writing of the manuscript. FK contributed to the data
collection and analysis. JC contributed to data collection and analysis. TP
contributed to the data analysis and the revision of the manuscript. EM
contributed to the data collection, their analysis, and the revision of the
manuscript. RP contributed to the data collection and revised the
manuscript. TS drafted the design of the study, and contributed to the
writing and the revision of the manuscript. AD conceived the study and
contributed to the data collection, analysis, statistics, and writing of the
manuscript. All authors read and approved the manuscript.
Matthieu Schmidt was supported by the French Intensive Care Society
(SRLF); the Fonds de dotation Recherche en Sant Respiratoire 2012 the
Collge des Enseignants de Ranimation Mdicale and the Fonds d'Etudes et
de Recherche du Corps Mdical-Assistance Publique des Hpitaux de Paris.
Written informed consent was obtained from the patients for publication of
their individual details and accompanying images in this manuscript. The
consent form is held by the authors and is available for review by the
1Sorbonne Universits, UPMC Univ Paris 06, UMR_S 1158 Neurophysiologie
Respiratoire Exprimentale et Clinique, F-75005 Paris, France. 2INSERM,
UMR_S 1158 Neurophysiologie Respiratoire Exprimentale et Clinique,
F-75005 Paris, France. 3AP-HP, Groupe Hospitalier Piti-Salptrire Charles
Foix, Service de Pneumologie et Ranimation Mdicale (Dpartement R3S),
F-75013 Paris, France. 4Universit Pierre et Marie Curie-CNRS-INSERM, ICM,
Equipe Neurologie et Thrapeutique Exprimentale, Hpital de la Salptrire,
Paris, France. 5U974, Institut National de la Sant et de la Recherche
mdicale, Paris, France. 6Service de Pneumologie et Ranimation Mdicale,
Groupe Hospitalier Piti-Salptrire, 47-83 boulevard de lHpital, 75651 Paris,
Cedex 13, France.
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