Acta Anaesthesiol Scand 2011; 55: 1261–1271
Printed in Singapore. All rights reserved
Neurally adjusted ventilatory assist vs. pressure support
ventilation in critically ill patients: an observational
study
J. Barwing, N. Linden, M. Ambold, M. Quintel and O. Moerer
Department of Anesthesiology, Emergency and Intensive Care Medicine, University of Göttingen Medical School, Göttingen, Germany
Background: During neurally adjusted ventilatory assist
(NAVA), the inspiratory support is controlled by the patients’
respiratory drive influenced by an operator-controlled gain
factor (NAVA level). The purpose of our observational study was
to transfer patients from conventional pressure support ventila-
tion (PSV) to NAVA safely. We compared two approaches to set
the NAVA level and evaluated the effect of NAVA.
Methods: We studied mechanically ventilated patients capable
of spontaneous breathing. For the change of the ventilator mode,
we used a NAVA level calculated to generate a peak inspiratory
pressure equal to PSV. We compared this NAVA level with a
NAVA level determined by a NAVA level titration. Ventilatory
and haemodynamic data were recorded during an observational
period of 6 h.
Results: All 20 patients included in the study could be trans-
ferred from PSV to NAVA and completed the observation inter-
val. Setting the NAVA level according to prior PSV settings
T he preservation of spontaneous breathing
during mechanical ventilation helps to avoid
atelectasis, improves oxygenation and preserves dia-
phragmatic function.1–5 The most frequently used
mode of assisted ventilation is pressure support
ventilation (PSV).6 Its benefits even in acute illness
are discussed.7,8 As in other modes, spontaneous
breathing is detected by changes in airway flow or
pressure in order to coordinate the ventilatory
assist.9 However, poor patient-ventilator interaction
might result from conventional pneumatic trigger-
ing of the ventilator.10 Furthermore, the potentially
beneficial variability of the breathing pattern of the
patient is not supported by PSV, as PSV applies fixed
pressure support regardless of the patients’ needs.11
Neurally adjusted ventilatory assist (NAVA) is a
new mode of assisted mechanical ventilation.12
Unlike in PSV, airway pressure is applied in propor-
© 2011 The Authors
Acta Anaesthesiologica Scandinavica
© 2011 The Acta Anaesthesiologica Scandinavica Foundation
ACTA ANAESTHESIOLOGICA SCANDINAVICA
doi: 10.1111/j.1399-6576.2011.02522.x
proved to be a feasible approach, but in 75% of our patients, we
modified the NAVA level according to the titration results. Gas
exchange and ventilatory mechanics during the observation
interval remained stable.
Conclusions: The ventilator mode NAVA seems to be well
tolerated in a heterogeneous group of critically ill patients.
Pre-setting of the NAVA level during PSV can result in an over-
estimation of the required ventilator support. An additional
titration of the NAVA level ads valuable information although
difficult to interpret in some cases.
Accepted for publication 3 August 2011
© 2011 The Authors
Acta Anaesthesiologica Scandinavica
© 2011 The Acta Anaesthesiologica Scandinavica Foundation
tion to the electrical activity of the diaphragm (EAdi)
assessed by esophageal electrodes mounted on a
gastric feeding tube.13 The tidal volume (Vt) during
spontaneous breathing is proportional to the EAdi
and reflects the neural output of the respiratory cen-
tre.14 With NAVA, the ventilator is controlled by the
patients’ physiologic regulation of respiratory drive,
which is influenced only by the feedback of the res-
piratory system itself and an operator-controlled
gain factor (NAVA level). It is the responsibility of the
clinician to choose a NAVA level high enough to
provide adequate support especially for those
patients who are at risk of fatigue. High NAVA level
may instead lead to over-assist and excessive inspira-
tory pressures when patients are unable to further
decrease the EAdi or have a compromised ventila-
tory regulation.15–18 In order to pre-set an adequate
NAVA level, a dedicated software (‘NAVA preview’,
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J. Barwing et al.
Maquet Critical Care, Solna, Sweden) allows adapt-
ing the anticipated assist to the PSV pressure cure,
taking into account the patients’ EAdi.16,19–21 System-
atically increasing the NAVA level to determine the
optimal setting with regard to unloading of the
patients’ respiratory muscles is suggested.15,18
In patients with intact respiratory drive and
neural pathways, NAVA might turn out to be an
ideal ventilator mode for assisted mechanical venti-
lation, but in critically ill patients, these require-
ments may not always be fulfilled.
Our objective was to transfer critically ill patients
from PSV to NAVA safely using the NAVA preview.
We evaluated the performance of a modified titra-
tion and compared the two methods to set the
NAVA level: first, NAVA preview; second, NAVA
level titration. A secondary aim was to observe the
effect of NAVA on pulmonary gas exchange, Vt and
the provided pressure support during the first 6 h.
Materials and methods
The study was performed on the intensive care unit
of the Department of Anesthesiology, Emergency
and Intensive Care Medicine (University Goettin-
gen Medical School, Germany) after approval of
the local ethics committee (University Goettingen
Medical School, Germany). Written consent of
the patients was waived by the ethics committee
because of the observational character of the study.
Patients were included into the study based on
the following criteria:
– mechanical ventilation > 24 h
– ability to breath spontaneously
– enteral nutrition via a nasogastric feeding tube
Exclusion criteria:
– age < 18 years
– known or suspected impairment of neuromuscu-
lar connection to the diaphragm
– contraindications for nasogastral tube insertion
(e.g. gastro-esophageal surgery or recent history of
bleeding)
– haemodynamic instability (e.g. active bleeding or
adrenergic agents other than dobutamin adminis-
tered to maintain blood pressure or cardiac output)
– increased intracranial pressure
– contraindications for continuing intensive care
treatment (e.g. documented will of patient)
Transfer to the NAVA mode
At the beginning of the observation, patients were
ventilated with PSV (Servo-I, Maquet Critical Care,
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Solna, Sweden). Pressure support was set aiming
at a Vt of approximately 6 ml/kg predicted body
weight (PBW) and a standardised positive end
expiratory pressure (PEEP)22 to ensure patient safety
and comfort and to allow a comparison. The
nasogastric feeding tube was replaced by a special
catheter capable of measuring electrical activation of
the diaphragm (16-Fr EAdi catheter, Maquet Critical
Care). Correct catheter placement was confirmed as
described previously.23 After a 30-min stabilisation
period in PSV baseline, measurements (PSVbl) were
recorded.
The dedicated software implemented in the ven-
tilator (‘NAVA preview’) was used to estimate the
NAVA level required to generate a pressure support
comparable with the PSV settings. With the ventila-
tor still in PSV mode, the software displays the
anticipated pressure curve of the NAVA mode,
depending on the NAVA level and EAdi signal. The
operator can fit the preview pressure curve to the
actual PSV pressure curve by adjusting the NAVA
level without influencing the physiologic feedback
of the patients’ respiratory system.
Patients were transferred to NAVA using the
NAVA level determined by the preview, and data
(NAVAprev) were recorded after adaptation to the
new mode (approximately 5 min); the EAdi trigger
was set to a default value (0.5 mV). All other ventila-
tor settings (FiO2, PEEP and pneumatic trigger)
were kept according to PSV settings. The peak
inspiratory pressure limit was set to 35 cm H2O.
(Because of a safety margin implemented to assure
peak pressure below 35 cm H2O, the resulting
plateau pressure is approximately limited to 30 cm
H2O.)
NAVA level titration
A NAVA level titration was performed decreasing
the NAVA level to zero first, allowing some time
(approximately 30–60 s) for the anticipated physi-
ologic answer to appear (i.e. an increase of the EAdi
signal up to a stable level). Thereafter, the NAVA
level was increased by 0.2 cm H2O/mV every second
breath until the peak inspiratory pressure stabilised
or reached the pressure limit (Fig. 1). Bedside analy-
sis of the curves consisted of visual inspection for
the appearance of a ‘first and second response’ as
previously described15 (first response: peak inspiratory
pressure and Vt increase with increasing NAVA level,
while EAdi remains stable; second response: peak inspira-
tory pressure and Vt remain stable with increasing
NAVA level, while EAdi decreases). The NAVA level
was then set to the lower limit of the second

Fig. 1. Example of tidal volume, EAdi and peak inspiratory pres-
sure tracings during a NAVA level titration. The figure shows the
NAVA level titration of patient no. 3. The anticipated response to
an increasing NAVA level can be determined clearly. First, the
peak inspiratory pressure and tidal volume increase, while EAdi
remains stable, then the peak inspiratory pressure and tidal volume
remain stable, while EAdi decreases. EAdi, electrical activity of the
diaphragm; NAVA, neurally adjusted ventilatory assist; PBW,
predicted body weight.
NAVA vs. PSV observation
response.10,15 When the discrimination of a ‘first
and second response’ was impossible, the NAVA
preview settings were used to guide the adjustment
of the NAVA level. The values thus found were used
during the observation interval. The NAVA level was
re-evaluated on a clinical basis after 1 h of the obser-
vation and adjusted to ensure patient safety and
comfort, aiming at peak pressures lower than 30 cm
H2O and normal Vts.
During the titration, data were recorded for off-
line analysis. Twelve consultants in intensive care
medicine (‘experts’) blinded for the titration result
reviewed the curves off-line for appearance of the
typical phases and a suggested setting for the NAVA
level. The same did 20 third year medical students,
evaluating only the pressure curves. We used Bland–
Altman plots to analyse the agreement between the
titration and the off-line analysis.24 For every patient,
the mean of the determined NAVA level [for
example, (titration + experts)/2] is plotted against
its difference (here, titration experts).
Data collection
Data were acquired before changing from PSV to
NAVA (PSVbl), after switching to the NAVA mode
(NAVAprev), 10 min after the NAVA level titration
(NAVAtitr) and 60 and 360 min (NAVA60, 360) after
NAVA level titration. Tidal volume, respiratory rate,
PEEP, mean and peak airway pressure and EAdimax
were analysed breath by breath during a 2-min
measurement interval. Data were recorded using
special software (NAVA tracker, Maquet, Solna,
Sweden). Oxygen saturation, haemodynamic data
and arterial blood gases were collected at each step
by a patient data management system.
Statistical analysis
Using standard statistical software (Statistica 9.0,
StatSoft, Tusla, OK, USA), normal distribution of the
better part of our data was rejected by Shapiro–
Wilks W-test. Data are therefore presented as
median with 25% and 75% quartiles [median (25%/
75% quartile)] unless stated otherwise. Wilcoxon test
and Friedmans analysis of variance were used to
compare between two and multiple variables.
Results
Table 1 depicts basic patient data of the 20 patients
included (Table 1). The average severity of illness
was high as documented by the simplified acute
physiology score II and sequential organ failure
assessment scores.
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J. Barwing et al.

Table 1
Basic patient data including SAPS II on ICU admission, SAPS II, SOFA, LIS and P/F on study inclusion and ICU outcome.
No. Gender Age Height BMI Primary diagnosis SAPS Incl. RS SAPS SOFA(N) P/F LIS ICU Outcome
II(I) (day) II(N) (day)
1 m 56 182 38 CHD 23 1 4 23 12 192 1.0 2 Transferred from ICU
2 m 41 190 24 TBI 24 4 4 24 8 263 1.0 5 Transferred from ICU
3 f 76 165 29 ACS, post-resuscitation 65 4 5 68 13 146 2.3 11 Exitus letalis
4 f 79 150 29 CHF, COPD 52 6 5 70 14 109 2.8 18 Transferred from ICU
5 m 65 168 27 ACS, pneumonia 50 2 3 40 7 194 1.5 17 Transferred from ICU
6 m 31 190 28 TBI 48 21 5 26 5 325 1.0 35 Transferred from ICU
7 f 75 160 30 Sepsis, ARDS 79 3 5 54 12 114 3.0 7 Exitus letalis
8 f 72 160 25 TBI, pneumonia 66 5 5 58 7 280 2.0 35 Transferred from ICU
9 m 73 174 26 TBI, pneumonia 59 7 4 69 7 258 1.0 26 Transferred from ICU
10 m 41 190 25 Sepsis, endocarditis 54 5 5 55 11 196 1.0 11 Exitus letalis
11 m 64 174 29 RCC, COPD 32 7 4 43 8 243 1.8 19 Exitus letalis
12 m 63 170 26 ICH, pneumonia 54 10 4 50 7 250 2.3 16 Transferred from ICU
13 m 77 176 24 CHD, pneumonia 56 18 2 52 5 323 1.3 96 Exitus letalis
14 f 64 162 25 Sepsis, pneumonia 59 3 4 39 11 236 2.3 24 Exitus letalis
15 m 85 175 26 Trauma, pulmonary contusion 63 8 5 68 6 203 1.8 9 Exitus letalis
16 f 87 155 27 CHF, COPD 45 3 4 71 11 244 2.0 16 Transferred from ICU
17 m 54 189 24 ICH 20 4 4 47 3 280 1.0 14 Transferred from ICU
18 f 63 165 22 ICH 58 6 5 39 6 181 1.0 21 Transferred from ICU
19 m 84 178 27 ACS 24 11 4 50 9 190 2.5 19 Exitus letalis
20 m 35 180 23 Sepsis, ARDS 47 2 5 67 15 184 3.0 14 Exitus letalis
64 173 27 49 6 4 51 9 220 1.8 21 (Mean)
17 12 3 16 5 1 16 3 60 0.7 20 (Standard deviation)

No., patient number; BMI, body mass index; SAPS II (I), simplified acute physiology score II (on ICU admission); incl., inclusion; RS, Ramsay score; SAPS II (N), simplified acute
physiology score II (day of inclusion to NAVA); SOFA (N), sequential organ failure assessment score (day of inclusion to NAVA); P/F, PaO2/FiO2 ratio; LIS, lung injury score;
ICU, intensive care unit; m, male; f, female; CHD, coronary heart disease; TBI, traumatic brain injury; ACS, acute coronary syndrome; CHF, congestive heart failure, COPD,
chronic obstructive pulmonary disease; ARDS, adult respiratory distress syndrome; RCC, renal cell carcinoma; ICH, intracranial haemorrhage; NAVA, neurally adjusted
ventilatory assist.

Table 2
Ventilatory parameters during the baseline measurements in PSV mode, the changes after switching to NAVA, with the NAVA level set
according to the ‘NAVA preview’ and the development of the parameters 10 min after adapting the NAVA level according to the titration.
PSVbl
Vt (ml/kg PBW) 6.9 (6.0/8.0)*
Ppeak (cm H2O) 17.8 (16.0/21.2)*
Pmean (cm H2O) 11.2 (10.1/12.5)
PEEP (cm H2O) 8 (7.7/10.0)
RR (bpm) 19 (14/23)*†
NAVA Lvl (cm H2O/mV)
EAdimax (mV) 5.0 (3.6/8.6)
pH 7.40 (7.36/7.43)
PaCO2 (mmHg) 41.8 (39.0/50.4)
PaO2/FiO2 219 (189/259)
Data displayed as median (25%/75% quartiles).
*P < 0.05.
†P < 0.001.
PSVbl, pressure support ventilation at baseline; NAVAprev, neurally adjusted ventilatory assist after preview; NAVAtitr, NAVA 10 min after
NAVA level titration; Vt, tidal volume in relation to predicted body weight; Ppeak, peak airway pressure; Pmean, mean airway pressure;
PEEP, positive end expiratory pressure; RR, respiratory rate; EAdimax, maximum electrical activity of the diaphragm.
Transfer to NAVA mode
All patients could be transferred from PSV to NAVA
after uneventful catheter placement. The EAdi
signal quality was good throughout the study
period. During PSV, the EAdimax was 5.0 (3.6/8.6) mV
at a pressure support of 8.0 (6.5/12.0) cm H2O to
achieve a Vt of 6.9 (6.0/8.0) ml/kg PBW. The NAVA
level setting determined by the preview was 1.9
(1.1/2.6) cm H2O/mV, resulting in a reduced Vt of
6.2 (5.2/7.6) ml/kg PBW compared with PSV
(P = 0.02). After the change to NAVA, the respiratory
rate increased from 19 (14/23) (PSV) to 23 (19/28)
(NAVAprev) bpm (P < 0.001). The EAdimax increased
to 6.0 (4.5/9.9) mV (P = 0.10). The resulting peak
inspiratory pressure was 19.7 (17.0/23.3) cm H2O
(Table 2). The pressure limit was reached in five
patients.
NAVA level titration
The NAVA level titration showed the anticipated
increase in peak airway pressure and decrease in
EAdimax in response to an increasing NAVA level in
all patients (Fig. 1). According to the titration, the
NAVA level had to be decreased in nine patients [0.4
(0.4/0.8) cm H2O/mV], increased in six patients [0.4
(0.2/0.5) cm H2O/mV] and in five patients, the
NAVA level was left unchanged. The median NAVA
level after the titration (NAVAtitr) was 1.4 (1.2/1.7)
cm H2O/mV. Peak inspiratory pressure, respiratory
rate and Vt remained stable (Table 2). The correla-
tion between the NAVA level found in the preview
and the titration is r = 0.71 (P < 0.05). In the course of
the titration, 11 patients reached the pressure limit.
NAVA vs. PSV observation
NAVAprev NAVAtitr
6.2 (5.2/7.6)* 6.8 (5.1/8.5)
19.7 (17.0/23.3)* 19.8 (16.8/23.8)
10.9 (10.1/12.3) 11.1 (10.3/11.8)
8 (8.1/10.0) 8 (8.1/10.0)
23 (19/28)† 24 (19/29)*
1.9 (1.1/2.6) 1.4 (1.2/1.7)
6.0 (4.5/9.9) 5.7 (4.7/11.4)
7.4 (7.37/7.45)
44 (39.2/48.0)
236 (193/271)
The intensive care medicine consultants found a
median NAVA level of 2.0 (1.4/2.2) cm H2O/mV in
the off-line analysis. In 22% of all cases, these
experts considered it impossible to set a NAVA level
according to the recorded data. The correlation of
the NAVA level between the titration and the expert
analysis is r = 0.64 (P < 0.05). The analysis by the
medical students found a median NAVA level of 2.3
(1.3/2.6) cm H2O/mV. In 48% of all cases, the stu-
dents considered it impossible to set a NAVA level
according to the pressure curve. The correlation
between the NAVA level found in the titration and
the student analysis is r = 0.45 (not significant)
(Fig. 2).
6-h trend
PSV compared with NAVA after 60 and 360 min
showed stable Vt of 6.86 (5.96/8.02) ml/kg
PBW compared with 6.16 (5.58/7.86) ml/kg
PBW (NAVA60) and 6.12 (5.18/8.16) ml/kg PBW
(NAVA360) (P = 0.33). While peak pressures increased
[PSVbl-NAVA60-NAVA360: 17.8 (16.0/21.2)-18.3 (16.7/
21.9)-20.1 (16.9/24.3) cm H2O], the mean pressures
remained constant [PSVbl-NAVA60-NAVA360: 11.2
(10.1/12.5)-10.7 (10.3/12.2)-11.5 (10.5/12.0) cm
H2O]. This results in a difference (Ppeak – Pmean)
of 6.45 (5.3/10.0) cm H2O for PSVbl, 7.7 (6.7/10.3) cm
H2O for NAVA60 and 8.85 (6.2/12.0) cm H2O for
NAVA360 (P = 0.04). The NAVA level did not change
from NAVA60 to NAVA360 [1.4 (1.2/1.7)].
No changes to PEEP were made and oxygenation
remained stable with PaO2/FiO2 values: 219 (189/
259) for PSVbl, 228 (206/257) for NAVA60 and 230
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J. Barwing et al.
Fig. 2. Bland–Altman plots comparing the results of the NAVA
level titration with the preview, the expert opinion on the NAVA
level and the student opinion. The figure shows a Bland–Altman
plot for the NAVA level determined by the NAVA level titration
compared with the NAVA level found by the preview (top), the
experts (middle) and the students (bottom) for each patient. The
mean difference is -0.1 cm H2O/mV for the experts and -0.2 cm
H2O/mV for the students. Solid line: mean of difference; dashed
line: mean ⫾ 1.96 ¥ standard deviation. NAVA, neurally adjusted
ventilatory assist.
(182/278) for NAVA360 (P = 0.52). PaCO2 was 41.8
(39.0/50.4) mmHg PSVbl, 42.5 (39.8/46.3) mmHg
NAVA60 and 39.4 (35.8/43.2) mmHg NAVA360
(P = 0.002). The respiratory rate increased from 19
(14/23) bpm PSVbl to 26 (19/28) bpm NAVA60 to 30
(24/33) bpm NAVA360 (P < 0.001). EAdimax values
tended to increase during the observation interval
with 4.96 (3.63/8.64) mV (PSVbl), 5.91 (4.67/11.50)
mV (NAVA60) and 7.42 (5.26/12.12) mV (NAVA360)
(P = 0.09) (Fig. 3).
All patients were stable throughout the study
regarding their Ramsay score (Table 1). Eight
1266
patients were weaned from sedatives; 12 patients
received a sedative medication. (Nine patients as a
continuous infusion and three patients as intrave-
nous sedatives adapted to their situation.) Seven
patients needed opioid analgesics for pain relief.
During the observation, interval heart rate and mean
arterial pressure remained stable, while systolic
blood pressure increased from 119 (107/137) mmHg
at PSVbl to 126 (109/146) mmHg at NAVA60 and 134
(115/152) mmHg at NAVA360 (P = 0.03).
Discussion
Our observations show that NAVA is a feasible alter-
native to conventional PSV in critically ill patients
capable of breathing spontaneously. All patients
included could be transferred to the NAVA mode as
planned. The titration of the NAVA level contributed
to the adjustment of the ventilator in the majority of
patients. All patients completed the 6-h observation
interval. The oxygenation remained stable, and we
found a tendency towards lower CO2 values, lower
Vts and higher peak pressures, as well as higher
respiratory rates. Looking at haemodynamic param-
eters, we found higher blood pressures towards the
end of the observation interval. Planned as an obser-
vational trial, the study was not powered to show
significant results and lacks a control group to
compare with. Therefore, its design leaves unan-
swered whether NAVA has advantages over PSV or
not. However, these changes seem to be relevant
and have been demonstrated by other authors as
well.16,20,25 The interpretation of our findings is diffi-
cult in a small population. The patients included in
the study were severely ill and analgesised with
respect to their situation. Pulmonary function as
measured by the lung injury score and PaO2/FiO2
was compromised. Nevertheless, we were able to
transfer these patients to the NAVA mode maintain-
ing protective ventilator settings and a stable pul-
monary function.
In a heterogeneous group of patients, the concept
of protective ventilation is debatable.26 Although
widely accepted for patients with acute lung injury,
the benefit for the others is not clear. Recent data
confirm that even in healthy animals, lung stress
(the ratio between Vt and functional residual capac-
ity) and strain (the transpulmonary pressure) can
induce lung injury at high values, corresponding to
Vts greater than 20 ml/kg.27 On the other hand,
lung protective ventilation appears to be safe
although a Vt of 6 ml/kg may not be beneficial for
all patients.28
 NAVA vs. PSV observation

Fig. 3. Ventilatory parameters displayed as box plot. The figure shows ventilatory parameters at PSV baseline, NAVA after 60 min and
NAVA after 360 min as box plot [median with 25–75% percentiles (boxes) and minimum to maximum range (whiskers)]. Note: While peak
pressure tends to increase together with EAdimax, the Vt tends to decreases over time. Respiratory rate increases to maintain minute
ventilation. *P < 0.05. EAdi, electrical activity of the diaphragm; NAVA, neurally adjusted ventilatory assist; PBW, predicted body weight;
PSV, pressure support ventilation; Vt, tidal volume.

During mechanical ventilation, Vt and resulting
inspiratory pressure may be variable depending on
the ventilatory effort of the patient and patient-
ventilator synchrony. Papazian et al. showed that
patients with acute lung injury profit from the
application of a neuromuscular blocking agent
and attributes this to asynchrony-related alveolar
collapse and overdistention.29 Assisted ventilatory
support, especially NAVA, may overcome this
problem without the use of neuromuscular blocking
agents.10,30
NAVA level setting
There are different approaches to set the NAVA
level. Starting from an inspiratory pressure
support under PSV delivering a Vt of 6–8 ml/kg
PBW, we estimated a NAVA level resulting in an
equivalent peak inspiratory pressure with help of
the dedicated software implemented in the venti-
lator (‘NAVA preview’). A similar proceeding is
suggested by several authors.19–21 Coisel and
co-workers adjusted the NAVA level with the
intention to maintain the same minute ventilation
as achieved under PSV.25 Both alternatives rely on
the PSV settings and are easy to implement for the
clinician. The ‘NAVA preview’ provides a NAVA
level before starting the new mode. Convenient for
the operator, this way harbours the risk of unpre-
dictable changes in EAdi after switching from PSV
to NAVA.
With NAVA, the patients’ inspiratory effort is sup-
ported according to his neural respiratory drive
reflected by the EAdi [EAdi (mV) x NAVA level (cm
H2O/mV) = inspiratory assist (cm H2O)] at every
moment of the inspiration. In this way, the inten-
sity and duration of diaphragmatic activation are
directly related to the pressure support given. In
PSV mode, the patient might trigger the full support
by a brief contraction of the diaphragm. The off-
cycling at 30% of maximum inspiratory flow results
in a more rectangle-shaped pressure curve com-
pared with a more dome-shaped pressure curve
under NAVA (off-cycling is set at 70% of EAdimax).
This may play a role especially in critically ill
patients, who often have limited capabilities to
respond to increased ventilatory demands.31 The
observed consequences are an increase in EAdimax
values and peak inspiratory pressures and a
decrease in Vt after changing to NAVA. The minute
volume is kept constant by increase of respiratory

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J. Barwing et al.
rate. These results are supported by data published
in previous research done by Spahija and
co-workers on 12 chronic obstructive pulmonary
disease patients. They found a significant reduction
of inspiratory times in NAVA when compared with
PSV.32
Because of higher EAdi and peak inspiratory
pressures after changing from PSV to NAVA, the
inspiratory pressure limit was reached in five
patients. Two of these patients had a high inspira-
tory support under PSV, peak inspiratory pressures
close to the pressure limit and a low (‘suppressed’)
EAdi. The ‘NAVA preview’ suggested a high NAVA
level. Because of the change of pattern of the inspira-
tory pressure under NAVA, the patients almost
doubled EAdi to maintain homeostasis of PaCO2
and pH value. Three patients had high EAdi signals
under PSV. Their blood gases showed a tendency to
high PaCO2 and low pH values compared with other
patients. The ‘NAVA preview’ suggested a low
NAVA level in these patients. Changing the ventila-
tor mode resulted in an increase of EAdi, which is
best explained by the patients’ attempt to change
PaCO2 and pH values towards normal limits. A
recently published trial by Karagiannidis et al. sup-
ports this interpretation. The authors treated
patients with acute respiratory distress syndrome on
extracorporeal membrane oxygenation with NAVA
and demonstrated that the patients’ EAdi signal is
correlated with pH and PaCO2 rather than PaO2.
Decreasing the extracorporeal CO2 elimination
resulted in a prompt increase in EAdi and peak
inspiratory pressure.33
Although high peak inspiratory pressures have
been reported previously,16,17 the issue of protective
ventilation has not been addressed there. As high
inspiratory pressures contribute to ventilator-
induced lung injury,34 we used a pressure limit that
is widely accepted to be save although currently
under discussion.35,36 The limit was reached by four
out of 20 patients after changing from PSV to NAVA
mode and by eight out of 20 patients during the
titration. The limitation of inspiratory pressure influ-
enced our results, which has to be taken into account
when looking at the changes of Vt and respiratory
rate. A thereby inhibited recruitment might have
influence on airway pressures in return. The fact that
we saw higher peak inspiratory pressures in NAVA
but constant tidal ventilation suggests higher peak
airway flow (Fig. 3). Considering the resistance of
endotracheal tubes, high airway pressures might not
have been transmitted into the lungs in full extent.
For patient safety, a pressure limitation should be
1268
considered when using NAVA in order to avoid
excess peak inspiratory pressures because of unfore-
seen increases in EAdi. Nevertheless, the ‘NAVA
preview’ is a practicable approach to set a NAVA
level before transferring patients from PSV to
NAVA.
Another approach to set the NAVA level is sug-
gested by Brander et al. and Lecomte et al.15,18 They
did not link the NAVA level to PSV but increased it
stepwise until a further increment in the NAVA
level did not result in a further increase of Vt and
peak inspiratory pressure. This NAVA level titration
aims at finding a NAVA level that provides ventila-
tory support to adequately unload the inspiratory
muscles.18 Brander and co-workers increased the
NAVA level every 3 min over a total time of 29 (21/
33) min (nine steps; range: five to 12) and therefore
allowed time for a physiologic response to altered
gas exchange to appear at every step.15 Our titration
procedure was faster [0.2 cm H2O/mV every second
breath, median 20 steps (range: eight to 30)]. With a
total increase of 1 cm H2O/mV in 10 breaths, we
considered this to be enough time for the patient to
adapt to changes in inspiratory support based on
the findings of Viale, who considered six to eight
breaths to be sufficient.37 Our proceeding appeared
to be well tolerated by the patient and more feasible
in clinical routine as it is less time consuming
(Fig. 4). We looked for the physiologic answer to
increasing inspiratory pressure (fast acting stretch
receptors) rather than to ventilatory regulation
(slow acting pH/PaCO2 receptors) and wanted the
patient to be stable with regard to haemodynamic
and gas exchange parameters during the titration.
Our proceeding seemed advantageous to us
although there is no evidence from the literature.
As mentioned earlier, we used an inspiratory
pressure limit. Especially during a NAVA level titra-
tion in patients with a compromised pulmonary
function (hypercapnia and vulnerable pulmonary
tissue) or an impaired neural control (traumatic
brain injury and intracranial haemorrhage), the risk
of barotrauma seems high. Animal experiments
demonstrated that a compromised ventilatory regu-
lation may lead to excess inspiratory pressure.18 On
the other hand, one might criticise that a brief
increase in pressure, even when exceeding 35 cm
H2O, would not have resulted in gross barotrauma.
We can only speculate about the inspiratory pres-
sures we would have seen without a limit. Other
publications in this field show that certain patients
have peak pressures above 35 cm H2O with increas-
ing NAVA level.15–17 For a NAVA level titration, the
 NAVA vs. PSV observation

Fig. 4. Example of tidal volume, EAdi and

peak inspiratory pressure tracings during a
NAVA level titration in two patients. The
figure shows the NAVA level titration of
patient no. 2 (left) and patient no. 8 (right).
There was a clear response of the EAdi
to the increase in NAVA level in patient
no. 8. The airway pressure increased as
anticipated; nevertheless, intensive care
medicine consultants were not in good
accordance with respect to the optimal
NAVA level in this patient (see Fig. 5).
Seven of the 12 intensive care medicine
consultants did not find a NAVA level
according to the titration in patient no. 2.
EAdi, electrical activity of the diaphragm;
NAVA, neurally adjusted ventilatory
assist; PBW, predicted body weight.

Fig. 5. Statistical spread of the NAVA

level for each patient defined by experts.
Intensive care medicine consultants
(n = 12) analysed the titration curves off-
line (see Figs 1 and 4) and defined the
NAVA level based on tidal volume, EAdi
and airway pressure curves. The figure
shows a box plot for every patient with the
median NAVA level, the 25–75% quartile
(boxes) and the minimum to maximum
range (whiskers). Below the number of
experts who considered it possible to decide
on a NAVA level according to the curves is
printed. Note: While the NAVA level could
be clearly identified in some patients (e.g.
patient no. 3), it was almost impossible to
draw reproducible conclusions in others
[e.g. patient no. 2 (n = 5 of 12) and 8
(range of NAVA level)]. EAdi, electrical
activity of the diaphragm; NAVA, neurally
adjusted ventilatory assist.

1269
J. Barwing et al.
gain of information has to be balanced against the
risk of high inspiratory pressures.
In those 11 patients who reached the pressure
limit, a pressure plateau because of the patients’
physiologic regulation was sometimes difficult to
distinguish from the pressure plateau because of the
set pressure limit. This is a systematic limitation of
our NAVA level titration. The interpretation by the
investigator at the bedside had a good correlation
with the off-line analysis by the consultants trained
to interpret such data. This is confirmed by the
Bland–Altman plot (Fig. 2). The large variance of the
expert results in some patients shows that the titra-
tion holds room for interpretation (Fig. 5). There-
fore, the usefulness of a NAVA level titration as
carried out in this study must be considered as
limited. Our findings are inconsistent with the pre-
viously published results by Brander et al., who
demonstrated a two-phased response to increasing
NAVA level and identified an adequate NAVA level
based on a titration.
Comparing the titration results with the NAVA
preview, the NAVA level was changed in 15 patients.
The NAVA level had to be reduced in nine of the 20
patients and led to high peak inspiratory pressures
in five patients. The changes were not significant
with regard to the median NAVA level but support
the trend of overestimated NAVA level according
to the NAVA preview. A NAVA level titration pro-
vides valuable information not included in the
‘NAVA preview’ and may improve patient safety
when setting the NAVA level. The mode of titration
must be improved to facilitate the interpretation of
its results.
Acknowledgements
The study was supported by departmental funding. The Depart-
ment of Anesthesiology, Emergency and Intensive Care Medi-
cine, University of Göttingen provides educational courses on
lung protective ventilation partially supported by Maquet Criti-
cal Care. Prof Quintel consults for companies that manufacture
ventilators including Maquet Critical Care and is compensated
for these consultations.
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Address:
Onnen Moerer
Department of Anesthesiology
Emergency and Intensive Care Medicine
Georg-August University of Goettingen
D-37099 Goettingen
Germany
e-mail: omoerer@med.uni-goettingen.de
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