Supplementary material
Neurally adjusted ventilatory assist versus non-invasive pressure support ventilation in COPD
exacerbation (NAVA-NICE): a randomized trial
Intervention
Patients of COPD with acute hypercapnic respiratory failure who fulfilled the inclusion criteria were
randomized to receive NIV either with pressure support ventilation (Group A) or NAVA (Group B) after
a written informed consent from the patient or his/her legally authorized relative. Randomization was
done based on computer generated random number sequence. The allocation codes were kept in an
opaque envelope which were only opened just before allocation of NIV. Non-invasive ventilation in both
the groups was provided by Servo-I Maquet-Critical Care Solna, Sweden NIV software V3.0.It is a
standard practice to place a nasogastric tube in patients of respiratory failure undergoing non-invasive
ventilation for purpose of feeding or aspiration of excessive air in case of gastric distension. A
specialized catheter with array of electrodes placed at the distal end known as EAdi catheter (electrical
activity of diaphragm) was placed in patients of both groups. EAdi catheter was placed at the level of the
diaphragm to detect the diaphragmatic electrical activity. EAdi catheter can also serve the purpose of
feeding and aspiration of excessive air in case of patient develops abdominal distension. (S.fig.1).
Assessment of correct position of EAdi catheter
NAVA uses the electrical activity of the diaphragm to trigger and cycle off the respiratory cycle.
Therefore, EAdi catheter was placed close to the diaphragm, so that the electrical activity is picked
adequately. The adequate insertion distance (Y) of the EAdi catheter was calculated by two methods. In
first method, NEX distance was calculated. NEX is equal to the sum of the distance measured from the
bridge of nose (Nose) to ear (Ear lobe) and from ear to Xiphoid process (X). The insertion distance was
then calculated by using the formula. (Y = NEX x 0.9 + 8 cm).
Once the EAdi catheter is inserted and connected to the ventilator, the ventilator screen displays four
wave forms. Correct position of EAdi catheter is indicated if the 2nd and 3rd wave form are highlighted
in blue and EAdi signal is present (S.fig 1). In case the first and second waveforms are highlighted in
blue, the EAdi cathter is pulled up gradually using marking on the catheter till second and third wave
forms are highlighted in blue. In the same way, if third and fourth wave form are highlighted in blue the
catheter is pushed down. After confirming the correct position of the catheter, the insertion distance was
recorded and checked regularly and adjusted whenever required.
Supplementary Fig.1. Shows that 2nd and 3rd waveforms displayed on the ventilator screen are
highlighted in blue indicates the correct positioning of the EAdi catheter.
Initial setting:
In patients of group A (NIV-PSV), pressure support and positive end-expiratory pressure (PEEP) levels
were set to achieve a tidal volume (Vt) of 6 to 8 mL/kg of ideal body weight. In patients of group B
(NIV-NAVA), NAVA level was adjusted to match peak airway pressures during PSV at pressure setting
that generated a tidal volume of 6-8ml/kg using manufacturer –supplied software (S.fig.3). Pressure
delivered during NAVA is equal to NAVA level times the difference of Edi max and Edi min plus
PEEP. {P = NAVA level x (Edi max – Edi min) + PEEP + 2 cm H2O}. In both groups the treating
physician was allowed to set and adjust the positive end expiratory pressure (PEEP) and fraction of
inspired oxygen (FiO2) to achieve an oxygen saturation of at least 92%.
Expiratory trigger threshold of 40-45% of peak inspiratory flow was used in PSV.(46) NAVA triggering
sensitivity and cycle-off value were fixed at 0.5µV and 70% of EAdi peak respectively. The Airway
pressure limit was set at 25 cm H2O. Back up ventilation was set using inbuilt pressure support
ventilation to provide uninterrupted ventilation in case of loss of EAdi signal.
Supplementary Fig. 2. Shows peak inspiratory pressure during PSV (yellow wave form) at pressure support of 6 cm H2O that generated a tidal volume 431 (approximately 7 ml/kg). Wave from (in grey) overlaps the pressure curve (in yellow) at a NAVA level of 0.3 cmH2O/µV. NAVA level was set at 0.3 cmH2O/µV during NAVA NIV.
Data acquisition and measurements
Initial ventilator settings including level of pressure support used, NAVA level, Maximum and minimum
airway pressure, level of PEEP, Fio2, percentage of air leak and EAdi peak were also recorded.
Supplementary Fig 3a. Recorded ventilator screen shows various ventilator parameters (Peak airway pressure, Respiratory rate, Tidal volume) over a period of 24 hours. Cursor is adjusted with a knob to get the ventilator parameters at a specific time period.
Supplementary Fig 3b. Recorded ventilator screen showing 24hour trends in EAdi (peak and min) and respiratory rate.
Quantification of patient ventilator asynchrony
Type of asynchrony (Definition)
Ineffective effort: Presence of a characteristic EAdi activity that is not followed by a ventilator-
delivered pressurization.
Supplementary Fig.4a. Ineffective effort during pressure support ventilation. Presence of EAdi signal in
absence of associated ventilator cycle.
Double-triggering: Two respiratory cycles separated by a very short expiratory time due to a biphasic
EAdi signal.
Supplementary Fig. 4b. Shows double triggering during PSV. Two ventilator cycles separated by a
short expiratory phase with biphasic EAdi signal.
Auto-triggering: Presence of a significant ventilator pressurization without EAdi signal.
Supplementary Fig 4c. Showing presence of a significant ventilator pressurization without EAdi signal.
Premature cycling: Duration of pressurization is shorter than neural inspiratory time determined from
visual analysis of EAdi wave form, Pressure and Flow curves.
Supplementary Fig. 4d: Shows Premature cycling, note that ventilator pressurization is more than
neural inspiratory time (EAdi signal) in 3rd ventilator cycle.
Delayed cycling: Duration of pressurization longer than Tin, determined by visual analysis of EAdi and
Pressure /Flow curves
Supplementary Fig.4e. Delayed cycling during PSV. Duration of pressurization more than neural
inspiratory time (EAdi signal) in 2nd ventilator cycle.
Table 1S. Initial ventilator setting in NAVA and PSV
Initial ventilatory setting Value
Inspiratory pressure cm H2O, (mean±SD) 12 ±1.8
PEEP, median (IQR) cm H2O 6(5-6)
Pressure support, (mean±SD) cm of H2O 6.85± 1.76
NAVA level, median (IQR) cm H2O /µV 1 (0.5-1.2)
FiO2 %, (mean±SD) 37.31 ± 6.37
Inspiratory trigger (NAVA), µv 0.5
Expiratory trigger
PSV, % of max peak flow value, [median (IQR)] 40 (40-45)
NAVA, % of max peak EAdi value 30
Table 2S. Various ventilator parameters during NAVA and PSV after initial stabilization
Ventilator parameters NAVA (n=20) NIV (n=20) p value
Pmax [mean ± SD] cm H2O 18.75±3.65 17.94±3.00 0.46
Pmin [mean ± SD] cm H2O 5.5±0.677 5.65±0.745 0.57
Tidal volume, mean ± SD] ml 431±33.08 408±32.97 0.029
TV ml/kg [median, IQR] 6(6-8) 6(6-7) 0.09
Minute ventilation [mean ± SD] L/min 10.88±1.73 10.56±1.00 0.482
Air leak, [mean ± SD] % 40±10.6 40±5.79 0.984
EAdi max, [mean ± SD] µV 34.21±16.68 36±10.09 0.68