Neurally adjusted ventilatory assist as an alternative to pressure support ventilation in adults

Demoule A. Intensive care medicine. 2016 Nov 1;42(11):1723-32. doi:10.1007/s00134-016-4447-8

Clinical Question

  • In intubated patients recovering from acute respiratory failure, does neurally adjusted ventilator assist mode (NAVA) compared to pressure support mode, (PSV) lead to fewer patients returning to assist-control ventilation?


  • As patients become more stable, it is common practice to move from assist-control ventilation modes to partial-support ventilation modes
    • Assist-control ventilation: VCV by Maquet, S-CMV by Hamilton or IPPV by Drager
    • Partial-support ventilation: SIMV, PSV or CPAP-ASB by Drager
  • Newer adaptive ventilation modes are becoming available, which may improve patient comfort and reduce the duration of ventilation
    • Adaptive-support ventilation: Adaptive Support Ventilation by Hamilton, NAVA by Maquet or Proportional Pressure Support by Drager
  • Prior to this trial, NAVA had been tested in small, single centre studies only


  • Randomised controlled trial
  • Multi-centre
  • Block randomisation, stratified by center
  • Allocation concealment was achieved by sequentially numbered sealed, opaque, envelopes
  • Physicians not blinded but all analyses done blindly
  • Intention-to-treat analysis
  • Sample size calculation was based on the assumption that 78% of patients will remain in partial ventilator support in the PSV group during the first 48 h
    • Allowing for an estimated 10% failure of ventilator data collection, a sample size of 128 patients would provide 80% power at a two-sided alpha level of 0.05 to detect a 17% absolute difference in primary outcome between NAVA group and PSV group


  • 11 ICUs in France comprising 6 medical ICUs, 4 medical-surgical ICUs and 1 surgical ICU
  • April 2012 to June 2013


  • Inclusion: Patients receiving endotracheal mechanical ventilation for more than 24 h for acute respiratory failure including de novo hypoxaemic respiratory failure, acute cardiogenic pulmonary oedema or acute-on-chronic respiratory failure meeting the following criteria:
    • Ability to sustain PSV for at least 30 min with inspiratory pressure below 30 cmH2O
    • Estimated remaining duration of mechanical ventilation > 48
    • Level of sedation at most 4 on the Ramsay scale in absence of medical decision to increase the level of sedation
    • Fraction of inspired oxygen (FiO2) at most 50 % with positive end-expiratory pressure (PEEP) no greater than 8 cmH2O
    • Not on high-dose vasopressor therapy defined as norepinephrine above 0.3 μg/kg/min or dopamine above 10 μg/kg/min
  • Exclusion:
    • Age < 18 years
    • Known pregnancy
    • Participation in another trial within the 30 days preceding completion of the eligibility criteria
    • Contraindication to placement of the NAVA oesophageal tube (i.e. any contraindication to placement of a gastric tube or repositioning of a tube already in place, recent gastrointestinal suture, rupture of oesophageal varices with gastrointestinal bleeding during the 4 days prior to inclusion)
    • Decision to withhold life-sustaining treatment
  • 3896 screened, 128 randomised, primary outcome available for 118 patients
    • Lost to follow-up 7.8%
  • Baseline characteristics
    • Evenly matched in terms of age, SAPS2 score, duration of mechanical ventilation prior to inclusion and cause of respiratory failure
    • Significant baseline differences in terms of gender distribution (more males in NAVA group) and Charlson score (higher degree of comorbidity in PSV group)


  • NAVA – Neurally Adjusted Ventilatory Assist
    •  FiO2 and PEEP were defined by treating clinicians according to local guidelines
    • NAVA levels were set to obtain a tidal volume of 6-8ml/kg idea body weight
    • Continued for 14 days unless patient met criteria for switch to controlled mechanical ventilation or met criteria for weaning and extubation


  • PSV – Pressure Support Ventilation
    • FiO2 and PEEP were defined by treating clinicians according to local guidelines
    • Pressure support levels were set to obtain a tidal volume of 6-8ml/kg idea body weight

Management common to both groups

  • EAdi nasogastric catheters were placed in all patients prior to randomisation
    • EAdi monitoring data were available to clinicians for patients in both groups
  • Criteria for switching to assist-control mechanical ventilation (i.e. failing partial-support ventilation)
    • Respiratory distress, hypoxaemia or hypercapnic acidosis despite optimisation of ventilator settings
    • Severe hypotension, shock or arrhythmias
    • Increased need for sedation for
      • Agitation
      • Patient–ventilatory asynchrony
      • Investigation or procedure
  • If criteria for partial-support ventilation were restored, patients remained in the same allocated treatment arm and NAVA or PSV were re-instituted
  • Patients were screened for weaning and extubation daily
    • If the following criteria were met, a spontaneous breathing trial (up to 1 hour on T-piece or PSV 7 cmH2O with zero PEEP) was conducted and patients were extubated if this was successful
      • Improvement in the causative pathology
      • SpO2 > 92% on FiO2 < 50% and PEEP < 5 cmH20
      • No vasopressor or sedation requirement
      • Response to simple commands


  • Primary outcome: Proportion of patients who remained continuously in partial ventilator support mode (either NAVA or PSV) during first 48 hours following inclusion or until extubation without any return to assist-control mode was not different between the groups
    • 67.2% (in NAVA group) vs 63.3% (in PSV group)
    • Relative risk reduction of 1.19 (95 % CI 0.56–2.54; P = 0.66)
    • Absolute risk reduction: 3.91% (95% CI -13.26% to 21.07%, P = 0.70)
  • Secondary outcome:
    • Patient-Ventilator asynchrony measured by asynchrony index
      • 14.7% (12.3-21.7) in NAVA group vs 26.7% (15.8-45.1) in PSV group
      • P <0.001
    • Dyspnea on day 1 as reported by patients
      • 28% in NAVA group vs 66% in PSV group
      • P=0.03
    • Dyspnea at 48 hours as reported by patients
      • 50% in NAVA group vs 52% in PSV group
      • P=0.54
    • Use of post-extubation non-invasive ventilation
      • 43.5% in NAVA group vs 66.6% in PSV group
      • P=0.008
    • Invasive Ventilator free days at day 7
      • 3 (0-4) in NAVA group vs 3 (0-4) in PSV group
      • P=0.87
    • Invasive Ventilator free days at day 14
      • 10 (2.5-11) in NAVA group vs 9 (4.8-11) in PSV group
      • P =0.91
    • Invasive ventilator free days at day 28
      • 24 (10.5-25) in NAVA group vs 23 (13.8-25) in PSV group
      • P=0.76
    • Death in first 28 days
      • 14.5% in NAVA group vs 22.7% in PSV group
      • P=0.25
    • Days of ICU stay
      • 18 (13.5-32) in NAVA group vs 18 (12-26) in PSV group
      • P=0.48

Authors’ Conclusions

  • NAVA does not increase the probability of remaining in a partial ventilator mode but decreases patient-ventilator asynchrony and is associated with less frequent application of non-invasive mechanical ventilation post-extubation


  • Randomised controlled trial
  • Multi-centre
  • Intention to treat Analysis
  • Blinded statistical analysis


  • The primary outcome chosen is not a very patient-important outcome
  • Although there was significant difference in use of post-extubation non-invasive ventilation, there were no clearly defined guidelines regarding use of post-extubation NIV
  • It was left to the discretion of the physicians who were not blinded
  • Although there was significant difference in asynchrony index between the two groups, data for calculating asynchrony index was missing in 14.5% of NAVA group and 24.2% of PSV group

The Bottom Line

  • This randomised controlled multi-centre trial failed to demonstrate that NAVA can increase the probability of remaining in a partial ventilator mode in intubated patients recovering from acute respiratory failure
  • NAVA was noted to decrease patient-ventilator asynchrony and was associated with less frequent application of non-invasive mechanical ventilation post-extubation
  • However, some of the methodical flaws limit the internal validity of the positive findings
  • NAVA does not seem to have an advantage over PSV when it comes to patient-significant outcomes such as ventilator free days, length of ICU or hospital stay, mortality etc.

External Links


Summary author: Vivek Jayaschandran and Alexandra Halalau
Summary date: 21 July 2017
Peer-review editor: Duncan Chambler

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