Neurally adjusted ventilatory assist in infants: A review article

Abstract

Neurally adjusted ventilatory assist (NAVA) and non-invasive (NIV)-NAVA are innovative modes of synchronized and proportional respiratory support. They can synchronize with the patients' breathing and promote patient comfort. Both techniques are increasingly being used these years, however experience with their use in newborns and premature infants in Taiwan is relatively few. Because increasing evidence supports the use of NAVA and NIV-NAVA in newborns and premature infants requiring respiratory assist to achieve better synchrony, the aim of this article is to discuss whether NAVA can provide better synchronization and comfort for ventilated newborns and premature babies. In a review of recent literature, we found that NAVA and NIV-NAVA appear to be superior to conventional invasive and non-invasive ventilation. Nevertheless, some of the benefits are controversial. For example, treatment failure in premature infants is common due to insufficient triggering of electrical activity of the diaphragm (EAdi) and frequent apnea, highlighting the differences between premature infants and adults in settings and titration. Further, we suggest how to adjust the settings of NAVA and NIV-NAVA in premature infants to reduce clinical adverse events and extubation failure. In addition to assist in the use of NAVA, EAdi can also serve as a continuous and real-time monitor of vital signs, assisting physicians in the administration of sedatives, evaluation of successful extubation, and as a reference for the patient's respiratory condition during special procedures. Neurally adjusted ventilatory assist (NAVA) and non-invasive (NIV)-NAVA are innovative modes of synchronized and proportional respiratory support. They can synchronize with the patients' breathing and promote patient comfort. Both techniques are increasingly being used these years, however experience with their use in newborns and premature infants in Taiwan is relatively few. Because increasing evidence supports the use of NAVA and NIV-NAVA in newborns and premature infants requiring respiratory assist to achieve better synchrony, the aim of this article is to discuss whether NAVA can provide better synchronization and comfort for ventilated newborns and premature babies. In a review of recent literature, we found that NAVA and NIV-NAVA appear to be superior to conventional invasive and non-invasive ventilation. Nevertheless, some of the benefits are controversial. For example, treatment failure in premature infants is common due to insufficient triggering of electrical activity of the diaphragm (EAdi) and frequent apnea, highlighting the differences between premature infants and adults in settings and titration. Further, we suggest how to adjust the settings of NAVA and NIV-NAVA in premature infants to reduce clinical adverse events and extubation failure. In addition to assist in the use of NAVA, EAdi can also serve as a continuous and real-time monitor of vital signs, assisting physicians in the administration of sedatives, evaluation of successful extubation, and as a reference for the patient's respiratory condition during special procedures. 1. IntroductionAdmitted neonates, and especially premature infants, usually require positive pressure ventilatory support during the transition period. With the administration of antenatal steroids and postnatal surfactant, most very low birth weight infants (VLBWIs) survive and need significantly long term respiratory support in the neonatal intensive care unit (NICU). Improving subject-ventilator synchrony is known to improve ventilation and decrease adverse effects. However, synchronously ventilating a premature infant is complicated because of the short inspiratory time, rapid respiratory rate, small tidal volume, and leakage around non-cuffed endotracheal tube. Neurally adjusted ventilator assist (NAVA) and non-invasive (NIV)-NAVA are innovative modes of neural-triggered ventilation that use the subject's electrical activity of the diaphragm (EAdi) as a trigger to deliver mechanical breaths that are synchronized to each breath of the subject. NAVA and NIV-NAVA can serve a potential solution for the difficult synchrony in ventilating premature infants. However, experience with their use in newborns and premature infants is limited in Taiwan because the fee of EAdi catheter was not included into national health insurance policy and patients must pay at their own expense. In this review, we describe the reasons for using NAVA, benefits of NAVA or NIV-NAVA, and how to set and titrate NAVA mode in premature infants and neonates. Lastly, we demonstrate how to use EAdi as a real-time monitor of respiration in these patients.2. Why NAVA? How personalized?Breathing is controlled by rhythmic discharge from the respiratory center of the brain which travels to excite the diaphragm muscle via the phrenic nerve, resulting in muscle contraction and movement of the diaphragm. This then leads to a reduction in airway pressure and consequently inflow of air into the lungs. Conventional synchronized mechanical ventilation involves the use of flow or pressure sensors to detect inspiration via a reversal of flow or fall in airway pressure.1Beck J. Sinderby C. Neurally adjusted ventilatory assist in newborns.Clin Perinatol. 2021; 48: 783-811Abstract Full Text Full Text PDF Scopus (7) Google Scholar However, this reversal of flow or fall in airway pressure is the last neurorespiratory event, leading to many triggering errors with a traditional synchronized ventilator, and increases sensitivity to hyperinflation and intrinsic positive end-expiratory pressure (PEEP). Especially in neonates and premature infants, synchronized ventilation is more difficult due to the need for small tidal volume, rapid respiratory rate and short inspiratory time. Leakage also reduces the reliability of monitoring of respiratory parameters. Moreover, neonates and premature infants have a strong vagal reflex leading to apnea and periodic breathing with a highly variable breathing pattern. In addition, traditional synchronized ventilators with present flow and pressure sensors only detect breathing initiation and deliver a preset ventilator breath. It then increases the difficulty of synchronization, especially with regards to tidal volume, breath triggering and breath termination. Mortamet et al.2Mortamet G. Larouche A. Ducharme-Crevier L. Fléchelles O. Constantin G. Essouri S. et al.Patient–ventilator asynchrony during conventional mechanical ventilation in children.Ann Intensive Care. 2017; 7: 122Crossref PubMed Scopus (18) Google Scholar described the characteristics of patient-ventilator asynchrony (PVA) in 34 critically ill children (median age 6 months) admitted to a pediatric intensive care unit (PICU) who received mechanical ventilation for at least 24 h. In total, 9806 breaths were analyzed, and their results showed that the 27% (interquartile 22–39%) of the time was asynchronous with the ventilator, most of which was due to errors with cycling-off and delays in triggering. An automated algorithm showed an asynchrony NeuroSync index of 45%, confirming the high prevalence of asynchrony. NAVA can optimize patient-ventilator synchronization through the EAdi. With NAVA, EAdi signals are captured by the electrodes of an EAdi catheter and sent to the ventilator, which then uses the signals to help the patient breathe. Since the diaphragm and ventilator use the same signal, mechanical coupling between the ventilator and diaphragm is almost immediate. The patient's EAdi triggers the mechanical ventilator to deliver synchronized breaths with the initiation, size and termination of the patient's breath. NAVA therefore offers a potential solution to many of the challenges posed by the ventilation of infants.3. Benefits of NAVA&NIV-NAVA compared to conventional mode in infantsNAVA allows the infants rather than the ventilators or physicians to regulate their own ventilation, and control the initiation, termination, size, rate and peak pressure of their breathing.3Jung Y.H. Kim H.S. Lee J. Shin S.H. Kim E.K. Choi J.H. Neurally adjusted ventilatory assist in preterm infants with established or evolving bronchopulmonary dysplasia on high-intensity mechanical ventilatory support: a single-center experience.Pediatr Crit Care Med. 2016; 17: 1142-1146Crossref PubMed Scopus (13) Google Scholar Shi et al.4Shi Y. Muniraman H. Biniwale M. Ramanathan R. A review on non-invasive respiratory support for management of respiratory distress in extremely preterm infants.Front Pediatr. 2020; 8: 270Crossref PubMed Scopus (21) Google Scholar reviewed NAVA and NIV-NAVA articles since 2012, and found that EAdi monitoring and NAVA were safe and feasible. In comparison with conventional ventilators, NAVA provides a better gas exchange and patient-ventilator interaction, lower peak inspiratory pressure (PIP), lower oxygen requirement, and reduced respiratory muscle load. Compared with conventional non-invasive ventilation (NIV) such as nasal continuous positive airway pressure (NCPAP) and non-invasive mandatory ventilation (NIMV), non-invasive pressure support ventilation (NIV-PS), NIV-NAVA improves synchrony, reduces reintubation, complications and oxygen requirement. Rong5Rong X. Liang F. Li Y.J. Liang H. Zhao X.P. Zou H.M. et al.Application of neurally adjusted ventilatory assist in premature neonates less than 1,500 grams with established or evolving bronchopulmonary dysplasia.Front Pediatr. 2020; 8: 110Crossref PubMed Scopus (9) Google Scholar also suggested that NAVA improves comfort and requires less sedation in premature infants with bronchopulmonary dysplasia. Mally et al.6Mally P.V. Beck J. Sinderby C. Caprio M. Bailey S.M. Neural breathing pattern and patient-ventilator interaction during neurally adjusted ventilatory assist and conventional ventilation in newborns.Pediatr Crit Care Med. 2018; 19: 48-55Crossref PubMed Scopus (10) Google Scholar reported a reduction in patient ventilator asynchrony, as quantified using the NeuroSync index, and central apnea with NAVA compared to synchronized intermittent mandatory ventilation (SIMV) in VLBW infants. Firestone et al.7Firestone K. Horany B.A. de Leon-Belden L. Stein H. Nasal continuous positive airway pressure versus noninvasive NAVA in preterm neonates with apnea of prematurity: a pilot study with a novel approach.J Perinatol. 2020; 40: 1211-1215Crossref PubMed Scopus (7) Google Scholar reported 17 preterm infants with apnea of prematurity, and found a decrease in clinical events from 17.9 ± 7.8/hour with CPAP to 10.2 ± 8.1/hour with NIV-NAVA of NAVA level 0 cmH2O/μV (NN0) (p = 0.00047). Gibu8Gibu C.K. Cheng P.Y. Ward R.J. Castro B. Heldt G.P. Feasibility and physiological effects of noninvasive neurally adjusted ventilatory assist in preterm infants.Pediatr Res. 2017; 82: 650-657Crossref PubMed Scopus (31) Google Scholar also found that NIV-NAVA decreased PIP, fraction of inspired oxygen (FiO2), frequency of desaturation and EAdi compared to NIMV. The EAdi catheter was used in 11 patients for a total of 81 days without complications. Xiao and colleagues9Xiao S. Huang C. Cheng Y. Xia Z. Li Y. Tang W. et al.Application of neurally adjusted ventilatory assist in ventilator weaning of infants ventilator weaning.Brain Behav. 2021; 11e2350Crossref Scopus (1) Google Scholar conducted a crossover study in which 25 infants were given CPAP and NAVA mode, and found no significant differences in hemodynamic indexes or partial pressure of carbon dioxide (PaCO2) between the two modes, and both were in normal range. Peak pressure, mean pressure, and EAdi signal were correspondingly lower in NAVA mode. Lee10Lee B.K. Shin S.H. Jung Y.H. Kim E.K. Kim H.S. Comparison of NIV-NAVA and NCPAP in facilitating extubation for very preterm infants.BMC Pediatr. 2019; 19: 298Crossref PubMed Scopus (22) Google Scholar et al. reported that extubation failed within 72 h in 6.3% of preterm infants (<30 weeks gestational age) who received NIV-NAVA and 37.5% of those who received NCPAP (p = 0.041). Reviewing all of these articles (Table 1), the results show that NAVA and NIV-NAVA can improve patient-ventilator interaction and comfort, decrease PIP, oxygen requirement, sedation requirement, apnea, clinically significant events, and extubation failure. Moreover, the application of NAVA and EAdi monitoring appears to be safe and feasible in premature infants.Table 1Studies published for NAVA or NIV-NAVA compared to conventional mechanical ventilators since 2016.First Author, YearInterventionType of studynPatientOutcomeJung et al.,3Jung Y.H. Kim H.S. Lee J. Shin S.H. Kim E.K. Choi J.H. Neurally adjusted ventilatory assist in preterm infants with established or evolving bronchopulmonary dysplasia on high-intensity mechanical ventilatory support: a single-center experience.Pediatr Crit Care Med. 2016; 17: 1142-1146Crossref PubMed Scopus (13) Google Scholar 2016NAVA/PC-SIMV + PSRetrospective29Preterm infants<1500 gLower PIP, Pmean, work of breathing, and FiO2 in NAVA.Shi et al.,4Shi Y. Muniraman H. Biniwale M. Ramanathan R. A review on non-invasive respiratory support for management of respiratory distress in extremely preterm infants.Front Pediatr. 2020; 8: 270Crossref PubMed Scopus (21) Google Scholar 2016NIV-NAVA/NCPAP/NIPPV/NHFVRetrospective, review52Preterm infants<1500 gNAVA has better blood gas with lower PIP and FiO2.Rong et al.,5Rong X. Liang F. Li Y.J. Liang H. Zhao X.P. Zou H.M. et al.Application of neurally adjusted ventilatory assist in premature neonates less than 1,500 grams with established or evolving bronchopulmonary dysplasia.Front Pediatr. 2020; 8: 110Crossref PubMed Scopus (9) Google Scholar 2020NAVA/TRADITIONAL infants<1500 in of respiratory decrease in the need of et P.V. Beck J. Sinderby C. Caprio M. Bailey S.M. Neural breathing pattern and patient-ventilator interaction during neurally adjusted ventilatory assist and conventional ventilation in newborns.Pediatr Crit Care Med. 2018; 19: 48-55Crossref PubMed Scopus (10) Google Scholar + in central apnea and patient-ventilator interaction with et K. Horany B.A. de Leon-Belden L. Stein H. Nasal continuous positive airway pressure versus noninvasive NAVA in preterm neonates with apnea of prematurity: a pilot study with a novel approach.J Perinatol. 2020; 40: 1211-1215Crossref PubMed Scopus (7) Google Scholar infants<1500 level 0 reduced of apnea and provide et C.K. Cheng P.Y. Ward R.J. Castro B. Heldt G.P. Feasibility and physiological effects of noninvasive neurally adjusted ventilatory assist in preterm infants.Pediatr Res. 2017; 82: 650-657Crossref PubMed Scopus (31) Google Scholar was a mode that has significant in PIP, frequency of of and EAdi with no catheter et S. Huang C. Cheng Y. Xia Z. Li Y. Tang W. et al.Application of neurally adjusted ventilatory assist in ventilator weaning of infants ventilator weaning.Brain Behav. 2021; 11e2350Crossref Scopus (1) Google Scholar is normal and not significantly Pmean, and mean pressure are lower in et B.K. Shin S.H. Jung Y.H. Kim E.K. Kim H.S. Comparison of NIV-NAVA and NCPAP in facilitating extubation for very preterm infants.BMC Pediatr. 2019; 19: 298Crossref PubMed Scopus (22) Google Scholar failure rate is lower in in a NAVA and in infantsNAVA involves the use of EAdi for ventilatory support. set NAVA level to how ventilatory support is In F. L. F. Beck J. H. C. et to increasing of neurally adjusted ventilatory assist PubMed Scopus Google G. A. G. S. et pattern during neurally adjusted ventilatory assist in respiratory failure Care Med. PubMed Scopus Google Scholar increasing the NAVA level has to the PIP, a EAdi a A in the NAVA level then reduces EAdi PIP a and H. Firestone K. NAVA ventilation in clinical and management 7: S. S. Stein H.M. of NAVA on peak inspiratory and electrical activity of the diaphragm in premature Perinatol. PubMed Scopus Google B. Firestone Stein H.M. neurally adjusted ventilatory assist (NAVA) in and Perinatol. 2016; PubMed Scopus Google Scholar reported that neonates on NAVA and NIV-NAVA have the as They also found that premature infants also have to the The is the NAVA level to the respiratory a condition which is the same in neonates. With regards to the of NAVA level extubation to NIV-NAVA, et B. Firestone Stein H.M. neurally adjusted ventilatory assist (NAVA) in and Perinatol. 2016; PubMed Scopus Google Scholar infants for titration. results showed that the NAVA level PIP at a and was a decrease in EAdi using The NAVA level was cmH2O/μV in NAVA which to cmH2O/μV in NIV-NAVA, because of the of ventilation and leakage we suggest increasing the NAVA level cmH2O/μV weaning patients from NAVA to NIV-NAVA to PIP, and then the NIV-NAVA level to 0 cmH2O/μV which is to a NIV-NAVA of NAVA level 0 cmH2O/μV (NN0) of NCPAP to support premature infants because of the lower extubation failure B.K. Shin S.H. Jung Y.H. Kim E.K. Kim H.S. Comparison of NIV-NAVA and NCPAP in facilitating extubation for very preterm infants.BMC Pediatr. 2019; 19: 298Crossref PubMed Scopus (22) Google Scholar and lower rate of clinically significant K. Horany B.A. de Leon-Belden L. Stein H. Nasal continuous positive airway pressure versus noninvasive NAVA in preterm neonates with apnea of prematurity: a pilot study with a novel approach.J Perinatol. 2020; 40: 1211-1215Crossref PubMed Scopus (7) Google Scholar of in preterm neonates is a physicians using NAVA to support premature infants because of clinical from reported that of preterm neonates at weeks of and all of those at weeks of have positive airway pressure versus for apnea in preterm Scholar The treatment for is and by NCPAP or the apnea NCPAP provides pressure controlled via a in an Nasal continuous positive airway pressure for the respiratory care of the Care. Google Scholar or of to help the breathing in premature neonates. However, no support is given to the during of apnea, increasing to clinically significant events such as and can provide ventilation in of apnea with no However, is with regards to the trigger of and breathing during support is not by the ventilator in neonates with K. Horany B.A. de Leon-Belden L. Stein H. Nasal continuous positive airway pressure versus noninvasive NAVA in preterm neonates with apnea of prematurity: a pilot study with a novel approach.J Perinatol. 2020; 40: 1211-1215Crossref PubMed Scopus (7) Google Scholar a NAVA level of 0 cmH2O/μV during NIV-NAVA (NN0) be an to deliver CPAP with ventilation in neonates with who Beck J. Stein H. Neurally adjusted ventilatory assist for noninvasive support in Perinatol. 2016; Full Text Full Text PDF PubMed Scopus (21) Google H. Beck J. M. ventilation with neurally adjusted ventilatory assist in Med. 2016; Full Text Full Text PDF PubMed Scopus Google Scholar this the neonates support CPAP during breathing, and ventilation during of The of triggering has not since the of initiation is via K. Horany B.A. de Leon-Belden L. Stein H. Nasal continuous positive airway pressure versus noninvasive NAVA in preterm neonates with apnea of prematurity: a pilot study with a novel approach.J Perinatol. 2020; 40: 1211-1215Crossref PubMed Scopus (7) Google set apnea time the ventilated infants have a respiratory of whether NAVA or NIV-NAVA is used in premature infants, a apnea time in more ventilation during of leading to and respiratory A apnea time in a of however can also in respiratory support and more clinically significant Firestone Stein H.M. of in apnea time on the clinical of neonates on Care. 2019; PubMed Scopus Google Scholar a study of neonates weeks of gestational age NIV-NAVA, and the ventilator and clinically significant events for apnea of and for Compared with the apnea time was with a rate of to ventilation from to (p the time ventilation also from to (p However, the of clinically significant events from to (p A apnea time to a rate of to ventilation and a of ventilation, however also in clinical suggest a apnea time for premature infants weeks of gestational age then increasing the apnea time as the infant and the apnea time can be to the infant is to NAVA ventilation allows the infants to control their PIP and tidal for each breath. are whether a premature can tidal especially et Lee J. Y.H. Neural is insufficient in preterm infants during neurally adjusted ventilatory 2019; Google Scholar reported in PIP and a rate of with a level of However, Firestone Stein H.M. peak inspiratory and tidal in premature neonates on NAVA Pediatr. 2021; PubMed Scopus Google Scholar et al. reported that the of breaths in premature neonates on NAVA were less than of or of PIP, which are the in neonatal neonates NAVA we suggest that these be intermittent or breaths for not with a level of NAVA, that a lower was with to these two Lee J. Y.H. Neural is insufficient in preterm infants during neurally adjusted ventilatory 2019; Google Firestone Stein H.M. peak inspiratory and tidal in premature neonates on NAVA Pediatr. 2021; PubMed Scopus Google Scholar an high NAVA level is not A to the A. F. G. Neural is in preterm infants during neurally adjusted ventilatory using clinically 2019; PubMed Scopus Google Scholar also that a NAVA level cmH2O/μV is and provides for premature EAdi monitoring the vital of a EAdi is no NAVA uses the EAdi to provide ventilated patients with synchronized and proportional support with invasive and non-invasive A respiratory and breathing pattern can be as a vital via the EAdi An in EAdi that the patient is not that is low or that the patient is not for a support ventilation mode. A decrease in EAdi that the patient is that is a high sedation phrenic or conventional mode use with diaphragm EAdi monitoring can provide with a continuous evaluation of the and frequency of diaphragm et J. R. Beck J. Sinderby C. et breathing pattern in infants 2017; PubMed Scopus (10) Google Scholar the EAdi and extubation to the successful extubation rate in infants, and found that EAdi peak and extubation in both successful and failure extubation extubation was with a in EAdi peak and et A. G. A. L. G. A. of on electrical activity in ventilated pediatric Care Med. PubMed Scopus (7) Google Scholar used EAdi monitoring to the effects of a of on the of respiratory in They found a significantly frequency of EAdi and the administration of with a mean decrease of EAdi physicians can the and of respiration With NAVA, a in EAdi triggers ventilation to The continuous monitoring of breathing by the EAdi signal allows for more of sedation improves patient and reduced the of sedation et the to by monitoring patient with a ventilator in neurally adjusted ventilatory assist a Care. Scopus (1) Google Scholar the to in infants with by monitoring EAdi EAdi peak pressure, mean pressure, respiratory rate, and flow the EAdi peak decreased from to and the respiratory rate decreased from to breaths EAdi monitoring can therefore show whether a is or and provide on the frequency and to et F. G. Essouri S. Beck J. A. et of in children with a study Pediatr. 2019; Full Text Full Text PDF PubMed Scopus (13) Google Scholar used EAdi to the benefits of the in infants with requiring noninvasive ventilation. results showed that the significantly decreased the inspiratory and the of breathing Lee et J. L. H. reduces the electrical activity of the diaphragm and respiratory infants.Pediatr Res. Scopus Google Scholar used EAdi monitoring to the of on respiratory in premature infants. NAVA and NIV-NAVA, EAdi EAdi respiratory rate, time on ventilation, and PIP were all significantly lower in than in monitoring can physicians whether the diaphragm mechanical ventilation and to adjust the settings to or insufficient support. In addition, a in EAdi peak and extubation that the patient need more respiratory support. Moreover, sedation with an lower EAdi signal can decrease the need for Lastly, treatment such as the or can be via the in EAdi. The EAdi signal can provide a control mode, and also continuous vital monitoring to more the patient's monitoring is an physiological which can be used to an breathing in time and physicians to in respiratory work and diaphragm the extubation and for NAVA is the only mode which can provide ventilation to the of each breath. Compared to conventional ventilation mode, can improve patient-ventilator synchrony, reduce FiO2 lower PIP and tidal volume, provide better comfort, reduce reduce the of days in and reduce the of using NAVA in premature infants, we the NAVA level pressure at PIP of the patient and as apnea time which can be to as the patient's condition extubation, a NIV-NAVA level of 0 can be used as a for and have that can reduce apnea and the rate of The NAVA and in infants a of is a flow to for the to 1. IntroductionAdmitted neonates, and especially premature infants, usually require positive pressure ventilatory support during the transition period. With the administration of antenatal steroids and postnatal surfactant, most very low birth weight infants (VLBWIs) survive and need significantly long term respiratory support in the neonatal intensive care unit (NICU). Improving subject-ventilator synchrony is known to improve ventilation and decrease adverse effects. However, synchronously ventilating a premature infant is complicated because of the short inspiratory time, rapid respiratory rate, small tidal volume, and leakage around non-cuffed endotracheal tube. Neurally adjusted ventilator assist (NAVA) and non-invasive (NIV)-NAVA are innovative modes of neural-triggered ventilation that use the subject's electrical activity of the diaphragm (EAdi) as a trigger to deliver mechanical breaths that are synchronized to each breath of the subject. NAVA and NIV-NAVA can serve a potential solution for the difficult synchrony in ventilating premature infants. However, experience with their use in newborns and premature infants is limited in Taiwan because the fee of EAdi catheter was not included into national health insurance policy and patients must pay at their own expense. In this review, we describe the reasons for using NAVA, benefits of NAVA or NIV-NAVA, and how to set and titrate NAVA mode in premature infants and neonates. Lastly, we demonstrate how to use EAdi as a real-time monitor of respiration in these

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