Home Print this page Email this page Small font sizeDefault font sizeIncrease font size
Users Online: 119
About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Advertise Login 

 Table of Contents  
Year : 2015  |  Volume : 4  |  Issue : 2  |  Page : 115-118

Resolution of localized pulmonary interstitial emphysema in two neonates - Why does neurally adjusted ventilatory assist work?

1 Department of Paediatrics and Adolescent Medicine, Pamela Youde Nethersole Eastern Hospital, Hong Kong, China
2 Department of Paediatrics and Adolescent Medicine, Princess Margaret Hospital, Lai King Hill Road, Kwai Chung, Hong Kong, China

Date of Web Publication6-Apr-2015

Correspondence Address:
Dr. Shing Yan Robert Lee
Department of Paediatrics and Adolescent Medicine, Pamela Youde Nethersole Eastern Hospital, 2 Lok Man Road, Chai Wan, Hong Kong
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2249-4847.154113

Rights and Permissions

Localized pulmonary interstitial emphysema (PIE) is a known complication of mechanical ventilation. Recently, we encounter two cases of localized PIE, which developed on the course of mechanical ventilation using high-frequency oscillatory ventilation, followed by conventional intermittent positive pressure ventilation. We then switched the ventilator mode to neurally adjusted ventilatory assist (NAVA). We observed that on switching to NAVA, there was a decrease in peak inspiratory pressure (PIP) in case 1 and case 2, and decrease in tidal volume in case 2. Localized PIE resolved in 6-9 days' time. Since high PIP and high tidal volume are risk factors for PIE, NAVA could lead to resolution of localized PIE by achieving lower PIP and lower, but optimal tidal volume. We suggest that NAVA is a treatment of choice in localized PIE.

Keywords: Neurally adjusted ventilatory assist, premature neonates, pulmonary interstitial emphysema

How to cite this article:
Lee SR, Shek CC. Resolution of localized pulmonary interstitial emphysema in two neonates - Why does neurally adjusted ventilatory assist work?. J Clin Neonatol 2015;4:115-8

How to cite this URL:
Lee SR, Shek CC. Resolution of localized pulmonary interstitial emphysema in two neonates - Why does neurally adjusted ventilatory assist work?. J Clin Neonatol [serial online] 2015 [cited 2020 Apr 7];4:115-8. Available from: http://www.jcnonweb.com/text.asp?2015/4/2/115/154113

  Introduction Top

Pulmonary interstitial emphysema (PIE) is an air leak syndrome, in which there is dissection of air into the pulmonary interstitium. The underlying mechanism is that the mechanical ventilation or continuous positive airway pressure (CPAP) lead to over-distension of alveoli with resultant alveolar and bronchiolar rupture and dissection of air into the pulmonary interstitium. In additional to mechanical factors, structural and maturational factors do play an important role according to animal studies [1] and a human report [2] of occurrence of PIE with no preceding mechanical ventilation nor CPAP.

Pulmonary interstitial emphysema is one type of air leak, which in turn is a form of ventilator-induced lung injury. Volutrauma with the increase in vascular filtration and stress fractures of capillaries, epithelium, and basement membranes and biotrauma with increased proinflammatory cytokines and subsequent inflammatory reactions are the main problems. [3] The repeated opening and collapse of the alveoli and bronchial tree end segments generate forces tangent to alveolar basement membranes (atelectrauma). The results of ventilator-induced lung injury include air leak, fibrosis and bronchopulmonary dysplasia.

According to a review article, the risk factors for the occurrence of PIE are: Prematurity, very low birth weight, low Apgar score and need of resuscitation, positive pressure ventilation, use of high peak inspiratory pressure (PIP), use of high tidal volume, use of high inspiratory time, respiratory distress syndrome, meconium aspiration syndrome, amniotic fluid aspiration, pneumonia, and pulmonary hypoplasia. [3]

Previous studies on the use of neurally adjusted ventilatory assist (NAVA) mode provided by the SERVO-i ventilator (Maquet, Solna, Swedan) in neonates showed some short-term benefits including better patient-ventilator interaction and synchronization, [4],[5],[6],[7] reduction in PIP [4],[5],[8],[9] and oxygen requirement. [8] We speculate that if PIP (a risk factor for PIE) is reduced by using NAVA, NAVA could be able to resolve localized PIE. We set out to apply NAVA on two neonates with localized PIE. This is the first report of successful treatment of localized PIE by applying NAVA.

  Case Reports Top

Case 1

This case is the authors' first encounter of resolution of localized PIE on NAVA and was published online. [10] A male baby was born at gestation of 41 + 4 weeks with birth weight of 3.2 kg. The patient developed persistent pulmonary hypertension of newborn in early hours of life requiring high-frequency oscillatory ventilation (HFO) (Sensormedics 3100A, Yorba Linda, CA, USA) and nitric oxide. Blood culture grew Group B streptococcus and Escherichia coli. The course was stormy, and the ventilator settings were high. Mean airway pressure ranged from 16 to 25 cm H 2 O and inspired oxygen concentration (FiO 2 ) ranged from 0.9 to 1 in the first 2 weeks of life. Nitric oxide was finally weaned off on day 14. On day 14 localized PIE was evident in the right upper lobe in chest X-ray (CXR). The patient was switched to conventional ventilation from day 14 to day 18, but the localized PIE became more severe [Figure 1]a: Case 1, localized PIE at right upper lobe before switching to NAVA]. On day 18, NAVA was started. It was noted that average PIP decreased on switching ventilator mode to NAVA from 23 cm H 2 O to 20 cm H 2 O. On day 27, CXR showed almost complete resolution of localized PIE [Figure 1]b: Case 1, almost complete resolution of PIE 9 days after start of NAVA] FiO 2 had come down to 0.35. The patient was extubated on day 28. An important thing to note in this case report is that resolution of PIE did occur despite the fact that an inappropriately high NAVA level (higher than three) had been used. [10]
Figure 1:

Click here to view

Case 2

A female fetus did not have any growth in utero since the gestation of 25 weeks due to placental insufficiency. At 27 + 1 week, emergency cesarean section was performed for reversed end-diastolic blood flow in the umbilical artery. The birth weight was 525 g. She had recurrent clonic seizure in the first 3 days of life. Cranial ultrasound on day 1 showed ventriculomegaly suggestive of cerebral atrophy, which was likely due to in-utero hypoxia. She also had hypotension and pulmonary hemorrhage requiring dopamine and epinephrine infusion. After two doses of surfactant on day 1, FiO 2 came down to 0.21. Because of her poor neurological status and unstable cardiovascular system, she was kept on intermittent positive pressure ventilation. From day 3 to day 8, she was switched to HFO (Sensormedics 3100A, Yorba Linda, CA, USA) in the hope of reduction of barotrauma and prevention of bronchopulmonary dysplasia. On day 8, mild, localized PIE had already developed affecting mainly the left lower lobe. Attempts were made to decrease mean airway pressure to around 9 cm H 2 O. At this low ventilator setting, there was frequent desaturation and retention of carbon dioxide. So from day 8 to day 16, she was put back on intermittent positive pressure ventilation - pressure support mode of SERVO-i ventilator. In view of PIE, attempts were made to decrease PIP gradually from 16 cm H 2 O on day 8 to 11 cm H 2 O on day 11, but we encountered more frequent desaturation and needed to increase PIP back to 15 cm H 2 O by day 12 . On day 16, chest X-ray revealed worsening of localized PIE [Figure 1]c: Case 2, localized PIE of the left lung with left lower lobe mostly affected before switching to NAVA] NAVA was then started. There was complete resolution of PIE 6 days after start of NAVA [Figure 1]d: Case 2, complete resolution of PIE 6 days after start of NAVA]. The ventilator data were retrieved [Table 1]. PIP and tidal volume decreased in the first 24 h of switching to NAVA, which was followed by decrease in FiO 2 in the next 24 h. Synchronization was well, and there was no need for the use of narcotics for sedation.
Table 1: Ventilator settings and measurements before and after start of NAVA for case 2. Parameters are averaged on 24 h. 6th day was the day when CXR showed complete resolution of PIE

Click here to view

  Discussion Top

Until date, there have been numerous case reports describing treatment modalities for localized PIE. Lateral decubitus positioning keeping patients lying on the sides of localized PIE achieved better ventilation and resulted in resolution of PIE. [11] Selective ventilation of the contralateral lung has been advocated. This is either achieved by selective intubation of the contralateral lung [12] or selective blockage of the ipsilateral main bronchus. [13] Surgical options include percutaneous puncture of the cysts at bedside [14] and surgical excision under general anesthesia. [15] All the above procedures are invasive. Ventilating a single lung may not be feasible at times when the contralateral lung has serious pathology, e.g. severe pneumonia, severe respiratory distress syndrome, persistent pulmonary hypertension of newborn, etc. In case 1 when the ventilator setting required was high, and the patient was prone to destabilize just recovering from persistent pulmonary hypertension of newborn and just having been weaned off inhaled nitric oxide, we were hesitant to try single-lung ventilation. Applying ventilator strategies obviating single-lung ventilation is a welcoming idea.

High-frequency jet ventilation is a ventilator mode of choice, [16] but the machine is not available outside USA. High-frequency ventilation using a lower frequency of 3-4 Hz was useful according to a report. [17] Our two cases show that NAVA also works in this situation of localized PIE. A further advantage is that there is good synchronization obviating the need of sedation with narcotics.

In both cases, PIP became low after switching ventilatory mode to NAVA. We did not keep detailed ventilator data for case 1. For case 2, in addition, we note that the tidal volume also decreased. This achievement by NAVA is important as high PIP, and high tidal volume are known risk factors for the development of air leak. [3]

On NAVA mode of ventilation, once the lungs have reached optimal inflation, the Hering-Breuer reflex occurs. Stretch receptors provide feedback to terminate Edi signal, which in turn, stops ventilator flow and protect the lungs from over-inflation. This intrinsic mechanism of NAVA makes it possible to ventilate babies with optimal lung volume avoiding volutrauma. This is in agreement with our observation of decreased PIP in case 1 and case 2, and decreased tidal volume in case 2. We speculate that decreased tidal volume and decreased PIP is the mechanism underlying resolution of localized PIE by NAVA. In case 1 and case 2, we encountered trouble of reducing ventilator pressure when the patients were on pressure support mode of conventional ventilation or HFO as each time when a lower pressure was used frequent desaturation was seen. It was especially hazardous for case 1 in the fear of recurrence of persistent pulmonary hypertension of newborn. After switching ventilator modes to NAVA, lower PIP was attained.

Inappropriately high NAVA level (>3) was used in case 1. [10] This illustrates the built-in safety features of NAVA. Once the lungs have reached optimal inflation, the Hering-Breuer reflex occurs. Stretch receptors provide feedback to terminate Edi signal preventing excessive pressure and excessive tidal volume delivered in spite of an inappropriately high preset NAVA level. The observed ill-effect of inappropriately high NAVA level in case 1 was recurrent apnea. For correct strategy of determining the appropriate NAVA levels, the concept of finding the set point is recommended, which is beyond the scope of this report and is covered in a review article. [18]

  Conclusion Top

Neurally adjusted ventilatory assist is a treatment of choice for localized PIE. It has the advantage of being less invasive and achieves synchronization obviating the need of sedation with narcotics.

  References Top

Willet KE, Jobe AH, Ikegami M, Newnham J, Sly PD. Pulmonary interstitial emphysema 24 hours after antenatal betamethasone treatment in preterm sheep. Am J Respir Crit Care Med 2000;162:1087-94.  Back to cited text no. 1
Bhojani S, Bird D, Alok G. Spontaneous diffuse pulmonary interstitial emphysema (PIE) in an unventilated infant. Internet J Pediatr Neonatol 2008;9:2.  Back to cited text no. 2
Jeng MJ, Lee YS, Tsao PC, Soong WJ. Neonatal air leak syndrome and the role of high-frequency ventilation in its prevention. J Chin Med Assoc 2012;75:551-9.  Back to cited text no. 3
Breatnach C, Conlon NP, Stack M, Healy M, O′Hare BP. A prospective crossover comparison of neurally adjusted ventilatory assist and pressure-support ventilation in a pediatric and neonatal intensive care unit population. Pediatr Crit Care Med 2010;11:7-11.  Back to cited text no. 4
Alander M, Peltoniemi O, Pokka T, Kontiokari T. Comparison of pressure-, flow-, and NAVA-triggering in pediatric and neonatal ventilatory care. Pediatr Pulmonol 2012;47:76-83.  Back to cited text no. 5
Clement KC, Thurman TL, Holt SJ, Heulitt MJ. Neurally triggered breaths reduce trigger delay and improve ventilator response times in ventilated infants with bronchiolitis. Intensive Care Med 2011;37:1826-32.  Back to cited text no. 6
Bordessoule A, Emeriaud G, Morneau S, Jouvet P, Beck J. Neurally adjusted ventilatory assist improves patient - Ventilator interaction in infants as compared with conventional ventilation. Pediatr Res 2012;72:194-202.  Back to cited text no. 7
Bengtsson JA, Edberg KE. Neurally adjusted ventilatory assist in children: An observational study. Pediatr Crit Care Med 2010;11:253-7.  Back to cited text no. 8
Stein H, Howard D. Neurally adjusted ventilatory assist in neonates weighing <1500 grams: A retrospective analysis. J Pediatr 2012;160:786-91.  Back to cited text no. 9
Lee R. A newborn baby with E. coli and Group B Streptococcus septicemia and hypoxemic respiratory failure - Successful treatment with NAVA. Crit Care News 22:14-7. From: www.criticalcarenews.com/upload/pdf/CCN_issue22_Critical%20Care%20News%20issue%20No%2022.pdf  Back to cited text no. 10
Schwartz AN, Graham CB. Neonatal tension pulmonary interstitial emphysema in bronchopulmonary dysplasia: Treatment with lateral decubitus positioning. Radiology 1986;161:351-4.  Back to cited text no. 11
Joseph LJ, Bromiker R, Toker O, Schimmel MS, Goldberg S, Picard E. Unilateral lung intubation for pulmonary air leak syndrome in neonates: A case series and a review of the literature. Am J Perinatol 2011;28:151-6.  Back to cited text no. 12
Rastogi S, Gupta A, Wung JT, Berdon WE. Treatment of giant pulmonary interstitial emphysema by ipsilateral bronchial occlusion with a Swan-Ganz catheter. Pediatr Radiol 2007;37:1130-4.  Back to cited text no. 13
Watanabe M, Momoi N, Sato M, Go H, Imamura T, Kaneko M, et al. Percutaneous evacuation of diffuse pulmonary interstitial emphysema by lung puncture in a baby with extremely low birth weight: A case report. J Med Case Rep 2012;6:325.  Back to cited text no. 14
Rao J, Hochman MI, Miller GG. Localized persistent pulmonary interstitial emphysema. J Pediatr Surg 2006;41:1191-3.  Back to cited text no. 15
Keszler M, Donn SM, Bucciarelli RL, Alverson DC, Hart M, Lunyong V, et al. Multicenter controlled trial comparing high-frequency jet ventilation and conventional mechanical ventilation in newborn infants with pulmonary interstitial emphysema. J Pediatr 1991;119:85-93.  Back to cited text no. 16
Squires KA, De Paoli AG, Williams C, Dargaville PA. High-frequency oscillatory ventilation with low oscillatory frequency in pulmonary interstitial emphysema. Neonatology 2013;104:243-9.  Back to cited text no. 17
Stein H, Firestone K. Application of neurally adjusted ventilatory assist in neonates. Semin Fetal Neonatal Med 2014;19:60-9.  Back to cited text no. 18


  [Figure 1]

  [Table 1]

This article has been cited by
1 Positional treatment without mechanical ventilation in a very preterm infant with unilateral pulmonary interstitial emphysema: case report and review of the literature
Xiaoping Lei,Oliver Stangl,Christina Bösche,Kristina Stuchlik,Roland Czorba,Christian Wieg
BMC Pediatrics. 2019; 19(1)
[Pubmed] | [DOI]


Similar in PUBMED
  Search Pubmed for
  Search in Google Scholar for
Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  In this article
Case Reports
Article Figures
Article Tables

 Article Access Statistics
    PDF Downloaded236    
    Comments [Add]    
    Cited by others 1    

Recommend this journal