News review 9 : Non invasive ventilation Dr Aparna & Dr Ashok Deorari share their view point .........

Non Invasive Ventilation in Newborns
Dr. Aparna C & Dr. Ashok Deorari
Division of Neonatology
Department of Pediatrics, WHO Collaborating Centre for
Training and Research in Newborn Care
All India Institute of Medical Sciences
New Delhi – 110 029

Although application of intermittent positive pressure ventilation to preterm infants using an endotracheal tube began in the 1960s, high mortality rates were reported and the high rates of air leak dampened initial enthusiasm.1 George Gregory first described the use of continuous positive airway pressure (CPAP) in 1971 for the early treatment of respiratory distress syndrome (RDS).2

Neonatologists know endotracheal intubation may be life saving, it causes considerable trauma to the larynx, increases risk of infection and predisposes to chronic lung disease (CLD). Intubation and ventilation of preterm infants is the single most important predictor of subsequent CLD.

Noninvasive ventilation (NIV), a term applied to a variety of devices capable of supporting neonatal ventilation without the use of an endotracheal tube, is receiving increasing attention as means to reduce damage often incurred with mechanical ventilation.

Non invasive ventilation (NIV)

CPAP stabilizes lung volume improving gas exchange and improves conditions such as apnoea, upper airway obstruction, and thoraco-abdominal asynchrony, it does not consistently improve ventilation and does not work in infants with poor respiratory effort. On the other extreme invasive ventilation causes baro-volutrauma, atelecto-trauma along with bio-trauma resulting in ventilator induced lung injury( VILI). In an effort to support ventilation and avoid need for invasive support the use of intermittent positive pressure ventilation via nasal devices has been proposed and tested in preterm infants.3

Modalities of delivering NIMV Initially, non -invasive ventilation was accomplished using conventional ventilators in IMV mode (N-IMV). With the advent of triggering devices these were introduced into non-invasive neonatal ventilation and enabled delivery of non-invasive assist/control (N-A/C) also known as non-invasive synchronized IPPV(N-SIPPV), pressure support ventilation (N-PSV) and synchronized IMV (N-SIMV).

Bilevel Continuous Positive Airway Pressure (BiPAP) cycles between two levels of CPAP while the infant breathes spontaneously at a higher rate. Although some consider BiPAP a form of NIV, the fact that the cycling rate is usually low and the change in pressure is modest and relatively slow, raises questions on its ability to enhance ventilation. The potential beneficial effects of this modality are most likely related to enhanced lung recruitment.3

Physiological effects of NIV

1. Apnoea: Nasal IPPV may improve patency of the upper airway by creating intermittently elevated pharyngeal pressures. This intermittent inflation of the pharynx may activate respiratory drive, by Head’s paradoxical reflex, where lung inflation provokes an augmented inspiratory reflex. This results in resumption of breathing in infants with apnoea following cycling of the ventilator.4

2. Ventilation and work of breathing: The use of flow synchronized N-A/C immediately after extubation increased tidal volume and minute ventilation resulting also in lower PaCO2. This led to a reduction in spontaneous respiratory rate and less breathing effort as reflected by a smaller negative esophageal pressure during spontaneous inspiration as reported by Moretti, et al.5 Aghai et al showed that the application of N-SIPPV in a group of low birth weight infants resulted in lower work of breathing when compared to N-CPAP while tidal volume remained unchanged.6

3. Chest wall distortion: The negative pressure generated during spontaneous inspiration often produces an inward motion of the chest wall weakening the inspiratory effort and delaying lung expansion. N-SIMV at 10 breaths per minute reduced thoraco-abdominal asynchrony in preterm infants compared to N-CPAP immediately after extubation. 7

Synchrony in NIV

1. The Infant Star ventilator with the StarSync module has been used in most of the published SNIPPV studies. Now, the Infant Star ventilator has been phased out of production, though it is still being used at some centers.

2. In Europe and Canada, synchronization is accomplished with the Infant Flow SiPAP Comprehensive Ventilator (Viasys Healthcare, Yorba Linda, CA, USA). In the United States, the Infant Flow SiPAP Ventilator is available, but the Comprehensive model (which provides synchronization) has not yet been approved by the FDA. The Si-PAP is a bi-level device, providing higher and lower pressures and typically the inspiratory time is much longer.

In SiPAP a small (2-3cm H2O) slow, intermittent increase in pressure for duration upto 3 seconds (normally it is 1-2 secs) is produced using sigh breaths (upto 6/min). This results in change of lung volume by 4-6 ml/kg. This increase and followed by decrease in lung volume helps in reducing work of breathing. Also it recruits unstable alveoli to improve lung volume. This offloads respiratory work by improving FRC resulting in better gas exchange.

3. The 840TM ventilator system (Puritan Bennett Inc., Pleasanton, CA, USA) is being modified to deliver SNIPPV.

4. Giulia (Ginevri, Italy) uses a special flow transducer with prongs and provides nasal synchronized IMV/SIPPV/CPAP.

Synchronising NIV inflations with an infant's own breaths is theoretically advantageous. Pneumatic Graseby capsules are used to detect abdominal movement at the start of inspiration. However, they are known to have time delays and variable efficacy.1

Now-a-days, unsynchronized NIV is being used in neonates and reported to be safe and effective (personal communication).


NIPPV may be delivered by nasal prongs, which can be short or long, single or bi-nasal or by nasal mask or nasopharyngeal ET. However, randomized trials are not available till date advocating superiority of one over other.

Clinical indications

Apnoea: The Cochrane meta analysis reports two trials enrolling 54 infants in total. Both reported only the short term results (4 to 6 hours) of the interventions. Only one infant randomised to NCPAP required intubation during this period.8 In a cross-over study of 20 infants, Ryan showed no significant difference in rates of apnea (events/hr) between the two interventions [WMD -0. 10 (-0. 53, 0. 33)].9 Lin randomized 34 infants and demonstrated a greater reduction in frequency of apneas (events/hr) with NIPPV compared to NCPAP [WMD -1.19 (-2. 31, -0. 07)].10

Post extubation: Pooled analysis from 3 RCTs showed a significant reduction in extubation failure [RR 0.21 (0.10, 0.45), RD −0.32 (−0.45−0.20), NNT 3 (2, 5)] using NIPPV. More infants on NIPPV compared to CPAP remained extubated at 48 - 72 hours. All 3 studies used synchronized NIPPV. Differences in rates of chronic lung disease approached but did not achieve statistical significance favouring NIPPV [typical RR 0.73 (95%CI 0.49, 1.07), typical RD -0.15(95% CI -0.33, 0.03). 11

Initial treatment of RDS: The use of NIV in the management of RDS is particularly appealing because of the possibility of reducing intubation rates and exposure to the potentially VILI . N-CPAP has been used for this purpose, but a significant proportion of the smaller infants fail. As reported in the COIN trial, 55% of infants born at 25–26 weeks gestation fail initial CPAP.11

Bhandari et al. conducted an RCT of infants who received surfactant which compared rapid extubation to NIPPV with ongoing conventional ventilation. No differences were detected in the duration of endotracheal intubation or oxygen requirement. There was a reduction from 52% to 25% (P = 0.03) in the NIPPV group for the combined outcome of CLD and death. At 22 months there were no differences in developmental outcomes.21 Results from another randomized controlled trial comparing N-IMV with N- CPAP showed that in infants born before 35 weeks with RDS, N-IMV reduced the intubation rate compared to N-CPAP from 49 to 25%. A more striking change was observed among infants in the BW below 1500 g strata with a reduction in intubation rate from 60 to 31%. Although the mean duration of invasive ventilation was similar, the rate of CLD in the infants initially supported with N-IMV was less than one fifth of that in the N-CPAP group.12 A possible explanation for reduction in CLD is the reduction in duration or complete avoidance of invasive ventilation during the initial phase of respiratory failure in preterm infants. Recent trial by same group from Brazil showed unsynchronized NIPPV to be more beneficial when compared with CPAP, especially for infants with a birth weight of >1000g needing rescue surfactant.13

Another RCT from India, 76 neonates (28 – 34 weeks gestation) with respiratory distress within 6 h of birth were randomized to receive NIPPV or NCPAP. The failure rate (defined as the need for intubation and mechanical ventilation) at 48 h and 7 days was significantly less among infants randomized to NIPPV. The failure rate of NIPPV was significantly less in the sub-group of 28 – 30 weeks gestation and those who did not receive surfactant. The combination (28 – 30 weeks gestation and not receiving surfactant) sub-group had the most benefit, with the number needed to treat being two. There were no differences in other outcomes (including CLD), comparing NIPPV to NCPAP.14

In a recent randomized control trial from Lucknow unsynchronized noninvasive ventilation using nasopharyngeal tube when compared with head box oxygen significantly reduced the rate of extubation failure in preterm neonates ventilated for varied causes.15


The most serious complication reported with use of NIPPV in neonates has been gastric perforation.16 All recent studies, however, have not reported any association with necrotizing enterocolitis or gastric or other intestinal perforations with (S)NIPPV use. One study noted an increase in abdominal girth following NIPPV use.17


Concerns about the damaging effects, and expense, of conventional mechanical ventilation have led neonatologists to seek new methods of respiratory support for the preterm infant such as non-invasive respiratory support. Whether NIV translates into meaningful clinical benefits such as reduced CLD and/or time on ventilator needs to be proved. The RCT studies carried out, to date, seem to be promising in terms of (S)NIPPV use in the primary mode in decreasing CLD. It is also important to note that significant lack of major complications of using(S) NIPPV in studies. Whether unsynchronized NIV will be safe and effective need to be proven .The caveats include the fact that most RCTs have included small numbers (especially the smallest premature infants), and there are limited data on long-term pulmonary and neuro-developmental outcomes.18


1. Davis PG, Morley CJ, Owen LS. Non-invasive respiratory support of preterm neonates with respiratory distress: Continuous positive airway pressure and nasal intermittent positive pressure ventilation. Semin Fetal Neonatal Med. 2009 Feb;14(1):14-20. Epub 2008 Oct 4.

2. G.A. Gregory, J.A. Kitterman, R.H. Phibbs, W.H. Tooley and W.K. Hamilton. Treatment of the idiopathic respiratory-distress syndrome with continuous positive airway pressure. N Engl J Med 284 (1971), pp. 1333–1340.

3. Bancalari E, Claure N. Non-invasive ventilation of the preterm infant. Early Hum Dev. 2008 Dec;84(12):815-9. Epub 2008 Sep 27.

4. Lin CH, Wang ST, Lin YJ, Yeh TF. Efficacy of nasal intermittent positive pressure ventilation in treating apnea of prematurity. Pediatr Pulmonol 1998;26:34 9– 53.

5. Moretti C, Gizzi C, Papoff P, Lampariello S, Capoferri M, Cal cagnini G, et al. Comparing the effects of nasal synchronized intermittent positive pressure ventilation (nSIPPV) and nasal continuous positive airway pressure (N-CPAP) after extubation in very low birth weight infants. Early Hum Dev 1999; 56:167– 77.

6. Aghai ZH, Saslow JG, Nakhla T, Milcarek B, Hart J, Lawrysh-Plunkett R, et al. Synchronized nasal intermittent positive pressure ventilation (SNIPPV) decreases work of breathing (WOB) in premature infants with respiratory distress syndrome (RDS) compared to nasal continuous positive airway pressure (N-CPAP). Pediatr Pulmonol 20 0 6;41:875 – 81.

7. Kiciman NM, Andreasson B, Bern stein G, Mannino FL, Rich W, Henderson C, et al. Thoracoabdominal motion in newborns during ventilation delivered by endo-tracheal tube or nasa l prongs. Pediatr Pulmonol 1998;25:175 – 81.

8. R. Ramanthan. Nasal respiratory support through the nares: Its time has come. Journal of Perinatology (2010) 30, S67–S72.

9. B. Lemyre, P.G. Davis and A.G. De Paoli, Nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) for apnea of prematurity. Cochrane Database Syst Rev (2007) CD002272.

10. C.A. Ryan, N.N. Finer and K.L. Peters, Nasal intermittent positive-pressure ventilation offers no advantages over nasal continuous positive airway pressure in apnea of prematurity. Am J Dis Child 143 (1989), pp. 1196–1198.

11. C.H. Lin, S.T. Wang, Y.J. Lin and T.F. Yeh. Efficacy of nasal intermittent positive pressure ventilation in treating apnea of prematurity, Pediatr Pulmonol26 (1998), pp. 349–353.

12. P.G. Davis, B. Lemyre and A.G. De Paoli, Nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) for preterm neonates after extubation, Cochrane Database Syst Rev (2007) CD003212.

13. V. Bhandari, R.G. Gavino and J.H. Nedrelow et al. A randomized controlled trial of synchronized nasal intermittent positive pressure ventilation in RDS. J Perinatol 27 (2007), pp. 697–703.

14. Meneses J, Bhandari V, Alves JG, Herrmann D. Noninvasive ventilation for respiratory distress syndrome. A randomized controlled trial. Pediatrics 2011; 127:300-307.

15. Kugelman, I. Feferkorn, A. Riskin, I. Chistyakov, B. Kaufman and D. Bader, Nasal intermittent mandatory ventilation versus nasal continuous positive airway pressure for respiratory distress syndrome: a randomized, controlled, prospective study, J Pediatr 150 (2007), pp. 521–526.

16. Sai Sunil Kishore M, Dutta S, Kumar P. Early nasal intermittent positive pressure ventilation versus continuous positive airway pressure for respiratory distress syndrome. Acta Paediatr 2009; 98: 1412 – 1415.

17. Mala Kumar, Avasthi S, Ahuja S, Malik GK ,Singh SN . Unsynchronized Nasal Intermittent Positive Pressure Ventilation to Prevent Extubation Failure in Neonates:A Randomized Controlled Trial. Ind J Ped 2011, 78(7):801–806.

18. Garland JS, Nelson DB, Rice T, Neu J. Increased risk of gastrointestinal perforations in neonates mechanically ventilated with either face mask or nasal prongs. Pediatrics 1985; 76: 406 – 410.

19. Robert M DiBlasi. Neonatal Noninvasive Ventilation Techniques: Do We Really Need to Intubate? Respiratory care September 2011: 56: 9.

20. Bhandari. V. Nasal intermittent positive pressure ventilation in the newborn: review of literature and evidence-based guidelines. Journal of Perinatology (2010) 30, 505 – 512.