1. Non-invasive positive pressure ventilation in the neonate
Peter C. Rimensberger
Pediatric and Neonatal ICU
University Hospital of Geneva
Switzerland

2. CPAP  intubation + ventilation
COIN-trial
610 infants, 25-to-28-weeks’ gestation, randomized to
CPAP  intubation + ventilation
at 5 minutes after birth
In the year 2008: BPD incidence = 35% < 29 wks
COIN-trial, NEJM 2008

3. Elastic work of breathing
Adult
Infant
(Reduced Compliance)
Volume
(%VC)
Pressure
Thorax
Lungs
Chest wall
Work = P * V
ACB: Move the chest wall from the resting position
AXC: Overcome resistive forces

4. Inward distortion of the rib cage on the volume displaced by the diaphragma
 Innefficient ventilation and waist of work

5. Thoraco-abdominal Asynchrony
(the noncoincident motion of the rib cage and abdomen during breathing)
If the rib cage is sucked in or retracted as abdominal excursions occur (e.g., in upper airway obstruction),
or the abdomen is retracted as the rib cage expands (e.g., diaphragmatic paralysis)
Prisk GK Pediatric Pulmonology 2002; 34:462–472

6. Thoracoabdominal Asynchrony  Synchrony
NCPAP
NIPPV
25 weeks: Abdominal (red) & Chest Wall (green) Movements Synchronized NIPPV: Better ventilation
Courtesy of Simon Bignall

7. SNIPPV
1) To avoid the need for endotracheal intubation in preterm infants with respiratory failure
Barrington KJ Pediatrics 2001; 107: 638–41 (RCT)
De Paoli AG Acta Paediatrica 2003; 92: 70–5 (review and meta-analysis)
Khalaf MN Pediatrics 2001; 108: 13–7 (RCT)
Santin R Perinatol 2004; 24: 487–93 (prospective observational study)
Friedlich P Perinat 1999; 19: 413 (RCT)
2) It has been shown to be particularly effective in decreasing reintubation when compared with nasal CPAP as an extubation mode
Barrington KJ Pediatrics 2001; 107: 638–41 (RCT)
Khalaf MN Pediatrics 2001; 108: 13–7 (RCT)
Friedlich P Perinat 1999; 19: 413 (RCT)
3) SNIPPV has been used as an alternative to continued endotracheal mechanical ventilation after surfactant therapy in 28- to 34-week gestation infants with respiratory distress syndrome
Santin R Perinatol 2004; 24: 487–93 (prospective observational study)
4) Work of breathing has also been shown to be decreased with the use of SNIPPV compared to nasal CPAP
Kiciman NM Pediatr Pulmonol 1998; 25: 175–81

8. Reintubation after extubation:
A prospective RCT comparing SNIPPV vs NCPAP
(Khalaf MN, et al. Pediatrics 2001;108:13-17)
Criteria for extubation:
1. MAP = 4-6 cm H2O
2. IMV  25/minute
3. PIP  16 cm H2O
4. PEEP  5 cm H2O
5. FiO2  0.35
6. Aminophylline level  8 mg/L
7. Hematocrit  40%
After extubation:
1. SNIPPV: PIP +4, same IMV-PEEP
2. NCPAP: 4- 6
3. FiO2: O2 saturations 90-96%
Criteria for re-intubation:
1. pH < 7.25
2. PaCO2 > 60 mmHg
3. PaO2 < 50 mmHg despite a FiO2 of 0.7
4. A single episode of apnea requiring bag
and mask resuscitation
5. Frequent ( 3/hr) apnea/bradycardia
spells
6. Multiple ( 3/hr) desaturation episodes
despite a FiO2 of 1.0

9. Reintubation after extubation:
(Khalaf MN, et al. Pediatrics 2001;108:13-17)
SNIPPV
(n =34)
NCPAP
(n =30) p
value
Age at study (d)
4 (1 -
83)
2.5 (1
106)
0.95
Wt. at study (gm)
1110 55
1200 75
0.32
Pre
MAP (cm H 2 O)
4.9
0.2
5.1
0.38
FiO
0.30
0.02
0.01
0.84
AR (cm/H
O/L/s)
169 16
205 21
0.18
LC (ml/cmH
0.74
0.8
0.1
0.57
Post pH
7.36 +
0.03
7.34
0.14 CO
(mmHg) 37
1.0 40
2.0
0.06
Apnea (n)
2.24
2.03
0.7
Success (n, %)
32 (94)
18 (60)
<

10. A Prospective Observational Pilot Study: SNIPPV as a Primary Mode of Ventilation In Infants > or = 28 Weeks with RDS
(Santin RS, et al. J Perinatol 2004;24:487-93)
SNIPPV (n=24)
CV (n=35)
P value
Birth weight (grams) *
1582 ± 77
1511 ± 103
0.92
Gestational age (weeks) *
31.2 ± 0.5
31.0 ± 0.4
0.89
Gender (male, n, %)
15 (63)
22(62)
0.88
Antenatal steroids (n, %)
18 (75)
24 (68)
0.90
Apgar at 5 minutes (median) 8
0.87
Age at surfactant instillation (h)*
3.1 ± 1.4
2.7 ± 0.49
0.49
Mean ± SEM

11. A Prospective Observational Pilot Study: SNIPPV as a Primary Mode of Ventilation In Infants > or = 28 Weeks with RDS
(Santin RS, et al. J Perinatol 2004;24:487-93)
SNIPPV (n=24)
CV (n=35)
p value
OI pre-surfactant instillation (cm H2O)
6.0 ± 1.0
5.5 ± 0.6
0.67
Duration of endotracheal intubation (days)
0.3 ± 0.0
2.40 ± 0.4
0.001
Duration of SNIPPV (days)
2.8 ± 0.4
3.1 ± 0.7
0.68
Duration of CPAP (days)
0.3 ± 0.3
0.2 ± 0.1
0.71
Duration of nasal cannula (days)
3.8 ± 1.5
5.1 ± 1.3
0.3
Duration of supplemental O2 (days)
8.2 ± 3.3
15.0 ± 3.2
0.04
Duration of parenteral nutrition (days)
8.4 ± 0.8
12.1 ± 1.6
0.02
Length of stay (days)
29.1 ± 3.3
37.5 ± 3.0
OI: Oxygenation Index
Mean ± SEM

12. NIMV versus NCPAP for Respiratory Distress Syndrome: A Randomized, Controlled, Prospective Study
Kugelmann A J Pediatr 2007;150:521-6

13. Infants treated initially with NIPPV needed less ETT ventilation than infants treated with NCPAP.
Infants treated with NIPPV had a decreased incidence of BPD compared with those treated with NCPAP
Kugelmann A J Pediatr 2007;150:521-6

14. SURF-N-SAVE STUDY: HYPOTHESIS
A RANDOMIZED CONTROLLED TRIAL OF SYNCHRONIZED NASAL INTERMITTENT POSITIVE PRESSURE (SNIPPV) VENTILATION IN RDS
(Bhandari V, et al. J Perinatol 2007;27: )
SURF-N-SAVE STUDY: HYPOTHESIS
Primary mode SNIPPV (defined as its use in the acute phase of RDS, following the administration of the first dose of surfactant) initiated shortly after birth would decrease the incidence of BPD and/or death in smaller premature babies when compared to conventional endotracheal mode of ventilation.

15. <32 weeks gestational age. 2. Birth weight 600-1250 grams 3.
A RANDOMIZED CONTROLLED TRIAL OF SYNCHRONIZED NASAL INTERMITTENT POSITIVE PRESSURE (SNIPPV) VENTILATION IN RDS
(Bhandari V, et al. J Perinatol 2007;27: )
INCLUSION CRITERIA 1.
<32 weeks gestational age. 2.
Birth weight grams 3.
RDS requiring intubation and surfactant therapy within one hour of birth.
The need for intubation /surfactant was based on the following:
a. Fi02 > 0.4 to maintain Sa02 > 90%.
b. Chest radiograph consistent with RDS
EXCLUSION CRITERIA (any one)
Nasopharyngeal pathology.
Choanal atresia.
Cleft lip or palate.
Major congenital anomalies, especially thoracic or cardiac defects.
Clinical parameters for exclusion ninety minutes after initial surfactant therapy (approximately 2½ hours after birth).
Oxygenation index (OI=[(Fi02)(mean airway pressure)]/Pa02) > 9.
No indwelling arterial line.
More than two isotonic fluid boluses.
Continuous medication infusion for blood pressure support.
Fi02 > 0.8.

16. A RANDOMIZED CONTROLLED TRIAL OF SYNCHRONIZED NASAL INTERMITTENT POSITIVE PRESSURE (SNIPPV) VENTILATION IN RDS
(Bhandari V, et al. J Perinatol 2007;27: )
Primary
Outcome: CV
SNIPPV P
(n=21)
(n=20)
value
Birth weight (grams)*
858 ± 27
915 ± 41
0.24
Gestational age (weeks)*
27.0 ± 0.4
26.9 ± 0.3
0.93
BPD or Deaths (n, %)
11 (52)
4 (20)
0.03
BPD (n, %)
7 (33)
2 (10)
0.04
Deaths (n, %)
4 (19)
2 (10)
0.66
Air leaks (n, %)
1 (5)
1 (5)
1.0
PDA (n, %)
3 (14)
4 (20)
0.70
IVH (n, %)
6 (29)
6 (30)
1.0
PVL (n, %)
1 (5)
2 (
10)
0.61
Longterm Outcome: Mental or Psychomotor Developmental Intex
There were no statistically significant differences in the MDI (mean  SD; CV (n=8) versus SNIPPV (n=7);  versus  17.54) or PDI (88.38 versus  19.47) scores in the infants, assessed at a median (25th –75th centile) corrected GA of 22 ( ) months.

17. CPAP  intubation + ventilation
COIN-trial
610 infants, 25-to-28-weeks’ gestation, randomized to
CPAP  intubation + ventilation
at 5 minutes after birth
In the year 2008: BPD incidence = 35% < 29 wks
COIN-trial, NEJM 2008

18. Strategizing SNIPPV - As extubation mode
- To control apnea, avoiding extubation
- Primary mode (with or without surfactant use): more data needed

19. Synchronization Principles
PSV

20. SNIPPV: Trigger systems for synchronization
Graseby Capsule
Infant Flow Advanced
Viasys “ SIPAP”
Flow sensor
Ginevri “ Giulia”
SLE 5000
Babylog 8000
NAVA-system
sensing of diaphragmatic electrical activity
Maquet “Servo-I”

21. ?
How to set Ti in a spontaneous breathing patient on a pressure support mode ?
Peak Flow
25%
“Flow termination criteria”
0 flow
0 flow
Flow
PIP
Tinsp. Ti Te
PS above PEEP
Pressure
PEEP
Pressure Control
Pressure Support

22. Termination Sensitivity = Cycle-off Criteria
Flow
Peak Flow (100%)
TS 30%
Leak
TS 5%
Time
Tinsp. (eff.)
Set maximal Tinsp.

23. Neural breathing pattern in the preterm (room air, no vent)
Sleeping, 30 weeks, 1158 g 1 2 3
Sleeping, 30 weeks, 1158 g
Sleeping, 30 weeks, 1205 g
Sleeping, 30 weeks, 1205 g
Feeding, baby moving
28 weeks, 1486g
Baby awake, 28 weeks, 1486g
200 a.u.
Beck et al, PAS 2006
10 seconds

24. Non-invasive neurally adjusted ventilatory assist (NAVA)
in rabbits with acute lung injury
Beck J et al. Intensive Care Med (2008) 34:316–323

25. Non-invasive neurally adjusted ventilatory assist (NAVA)
in rabbits with acute lung injury
Beck J et al. Intensive Care Med 2008; 34:316–323

26. baby 440 grams

27. 1st experience
baby 440 grams

28. baby 440 grams

29. baby 440 grams

30. J.Beck ICM 2008
“NAVA can deliver assist in synchrony and proportionally to EAdi after extubation, with a leaky non-invasive interface”

31. Conclusions
Meta-Analysis: “NIPPV is a useful method of augmenting the beneficial effects of NCPAP in preterm infants…..reassuring absence of the gastrointestinal side-effects that were reported in previous case series.” (Cochrane Collaboration)
Issues to be solved
Patient selection
Indications
Synchronization during NIPPV