Non-Invasive Positive Pressure Ventilation –
evidence base in preterm infants
Methods used to avoid tracheal intubation
“And he went and lay upon the child.. Put his mouth upon his
mouth.. And the flesh of the child waxed warm” Kings 4:32
Lord Leighton “Elisha reviving the Shunammite child”
OUTLINE
1. Why does non-invasive support matter?
 endotracheal intubation damages
airway mucosa from top to bottom
 Long term adverse effects of BPD
2. Some relevant physiology
3. Methods to avoid intubation
 NIPPV
 Evidence from randomized trials
Sato K Ann Otol Rhinol Laryngol. 2006 115:816
Necrotizing TracheoBronchitis Kirpalani H CCM1985
Grossmann G, Eur J Pediatr 1986 145:361
Reyburn M. Am J Respir Crit Care Med. 2008
Control
Ventilation no SFT
Ventilation + SFT
Probability
of a poor
outcome at
18 months
(n=910)
Baseline Risk
Number of Morbidities at 36 weeks: BPD, ROP, Brain Injury
Objectives
1. Why does non-invasive support
matter?
 BPD and endotracheal intubation
 Long term effects of BPD
2. Physiology
3. Methods to avoid intubation
 CPAP, NIPPV
 Evidence from randomized trials
Historical Surgical Therapy for HMD: Sternal traction
Warley & Gairdner Arch Dis Child 1962; 37: 464
Newborn chest wall and lung pressure-volume curves
Agostino E and Mead J 1964; Handbook of Physiology
Chest Wall
Newborn
Adult
Lung
Pressure
Ped Pulmonol 1998; 25; 175
Normal or abnormal
chest wall-abdominal
movements
90°
135 °
45°
Effects of Synchronization During Nasal Ventilation
Hung-Yang Ang C Pediatr Res 69: 84, 2011
Synchronized
Non - Synchronized
Synchronization did not affect tidal volumes;
phase angles; apnea spells; hypoxemic spells
Moretti C: Comparing nasal synchronized intermittent
positive pressure ventilation (nSIPPV) and nCPAP) after
extubation in VLBW. Early Hum Dev. 1999;56:167
Objectives
1. Why does non-invasive support
matter?
 BPD and endotracheal intubation
 Long term effects of BPD
2. Physiology of NIPPV
3. Methods to avoid intubation
 CPAP, NIPPV
 Evidence from randomized trials
Repetitive themes in ventilation
Circular philosophy: “The thing that hath been, it is that which shall be;
and that which is done is that which shall be done: and there is no new
thing under the sun” Ch 1, v9 Ecclesiastes
Spiral philosophy: “The progress .. raises to each next stage of
determination the whole content, and … enriches and concentrates
itself...” G.F.Hegel “Science of Logic”; ‘The Absolute Idea; 812’;
1889 ALEXANDER GRAHAM BELL:
“Presented results to a meeting of the
American Association for the
Advancement of Science at
Montreal… ‘his invention met with little
enthusiasm.’
Stern L: Symposium on
Artificial Ventilation Paris 1969;
Biol. Neonate 16: 2429 (1970)
1890’s Wilhelm Schwake:
Pneumatic Chamber
Drinker P, Shaw LA. J Clin Invest.
1929 Jun;7(2):229-47.
Simple device for producing continuous negative pressure in infants
with IRDS. Bancalari E, Gerhardt T, Monkus E. Pediatrics.
1973;52:128
NEGATIVE PRESSURE
ISOLETTE NPV: RCTs
(i) Silverman WA Pediatrics
1967 Sequential RCT:
NPV vs IPPV in >1000 g
BW; Stopped early for
‘no benefit’ after 27
pairs.
(ii) Fanaroff AA J Pediatr
1973 Sequential analysis
RCT: NPV vs IPPV;
‘benefit’ in oxygenation
(iii) Alexander G: AJDC:1979
RCT n=36; NPV vs
CPAP: ’equivalent’
HEAD
Treatment of RDS – CPAP
Gregory GA: N Engl J Med. 1971; 284:1333
PICOT CPAP
P:
In infants VLBW or ELBW in DR
I:
does randomization to nCPAP
C: compared to intubation IMV
O: increase survival without BPD
T: at 36 weeks PMA?
N Engl J Med 2008;358:700
Wright CL, Kirpalani H 2011: 128: 111
Primary Outcome Death or BPD 36 weeks
0.91 (0.83, 1.00)
RCT of ventilation using oro-nasal mask
Llewellyn MA, Tilak KS, Swyer PR: 1970; Arch Dis Child 45:453
“Mortality similar… Nevertheless we encountered
complications … stomach distension... Oedema of the face”
Garland JS: Increased risk of GI perforations in neonates mechanically
ventilated with either face mask or nasal prongs. Pediatrics,1985, 76:406
Retrospective Matched Case control study (1 case: 4 controls)
Updated: Trials of NIPPV vs nCPAP
Outcome
NIPPV
n/N
nCPAP
n/N
Relative Risk
(95% CI)
PostExtubation
BPD
Death
26/93
38/88
3/56
3/55
0.64 (0.44, 0.95)
0.97 (0.21, 4.44)
Un-intubated
BPD
3/80
10/80
Death
5/79
9/85
Lemyre B, DePaoli A, Kirpalani H, Davis P; and
Salter S, Laughon M, Lemyre B, Bose C;
Cochrane
0.2 (0.05, 0.87)
0.59 (0.22, 1.59)
0.2
0.5
Favours NIPPV
1
2
5
Favours nCPAP
V Rajadurai
B Urlesberger
K Abubakar
F Reiterer
P Maton
A Chaudhary
G Dempsey
M Roy
D Millar
R van Lingen
E Boyle
S Rahman
J Frank
K Sankaran
P Srinivasan
E Asztalos
J Cairnie
P McNamara
B Lemyre
C O’Donnell
NIPPV: The Nasal Intermittent Positive
Ventilation for Prematures Trial
R Whyte
T Ibrahim
L Costantini
N Rashid
W Marion
I Herlihy
C Thiel
M Finelli
P Dijk
S Godambe
I Frantz
B Simma
I Hand
W Stelzl
M Hyndman
B Jonsson
J Miletin
P Gerhard
S Ranu
J Zupancic
R Roberts
A O’Sullivan
H Kirpalani
R Kim
L Legnevall
N Engl J Med. 2013 Aug 15;369(7):611-20
PICOT NIPPV QUESTION
P:
In infants <1000 g <30 weeks < 28
days requiring non-invasive support
I:
does randomization to NIPPV
C:
compared to nCPAP
O: increase survival without BPD
T: at 36 weeks PMA?
Population: Inclusion Criteria
•
•
Infants <1000 g BW and <30 w GA;
Considered candidates for noninvasive respiratory support:
non-intubated group: in first 7 days of
life and < 24 hours of intubation
or
intubated group: in first 28 days of life
and >24 hours intubation
Population: Exclusion Criteria
• Considered non-viable
• Life-threatening congenital anomaly
• Requiring surgical treatment
• Abnormal airway (upper or lower)
• Neuromuscular disorders
Intervention
• Pragmatic trial randomizing to
NIPPV or nasal CPAP
• Any device, binasal prongs, masks
• Synchronization not mandatory
• Guidelines for post-randomization
intubation and extubation
Primary Outcome
Prior death or survival with BPD at
36 weeks PMA
Definition of BPD:
• On respiratory support (IMV, nCPAP, NIPPV) or
• > 30% supplemental oxygen; or
• < 30% supplemental oxygen, and failed
Oxygen Reduction test (ORT) (J Perinatol 2003)
Ascertainment of primary outcome
1009 infants randomized
2 withdrew
consent
504 NIPPV
497
98%
503 nCPAP
Primary outcome
BPD-ORT
490
97%
Baseline Characteristics
Mother
NIPPV
nCPAP
Race
56%
57%
Age Years
30.3  6.3
30.5  6.1
Antenatal
Steroids
92%
91%
White
Baseline Characteristics
Infant
NIPPV
nCPAP
BW - g
802  131
805  126
GA - wks
26.1  1.5
26.2  1.5
Male
53%
46%
Multiples
23%
24%
SNAP II
30.6  13.6
30.4  13.4
Primary Outcome:
Death or BPD by ORT at 36 weeks
NIPPV
nCPAP
191 of 497 180 of 490
38%
37%
OR=1.1
95% CI 0.8 to 1.4
p=0.6
Sub-Group effects: Synchronization
NIPPV adjusted Death or ORT-BPD
sNIPPV
NIPPV
nCPAP
36 of 101
108 of 279
180 of 490
36%
39%
37%
p = 0.6
Number of post-randomization failures of
respiratory support, requiring re-intubation
and subsequent extubation by group
NIPPV Median (IQR)
nCPAP Median (IQR)
1 (0,1)
1 (0,1)
Cochrane: Greenough A 2008:
Synchronised ventilation newborns
Death
RR 1.19 (0.95,1.49)
Favours
Synchronized
Favours
Control
Peak Trans-Diaphragm Electrical Potential
Brigitte Lemyre, Peter G Davis, Antonio G De Paoli, Haresh Kirpalani Nasal intermittent
positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure
(NCPAP) for preterm neonates after extubation Cochrane; 4 SEP 2014 CD003212.pub2
Some current barriers to sNIPPV
1. Available flow triggers rendered dependent on minimalno leak nose and mouth
2. Devices for abdominal wall movement synchrisation no
longer available (Graseby capsule)
3. Limited data on NAVA
Needed now
1. Moderate to large scale trials with synchronizing
devices, with a relevant primary outcome
2. Improved patient-device-interfaces
C.T.Roberts, P.G.Davis, LS.Owen Neonatology 2013; 104:203
Bancalari E, Claure C Arch Dis Child (F&N): 2013: 98; F98
Conclusions:
Non-invasive support using
CPAP does reduce BPD
Superior methods still
needed
Simple non-synchronized
NIPPV does not improve
BPD
Synchronization for NIPPV
needs further trials
Leonardo Da Vinci
(1452-1519) Notebook
 HFNVpromising – trials
needed
Technology marches on but is
too often untested
Diego Rivera (1886-1957) Hospital Mural