Non-Invasive Ventilation for Preterm Infants

Non-Invasive Ventilation
for Preterm Infants
Mark Weems, MD
April 2, 2015
University of Tennessee Health Science Center
Division of Neonatal-Perinatal Medicine
Regional One Health
Le Bonheur Children’s Hospital
Memphis, Tennessee

Disclosures
• I have no conflicts of interest or relevant
financial relationships to disclose
• I will discuss a specific oxygen delivery device
and its off-label use for non-invasive ventilation

INTUBATION & MECHANICAL
VENTILATION
The Thrill is Gone

Life Magazine, 1939.
http://www.neonatology.org/pdf/life1939.pdf
Early
Non-Invasive
Ventilation
Oxygen Unit for Premature and
Very Young Infants.
Dr. Julius H. Hess, Chicago
American Journal of Disease of
Children 47:916-917, 1934
– 147 infants treated with 38-
95% O2
– Mortality 41%

Early
Non-Invasive Ventilation
Flagg PJ, The Art of Resuscitation, Reinhold Publishing Corp., 1944.
http://www.neonatology.org/pinups/flagg.html
Iron Lung: The negative pressure ventilator could be used to
facilitate gas exchange in an infant with weak respiratory drive.

Invasive Ventilation
Flagg PJ, The Art of Resuscitation, Reinhold Publishing Corp., 1944.
http://www.neonatology.org/pinups/flagg.html
Intubation & mechanical ventilation saved many babies with
respiratory distress, but also introduced new complications.

Traumatic Intubation
Esophageal intubation
Esophageal perforation
Tracheal perforation
Vocal cord injury
Subglottic stenosis
The Laryngoscope Volume 112, Issue 8, pages 1387-1393, 2 JAN 2009 DOI: 10.1097/00005537-200208000-00012
http://onlinelibrary.wiley.com/doi/10.1097/00005537-200208000-00012/full#fig3
Esophageal intubation with perforation

Intubation Success Rate
Laura Y. Haubner , James S. Barry , Lindsay C.
Johnston , Lamia Soghier , Philip M. Tatum , David
Kessler , Katheryne Downesa, Marc Auerbach
Neonatal intubation performance: Room for
improvement in tertiary neonatal intensive care
units
Resuscitation, Volume 84, Issue 10, 2013, 1359 - 1364
http://dx.doi.org/10.1016/j.resuscitation.2013.03.014
Fig. 2 Intubation success rates by provider ( n ) where n = number of
attempts by that provider-type.

Box plot showing median, interquartile range, outliers, and extremes of
duration of successful intubation attempts by grade of doctor.
Colm P.F. O'Donnell et al. Pediatrics 2006;117:e16-e21
©2006 by American Academy of Pediatrics

ETT Ventilation in 1st Week
Infants ≤30 weeks receiving primarily ETT
ventilation were at increased risk for BPD or
death compared to those receiving non-
invasive respiratory support
OR 3.1 (95% CI 1.3-7.8)
Adjusted for gender, BW, Sepsis, PDA, Race,
Surfactant, & Time to regain BW.
Dumpa, et al. AmJPerinatology, 2011.

Effect of avoiding eMV on death or BPD
Hendrik S. Fischer, and Christoph Bührer Pediatrics
2013;132:e1351-e1360
Preterm infants, GA <30 weeks

2013;132:e1351-e1360
Avoiding ETT ventilation decreases
risk of BPD/death.

NON-INVASIVE SUPPORT
There Must Be a Better World Somewhere

Non-Invasive Modes
High Flow Nasal Cannula
HFNC (HHNC)
Nasal Continuous Positive Airway Pressure
NCPAP
Non-Invasive Positive Pressure Ventilation
NIPPV (NIV, NC-IMV)
Non-Invasive NAVA
NIV-NAVA (not reviewed here)

HIGH-FLOW NASAL
CANNULA
Gambler’s Blues

High-Flow Nasal Cannula
https://www.fphcare.com/respiratory/infant-care/optiflow/humidification-systems/
Gas source
Humidifier
Nasal interface
Pressure relief valve
45cm H2O

HFNC
12 physiologic studies 1993-2013
– Pressure delivered is variable and unpredictable
– Affected by mouth-opening, flow rate, and infant
size
12 clinical studies 2005-2013
– Flow-rates up to 8 lpm without significant
morbidity
– HFNC more effective than low flow NC for
preventing intubation
– Minimal differences verses NCPAP
Haq, et al. Paediatr Respir Rev, 2014.

HFNC vs. NCPAP
Extubated to HFNC 5-6 lpm or NCPAP 7cm
Extubation failure rate was equal
– Most likely due to apnea
HFNC Group
– Decreased nasal trauma compared to nasal
prong CPAP
– Increased extubation failure <26 weeks
– Half HFNC failures rescued with NCPAP
303 Preterm infants
GA <32 weeks
Manley, et al. NEJM, 2008.

HFNC Conclusions
Easy to use
Works fairly well
Pressure delivered is variable
but may be excessive
Not as effective as NCPAP for
more premature infants
https://www.fphcare.com/respiratory/infant-care/optiflow/humidification-systems/

NASAL CPAP
Call It Stormy Monday

Nasal CPAP
https://www.fphcare.com/respiratory/infant-care/cpap-therapy/humidification-systems/
Gas source
Humidifier
Nasal interface
Pressure control
system

Nasal CPAP Devices
Nasal Interface
– Long nasopharyngeal
tube
– Single nasal prong
– Nose mask
– Short bi-nasal prongs
– Nasal cannula
Pressure Control
– Bubble CPAP
– Variable flow device
– Ventilator
Each device delivers controlled and
relatively constant airway pressure

Nasal CPAP Effects
Splints open upper airway
– Reduces obstruction & apnea
Prevents alveolar collapse
– Reduces atelectasis
– Reduces QV mismatch
– Conserves surfactant

Nasal CPAP Complications
Leak
Trauma

CPAP vs. Headbox O2
Cochrane Review, 2003
– Preterm infants extubated after IPPV
Nasal CPAP reduces
– Apnea
– Respiratory acidosis
– Oxygen requirement
Davis & Hednerson-Smart. Cochrane Neonatal Reviews, 2003.
Nasal CPAP is effective in preventing failure of
extubation in preterm infants following a period of
endotracheal intubation and IPPV

COIN Trial
CPAP vs. Intubation in DR
CPAP Group:
– Decreased use of O2 at 28 days
– Increased pneumothorax
But…
– ½ CPAP group was intubated
– Initial CPAP was 8cm H2O
610 Preterm infants
GA 25-28 6/7 weeks
Morley, et al. NEJM, 2008.

SUPPORT Trial
CPAP vs. Intubation in DR
CPAP Group:
– Fewer intubated days
– Decreased need for post-natal steroids for
BPD
But…
– ¾ CPAP group was intubated
1316 Preterm infants
GA 24-27 6/7 weeks
SUPPORT Study Grouop. NEJM, 2010.

2013;132:e1351-e1360
COIN & SUPPORT may have seen bigger
reduction in BPD if they had fewer babies on
ETT ventilation

NCPAP Conclusions
Easy to use
Helps prevent extubation
failure
Reduces BPD compared to
ETT ventilation
Commonly used devices
can cause pressure injury

NON-INVASIVE PPV
(I Got Everything I Need) Almost

Nasal PPV
https://www.fphcare.com/respiratory/infant-care/cpap-therapy/humidification-systems/
Gas source
Humidifier
Nasal interface
Pressure control
system

Nasal PPV Devices
Nasal Interface
– Long nasopharyngeal
tube
– Single nasal prong
– Nose mask
– Short bi-nasal prongs
– Nasal cannula
Pressure Control
– Ventilator
– Variable flow device
Similar to CPAP, but pressure control
must provide variable pressure
at set rate

Nasal PPV Effects
Splints open upper airway
– Reduces obstruction & apnea
Prevents alveolar collapse
– Reduces atelectasis
– Reduces QV mismatch
– Conserves surfactant
Causes lung expansion during apnea
– Assists alveolar recruitment
– Increases respiratory drive

Nasal PPV Complications
Leak
Trauma

NIPPV vs. NCPAP
Cochrane Review, 2014
– Preterm infants after extubation
NIPPV reduces extubation failure
Device and synchronization may be
important variables
Lemeyre, et al. Cochrane Neonatal Reviews, 2014.

NIPPV vs. NCPAP
Randomized to NIPPV or NCPAP after
extubation
No difference in death or BPD
But…
– No standardization of NIPPV practice
Kirplanai, et al. NEJM, 2013.
1009 Preterm infants
GA <30 weeks, BW <1000g, Age <28 days
NIPPV intervention not well defined

NIPPV vs. NCPAP
Randomized to NIPPV or NCPAP
No difference in BPD
NIPPV Group:
– Fewer failures 24-72hrs
– Fewer failures for babies >1000g
But…
– NIPPV rate was 20-30; too low for smaller babies
– NIPPV weaned to NCPAP after 72hrs
200 Preterm infants
GA 26-33 6/7 weeks
Meneses, et al. PEDIATRICS, 2011.

sNIPPV vs. NCPAP
Randomized to synchronized NIPPV or
NCPAP
sNIPPV Group
– Decreased BPD
– Decreased BPD/Death
If intubated, all were extubated <90min after
surfactant
Bhandari, et al. PEDIATRICS, 2007.
41 Preterm infants
GA <32 weeks, BW 600-1250g

sNIPPV vs. NCPAP
Retrospective sNIPPV vs. NCPAP
sNIPPV Group
– Decreased BPD
– Decreased BPD/Death
– Most significant in smaller patients: 500-750g
Bhandari, et al. PEDIATRICS, 2009.
469 Preterm infants
Retrospective - BW <1250g

Blood-gas values of Pco2 in infants in the SNIPPV versus
no-SNIPPV groups on postnatal days 1, 3, 7, 14, 21, and 28.
Vineet Bhandari et al. Pediatrics 2009;124:517-526

NIPPV vs. NCPAP
Primary and secondary outcomes. †Logistic regression to control for potentially confounding effects of GA, gender,
center, antenatal steroid use and multiple births was done; #P=0.005, *P=0.001, **P=0.04, MVET, mechanical
ventilation via endotracheal tube; BPD, bronchopulmonary dysplasia; PMA, postmenstrual age.
110 Preterm infants GA 26-29 6/7 weeks
Randomized to NIPPV vs. NCPAP
Ramanathan, et al. J Perinatology, 2012.
NIPPV Group:
- Fewer extubation
failures
- Fewer days with
supplemental O2

NIPPV vs. NCPAP
Primary and secondary outcomes. †Logistic regression to control for potentially confounding effects of GA, gender,
center, antenatal steroid use and multiple births was done; #P=0.005, *P=0.001, **P=0.04, MVET, mechanical
ventilation via endotracheal tube; BPD, bronchopulmonary dysplasia; PMA, postmenstrual age.
110 Preterm infants GA 26-29 6/7 weeks
Randomized to NIPPV vs. NCPAP
Ramanathan, et al. J Perinatology, 2012.
NIPPV Group:
- Fewer extubation
failures
- Fewer days with
supplemental O2
Protocol was similar to guidelines
on slide 69

Dr. Ramanathan then designed the Ram
Cannula. Approved as an oxygen
delivery device; not approved as an
interface for NCPAP or NIPPV.
Because many NICUs use Ram
Cannula for NCPAP & NIPPV and
Cochrane review concluded that
differences among devices may be
important, the remainder of this
presentation will refer to NIPPV using
Ram Cannula.
http://www.ramcannula.com/

Select a Size by Weight
Infant >2500g
– Orange 4.0mm prong
Newborn 1000-2500g
– Blue 3.5mm prong
Preemie <1000g
– Green 3.0mm prong
Micro Preemie <750g
– White 3.0mm prong
http://www.ramcannula.com/

Attach to Oxygen Source
Oxygen tubing
adapter will
connect to standard
oxygen tubing just
like regular nasal
cannula.
Will connect to
ventilator
circuit without
adapter.
http://www.neotechproducts.com/products/neotech-ram-cannula/

Insert Cannula into Nares
Inserts just like regular
nasal cannula
Bevel down
http://www.ramcannula.com/neotech-ram-cannula-online-inservice/

Secure to Face
Secure just like regular
nasal cannula
May go above or under
ears
Ensure the head is not
resting on O-ring
http://www.ramcannula.com/neotech-ram-cannula-online-inservice/

Micropreemie less than 1 hour old with
NIPPV.

LAC+USC/CHLA NIPPV Protocol
PIP, cm
H2O
PEEP, cm
H2O
Inspiratory
Time, s
Rate,
bpm
Slope
Initial
Settings
20-25 5-6 0.5 40 0.1-0.2
Maximum
Settings
30 8 1 50 0.2
Heater is set to invasive mode. May be set to noninvasive mode for a
few hours if there is excessive condensation.
Wean PIP to 10 then wean rate to 10 then change to CPAP.

1-3kg apneic neonate models and test
lung using 3 sizes of Ram Cannulas to
allow up to 30% leak & a worst-case
scenario with 58% leak.
RAM Pressure Delivery
0%
20%
40%
60%
80%
100%
30% Leak >50% Leak
PIP
PEEP
Iyer & Chatburn. Respir Care, 2014.
%ofSetPressureDelivered
toTestLung

RAM Pressure Delivery
0
5
10
15
20
25
30
30/8 25/6 20/5 10/5 10/4
PIP
PEEP
Iyer & Chatburn. Respir Care, 2014.
EstimatedPressureDelivered,cmH2O
Set PIP / PEEP on Vent

Rate = 40 iTime = 0.5
Spontaneous
Breath65bpm
Ventilator
Breath40bpm
Owen, et al. Arch Dis Child Fetal Neonatal Ed, 2011.

Spontaneous
Breath65bpm
Ventilator
Breath40bpm
Transmission of pressure occurs only when
vent is in synchrony with baby’s inspiration.

Spontaneous
Breath65bpm
Ventilator
Breath40bpm
Asynchronous breaths are not supported.

Spontaneous
Breath65bpm
Ventilator
Breath40bpm
Shorter iTime allows fewer breaths to be
supported.

Spontaneous
Breath65bpm
Ventilator
Breath30bpm
There is very little respiratory support with
this low rate.

NIPPV Contraindications
• Absolute
– Choanal atresia
– Cleft lip/palate
– Persistent apnea
• Relative
– NIPPV FiO2 >60% or ETT FiO2 >40%
– Frequent apnea
• >4/hour with stimulation
• >2/hour with bag/mask ventilation

THE DELIVERY ROOM
Early In The Morning

Mask Resuscitation Complications
Finer, et al, PEDIATRICS, 2009
– 24 ELBW, GA <32 weeks
– 18 (75%) had airway obstruction corrected by
repositioning head
Schmӧltzer, et al, Arch Dis Child Fetal Neonatal
Ed, 2011
– 56 infants, GA 24-30 weeks
– 14 (25%) had obstruction
– 27 (48%) had leak
– 8 (14%) had both

Mask group had 10x more intubations
and 5x times more chest compressions
than the nasal cannula group.
Nasal Cannula Resuscitation
Mask (n=314)
Nasal cannulae
(n=303)
p
Sex (females) 147 (46.8%) 152 (50.1%) >0.05b
Gestational age (wk) 36.32±3.7 36.57±3.7 n.s.a
Gestational age <34 wk 76 (24,2%) 63 (20.7%) >0.05b
Birthweight 2.678±875 2.780±1133 n.s.a
Birthweight <2000 g 74 (23.5%) 65 (21.4%) >0.05b
Caesarean sections 104 (33.1%) 92 (30.3%) >0.05 b
Apgar score >7 at 5 min 289 (92%) 290 (95.7%) 0.08b
Prenatal steroids (for GA
<34 wk)
54 (71%) 44 (69.8%) n.s.a
Intubations 20 (6.36%) 2 (0.6%) <0.001b
Chest compressions 26 (8.28%) 5 (1.65%) <0.001b
Admitted to NICU 136 (43.3%) 114 (37.6%) >0.05b
Deaths 17 (5.41%) 8 (2.64%) >0.05b
aANOVA.
bχ2 test.
n.s.: not significant.
Capasso, et al. Acta Paediatrica, 2005.
Randomized to Mask or Nasal Cannula in DR

Nasal Cannula Resuscitation
Characteristics of patients resuscitated with nasal
cannula in the delivery room (n = 102)
Birth weight (g)
Mean ± SD (range) 2,106 ± 1,094 (270–4,675)
< 1,000 g, n (%) 20 (19.6%)
1,001–1,500 g, n (%) 20 (19.6%)
1,501–2,500 g, n (%) 19 (18.6%)
> 2,500 g, n (%) 43 (42.2%)
Gestational age (wk)
Mean ± SD (range) 32.8 ± 5.3 (23–41)
≤ 28 wk, n (%) 29 (28.4%)
29–32 wk, n (%) 18 (17.6%)
33–36 wk, n (%) 22 (21.5%)
≥ 37 wk, n (%) 33 (32.4%)
63 transported to NICU
on NIPPV
8 successful intubations
3 failed intubations
stabilized on NIPPV
5 received chest
compressions
– 2 bradycardia with
intubation
– 3 with perinatal
depression (Apgar 1)
Paz, et al. AmJPerinatology, 2014.
Retrospective Report of NC in DR

Benefits of NC Resuscitation
Less obstruction than mask
More stable PEEP
Simultaneous ventilation, suction, and
gastric venting
Decreased gastric distention
Decreased need for intubation
Continued O2 delivery during intubation

Risks of NC Resuscitation
Ineffective if nasal passage is obstructed
May have excessive mouth leak

SURFACTANT
I Can’t Turn You Loose

INSURE
Intubate
Surfactant
Extubate
Verder, et al
– 1994: 68 infants on NCPAP,
GA 25-35 weeks
• Rescue INSURE reduced need
for MV: 33% vs. 83% (p<0.001)
– 1999: 60 infants with RDS on
NCPAP, GA <30 weeks
• Earlier INSURE improved
oxygenation and reduced
MV/Death and MV
Verder, et al. NEJM, 1994. Verder, et al. PEDIATRICS, 1999.

INSURE
Intubate
Surfactant
Extubate
INSURE-treated infants, GA 27-34 weeks, had
improved oxygenation from 30 min to 48 hours
compared to Surf+MV-treated infants.
Implementation of INSURE reduced MV by 50%.
Bohlin, et al. JPerinatology, 2007.

PRACTICE
RECOMMENDATION
Baby What You Want Me To Do

NIPPV Guideline
PIP, cm
H2O
PEEP, cm
H2O
Inspiratory
Time, s
Rate,
bpm
Slope
Initial
Settings
20-25 5-6
(ET PEEP +1)
0.5 40 0.1-0.2
Maximum
Settings
30 8 1 50 0.2
Heater is set to invasive mode. May be set to noninvasive mode for a
few hours if there is excessive condensation.
Wean PIP by 2s to 10 with daily gas.
If stable on 10/5 x24 hours, wean rate by 10s as tolerated.
If stable on rate 10, change to CPAP.
If stable on CPAP 5cm x24 hours, change to NC ≤2L.

Nasal Cannula with NRP
NC-PPV
NC-CPAP

Surfactant after NC Resuscitation
Leave NC in place
INSURE for surfactant per standard practice
Immediately extubate to NIPPV
– Do not contemplate getting a gas
– Do not hesitate while you check an X-ray
– Do not procrastinate

Suggested Reading
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.
Paz P, Ramanathan R, Hernandez R, Biniwale M. Neonatal
resuscitation using a nasal cannula: a single-center experience. Am
J Perinatol. 2014 Dec;31(12):1031-6.
Ramanathan R. Nasal respiratory support through the nares: its time
has come. J Perinatol, 2010 Oct;30 Suppl:S67-72.
Ramanathan R, Sekar KC, Rasmussen M, Bhatia J, Soll RF. Nasal
intermittent positive pressure ventilation after surfactant treatment
for respiratory distress syndrome in preterm infants <30 weeks'
gestation: a randomized, controlled trial. J Perinatol, 2012
May;32(5):336-43.

Non-Invasive Ventilation for Preterm Infants

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