Neonatal Non-Invasive

Respiratory Support:
Overview and Challenges
Jeffrey S. Gerdes, MD, MBA
Associate Chair, Department of Pediatrics
Children’s Hospital of Philadelphia
Associate Professor, Perelman School of Medicine

Emidio M. Sivieri, MSE

Research Bioengineer, CHOP Newborn Care at Pennsylvania Hospital
 Why Non-Invasive Support?
• Airway distending pressure to maintain FRC is the
cornerstone upon which all other support modalities
are built
• Less Chronic Lung Disease
• Fewer airway complications
• Fewer Infections
• Reduced inflammation
• Less stress for babies, families, and staff
• Lower cost
Increasing HFNC Use
All
All Patients
Patients during
during NICU
NICU Stay
Stay

Courtesy of Dr. Reese Clark, Pediatrix

 HFNC NIV using
NCPAP RAM
Cannula
NIPPV
SiPap
NAVA
HFONC

• Mechanisms of Action
• Physiologic Rationale
• Challenges for Clinical
Research
Question
of the day

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 Nasal CPAP: Physiologic Rationale
• Distending pressure recruits lung volume
• Increases and stabilizes FRC
• Splints upper airways and compliant chest wall
• Improves lung Compliance
• Reduces airway Resistance
• Decreases Work of Breathing
• Improves gas exchange
• Reduces apnea
 NCPAP: Mechanisms of Delivery
• Constant flow: flow • Patient expiratory flow
opposition (conventional opposes system flow and an
vent) expiratory resistor valve

• Constant flow: liquid seal • Expiratory limb submerged in

(bubble) liquid, with oscillatory nature

• Variable flow: “fluidic • Inspiratory and expiratory

flip” (Infant Flow) flow compensation via
fluidics engineering
 All NCPAP devices are not created equal
Examples:
• Variable flow reduces WOB compared to conventional vent CPAP
(Lipsten et al, J Perinatol 2005)

• Variable flow may compensate better for mouth or seal leakage

• Bubble oscillations may improve lung recruitment
(Pillow et al, Am J Crit Care Med 2007)

• Bubble CPAP pressure delivery is flow dependent and not reliably

delivered relative to liquid depth (Kahn et al, Pediatr Res 2007)
• Bubble CPAP pressure delivery varies more than variable flow
CPAP (Kahn et al, Pediatr 2008)
• Nasal interfaces vary in resistance to flow
(DePaoli et al, Arch Dis Child Fetal Neonatal Ed 2002)

• Variable safety regarding alarms and expiratory limb obstruction risk

Pressure-drop across prongs - by manufacturer

RAM (micro-preemie )

RAM (preemie)

at 6 L/min

RAM (Newborn)

(All at 6 L/min Flow)

0 2 4 6 8 21
Pressure drop (cmH2O)
Modified from: De Paoli, Morley, Davis et al. Arch Dis Child Neonatal Ed 2002
 Effect of mouth leak
8

7
Pharyngeal pressure

5
(cm H2O)

0
3 4 5 6 7 8
Set CPAP (cm H2O)
De Paoli, et al. Arch Dis Child Neonatal Ed 2005
Bubble CPAP vs. CPAP with Mech. Ventilator
Bubble CPAP pressure is flow dependent

Bubble CPAP
12 Ventilator
Mean Pressure (±SD)

10
(cm H2O)

8 8
Set
6
CPAP
4 4

2 No Leak
4 6 8 10 12
Bubble Bias Flow (L/min)
Kahn, Habib, Courtney, Pediatrics 2008
 Clinical Correlations of different CPAP
Drivers and Interfaces
• Clinical studies often do not offer clear actionable
results
• Do mechanistic differences matter, or have they not
been discoverable with current studies?
• Babies have widely variable pathophysiology and
severity of illness
• Do the large pragmatic trials of NIRS strategies deliver
specific answers for relative efficacy when the “gold
standard” of CPAP is delivered with widely divergent
modalities?
 NIPPV or SNIPPV:
Physiologic Rationale
• Benefits of NCPAP + additional tidal ventilation and/or lung
recruitment from higher MAP
• May reduce WOB relative to CPAP
(Aghai et al, Pediatr Pulmonol 2006; Chang et al, Ped Res 2011)
• Airway pressures actually delivered vary considerably from
settings (Owen et al, Arch Dis Child Fetal Neonat Ed. 2010 )
• Is variable pressure delivery favorable to lung function?
• Is apnea Improved through cyclic receptor stimulation?
• Synchronization may improve efficacy
• Unclear if NIPPV or bi-level CPAP is more efficacious
(Roberts et al, Pediatrics 2013)
• Are these modalities “Super CPAP”?
Heated and Humidified High Flow Nasal Cannula
HFNC: Mechanisms of Action

Gas Conditioning Effects

Flow Effects

Pressure Effects
 HFNC: Mechanisms of Action
Gas Conditioning Effects
• Reduces patient’s metabolic workload needed
for Heating and Humidifying
(Waugh et al, Granger, RespCare 2004)

• Improves mechanics
-H&H Increases Compliance and Conductance
(Greenspan et al, J Peds 1991)
 HFNC: Mechanisms of Action
Flow Effects
• Improves lung mechanics
- Reduced inspiratory resistance => Reduced resistive Work of
Breathing (Saslow et al, J Perinatol 2006)
- Expiration: possible “Coanda” effect (Dysart et al, Resp Med 2009)

• Washout of Nasopharyngeal dead space => Improved gas

exchange (Frizzola et al, Pediatr Pulm 2011)
As flow increases, CO2 elimination > increase in MAP
Analogous to Trans Tracheal Catheter TGI
 Washout of anatomical dead space

• Continuous flow washes out

the upper airways and leads Proposed flushing of
dead space at higher flows

to improved oxygenation
Schibler et al, Int Care Med 2011

Washout of
nasopharyngeal
Washout cavity

• Reservoir of fresh gas in

flow exiting
the mouth
Nasal cannula

upper airway
• Avoids rebreathing of high- Courtesy of Walsh et al, Resp Care 2009

CO2 gas in dead space

 HFNC: Mechanisms of Action
Pressure Effects
• HFNC has been shown to provide positive distending
pressure
- Highly dependent on prong-to-nares diameter ratio
and degree of mouth closure (Locke et al, Pediatrics 1993;
Sivieri et al, Pediatr Pulm 2013)
Nares I.D.

Prongs
O.D.
 HFNC Pressure Delivery:
Effect of flow rate, % nares occlusion,
and mouth leak
Mouth Fully Closed Mouth Fully Open
F&P Neonatal Cannula (3.0mm prongs)
F&P Infant Cannula (3.7mm prongs)
25 2.5
Mean Airway Pressure (cmH 2O)

20 2.0 Percent
Occlusion

Pressure Limiting Percent

15 Safety Valve opens
Occlusion 1.5
100%
prongs nares 86%
O.D. I.D.
10 74%
1.0
3.0 3.5
74%
3.7 4.5 68% 68%
5 3.7 5.0 55% 0.5 55%
3.0 4.5 44% 44%
36%
3.0 5.0 36%
0 0.0
0 1 2 3 4 5 6 0 1 2 3 4 5 6
HFNC set flow (L/min) HFNC set flow (L/min)

Sivieri, Gerdes, Abbasi. Pediatr. Pulm. 2013

 HFNC delivered pressure
Pharyngeal Pressure (cmH2O)

Flow 6 Lpm
Flow 4 Lpm
Flow 2 Lpm

1 minute

Wilkinson et al, J Perinatol 2008

 Causes of variability of delivery of HFNC
• % nasal occlusion by catheter
• Characteristics of catheter design
• Characteristics of gas conditioning with heat and
humidity
• Mouth leak
• Variability in disease state of the patient
 RAM CannulaTM
(Neotech Products)
• Soft nasal prong interface, relatively large ID
• FDA approved as a Class I medical device, as a nasal
cannula for delivering oxygen: CPAP interfaces are
Class 2 Medical Devices
• 3 sizes: micro-preemie (ID 2.0 ,OD 2.7), preemie (ID 2.0, OD 2.9),
newborn (ID 2.5, OD 3.1 )
• “Expiratory limb” much smaller diameter than CPAP
interfaces
• Recommended % nasal occlusion: 60-80%
• Connector attaches to standard ventilator tubing
• Has been used to deliver CPAP, NIMV, HFONV
 RAM CannulaTM
(Neotech Products)
 RAM CannulaTM
(Neotech Products)
• Soft nasal prong interface, relatively large ID
• FDA approved as a Class I medical device, as a nasal
cannula for delivering oxygen: CPAP interfaces are
Class 2 Medical Devices
• 3 sizes: micro-preemie (ID 2.0 ,OD 2.7), preemie (ID 2.0, OD 2.9),
newborn (ID 2.5, OD 3.1 )
• “Expiratory limb” much smaller diameter than CPAP
interfaces
• Recommended % nasal occlusion: 60-80%
• Connector attaches to standard ventilator tubing
• Has been used to deliver CPAP, NIMV, HFONV
 RAM Cannula Pressure Delivery:
Bench Test
Percent
Mouth Fully Closed Occlusion Mouth Fully Open
Nares
9 Dräger BabyFlow M prongs 4.5mm O.D. I.D. 9
RAM Preemie Cannula 3.1 mmO.D. prongs 4.5 100%
Mean Airway Pressure (cmH 2O)

8 3.0 100% 8

7 7

6 6
3.5 78%
5 5
`
4 4

3 3
4.0 60%
2 2
4.5 48%
1 1
5.0 38%
0 0
4 5 6 7 8 4 5 6 7 8
Nasal CPAP setting (cmH2O) Nasal CPAP setting (cmH2O)

Gerdes, Sivieri, Abbasi, EAPS Congress 2014

 RAM Cannula used for “NCPAP”
• In bench tests, RAM cannula interface delivers 60% less
than the MAP set on the ventilator, even with mouth
closed
• With mouth open, delivered MAP is further reduced
• By design, RAM cannula is neither NCPAP nor HFNC
• Using 60-80% nares occlusion does not provide
sufficient seal to deliver CPAP.
• Due caution should be applied if using RAM cannula
interface to provide CPAP, pending further studies and
classification as a Class II Medical Device
 Nasal High Frequency Ventilation
Infant Star,
Single Nasopharyngeal tube
Frequency 10Hz
75
Amplitude 50 torr
pCO2 (mm Hg) 70

65
n=14 Infants
60
GA 27 (25-30) wks
55
BW 1.6 (1.1-2.9) kg
50

45
p = 0.011
40

35

30
2 hours NHFV
Initial pCO2 Final pCO2
Colaizy et al, Acta Paediatr. 200
 HFNC NIV using
NCPAP RAM
Cannula
NIPPV
SiPap
NAVA
HFONC

• Mechanisms of Action
• Physiologic Rationale
• Challenges for Clinical
Research
Question
of the day

Does it matter which NIRS strategy is

used in a given patient or NICU?
 Pulmonary Factors to Consider When
Evaluating NIRS Systems
Physiologic mechanisms imply that:
- NCPAP/NIPPV might be better for lung recruitment
- HFNC might be better for CO2 retention
- NIPPV might be better for apnea

BUT
Are we reasonably able to study these differences,
And are these differences clinically important?
 Extra-pulmonary Factors to Consider
When Evaluating NIRS Systems
• Minimizing nasal septal injury
• Ease of nursing and respiratory therapy care
• Comfort for baby and family
• Noise pollution
• Promotion of infant development
• Cost –interface and disposables, amortized cost of
the driver, RRT and RN time, and possible impacts on
length of stay or severity of illness
NIRS: Summary and Challenges for this conference
• NCPAP, NIPPV, and HFNC all have physiologic
rationales and feasible mechanisms of action
• All provide varying degrees of respiratory support
which improve physiologic parameters and gas
exchange in neonates
• Little is known about which devices may be better
for different patho-physiologies or different
severities of illness
• Do the clinical trials have sufficient numbers or
stratification of diagnoses and severity of illness to
differentiate the utility of these modalities? OR,
NIRS: Summary and Challenges for this conference

• Are we left with the current state in which

clinicians apply well-studied, safe NIRS
techniques according to unit or provider
preference, matching the device to the baby’s
needs, and response to therapy?
• Are “more randomized trials” the answer, or
should we steer towards other research
methodologies?