Neonatal Non-Invasive Respiratory Support:

Overview and ChallengesJeffrey S. Gerdes, MD, MBA

Associate Chair, Department of PediatricsChildren’s Hospital of Philadelphia

Associate Professor, Perelman School of Medicine

Emidio M. Sivieri, MSEResearch 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 UseAll Patients during NICU Stay

Courtesy of Dr. Reese Clark, Pediatrix

All Patients during NICU Stay

NIPPVSiPapNAVA

NCPAPNIV using

RAM Cannula

HFONC

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HFNC

Questionof the day

• Mechanisms of Action• Physiologic Rationale• Challenges for Clinical

Research

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

opposition (conventional vent)

• Constant flow: liquid seal (bubble)

• Variable flow: “fluidic flip” (Infant Flow)

• Patient expiratory flow opposes system flow and an expiratory resistor valve

• Expiratory limb submerged in liquid, with oscillatory nature

• Inspiratory and expiratory flow compensation via fluidics engineering

All NCPAP devices are not created equal

• 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

Examples:

at 6 L/min

Pressure-drop across prongs - by manufacturer

RAM (micro-preemie )

RAM (preemie)

RAM (Newborn)

Modified from: De Paoli, Morley, Davis et al. Arch Dis Child Neonatal Ed 2002

(All at 6 L/min Flow)

0 2 4 6 8 21Pressure drop (cmH2O)

Effect of mouth leak

3 4 5 6 7 8

8

7

6

5

4

3

2

1

0

Set CPAP (cm H2O)

Pha

ryng

eal p

ress

ure

(cm

H2O

)

De Paoli, et al. Arch Dis Child Neonatal Ed 2005

4 6 8Bubble Bias Flow (L/min)

Mea

n Pr

essu

re (±

SD)

(cm

H2O

)

210 12

Set CPAP

Bubble CPAP vs. CPAP with Mech. Ventilator

Kahn, Habib, Courtney, Pediatrics 2008

Bubble CPAP pressure is flow dependent

Bubble CPAPVentilator

No Leak

12

10

8

6

4

8

4

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 ActionFlow 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 to improved oxygenation

• Reservoir of fresh gas in upper airway

• Avoids rebreathing of high-CO2 gas in dead space

Schibler et al, Int Care Med 2011

Courtesy of Walsh et al, Resp Care 2009

Nasal cannula

Proposed flushing of dead space at higher flows

Washout of nasopharyngeal cavityWashout

flow exitingthe mouth

HFNC: Mechanisms of ActionPressure 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)

ProngsO.D.

Nares I.D.

HFNC set flow (L/min)0 1 2 3 4 5 6

Mean A

irway Pressure (cm

H2O)

0

5

10

15

20

25

F&P Neonatal Cannula (3.0mm prongs)F&P Infant Cannula (3.7mm prongs)

prongsO.D.

naresI.D.

3.0 5.0 3.0 4.5

3.7 5.03.7 4.5

3.0 3.5

HFNC set flow (L/min)0 1 2 3 4 5 6

0.0

0.5

1.0

1.5

2.0

2.5

74%

68%55%

44%36%

Intra-cannula

pressure (74% occl.)

Pressure Limiting Safety Valve opens

PercentOcclusion

74%68%55%44%36%

PercentOcclusion

100%86%

Mouth Fully Closed Mouth Fully Open

HFNC Pressure Delivery:Effect of flow rate, % nares occlusion,

and mouth leak

Sivieri, Gerdes, Abbasi. Pediatr. Pulm. 2013

HFNC delivered pressurePh

aryn

geal

Pre

ssur

e (c

mH

2O)

Flow 2 Lpm Flow 4 LpmFlow 6 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

`

Nasal CPAP setting (cmH2O)4 5 6 7 8

Mean A

irway Pressure (cm

H2O)

0

1

2

3

4

5

6

7

8

94.5

3.0

3.5

4.0

4.5

5.0

Nasal CPAP setting (cmH2O)4 5 6 7 8

0

1

2

3

4

5

6

7

8

9100%100%

78%

60%

48%

38%

Percent OcclusionMouth Fully Closed Mouth Fully Open

RAM Cannula Pressure Delivery:Bench Test

Gerdes, Sivieri, Abbasi, EAPS Congress 2014

Dräger BabyFlow M prongs 4.5mm O.D.RAM Preemie Cannula 3.1 mmO.D. prongs

Nares I.D.

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

Initial pCO2 Final pCO2

2 hours NHFV

pCO

2 (m

m H

g)75

70

65

60

55

50

45

40

35

30

Colaizy et al, Acta Paediatr. 200

Infant Star, Single Nasopharyngeal tubeFrequency 10HzAmplitude 50 torr

n=14 InfantsGA 27 (25-30) wksBW 1.6 (1.1-2.9) kg

p = 0.011

NIPPVSiPapNAVA

NCPAPNIV using

RAM Cannula

HFONC

• Mechanisms of Action• Physiologic Rationale• Challenges for Clinical

Research

Does it matter which NIRS strategy is used in a given patient or NICU?

HFNC

Questionof the day

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

Are we reasonably able to study these differences, And are these differences clinically important?

BUT

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,

• 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?

NIRS: Summary and Challenges for this conference