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 NCPAP HFNC NIV using RAM Cannula NIPPV SiPap NAVA HFONC • Mechanisms of Action • Physiologic Rationale • Challenges for Clinical Research Question of the day ?????????????????? 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) • Patient expiratory flow opposes system flow and an expiratory resistor valve • Constant flow: liquid seal (bubble) • Expiratory limb submerged in liquid, with oscillatory nature • Variable flow: “fluidic flip” (Infant Flow) • Inspiratory and expiratory 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 6 (cm H2O) Pharyngeal pressure 7 5 4 3 2 1 0 3 4 5 6 7 Set CPAP (cm H2O) 8 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 Ventilator 10 (cm H2O) Mean Pressure (±SD) 12 8 8 6 Set CPAP 4 4 No Leak 2 4 6 8 10 Bubble Bias Flow (L/min) 12 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 to improved oxygenation Proposed flushing of dead space at higher flows Schibler et al, Int Care Med 2011 • Reservoir of fresh gas in upper airway • Avoids rebreathing of highCO2 gas in dead space Washout flow exiting the mouth Washout of nasopharyngeal cavity Nasal cannula Courtesy of Walsh et al, Resp Care 2009 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 Mean Airway Pressure (cmH 2O) Mouth Fully Closed Mouth Fully Open F&P Neonatal Cannula (3.0mm prongs) F&P Infant Cannula (3.7mm prongs) 25 2.5 2.0 20 Pressure Limiting Safety Valve opens 15 Percent Occlusion 5 1.5 100% 86% prongs nares O.D. I.D. 10 Percent Occlusion 3.0 3.5 74% 3.7 3.7 4.5 5.0 68% 55% 3.0 3.0 4.5 5.0 44% 36% 1.0 74% 68% 0.5 55% 44% 36% 0.0 0 0 1 2 3 4 HFNC set flow (L/min) 5 6 0 1 2 3 4 5 6 HFNC set flow (L/min) Sivieri, Gerdes, Abbasi. Pediatr. Pulm. 2013 Pharyngeal Pressure (cmH2O) HFNC delivered pressure Flow 6 Lpm Flow 2 Lpm Flow 4 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 Occlusion Mouth Fully Closed Mean Airway Pressure (cmH 2O) 9 Dräger BabyFlow M prongs 4.5mm O.D. RAM Preemie Cannula 3.1 mmO.D. prongs Nares I.D. 4.5 100% 3.0 100% 8 Mouth Fully Open 9 7 8 7 6 6 3.5 5 78% ` 4 5 4 3 4.0 60% 4.5 48% 5.0 38% 2 1 0 3 2 1 0 4 5 6 7 Nasal CPAP setting (cmH2O) 8 4 5 6 7 Nasal CPAP setting (cmH2O) 8 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 n=14 Infants GA 27 (25-30) wks BW 1.6 (1.1-2.9) kg pCO2 (mm Hg) 70 65 60 55 50 45 p = 0.011 40 35 30 2 hours NHFV Initial pCO2 Final pCO2 Colaizy et al, Acta Paediatr. 200 NCPAP HFNC NIV using 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?