1. Measuring Neonatal Lung Volume Advisor: Dr. Bill Walsh Doug Anderson David Lammlein Janine McKinnon

2. Background  The Division of Neonatology at Vanderbilt Children’s Hospital has an interest in determining the Functional Residual Capacity (FRC) in neonates who are mechanically ventilated  Methods must be simple, non- invasive, and allow free access to neonates  Neonatal Intensive Care Unit (NICU) includes 60 intensive and intermediate beds, a 3 bed ECMO unit, and 10 bed intensive care nursery

3. Extracorporeal Membrane Oxygenation (ECMO)  ECMO is a form of long-term heart-lung bypass used in infants, children, and adults in cardiac and/or respiratory failure despite maximal medical treatment  Similar to heart-lung bypass used in the operating room  Respiratory failures for infants include:  Acute Respiratory Distress Syndrome (ARDS)  Pneumonia  Sepsis  Congenital Diaphragmatic Hernia (CDH)  Pulmonary Hypertension  Inborn Errors of Metabolism  ECMO is used when a ventilator does not provide sufficient oxygen or remove enough carbon dioxide.  ECMO takes over the work for the lungs so they can rest and heal

4. Problem Description  Problem: Too small a FRC results in the inability to oxygenate blood and consequently death because blood entering the lung actually exits the lung without coming into contact with a gas surface  Solution: Designing a device that measures FRC in neonates can allow doctors and researchers to optimize ventilator settings so as to prevent this sort of shunting  Benefit: Allows physicians to utilize appropriate methods to facilitate breathing in neonates suffering from lung pathologies, and specifically allows physicians to assess the need for ECMO

5. Functional Residual Capacity (FRC)  Functional Residual Capacity (FRC) of the human lung is the volume remaining in the lungs at resting expiratory level  Equivalent to the alveolar volume (Va) which contains 60-70% of the total lung volume  Normal FRC in adults is 1.8 to 3.4 L  Estimated FRC in healthy neonates 5 to 12 mL

6. Measuring FRC Helium Dilution Method Inspiration of known [He] Gas in lungs dilutes He and [He] drops Gases equilibrate Measure difference in [He] to determine initial lung volume Nitrogen Washout Method Unknown FRC contains about 78% N2 and an unknown amount of O2 and CO2 Washout N2 by breathing 100% O2 Exhale so that expired [N2] falls between 1 and 1.5%

7. “Functional Residual Capacity and Ventilation Homogeneity in Mechanically Ventilated Small Neonates” (1992)  Modification of computerized tracer gas (SF6) washout method  Designed for serial measurements of FRC and ventilation homogeneity in mechanically ventilated infants  Very low birth weight  Tidal volume down to 4 mL  Mild to moderate RDS  FRC increased with body weight  FRC (mL) = -1.4 + 17 x weight (kg)  The method gave reproducible results in a lung model and good agreement compared with He dilution in rabbits Previous Attempt to Measure FRC (Journal of Applied Physiology)

8. “Modification of the Open Circuit N2 Washout Technique for Measurement of Functional Residual Capacity in Premature Infants” (1997)  Compared standard N2 washout technique for measuring FRC with a modified technique using heliox as a washout gas  Volumes can be measured with high precision and reproducibility, even in premature infants with low lung volumes and/or high baseline FIO2  Correction factor may be needed because using heliox Previous Attempt to Measure FRC (Pediatric Pulmonology)

9. Our Choice 1978 - A Method for Measuring Functional Residual Capacity in Neonates with Endotracheal Tubes

10. The Device PFM or

11. Evita 4 Ventilator

13. Results  In Vitro  Confirmed expected exponential relationship  Real vs. Calculated: r = 0.995, p<0.001  In Vivo  Used in infants as small as 600 g CPAP (cm H 2 O) 03 FRC 22.0  1.9 25.8  1.4 N1530

14. Advantages  Easy to set up  Uses common equipment  Can be used for a large range of infants  Useable with both CPAP and ventilator support  Relatively inexpensive

15. Limitation  Breathing rate and tidal volume assumed constant  No calculation if minute ventilation (respiratory rate X tidal volume) changed by more than 25% over measurement period  Obstructive diseases may delay equilibration  Research into subsequent efforts into this limitation is ongoing

16. Assembling Prototype  Compile list of necessary supplies and equipment  Procure or obtain access to all necessary items, contacts: Chris Lynn  Assemble and test prototype  Refine and upgrade prototype

17. Supplies and Equipment  Medical grade tubing  Valves and stopcocks  Expandable membranes  Solenoid Valve Inexpensive Purchaseables VUMC Equipment Air Pumps Digital Helium Meter Pulmonary Function Machine

18. Design Goals  Use primarily existing equipment  Avoid complicated, dangerous, or invasive procedures  Allow for uncooperative nature of infants  Mobility of device  Continued free access to neonate

19. Market Potential  Clients: Neonatal Intensive Care Units  Competitors: No current patents exist on this exact device; however, other more costly methods (i.e. tomography, ultrasonic flow meter) exist.  Production: Creating simple modification to existing equipment will result in lower production costs and overhead.

20. Social Impact  Profound: Families and friends of critically ill neonates  Minimal: Environment, helium is an inert gas

21. References  Schwartz JG, Fox WW, Shaffer TH. A Method for Measuring Functional Residual Capacity in Neonates with Endotracheal Tubes. IEEE Trans. On Biomed. Engineering. 25(3): 304-7. 1978 May.  Journal of Applied Physiology. 73(1): 276-83. 1992 July.  Pediatric Pulmonology. 23(6): 434-41. 1997 June.

22. Questions