Research in physiology – the forgotten ‘basic science’

1. Research in physiology – the forgotten ‘basic science’ Rob Ross Russell Consultant Paediatrician Cambridge

2. My background • Trained in paediatrics since 1983 • Worked in PICU or respiratory throughout • Moved to Cambridge as consultant in PICU in 1992 • NHS post • Associate lecturer at University • Director of Studies at Peterhouse

3. Jenny is a known asthmatic of 7 years of age. She presents to the ED with a 2 days history of URI and increasing wheeze Her blood gases show: pH 7.5 pCO2 3.6 kPa pO2 6.4 kPa, sat 87% BE -3.6 HCO3 21 mmol/L Three cases Jude is a 5 month old with Fallot’s Tetralogy Although he has been clinically well he is still awaiting surgery His blood gases show: pH 7.42 pCO2 4.8 kPa pO2 6.4 kPa, sat 87% BE 0 HCO3 25 mmol/L John is an ex 25/40 gestation baby. He was ventilated for 4 weeks and in oxygen until 4 months of age He is now 5½ months old, with an URI His gas shows: pH 7.4 pCO2 9.6 kPa pO2 6.4 kPa, sat 87% BE +12 HCO3 32 mmol/L

4. Jenny is a known asthmatic of 7 years of age. She presents to the ED with a 2 days history of URI and increasing wheeze Her blood gases show: pH 7.5 pCO2 3.6 kPa pO2 6.4 kPa, sat 87% BE -3.6 HCO3 21 mmol/L Three cases Jude is a 5 month old with Fallot’sTetralogy Although he has been clinically well he is still awaiting surgery His blood gases show: pH 7.42 pCO2 4.8 kPa pO2 6.4 kPa BE 0 HCO3 25 mmol/L John is an ex 25/40 gestation baby. He was ventilated for 4 weeks and in oxygen until 4 months of age He is now 5½ months old, with an URI His gas shows: pH 7.4 pCO2 9.6 kPa pO2 6.4 kPa, sat 87% BE +12 HCO3 32 mmol/L

5. Three cases Jenny is a known asthmatic of 7 years of age. She presents to the ED with a 2 days history of URI and increasing wheeze Her blood gases show: pH 7.5 pCO2 3.6 kPa pO2 6.4 kPa, sat 87% BE -3.6 HCO3 21 mmol/L Jude is a 5 month old with Fallot’sTetralogy Although he has been clinically well he is still awaiting surgery His blood gases show: pH 7.42 pCO2 4.8 kPa pO2 6.4 kPa BE 0 HCO3 25 mmol/L John is an ex 25/40 gestation baby. He was ventilated for 4 weeks and in oxygen until 4 months of age He is now 5½ months old, with an URI His gas shows: pH 7.4 pCO2 9.6 kPa pO2 6.4 kPa BE +12 HCO3 32 mmol/L

6. All three children have hypoxia (paO2 6.4 kPa, saturation 87%), but very different pathology • All three children have more than enough surface area to their lungs to allow entirely normal oxygenation • So.. What is happening?

7. Graph showing ventilation at different levels in the lung

8. Graph showing ventilation (red) and perfusion (blue) at different levels in the lung

9. Low VQ ratio High VQ ratio Graph showing ventilation (red) and perfusion (blue) at different levels in the lung

10. VQ ratios

12. Measuring VQ and shunt

16. Measuring oxygenation in infantsInitial results and analysis T. Dassios Cambridge, January 2014

17. Regression: V/Q vs. CGA

18. Shift and FiO2 requirement

19. So what about SSCs?? • To do these studies we need to make patients hypoxic (sats<90%) • If this does not happen in air, we need to reduce FiO2 • Hypoxic gas mixes are expensive and inflexible

20. ACE Venturi to the rescue… Venturis are used widely in ED. They work by taking a driver gas (usually oxygen) in through a narrow inlet, then changing to a wide bore. This causes a drop in pressure in the driver gas, which draws air through the portholes, giving a fixed concentration of oxygen.

21. ACE Venturi to the rescue… Different colours have different sized portholes, and so deliver different concentrations of oxygen from 24% to 60%..

22. The SSCs Jenny Wilson • Took the question ‘Can we use nitrogen as a driver gas and deliver a reliable (hypoxic) concentration of oxygen?’

23. Answer • Yes… • But…

24. Answer • Yes… Nitrogen reliably delivers a flow independent FiO2 of between 19% and 10.5% oxygen • But… you can’t add a reservoir to the system without altering the FiO2

25. SSC 2 Amelia Robinson • Looked at the repeatability of the results • Studied a group of children with scoliosis – dropping their FiO2 to 10.5% (‘top of Mt Blanc’ levels!)

26. Answer • The technique is reliable and repeatable, but hyperventilation affects the gas concentration • Scoliosis does not affect VQ in idiopathic disease

27. What next? • We found that the reason we could not develop a reservoir was due to the effect of downstream resistance on the characteristics of the Venturi • So what happens when you put a tight face mask on patients in ED???

28. Hannah Fox • Currently evaluating the effect of face mask application on the FiO2 delivered with a Venturi. • Watch this space…

29. Summary • We have developed a mathematical model of gas exchange in the lung that allows measurement of shunt and VQ. • Several SSC projects have helped with the process and methodology, but have also raised important clinical questions about an everyday technique in ED

30. Acknowledgements • Prof Gareth Jones • Dr David Sapsford • Joan Lasenby • Nick Fung • Dr Ben Stenson • Prof Colin Morley

31. Thank you