Hypoxaemia What is the limit ?

1. HypoxaemiaWhat is thelimit? Dr. Koo Chi Kwan Director, Intensive Care NTWC - Hong Kong

2. To begin with…. • As anaesthetist and/or intensivist, one of our most important tasks is to maintain normal oxygenation in our patients..

3. What is normal arterial oxygenation? • Sp02 90% • Pa02 8 kPa Are commonly accepted as cut-off points between hypoxaemia and normoxia

4. What is normal arterial oxygenation? • Detectable compensatory mechanisms are triggered once the body dips below these set points • Increase cardiac output • Increase minute ventilation

5. Compensatory mechanism? • Acute • Cardiac output • Chronic • Structual changes in cardiovascular system • Hyperventilation • Polycythaemia

6. What is normal arterial oxygenation? • In conditions where “ normal “ arterial oxygenation cannot be maintained by all conventional means, what is the lower limit of arterial oxygenation before permanent organ damage sets in?

7. Lower limit • How much “ margin” the patient have below 90%? • Any hints or suggestions from science?

8. Experience in children with cyanotic heart disease • Sensors were place in 10 children with cyanotic heart disease of median age 5.43 ( range 0.03 – 45) months, median weight 3.74 kg (2.79-15.4) • Duration of monitor - 27 hours • P02 values were 2.5-8.2 kPa ( median 5.3) • Co-oximeter saturation ranged from 37.1%-90.6% ( median 75.8%) British Journal of Anaesthesia 1997;79:665-7

9. Experience in children with cyanotic heart disease • These figures did not tell us how safe these values were. • Though these patients did not have immediate danger, many had shortened survival. • Cannot be used as reference for limit of hypoxia

10. Scaling the height • Scientific study of hypoxaemia The medical expeditions to Mt. Everest

11. Alveolar gas sampling at the summit of Mt Everest ( Oct 81)

12. At the end of a normal inspiration, AMREE team members would expire quickly and deeply through the mouthpiece and hold their breath for a second or so at residual volume. By pulling a lever on the alveolar gas sampler, the valve on the small pre-evacuated aluminum canister would open. Once the sample was collected, the valve could be closed by releasing the lever.

13. Who is this Guy ?

14. Pulmonary gas exchange on the summit of Mount Everest Journal of Applied Physiology, Vol 55, Issue 3 678-687, 1983, J. B. West, P. H. Hackett, K. H. Maret, J. S. Milledge, R. M. Peters Jr, C. J. Pizzo and R. M. Winslow

15. Alveolar gas and estimated arterial blood values on the summit of Mt Everest (8848 m)

16. Caudwell Xtreme Everest 2007 • It is a large medical expedition to Mount Everest to study the physiology of hypoxaemia that took place in Summer 2007 • The main aim is to measure how individuals’ bodies change as they are exposed to lower and lower levels of oxygen.

17. Caudwell Xtreme Everest 2007 • The expectation is that there will be a difference between those that adapt well, and those that adapt poorly. If it can be determined what that difference is, then they can start to look at treatments that can help poor adaptors use oxygen more efficiently. • This may have implications in intensive care unit to improve survival rates in patients.

19. Caudwell Xtreme Everest • The Caudwell Xtreme Everest team climbed from the south, via the South East Ridge, setting up laboratories at Base Camp (5300m), in the Western Cwm (6400m) and even doing some experiments on the South Col (7950m). • The climbing team sampled arterial blood on the Balcony at 8400m.

20. Caudwell Xtreme Everest • The scientific yield will derive from more than 220 healthy volunteers progressively exposed to hypobaric hypoxia whilst trekking to Everest Base Camp

21. Base Camp(5300)

22. Muscle Biospy at Base Camp Exercise test at Base Camp (5,300m)

23. Camp 2 (6400m) Camp 2 – Erecting Drash Lab

24. Arterial blood sampling Microcirculation test at Camp 2

25. South Col Lab ( 8000m)

26. Challenging the height – Mt Everest • Above 8000m, it is called the Death Zone • In the “Death Zone", no human body can acclimatize. The body uses up its store of oxygen faster than it can be replenished. • An extended stay in the zone without supplementary oxygen will result in deterioration of body functions, loss of consciousness and, ultimately, death • The mortality rate of climbing Mt Everest over the last 56 years is 9%

27. Death Zone

28. Summit

29. Summit

30. Blood Gas at 8400m

31. Arterial blood gas in the death zone

32. What can we learn? • Dramatic “depth“ of hypoxaemia have been reached in these settings • They are possible because “time” has been allowed for various compensatory process (Acclimatization) • Respiratory • Cardiovascular • Haematological

33. Physiology of hypoxaemia • Adaptive responses to sub-lethal hypoxia are believed to enhance tissue tolerance during subsequent stress • Mechanism includes increase expression of • Heme-oxygenase ( HO)-1 • Heat-shock protein (HSP) • Growth factors : vascular endothelial factor, erythroprotein • Hypoxic pre-conditioning

34. Hypoxia inducible factors ( HIF) Prolyl-4-hydroxylases( PHDs) serves as oxygen sensors and under normoxic conditions promote degradation of HIF-1a following binding with ubiquitin ligase, Von-Hippel-Lindau protein ( VHL)

36. Physiology of hypoxaemia • Potential therapeutic interventions: • PHDs( Prolyl hydroxylase domain enzyme) inhibition by induction of cellular hypoxia, eg. Carbon monoxide admixture to ambient air • Chemical inhibitions of PHDs, e.g.CoCl2, Mimosine • Molecular biology techniques, e.g. Von-Hippel-Lindau knockout

37. What is the implication to daily clinical practice? • But in our day-to-day practice, many of our patients suffer from hypoxaemia acutely without any time for adaptation..or pre-conditioning..

38. What is the implication to daily clinical practice? • What if severe hypoxaemia occurs acutely for the first time? • As in many day-to-day clinical scenario; one lung ventilation, airway surgery, ARDS

39. A patient with severehypoxaemia • Ms LYC, F/39, Lives with family • Merchandiser, frequent travel to Shenzhen • Good past health, nonsmoker • Presented to A&E with shortness of breath and admitted to ICU for respiratory failure • History: URI symptoms and fever for one week without improvement after being given steroid and theophylline by General Practitioner

40. A patient with severehypoxaemia • Found to have severe desaturation in A&E ( SaO2 50% despite high flow O2 )and was intubated. Remained hypoxemic despite mechanical ventilation with FiO2 1.0 • Started on: tamiflu, rocephin, azithromycin

41. A patient with severehypoxaemia Lowest recorded Sp02 – 49% Highest –72 % VV-ECMO established

42. A patient with severehypoxaemia Kpa Lowest recorded PaO2 – 2.9kPa Highest –8.06kPa

43. A patient with severehypoxaemia

44. The first 3 Chest X-Ray On admission 2 hours later 4 hours later

45. A patient with severehypoxaemia • Started on Venous-venous Extracorporal Membranous Oxygenation (VV-ECMO) about 12 hours after hospital admission • Oxygenation improved immediately after ECMO

46. The Chest X-Ray while on ECMO Immediately after ECMO 2 days after ECMO 6 days after ECMO

47. Weaning off ECMO 8 days post ECMO off ECMO 10 days after admission Extubated 11 days after admission

48. A patient with severehypoxaemia • On ECMO for 9 days • Extubated the next day after ECMO was off

49. Recovery 4 days after extubation On discharged from hospital

50. A patient with severehypoxaemia Sequelae • Noted occasional disorientation & irrelevant speech 4 days after extubation • Psychiatric assessment → ?organic psychosis, ? tamiflu psychosis • CT Brain - bilateral frontal hypo-densities • EEG - Fair amount of general slow wave over frontal area. • CSF - clear & colorless, Gram Stain & AFB smear -ve, • WBC 2, RBC 55, Prot/Glu normal