Microvascular oxygen delivery A talk by Knut Kvernebo at TBS23

1. Microvascular oxygen delivery
Professor em. Knut Kvernebo, MD, PhD

2. disclosure
Founder, shareholder and and CMO

3. outline
• from the Big Bang to circulatory failure
• monitoring of circulatory function
• circulatory failure?
• basic microcirculation
• diffuse reflectance spectroscopy (DRS)

4. from the Big Bang to Circulatory Failure:
the hierarchy of Laws of Nature

5. evolution of the universe
Big
Bang
13.75 ± 0.11 billion years
Log. time
energy
atoms
molecules (chemistry)
organic chemistry
life (3.7 billion years)
1. anaerobic metabolism
2. aerobic metabolism
homo sapiens
200 000 years
life
Laws
of
nature
Prof. Jean-Marie Lehn
Nobel prize laureate
Chemistry 1987

6. top of the hierarchy of Laws of Nature of physiology:
delivery of O2 to all cells of the body

7. Example: prematurity

8. Oxygen - O2
the molecule that created life
1. Uploading of oxygen
2. Transport of oxygen
3. Delivery of oxygen

9. respiratory and cardiovascular monitoring
© ODI Medical AS
• respiratory function
o blood gases
o pulse oximetry
• central hemodynamics
o blood pressures
o cardiac function
• blood test
o lactate

10. extra corporeal membrane oxygenation
(ECMO) for acute heart failure
case example

11. 11
va-ECMO
picture address https://www.saintlukeshealthsystem.org/frequently-asked-questions-ecmo

12. results of ECMO treatment for acute heart failure?
[1] Extracorporeal Life Support Organization (ELSO) Registry, https://www.elso.org
[2] Mishra V: Cost of extracorporeal membrane oxygenation. Eur J Cardio-thoracic Surgery 37 (2010) 339—342

13. results of ECMO treatment for acute heart failure?
• short term survival: <50%1
[1] Extracorporeal Life Support Organization (ELSO) Registry, https://www.elso.org
[2] Mishra V: Cost of extracorporeal membrane oxygenation. Eur J Cardio-thoracic Surgery 37 (2010) 339—342

14. results of ECMO treatment for acute heart failure?
• short term survival: <50%1
• average cost (Norway)2
• 235 000 USD (in 2010 value)
[1] Extracorporeal Life Support Organization (ELSO) Registry, https://www.elso.org
[2] Mishra V: Cost of extracorporeal membrane oxygenation. Eur J Cardio-thoracic Surgery 37 (2010) 339—342

15. results of ECMO treatment for acute heart failure?
• short term survival: <50%1
• average cost (Norway)2
• 235 000 USD (in 2010 value)
• average cost USA > cost in
Norway
[1] Extracorporeal Life Support Organization (ELSO) Registry, https://www.elso.org
[2] Mishra V: Cost of extracorporeal membrane oxygenation. Eur J Cardio-thoracic Surgery 37 (2010) 339—342

16. results of ECMO treatment for acute heart failure?
• short term survival: <50%1
• average cost (Norway)2
• 235 000 USD (in 2010 value)
• average cost USA > cost in
Norway
• average number of days on
ECMO (Norway)2
• 9 days
[1] Extracorporeal Life Support Organization (ELSO) Registry, https://www.elso.org
[2] Mishra V: Cost of extracorporeal membrane oxygenation. Eur J Cardio-thoracic Surgery 37 (2010) 339—342

17. results of ECMO treatment for acute heart failure?
• short term survival: <50%1
• average cost (Norway)2
• 235 000 USD (in 2010 value)
• average cost USA > cost in
Norway
• average number of days on
ECMO (Norway)2
• 9 days
• Accumulated one year
survival: ≈ 15%
[1] Extracorporeal Life Support Organization (ELSO) Registry, https://www.elso.org
[2] Mishra V: Cost of extracorporeal membrane oxygenation. Eur J Cardio-thoracic Surgery 37 (2010) 339—342

18. © ODI Medical AS
10 days of ECMO treatment
(and ≈ 1 mill €, blood from 70 donors….)

19. circulatory failure (CF)?

20. human life?
• the sum of the function of all the cells of the body (n ≈ 1014 cells)
• all these cells are dependent on delivery of oxygen to function
definition:
respiratory/circulatory failure
• failure to deliver sufficient oxygen to maintain life and function of
all the cells of the body
• CF can be systemic or local

21. respiratory/circulatory failure?
1. reduced lung function (loading of oxygen)
• SaO2/SpO2
2. reduced cardiac function (cardiac output)
• central hemodynamics/cardiac ultrasound
3. microvascular dysregulation
• mal-distribution of cardiac output
between and within organs

22. “business side of circulation”
microcirculation - a chaos system

23. “business side of circulation”
microcirculation - a chaos system

24. 18
the logistics of the life:
delivering oxygen to the right place, at the right time to maintain life!
Do not distribute

25. 18
the logistics of the life:
delivering oxygen to the right place, at the right time to maintain life!
well balanced transport system
Do not distribute

26. 18
the logistics of the life:
delivering oxygen to the right place, at the right time to maintain life!
well balanced transport system lack of moving transport vehicles
Do not distribute

27. 18
the logistics of the life:
delivering oxygen to the right place, at the right time to maintain life!
well balanced transport system
lack of moving transport vehicles
lack of moving transport vehicles
Do not distribute

28. transport impossible
18
the logistics of the life:
delivering oxygen to the right place, at the right time to maintain life!
well balanced transport system
lack of moving transport vehicles
lack of moving transport vehicles
Do not distribute

29. basic microcirculation

30. August Krogh
Editorial, JAMA, 1967: August Krogh (1874-1949):
“The physiologist's physiologist"
Nobel Prize laureate in Physiology or Medicine 1920
"for his discovery of the capillary motor regulating
mechanism"
Capillary
Nutrition
• Morphology
• Perfusion
• oxygenation

31. skin measurements?

32. 22
skin microcirculation:
Erythromelalgi
findings
• increased skin blood flow
• skin hypoxia
Pathogenesis
• maldistribution of skin blood flow
• increased thermoregulatory
perfusion
o regulated by autonomous
nerves
• reduced nutritive papillary capillary
perfusion
o regulated by local metabolic
needs

33. skin microvascular anatomy, function and regulation

34. skin microvascular anatomy, function and regulation

35. regulation of nutritive microcirculation

36. regulation of nutritive capillary perfusion:
pericytes!

37. heterogeneity of microvascular perfusion
Male 23 years: VF; CPR without ROSC;
ECMO after 80 min.

38. diffuse reflectance spectroscopy (DRS)
oxygen saturation of capillary erythrocytes
(≠ pulse oximetry)
decomposition
oxy-hemoglobin deoxy-hemoglobin
Measuring volume ≈ 0.1mm3

39. Example: Covid 19 (n=40) hospitalized at MGH, Harvard University
microvascular oxygen saturation (SmvO2)
**
p=0.002
**
p=0.0002
**
p<0.00001
*
p=0.01
Significant difference between controls and other groups
Significant difference between early discharged versus non survivors
and survivors versus non survivors

40. Fick´s law of gas diffusion
(O2 diffusion across the capillary membrane)
k: Diffusion constant - dependent on gas solubility and temperature
A: Area of diffusion membrane
D: Thickness of diffusion membrane
pO2 cap : Calculated based on measurements of SmvO2 (oxyhemoglobin dissociation curve)
pO2 tissue : Unknown
Rate of O2 diffusion = k x A x
pO2 cap pO2 tissue
D
-
We have developed a non-invasive technique
for assessing tissue pO2