The document discusses monitoring the microcirculation and distributive shock. It summarizes that imaging of the microcirculation is required to monitor distributive shock. It also mentions that both passive leg raising and volume expansion can improve sublingual microcirculation in preload-dependent septic patients. Finally, it states that the microcirculation is where fluid is primarily managed in the body.

1. The future of monitoring starts today:
Capturing capillary leak
Can Ince PhD
Dept. of Intensive Care Dept. of Translational Physiology
Erasmus Medical Center Academic Medical Center
Erasmus University Rotterdam University of Amsterdam
Declared interests:

2. Hypovolemic
(no fluid left in the barrel)
Cardiogenic
(pump malfunction)
Obstructive
(tap shut)
Distributive
(shunting)
Circulatory shock: An update
A tribute to Professor Max Harry Weil
Vincent JL, Ince C Bakker J
(2012) Crit Care (in press)
Max Harry Weil Crit Care Med( 2007) 35
Weil MH, Shubin H (1971)
Adv Exp Med Biol 23:13-23.
Distributive Shock : the challenge in defining a perfusion deficit

3. Balancing fluids; a tricky affair

4. The main function of red blood cells is to
transport oxygen to the tissue cells.
Don’t forget oxygenation.
of all oxygen in
blood~97% is

5. Fluids are drugs.
• blood flow (distribution)
• pO2
• Hb
• Acid-base/SID
• osmotic balance
• volume
• blood sheer stress
• (auto) regulation
• Ht
• Viscosity
• metabolic
• inflammation

6. =
50 bags of chips= 1 liter 0.9% NaCl
(Sean Bagshaw)

8. Passive transport: 1) Diffusion (concentration gradient) 2) Convection (pressure gradient)
In the glomerular capillaries there is a net fluid filtration of about 180 litres/day.
In the rest of the body’s capillaries it is about 28.8 litres/day.
H2O:Hart min.
vol. 84.000 L
Capillary Bed
Lymph vessels
Diffusion
Filtration Absorption
Interstitium
Lymph: 2 LDiffusion 80.000 L
Convection: 20 L
Fluid exchange in 24 hours
The Microcirculation is where fluid is managed

9. For monitoring distributive shock imaging of the
microcirculation is required.

10. First direct visualizations of the microcirculation inFirst direct visualizations of the microcirculation in
human internal organs using OPS/SDF imaginghuman internal organs using OPS/SDF imaging..
Groner et al. (1999) Nature Med 5:1209
Mathura et al. (2001) The Lancet 58:1698
Spronk et al. (2001) The Lancet 360:1395
Pennings et al. (2004) Stroke 35:1284
Meidema et al (2009) N Engl J Med 360:
Brain tumours
before HV
Subarachnoid hemh. cortex
Leukemia
before and after chemotherapy
after HV

11. 14 Megapixel sensor, pixelsize 1,4 μm
Light weight (150 grams)
Optics /sensor resolution optimized
Camera and illumination PC control
Stepping motor focus control
Allow quality control of image acquisition
Allows automatic image quantification
CytoCam: Incident Dark Field (IDF) Imaging
Sherman H, Klausner S, Cook WA: Incident dark-field illumination:
a new method for microcirculatory study. Angiology 1971, 22:295-303.
Bezemer R, Bartels SA, Bakker J, Ince C: Microcirculation-targeted therapy – almost there.
Crit Care 2012, 19;16(3):224-228.

13. BOTH PASSIVE LEG RAISING AND VOLUME EXPANSION IMPROVE
SUBLINGUAL
MICROCIRCULATION IN PRELOAD-DEPENDENT SEPTIC PATIENTS
J. Pottecher*1, S. Deruddre1, J. F. Georger2, E. Vicaut3, D. Benhamou1, J.
L. Teboul2,
J. Duranteau1
Therapy for the microcirculation in sepsis

15. Why Rudolph’s nose is red.
Ince C, van Kuijen A, Milstein D, Yuruk Y, Folkow L, Fokkens W, Blix A
British Medical Journal (2012 in press)

16. D x A ( cappO2 - mitpO2)
VO2 =
_____________________________
L
Where VO2 volume of transported O2sported by diffusion
D diffusion constant
A systemic capillary surface area
cappO2 capillary pO2
mitpO2 mitochondrial pO2
L distance from RBC to mitochondria
Convection (flow) and Diffusion (functional capillary density rate limite
oxygen transport to the tissues.
heart failure normal diffusion low convection

17. Fresenius F8- HPS low-flux dialyser or
Fresenius FX60 high-flux dialyser

18. Microcirculatory changes in one and the same sub-lingual location
before and after switch to CPB for cardiac surgery show diffusion limitation

20. Blood Transfusions Recruit the Microcirculation during Cardiac Surgery
Yuruk K, Almac E, Bezemer R, Goedhart P, de Mol B, Ince C
Transfusion (2010)51(5):961-7 ,
Results show that blood transfusion s improve oxygen tranport by reducing
diffusion distances and not by augmenting convection.
Lipowsky Am. J. Physiol. 1999.

22. The endothelial glycocalyx is a network of membrane-bound proteoglycans and
glycoproteins, covering the endothelium luminally.
The role of the glycocalyx in vascular physiology and pathology, including
mechanotransduction, hemostasis, signaling, and blood cell– vessel wall interactions.
The glycoaclyx is central to the function of the endothelial cells and its function and
integrity plays a key role in diabetes, ischemia/reperfusion, atherosclerosis, sepsis, shock
and resusciation .
5 µm
2 µm2 µm
Endothelial
cell
Glycocalyx
0.2 µm0.2 µm
The Glycocalyx

24. Pericapillary space (µm)
0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0
Percentageoftotal
0
10
20
30
40
Pericapillary space (µm)
0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0
Percentageoftotal
0
10
20
30
40
No treatment Hyaluronidas
e
Median 0.28µm
Median
0.46µm
(P < 0.001)

25. Acute hyperglycemia (25mM) but not chronic hyperglycemia (db/db
mice) causes reduction in glycocalyx and microcirculatory alteration
(reduced FCD observed by OPS imaging)
(2005) J Appl Physiol 99: 1471–1476

27. Hans Vink
GlycoCheck

29. Components AQIX Volulyte Saline Human serum
Na+
135 137 154 131-148
K+
5.00 4.00 3.4-5.2
Ca+
1.25 1.12-1.46
Mg++
0.45 1.50 0.38-0.72
Cl-
119 110 154 101-111
HCO3 25.0 21-29
Glucose 10.0 3.6-6.1
Glycerol 0.11 0.131
Glutamate 300 20-110
Glutamine 400 140-570
Aspartate 20 µmol/L 1-11 µmol/L
Carnitine 50 µmol/L 35-85 µmol/L
Choline 10 µmol/L 18-70 µmol/L
Thiamine Phosphate 40.0 nmol/L 6-135 nmol/L
Human insulin 28.0 mIU/L 6-35 mIU/L
BES taurine-based Good's buffer 5.00
Acetate (CH3COO-
) 34.0
Hydroxyethyl starch (130/0.4) 6%
pH 7.30-7.46 5.7-6.5 4.5-7.0 7.32-7.45
Osmolality (mOsm/L) 265-286 287 290 264-290
Composition of the resuscitation fluids and human serum.
Values represent the concentration in mmol/L unless otherwise stated.

30. Fluids lack benefit on inflammatory markers
in sepsis induced AKI
All values of lactate go up with LPS
no significance difference between groups

31. What about the lungs?

32. Kupper S et al (2007) Shock 28:300-308
Sticking leucocytes

34. Round Table 2012: Types of intravenous fluids
John A Myburgh
MBBCh PhD FCICM
Professor of Critical Care Medicine
The George Institute for Global Health
University of New South Wales
St George Hospitals, Sydney
Monty Mythen
MBBS FRCA MD FFICM
Professor of Anaesthesia and Critical Care
University College, London

35. Volume is prime!
Physiology is the only polar star we have.
L. Gattinoni March 17, 2012 Brussels
Hemodynamic targets are not taken into consideration
We don’t care how or why fluids work.
Only large RCT with a positive clinical
outcome provide the only true relevant evidence.
S Finfer March 17,2012 Brussels

36. N=800

37. The physiological compartment which manages
fluids in the body is the microcirculation.
That is why titrating iv fluids based on
macrocirculatory parameters can lead to
inappropriate administration of fluids leading
to overload and organ dysfunction.

38. Alle Ding' sind Gift, und nichts ohn' Gift; allein die
Dosis macht, daß ein Ding kein Gift ist
"All things are poison, and nothing is without poison;
only the dose permits something not to be poisonous.“
Paracelsus (Philippus Aureolus Theophrastus Bombastus von Hohenheim, 1493 – 1541)

39. Conclusions
0.9% NaCl solutions should be banned
Too much or too little fluids are bad.
Don’t forget tissue oxygenation.
Convection and diffusion are key elements in O2 transport to tissue
Don’t keep your patients anemic.
Blood transfusions are not as bad as you may think.
Watch out for the glycocalyx and reduce oxidative stress
Oxygen delivery and microcirculatory flow
are key targets for fluid therapy and can be clinically monitored.
Be wary of blinded trials.
New clinical tools targeting the microcirculation may provide tools
for optimizing fluid therapy.

40. Thank you for the invitation !