Microcirculation in critical care

2. • The resuscitation targets during shock state can be
achieved successfully by understanding the physiological
basis of normal hemodynamic which is divided into three
parts.
• The first part concerns the systemic circulation,
consisting of blood pressure, cardiac output, and
vascular resistance.
• The second part concerns the peripheral
microvasculature, transporting oxygen-carrying red
blood cells within each organ.

3. • The final pathway of oxygen transport is from the
microcirculation to the mitochondria where oxygen is
utilized by the respiratory chain.
• Mainly the macrocirculation is targeted in ; cardiac
output, perfusion pressure achieved by heart filling,
adjustment of cardiac contractility, and vascular tone all
with the aim of achieving adequate amounts of oxygen
delivery to the circulation.
• Most of times although macrodynamics targets achieved
NO IMPROVEMENT ?

6. • What makes the condition of shock complicated is that :
 These three compartments are not coupled, and that one
compartment can be in shock in the presence of a relatively normal
other compartment.
 Resuscitation will have to target the microcirculation and
cellular perfusion, since correcting systemic macrodynamic
variables does not always lead to a parallel improvement in the
microcirculation.

7. • That is why an integrative and combined monitoring of the
macro- and microcirculation is required.
• Conditions of inflammation, hypoperfusion, anemia, and
reperfusion injury can cause a loss in the oxygen carrying
capacity of the microcirculation, resuscitation of this condition
of microcirculatory shock requires different approaches than
that of the macrocirculation.

8. Intravascular volume:
a. Stressed volume: causes stretch of the vessel walls and
increases the pressure within the vessels.
b. Unstressed volume :Fills the vessels but does not
generate any pressure.
• Controlled by SYMPATHETIC, PARASYMPATHETIC,
RASS, VASOPRESSIN, ANP.
• Has to be optimized as soon as possible within the first
hours from the initial hit.

10. • The microcirculation consists of a complex network
of small blood vessels (<100 μm diameter) such:
1- Arterioles (responsible for modulating local arterial
tone to match local metabolic demands).
2- Capillaries (acting as the primary exchange place for
supplying oxygen and transporting metabolic cell waste
products).
3- The outflow venules (where leukocyte interactions
take place and vascular permeability changes largely take
place).

12. • Homeostasis of end organs.
• Regulating tissue perfusion.
• Thermoregulation by controlling coetaneous blood.
• Local mechanisms regulate vascular tone.
• Active metabolites : Prostaglandins, Nitric oxide &
Endothelin.
• Control blood flow metabolite stimuli like : Adenosine,
Hydrogen, CO2 & Oxygen tension.

13. • Microcirculatory impairments is due to:
 Endothelial dysfunction.
 Glycocalyx rupture----- Microthrombi.
 Endotoxin mediated.
 Vasoplegia (loss of vasomotor tone).
• Fluid administration targeting microcirculatory parameters:
 Increase flow in the vessels.
 Recruiting non perfused vessels.
 Improve O2 Delivery.
 Improve tissue perfusion.

16. • There are two main determinants of oxygen transport
to tissue:
1- The first: Convective transport of oxygen-carrying red
blood cells to the capillaries.
2- The second : Passive diffusion of oxygen leaving the
red blood cells to the respiring mitochondria to
achieve ATP production by oxidative phosphorylation
.
Hemodynamic targets are conventionally targeting
convective flow, on the assumption that shock state is
mainly associated with decreased blood flow.

18. • In daily practice, when hypovolemia and tissue hypoperfusion is
suspected, fluids are given with the expectation that tissue
perfusion and oxygenation will be restored.
• Recent randomized controlled trials suggest that goal directed
therapy aimed at optimizing systemic oxygen transport fails to
improve survival:
1- Pottecher and co-workers observed that changes in cardiac
output and microvascular variables after fluid administration did
not follow each other, suggesting that mechanisms other than
changes in cardiac output may affect the microvascular perfusion.

19. 2- Ospina-Tascon et al & Pranskunas et al, reported
similar results when analyzing simultaneously systemic and
microcirculatory effects of fluid administration.
3- De Backer et al. reported that the relation between
systemic hemodynamic and the microcirculation is not
fixed, even though cardiac output and blood pressure
values may be within normal ranges.

20. • These studies suggest that organ function is more directly
related to the success of perfusion and oxygenation of the
microcirculation than simply the restoration of systemic
hemodynamic variables.
• Achievement of good microcirculatory function can, in this
context, be considered to be the primary target of
cardiovascular resuscitation.
• Hence, simply correcting global systemic variables is
ineffective in promoting microcirculatory and tissue
oxygen perfusion.
• Coherence = Macrocirculatory resusetation causes parallel
improvement in the microcirculation.
• Loss of coherence means correction of macrodynamics
doses not go with microcirculation.

21. • Type-I: Hetrogenicity: Microcirculatory blood flow
alterations due to endothelial & red blood cell dysfunction &
leukocyte activation as occurs in sepsis; result in shunting of
microcirculatory weak units & lead to regional tissue hypoxia.
• Type-II: Hemodilution: Reductions in the oxygen-carrying
capacity of blood due to hemodilution can cause a decrease in
oxygen availability to the parenchymal cells.

22. • Type-III: Vasoconstriction / Tamponade: fluid
administration targeting elevated central venous pressure
results in impaired microcirculatory blood flow because of
venous tamponade or due to excessive vasoconstrictors, this
effect is amplified when using fluid therapy strategies
targeting raised venous pressures.
• Type- IV: Tissue edema: capillary leak lead to tissue edema
which can be aggravated when fluids are infused, greatly
worsening the diffusive component of the oxygen transport
to the tissue cells.

26. • Peripheral Perfusion of the skin is a mirror to evaluate the
function of the microcirculation; Cool peripheries, delayed
capillary refill time and skin mottling are used as indicators
of reduced peripheral perfusion/circulatory failure.
• Mottling is an irregular patchy discoloration of the skin
caused by heterogeneous blood flow and has been assessed
as potential prognostic feature in sepsis.

29. A. Near-Infrared Spectroscopy (NIRS)
NIRS uses specific and calibrated wavelengths of
near-infrared light to noninvasively illuminate the tissue
below a sensor placed on the skin.
• Parameters measured by NIRS:
=========================
1- StO2------- Direct
2- Mitochondrial Citochrome oxidase (Citaa3)----Direct
3- Vascular occlusion test

35. B. Tissue PCO2 and PCO2 GAP
The local increase in tissue PCO2 is sensitive indicator for tissue
hypoperfusion by tissue-arterial CO2 gradients, (∆PCO2). More
than 20 mmHg.
Tissue CO2 is measured by gastrointestinal tonometry, sublingual
capnometry.
Inversely related to perfusion.

37. C. Transcutaneous PO2/PCO2 measurements
Non invasive electrodes connected to the skin after local
heating for the skin.
PtcO2 and PaO2 ---------- equal when the blood flow is adequate.
Oxygen challenge test--- lack of PtcO2 increase in response to
high inspired fiO2.

40. D. Lactate and Base Excess
Lactic acidosis is a common feature of tissue hypoxia.
E. Redox state
Mitochondrial respiratory chain, NADH is changed into
NAD+ In the presence of O2, Inadequate O2 increase
NADH, NADH fluorescence absorbs light and can be
measured.

41. • Allows quantitative determination of capillary density microvessels
morphology and dynamics of microcirculatory blood flow.
1-Video microscopic techniques:
1st Orthogonal polarized spectroscope.
2nd generation sidestream darkfield (SDF).
3rd generation - Cytocam.(HD , lower wt, Digital signal & computer
analysis).
• These first and second generations require video capture and
storage of movies followed by off-line analysis of images to quantify
abnormalities.
• These devices emit green light with a wavelength (530 nm) which is
absorbed by hemoglobin, thereby identifying erythrocytes as dark
moving cells through the microcirculation.

50. • A third-generation device has recently been introduced, called
Cytocam incident dark field (IDF) imaging, based on a
computer-controlled imaging sensor which allows automatic
quantification of images.
• The device is a pen-like probe incorporating IDF illumination
with a set of high-resolution microscope lenses projecting
images on to the image sensor, the probe is covered by a
sterilizabled cap.

54. 2- Laser Doppler flowmetry:
• Laser Doppler flowmetry (LDF) is a noninvasive,
continuous measure of microcirculatory blood flow, and it
has been used to measure microcirculatory blood flow in
many tissues including the neural, muscle, skin, bone and
intestine.

56. • Dysfunctioning endothelial cells or parenchymal cells may
require tissue protective agents (TPA) such as anti-
inflammatories , specific treatments , or tissue
regenerative compounds currently under development , if a
low vascular density with normal flow (diffusion limitation)
is observed, it indicate hemodilution, requiring diuretics or
red blood cell transfusion.
• Corticosteroids inhibit inducible nitric oxide synthase (i-
NOS) and improving hemodynamic , High-dose steroids
prevent endotoxin induced hypotension, Late
administration, however, had no beneficial effect.

57. • Use of vasodilators in sepsis is based on the experimental
findings of pockets of ischemic areas lying close to well
perfused zones.
• Vasodilators may increase the driving pressure of blood flow
and perfuse Hypoxic zones, NO donors in combination with
fluids improved microcirculatory oxygenation and corrected
gastric pCO2 .
• Spronk et al found an improvement in sublingual perfusion
after a bolus of 0.5 mg followed by an infusion of 2 mg/h
nitroglycerin in the pressure resuscitation of septic shock
patients.

59. • Effects of titration of a norepinephrine infusion on the
sublingual microcirculation to increase the MAP from 65 to
75 and then to 85 mm Hg, found that increasing the MAP
with norepinephrine failed to improve sublingual
microcirculation or any other variable related to tissue
oxygenation or perfusion such as arterial lactate, anion
gap, ∆CO2, and oxygen-derived parameters.
• Interestingly, there were considerable variations in the
individual responses that were strongly dependent on the
basal condition of the microcirculation.

60. • These data suggest that the optimal MAP for the
microcirculation should be selected on an individual basis
whereby microcirculatory compromise should be taken into
account.

61. • De Backer et al studied the effects of dobutamine (5
mg/kg/min for 2 hours) in 22 patients with septic shock
which significantly improved capillary perfusion, but the
changes were independent of changes in systemic
hemodynamic variables, In addition, it was found that a
reduction in lactate levels was not associated with changes
in the cardiac index or MAP but rather in improved
microcirculatory perfusion.
• Morelli-et al: Esmolol in sepsis they found that B-blocker
maintain sublingual and gut microcirculation during sepsis.

73. • Microcirculatory flow index > 2.
• Perfused vessels >80%.
• ∆PCO2 ˂20mmHg
• NIRS ascending slope > 2.5% / sec.
• Lactate ˂ 2mEq/L.

79. Conclusion
Microcirculatory derangement is
common in patients with sepsis
and cannot necessarily be
predicted from macro
hemodynamic values.
01
Improvement in macro
hemodynamic values in the
critically ill does not imply
improvement in
flow and patients whose
microcirculation fails to improve
following resuscitation are at
increased risk of mortality.
02
Detection of microcirculatory
dysfunction may aid diagnosis
and risk stratification in patients
with sepsis; restoration of the
function of the microcirculation
may be a useful therapeutic
target for resuscitation but
further data are needed.
03