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E X PE RT O P I N I O N
ABSTRACT
Microcirculatory alterations are frequent in sepsis and different mechanisms can be implied and variously studied. The
severity of microvascular alterations is associated with organ dysfunction and mortality. The aim of this review is to
make an overview of the most actual and used techniques applied on septic humans. We aimed at focus on the impact
of different techniques on the evaluation of patients management and outcome. (Minerva Anestesiol 2015;81:533-40)
Key words: Sepsis - Microcirculation - Perfusion - Cell respiration - Multiple organ failure.
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534
dark/grey bodies as the used wavelength is absorbed by the hemoglobin. In septic animal,
these have been used to evaluate the microcirculation of several organs as the tongue,17-19 conjunctiva,20 gut,17, 18, 21 and brain.22, 23 In septic
humans, these techniques have been mostly used
to study the sublingual area.2, 4, 24-27 Secretions
and movement artifacts may impair image quality, and the investigation of the sublingual area is
only feasible in sedated or cooperative patients.
Vascular (capillary) density and heterogeneity
of perfusion (the proportion of perfused vessels,
mean flow index, heterogeneity index), should
be measured.28 The microvascular flow index
(MFI) is a composite and non linear score that
combines gross evaluation of perfusion and its
heterogeneity. These are measured using a semiquantitative analysis, which can easily be performed by experienced investigators, with excellent reliability.2, 27, 29 The measurement of blood
flow cannot be obtained with the scores in use.
Computer-assisted microcirculation assessment
allows the measurement of vessel density 30 and
blood flow in microvessels but still require major human intervention. Measuring blood flow
in selected microvessels is irrelevant but measuring blood flow in all visible vessels is probably
more relevant, but this is not yet feasible, at least
in clinical practice. This quantitative assessment
was performed in patients with severe sepsis.31
Indirect measurements/estimates
An impaired microvascular perfusion may be
inferred from a general clinical examination.32-34
However, the link between skin hypoperfusion
and more central beds is loose, as well as with
biological markers; indeed, blood lactate levels
also have poor sensitivity and specificity to detect microcirculatory alterations.4, 6-8 Evaluation
of tissue oxygenation is an indirect evaluation of
tissue perfusion, inferring the balance between
O2 transport (DO2) and O2 consumption (VO2)
in a tissue. Flow, hemoglobin content, arterial
PO2, and VO2 are all of influence. Near-infrared
spectroscopy (NIRS) uses near-infrared light
to measure tissue oxy- and deoxyhemoglobin,
myoglobin, and cytochrome aa3 (the so-called
chromophores). Tissue O2 saturation (StO2)
MINERVA ANESTESIOLOGICA
May 2015
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or other proprietary information of the Publisher.
DE BACKER
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or other proprietary information of the Publisher.
Figure 3.Sublingual microcirculation of a septic patient. Visualization of sublingual microcirculation of a patient with septic shock
using a SDF imaging technique. Note the decreased density of
capillaries and the presence of many capillaries with stopped flow.
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means which may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is
not permitted. It is not permitted to remove, cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo,
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DE BACKER
red blood cell transfusions may depend on the severity of underlying microcirculatory alterations,
with an improvement in microvascular perfusion
in the most severe septic patients and a worsening
in patients with microcirculation closer to normal
values;54 even though blood was leukodepleted in
that trial, recent data suggest that transfusion of
leukodepleted blood may better preserve the microcirculation than non leukodepleted blood.55
Beta-adrenergic agents were shown to improve microvascular perfusion,8 independently
from their effects on systemic hemodynamics,8
even though these effects can be quite variable
among individuals.8, 56, 57 Of note, both enoximone 58 and, on a greater degree, levosimendan,
demonstrated similar effects on microvascular
perfusion.59
Vasopressor agents, when used to reverse severe
hypotension, may improve microvascular perfusion,60, 61 but increasing mean arterial pressures
to higher levels (65-75-85 mmHg) had variable
effects on microvascular perfusion.62, 63 Increasing arterial pressure with norepinephrine was
beneficial only in the most severe cases, while it
was detrimental on sublingual microcirculation
in patients with close to normal microcirculation
at baseline.63
Could vasodilatory agents be used? In septic
patients the topical administration of a large dose
of acetylcholine, an endothelium-dependent vasodilating agent, restored the microcirculation,
which achieved a state similar to that of healthy
volunteers and non-septic ICU patients.2 Subsequently, nitroglycerin administration was shown
to improve the microcirculation in a small series
of patients with septic shock 26 but these effects
were not confirmed in a randomized trial.27 Vasodilating agents such as nitroglycerin are not
selective and may vasodilate not only the nonperfused vessels but also the already perfused ves-
Effects
Comments
Fluids
Red blood cells
Improve or ineffective
Variable
Inotropic agents
Vasopressor agents
Improve or ineffective
Variable
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or other proprietary information of the Publisher.
538
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May 2015
This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies
(either sporadically or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other
means which may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is
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DE BACKER
Buchele G, Simion D et al. Effects of fluids on microvascular perfusion in patients with severe sepsis. Intensive Care
Med 2010;36:949-55.
8. De Backer D, Creteur J, Dubois MJ, Sakr Y, koch M, Verdant C et al. The effects of dobutamine on microcirculatory
alterations in patients with septic shock are independent of
its systemic effects. Crit Care Med 2006;34:403-8.
9. Morelli A, Donati A, Ertmer C, Rehberg S, Kampmeier
T, Orecchioni A et al. Effects of vasopressinergic receptor
agonists on sublingual microcirculation in norepinephrinedependent septic shock. Crit Care 2011;15:R217.
10. De Backer D, Ospina-Tascon G, Salgado D, Favory R, Creteur J, Vincent JL. Monitoring the microcirculation in the
critically ill patient: current methods and future approaches. Intensive Care Med 2010;36:1813-25.
11. Boyle NH, Roberts PC, Ng B, Berkenstadt H, McLuckie A,
Beale RJ et al. Scanning laser Doppler is a useful technique
to assess foot cutaneous perfusion during femoral artery
cannulation. Crit Care 1999;3:95-100.
12. Altintas MA, Altintas AA, Guggenheim M, Aust MC, Niederbichler AD, Knobloch K et al. Insight in microcirculation and
histomorphology during burn shock treatment using in vivo
confocal-laser-scanning microscopy. J Crit Care 2010;25:1-7.
13. Favory R, Poissy J, Alves I, Guerry MJ, Lemyze M, Parmentier-Decrucq E et al. Activated protein C improves macrovascular and microvascular reactivity in human severe sepsis
and septic shock. Shock 2013;40:512-8.
14. Legrand M, Bezemer R, Kandil A, Demirci C, Payen D,
Ince C. The role of renal hypoperfusion in development of
renal microcirculatory dysfunction in endotoxemic rats. Intensive Care Med 2011;37:1534-42.
15. Bezemer R, Legrand M, Klijn E, Heger M, Post IC, van
Gulik TM et al. Real-time assessment of renal cortical microvascular perfusion heterogeneities using near-infrared
laser speckle imaging. Opt Express 2010;18:15054-61.
16. Fagrell B, Fronek A, Intaglietta M. A microscope-television
system for studying flow velocity in human skin capillaries.
Am J Physiol 1977;233:H318-321.
17. Dubin A, Edul VS, Pozo MO, Murias G, Canullan CM,
Martins EF et al. Persistent villi hypoperfusion explains intramucosal acidosis in sheep endotoxemia. Crit Care Med
2008;36:535-42.
18. Verdant CL, De Backer D, Bruhn A, Clausi C, Su F, Wang
Z et al. Evaluation of sublingual and gut mucosal microcirculation in sepsis: a quantitative analysis. Crit Care Med
2009;37:2875-81.
19. Wang Z, Forceville X, Van Antwerpen P, Piagnerelli M,
Ahishakiye D, Macours P et al. A large-bolus injection, but
not continuous infusion of sodium selenite improves outcome in peritonitis. Shock 2009;32:140-6.
20. Pranskunas A, Pilvinis V, Dambrauskas Z, Rasimaviciute R,
Milieskaite E, Bubulis A et al. Microvascular distribution in
the ocular conjunctiva and digestive tract in an experimental setting. Medicina (Kaunas) 2012;48:417-23.
21. Edul VS, Ferrara G, Pozo MO, Murias G, Martins E,
Canullen C et al. Failure of nitroglycerin (glyceryl trinitrate)
to improve villi hypoperfusion in endotoxaemic shock in
sheep. Crit Care Resusc 2011;13:252-61.
22. Taccone FS, Su F, Pierrakos C, He X, James S, Dewitte O et
al. Cerebral microcirculation is impaired during sepsis: an
experimental study. Crit Care 2010;14:R140.
23. Taccone FS, Su F, De Deyne C, Abdellhai A, Pierrakos C,
He X et al. Sepsis is associated with altered cerebral microcirculation and tissue hypoxia in experimental peritonitis.
Crit Care Med 2014;42:e114-e22.
24. De Backer D, Creteur J, Dubois MJ, Sakr Y, Vincent JL.
Microvascular alterations in patients with acute severe heart
failure and cardiogenic shock. Am Heart J 2004;147:91-9.
25. Trzeciak S, Dellinger RP, Parrillo JE, Guglielmi M, Bajaj J,
Abate NL et al. Early microcirculatory perfusion derangements in patients with severe sepsis and septic shock: rela-
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This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies
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means which may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is
not permitted. It is not permitted to remove, cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo,
or other proprietary information of the Publisher.
Conflicts of interest.The authors certify that there is no conflict of interest with any financial organization regarding the material discussed
in the manuscript.
Received on January 9, 2014. - Accepted for publication on June 17, 2014. - Epub ahead of print on June 19, 2014.
Corresponding author: D. De Backer,Department of Intensive Care,Erasme University Hospital,Route de Lennik 808,B-1070 Brussels,
Belgium. E-mail: ddebacke@ulb.ac.be
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