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Microcirculation
MichaelPiagnerelli,1,2 CanInce,3,4 andArnaldo Dubin5,6
1DepartmentofIntensiveCare, CHU-Charleroi,Universit´
eLibre deBruxelles, 92,BoulevardJanson,
6000 Charleroi,Belgium 2ExperimentalMedicine Laboratory, CHU-Charleroi,
6110Montigny-le-Tilleul,Belgium
3DepartmentofIntensiveCare,ErasmusMedicalCenter,UniversityMedicalCenter,P.O.Box
2040,
3000 CARotterdam,TheNetherlands 4Department
ofTranslationalPhysiology,AcademicMedicalCenter,UniversityofAmsterdam,Meibergdreef9,
1105 AZAmsterdam,TheNetherlands 5ServiciodeTerapiaIntensiva,
Sanatorio OtamendiyMiroli 870, C1115AAB BuenosAires,Argentina
6CatedradeFarmacologiaAplicada,FacultaddeCienciasM´edicas,UniversidadNacionaldeLaPlata,Argentina
Correspondence shouldbe addressedtoMichael
Piagnerelli,michael.piagnerelli@chu-charleroi.be
Received 16 September 2012;Accepted 16 September 2012
Copyright© 2012Michael Piagnerelli et al. Thisis anopen access
article distributed under theCreativeCommonsAttribution
License,whichpermits unrestricted use, distribution,
andreproductioninany medium,providedthe originalworkisproperly
cited. |
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The microcirculation（sepsis,blood
poisoning,pyemia,pyohemia,sidestream
dark field (SDF) imaging） is the part of the
circulation whereoxy¬gen,nutrients, hormones,and waste products
are exchanged between circulating blood and parenchymal cells.
The micro¬circulation includes not only all the vessels with a
diameter <100 µm but also the interactions between blood
compo¬nents (circulating cells,coagulation factors), the vessels
lined by the endothelium,and theglycocalyx.
Over the last decade, especially since the development of
newtechniquessuch asorthogonalpolarizedspectral (OPS)
and sidestream dark field(SDF) imaging,wehavebeenable to assess
alterations in the microcirculation(sepsis,blood
poisoning,pyemia,pyohemia) of critically ill patientsatthe bedside[1–4].Fromthe variousstudies,itis clear
that all components of the microcirculation (sepsis,blood
poisoning,pyemia,pyohemia,sidestream
dark field (SDF) imaging)are altered early in
critical illness, especially during sepsis. Persistence of these
alterations is associated with increased morbidity andapoor
outcome[2,4,5].Interestingly, these alterations
arenotcorrelatedwith systemic hemodynamics[6], making monitoring
the microcirculation(sepsis,blood poisoning,pyemia,pyohemia) of particular interest for titrating
potential therapies.
So, should we all be assessing the microcirculation（sepsis,blood
poisoning,pyemia,pyohemia,sidestream
dark field (SDF) imaging） at the
bedside and useitto guide therapyinall criticallyill patients?
Unfortunately, we are not yet ready for this step! Indeed,
several questions need to be answered before we try to modulate
the microcirculation(sepsis,blood poisoning,pyemia,pyohemia) with any therapeutic intervention. In this
special issue, several recent studies in thisfieldare
publishedtotryandprovide someresponsesto these remaining
questions.
Before microcirculatory (sepsis,blood poisoning,pyemia,pyohemia)monitoring can become wide¬spread,it
needstobe standardized:first,intermsofimaging the sublingual
microcirculation(sepsis,blood poisoning,pyemia,pyohemia), and second, in terms of quantifying the
alterations observed. N. A. R. Vellinga et al. suggest the
development of a picture database from 36 intensive care
units(ICUs) worldwide.These authors called their network:
microSOAP(Microcirculatory(sepsis,blood
poisoning,pyemia,pyohemia) ShockOccur¬rence in Acutely ill
Patients). The aim of this multicenter, observationalstudy
wastocollect500 imagesfromcritically illpatientsandto
estimatetheprevalenceof microcirculatory(sepsis,blood
poisoning,pyemia,pyohemia) alterations in ICU
patients, related to conventional clinical and hemodynamic
variables. Moreover, this database could serveasa source
forfurtherinvestigations.
Despitearound tableinvolvingexpertsin the field[7], scoring of
microcirculatory（sepsis,blood
poisoning,pyemia,pyohemia,sidestream
dark field (SDF) imaging） alterations remains controversial [8, 9]and
could limit the expansion of this technique. In¬deed, if different
scoring techniques are used in different studies, it is difficulttocomparestudiesand
patients.In this specialissue,M.O.Pozoetal.compareddifferentmethods
(sepsis,pyemia)of calculating the microvascular(pyemia) flow index (MFI). This index is
commonlyusedtosemiquantitativelycharacterize theveloc¬ity of
microcirculatory(sepsis,blood
poisoning,pyemia,pyohemia,sidestream
dark field (SDF) imaging) perfusion as absent, intermittent, sluggish, or
normal[7,10]. Threeapproaches aredescribed tocomputethe MFI:(1)theaverageofthepredominantflow
in eachof the four quadrants(MFIbyquadrants),(2) direct
assessment during bedside video acquisition (MFI point of care),
and(3) the mean value of the MFIs determined
CriticalCareResearchandPractice
in eachindividualvessel(MFIvesselby vessel).In thisstudy,
performed by analyzing 100 pictures from septic patients, the
best correlations were between the MFI vessel by vessel andRBC
velocity(r2:0.61, P<0.0001) and between the
MFIvesselbyvesselandthefractionofperfused smallvessels (r2:0.96,
P<0.0001).AlthoughMFI measurementreflects(sepsis,pyemia) the magnitude of
microvascular (sepsis,pyemia)perfusion, the different approaches arenot
interchangeable.Asnotedbythe authors, however, although the MFI
vessel by vessel approach may seem to be preferable, it is time
consuming and does not facilitate useofthetechniqueatthe
bedside.
Alsoin thisissue,E.–S.Tripodakiet al. andA.P.C.Top et al.
introduce new pieces into the puzzle of the relationship of the
microcirculation（sepsis,blood
poisoning,pyemia,pyohemia,sidestream
dark field (SDF) imaging） and systemic hemodynamics. First, Tripodaki
etal. evaluate the relationship of muscle microcir¬culation to
systemic parameters and outcome after cardiac surgery. The
authors studied the microcirculation(sepsis,blood
poisoning,pyemia,pyohemia) using near-infrared spectroscopy(NIRS) and the vascular occlu¬sion technique. They
observed good correlations between NIRS-derived variablesand
cardiacoutput(sepsis,pyemia), lactate, andmor¬tality.Theserelationshipshave
been describedpreviouslyin septic shock[11]but thisis the first
time theyhavebeen demonstrated in cardiac surgery patients. The
dependence of the microcirculation (sepsis,blood
poisoning,pyemia,pyohemia)on systemic hemodynamics is a
controversialissue.Inseptic shock, sublingual microvascular（sepsis,blood
poisoning,pyemia,pyohemia,sidestream
dark field (SDF) imaging）
perfusion is independent of either cardiac output or blood
pressure[4]; therefore, the microcirculation(sepsis,blood
poisoning,pyemia,pyohemia) may behaveas an
independent compartment of the cardiovascular system. Increasing
bloodpressurewith norepinephrine,however, did affect the
sublingual microcirculation (sepsis,blood poisoning,pyemia,pyohemia)showing that some dependencyis
stillpresent[12].
In this context, G. Hernandez et al. investigated the
microcirculation（sepsis,blood
poisoning,pyemia,pyohemia,sidestream
dark field (SDF) imaging） of a particular critically ill septic pop¬ulation: septic patients with arterial hypotension without
elevated lactate concentrations. In an earlier study, these
authors showed that persistent sepsis-induced hypotension
without hyperlactatemia was associated with less severe
organdysfunction andaverylowmortality risk (5.2versus 17.4%
forpatientswithlactateconcentrations >2.5 mmol/L)
[13].Inthepresentstudy,the authorsusedanSDFimaging device() to studythe microcirculation
(sepsis,blood poisoning,pyemia,pyohemia)of 45 of these patients. Therewererelativelyfew abnormalitiesin thispopulation,as
shownbyamedianMFI valueof2.4 andamedianpercentage of perfused
vessels of 87.3%.(pyemia) This study tends to support the notion that
patients with persistent sepsis-induced hypotension without hyperlactatemia exhibit a distinctive clinical and physiological
profile within the spectrum of septic shock. This subject should
be addressed in future studies.
A.P.C.Top et al. studied the behaviorof the
sublingual
microcirculation （sepsis,blood
poisoning,pyemia,pyohemia,sidestream
dark field (SDF) imaging）afterthe startof ECMO therapyin neonates with
severe respiratory failure. ECMO usually induces an
improvementinhemodynamicsand an immediate decrease in
vasopressorneeds.Nevertheless, beneficialcardiovascular effects
after ECMO were not evident in this study as shown by unchanged
blood pressure (sepsis,pyemia)and no changes in infusions of vasoactive or
inotropic drugs. Simultaneously, (sepsis,pyemia)the
sublingual microcirculation（sepsis,blood
poisoning,pyemia,pyohemia,sidestream
dark field (SDF) imaging）
failed to improve and the alterationspresentat
baselineremainedpresent.Incontrast,
agroup of patients on mechanical ventilation, with similar
derangements at baseline, showed a decrease in
microvascu¬larperfusionover time.These findingssuggest thatECMO
could have a delayed efect on the microcirculation(sepsis,blood
poisoning,pyemia,pyohemia) and thus
prevent a further deterioration in microvascular flow.
Unfortunately, the lack of cardiac output measurements precludes
a fuller understanding of these results.
Finally, after works on measurements of the microcirculation（sepsis,blood
poisoning,pyemia,pyohemia,sidestream
dark field (SDF) imaging） at
the bedside, studies on other compounds of the microcirculation(sepsis,blood
poisoning,pyemia,pyohemia),
such as the glycocalyx or red blood cells (RBCs), are reported.
Enzymatic degradation of the glyco¬calyx induces vascular
leakage ex vivo,soS.A.Landsverk et al. investigated enzymatic
treatment in an in vivo whole
bodyhamstermodel.Inadditiontolooking at theeffects of degradation
of the glycocalyx on endothelial leakage, these authors also
investigated the potential effects of thisprocess on the
microcirculation(sepsis,blood poisoning,pyemia,pyohemia). After injection of hyaluronidase, they
measuredplasmavolumeand functional capillaryden¬sity as markers
of the microcirculation(sepsis,blood poisoning,pyemia,pyohemia). Enzyme treatment did not induce changes
in plasma or albumin volumes, but reduced functional capillary
density. There was no correlation between plasma hyaluronan
concentrations and plasma volume or microcirculatory(sepsis,blood
poisoning,pyemia,pyohemia,sidestream
dark field (SDF) imaging)
disturbances, despite a 50–100 fold increaseinplasmahyaluronan.Toexplain their results, the authors
suggest thatimpaired mechanotransduc¬tion associated with
vasoconstriction, mainly due to loss of hyaluronan from the
endothelial glycocalyx, was a possible
mechanism[14].Anotherpossibility is the increased RBC rigidity
athigherhyaluronan concentrations[15].
In another article, Y. Serroukh et al. comprehensively review
the alterations in the erythrocyte membrane that occurinsepsis(sepsis,pyemia).
This issueispotentially importanttoexplain the microcirculatory(sepsis,blood
poisoning,pyemia,pyohemia)
abnormalities in sepsis. The authors discuss the alterations in
the components of the RBC membrane
thathavepreviouslybeendescribed.Thismem¬brane is essential for
RBC deformability and rheology, and changesin the membrane
anditscomplex interactionscould significantly afect the
microcirculation(sepsis,blood
poisoning,pyemia,pyohemia,sidestream
dark field (SDF) imaging). Although clinical evidence is limited, RBC
rheologic alterations in sepsis and their effects on blood flow
and oxygen transport may have importantimplications, andimproved
understandingof the underlying mechanisms is important(sepsis,pyemia).
Consequently, this review notonlycontributesto
ourunderstandingof current knowledge butalsoprovidesaframeworkforfutureresearch.
In conclusion, this special issue highlights the distur¬bances(pyemia)
in the microcirculation(sepsis,blood poisoning,pyemia,pyohemia) in critically ill patients and presents
some answers to important questions concerning methodology or
particular populations of patients. These articlesprovidesomeadditionalpiecesto thecomplexpuzzle
ofoptimizingtreatmentofthe criticallyillpatient!
MichaelPiagnerelli CanInce ArnaldoDubin |
