ARTICLE IN PRESS

Journal of Cardiothoracic and Vascular Anesthesia 000 (2023) 110

Contents lists available at ScienceDirect

Journal of Cardiothoracic and Vascular Anesthesia

journal homepage: www.jcvaonline.com

Review Article
Microcirculatory Alterations in Cardiac Surgery:
A Comprehensive Guide
H
elene De Cuyper, MD* y , Jan Poelaert, MD, PhDy,z
, ,1

*
Department Anesthesiology and Perioperative Medicine, UZ Brussels, Brussels, Belgium
y
Free University Brussels VUB, Brussels, Belgium
z
Department Anesthesiology, ICU and Chronic Pain Therapy, Maria Middelares, Ghent, Belgium

Microcirculation is essential for cellular life and its functions. It comprises a complex network of capillaries, arterioles, and venules, which dis-
tributes oxygenated blood across and within organs based on regional metabolic demands.
Because previous research indicated that organ function is linked to microcirculatory function, it is crucial to maintain sufficient and effective
microcirculatory function during major surgery. Impaired microcirculation can lead to inadequate tissue perfusion, potentially resulting in peri-
operative complications and an unfavorable outcome. Indeed, changes in microcirculation in cardiovascular disease and cardiac surgery have a
direct correlation with prolonged stays in the postoperative intensive care unit and high mortality rates within 30 days. Additionally, cardiopul-
monary bypass, a regularly employed method in cardiac surgery, has been proven to induce microcirculatory malfunction and, thus, lead to post-
operative multiple organ dysfunction. As global hemodynamic parameters can remain stable or improve, whereas microcirculation is still
compromised, tracking microcirculatory variables could lead to the development of targeted microcirculatory treatment within hemodynamic
management. Therefore, it is necessary to enhance the use of microcirculatory monitoring in the medical domain to assist physicians in the thera-
peutic management of patients undergoing cardiac surgery. This potentially can lead to better hemodynamic management and outcomes.
This review article concentrates on the use of handheld video microscopes for real-time microcirculatory assessment of cardiac surgery
patients in the immediate and early postoperative period. Emphasis is placed on integrating microcirculatory monitoring with conventional
hemodynamic monitoring in the therapeutic management of patients undergoing cardiac surgery.
Ó 2023 Elsevier Inc. All rights reserved.

Keywords: microcirculation; sublingual; cardiovascular disease; cardiac surgery; cardiopulmonary bypass; hemodynamic management; outcome

MICROCIRCULATION PLAYS a crucial role in the car-
diovascular system to promote cell survival and function.1,2
The network is composed of arterioles, capillaries, and ven-
ules, which connect the arterial and venous systems.3-6 Its pri-
mary function is to regulate organ perfusion and oxygen flux
distribution to maintain a proper balance between tissue oxy-
gen demand and supply.2,3,7 At the microcirculatory level,
tasks such as O2 exchange, removal of CO2 and protons, trans-
portation of hormones, nutrition, medication, and immune
response occur.8,9
1
Address correspondence to H
elene De Cuyper, Anesthesiologist, MD,
Department of Anesthesia and Perioperative Medicine, Brussels University
Hospital Department of Anesthesiology, Laarbeeklaan 101, Jette, Brussel
1090, Belgium.
E-mail address: Helene.De.Cuyper@vub.be (H. De Cuyper).
In cardiovascular surgery, previous research has demon-
strated that microcirculation may be significantly reduced
during the perioperative period due to decreased cardiac out-
put, nonpulsatile blood flow during cardiopulmonary bypass
(CPB), inflammation, hemodilution, and hypothermia.3,5,9-15
Microcirculatory alterations can pose a challenge in clinical
practice because they can arise regionally despite maintaining
global hemodynamics.3,9,16,17 This results in hemodynamic
incoherence, a pathology in which resuscitation procedures
focusing on the correction of systemic hemodynamic
variables prove futile for remedying microcirculatory
perfusion.4,5,9,13,18-20 An underlying mechanism for this hemo-
dynamic incoherence could be persistent damage to the endo-
thelial glycocalyx,5,14,21,22 facilitating organ dysfunction.11,21
Nonetheless, it is important to objectively assess the microcir-
culatory response to therapy, as improving microvascular

https://doi.org/10.1053/j.jvca.2023.11.042
1053-0770/Ó 2023 Elsevier Inc. All rights reserved.
 ARTICLE IN PRESS
2 H. De Cuyper and J. Poelaert / Journal of Cardiothoracic and Vascular Anesthesia 00 (2023) 110
perfusion can enhance tissue oxygenation and prevent organ
failure.8,12,16,23
A search was performed on PubMed and Google Scholar
using the following search terms: sublingual, microcirculation,
microcirculatory monitoring, Cytocam Incident Dark Field,
cardiovascular disease, cardiac surgery, cardiopulmonary
bypass, coronary bypass graft, transfusion, anesthesia, extra-
corporeal membrane oxygenation, hemodynamic manage-
ment, and endothelial glycocalyx. The eligibility criteria
consisted of systematic and narrative reviews, as well as ran-
domized controlled and nonrandomized trials. Excluded sour-
ces included case reports, case series, animal studies, and
non-English literature. A reliable source was found in a com-
parable review article published 4 years prior in the Journal of
Cardiothoracic and Vascular Anesthesia by Flick et al.5
This review article enhances current knowledge in an objec-
tive way, promoting scientific comprehension. It critically
appraises previously published works, identifying and synthe-
sizing pertinent literature to assess the role of microcirculation
in cardiac surgery. Furthermore, the research insights, gaps,
and future research directions concerning the use of hand-held
video microscopes for microcirculatory assessment in cardiac
surgery patients during the immediate and early postoperative
period are discussed.
Factors Influencing Microcirculation
Cardiovascular Disease
Microcirculatory dysfunction is associated with different
cardiovascular disease states, and may result from critical
medical conditions such as sepsis, heart failure, high-risk sur-
gery, and respiratory failure.3,7,9,21,23 Additionally, there is a
correlation with various other medical conditions, such as
peripheral vascular disease, diabetes, obesity, advanced age,
high cholesterol, hypertension, chronic kidney failure, and
abdominal aortic aneurysm disease.24 Microcirculatory dys-
function is an independent risk factor for mortality because it
is the primary mechanism of tissue oxygenation failure and
early organ dysfunction.3,7,16,20 As a result, restoring microcir-
culation is essential.2,4,5,7,25
Cardiac Surgery
Organ function requires the maintenance of microcircula-
tory perfusion and oxygenation. Several studies have shown
that significant microcirculatory changes occur after cardiac
surgery.3,9,12,15,26,27 Cardiac surgery, especially when employ-
ing CPB, has been associated with the activation of inflam-
matory mediators12 and systemic inflammatory response
syndrome,5,14,15,28 which have been linked to microcirculatory
dysfunction and neurocognitive decline.5,16,26,29 Systemic
inflammatory response syndrome arises from the activation of
the innate immune system, causing interaction between leuko-
cytes and endothelium, and leading to leukocyte transmigra-
tion into tissues.26 This, in turn, results in an increase
in endothelial permeability and the formation of
edema.4,12,15,18,30 The following explains what happens to
the microcirculation during off-pump surgery and on-pump
surgery using CPB with pulsatile versus nonpulsatile flow.
Observations in Off-Pump Cardiac Surgery
Atasever et al. discovered a link between off-pump cardiac
surgery and significant changes in sublingual microcirculatory
perfusion and hemoglobin oxygenation.15,31 Off-pump surgery
caused a cessation of flow during cardiac luxation, leading to
reduced convection of oxygen transport.31 On the other hand,
Koning et al. found that microcirculatory perfusion remained
unaffected during off-pump cardiac bypass.32
Observations on On-Pump Cardiac Surgery
Cardiopulmonary bypass is a commonly used technique
in cardiac surgery associated with an immediate decrease
in microcirculatory perfusion, leading to microcirculatory
dysfunction,5,12,16 which is directly related to prolonged post-
operative intensive care unit stay and high 30-day and long-
term mortality.3,11-13,16,25 Cardiopulmonary bypassinduced
microcirculatory perfusion disturbances are most profoundly
observed by changes in functional capillary density, perfused
vessel density (PVD), or percentage of perfused vessels
(PPV), which have been shown to remain impaired throughout
the perioperative period.3,12,14,28 In contrast, previous studies
have failed to demonstrate an effect of CPB on total vessel
density (TVD), small vessel density, or vessel density,12,13,32-36
suggesting that CPB does not necessarily affect the absolute
number of microvessels, but mainly impairs microcirculatory
red blood cell flow patterns, as reflected by a reduced PVD.13
Heterogeneity in vascular receptor types, receptor density, and
the importance of local blood flow autoregulation, which
mainly reflects the strength of the metabolic component of
microcirculatory regulation in the tissue,5,13 may explain the
variability in microcirculatory blood flow and oxygen delivery
to different organ beds. In addition, the use of vasopressors,
low-cardiac-output syndrome, hemoglobin level, oxygenation,
temperature, and the method and software used may add to this
variability.6,24
Atasever et al. discovered a link between on-pump CAB and
significant changes in sublingual microcirculatory perfusion and
hemoglobin oxygenation.15,31 On-pump CAB caused a reduction
in capillaries, resulting in a decreased oxygen extraction.31 Fur-
thermore, Koning et al. observed that microcirculation was seri-
ously impacted once CPB was initiated.32 Early postoperative
microcirculatory perfusion did not recover for at least 24 hours
after surgery,1,3,12 suggesting a persistent impairment of micro-
circulatoryperfusionduringthepostoperativeperiod,albeitwith-
outanyimpactonpostoperativeorganfunction.5,17
The various mechanisms by which CPB induces microcircu-
latory changes (Fig 1) are summarized below.11,13,16,28,31
1. Acute decrease in capillary density, primarily due to endo-
thelial dysfunction
2. Systemic inflammation and microthrombosis both due to
activation of blood cells and plasma proteins by exposure
 ARTICLE IN PRESS
H. De Cuyper and J. Poelaert / Journal of Cardiothoracic and Vascular Anesthesia 00 (2023) 110
Fig 1. The effect of cardiopulmonary bypass on macro- and microcirculation.
to nonbiocompatible polymers.13 Systemic inflammation
results in microvascular leakage, leading to a reduction in
microcirculatory perfusion.25,37
3. Bypass-associated hemodilution leading to decreases in
hemoglobin and blood viscosity, resulting in red blood cell
flow redistribution, which accounts for only part of the
microcirculatory perfusion abnormalities.13,14,38
Pulsatile Versus Nonpulsatile Flow
Several studies have investigated the impact of pulsatile and
nonpulsatile CPB on microcirculation.3,12,13,30,32,35,36 Some of
these studies indicated that microcirculatory perfusion was
restored after weaning from CPB with pulsatile flow, as com-
pared with nonpulsatile flow.9,13,25,30 Conversely, other studies
reported the preservation of microcirculatory perfusion during
CPB with pulsatile flow, as compared with nonpulsatile
flow.13,35,30 Unfortunately, those studies lacked sufficient
power to draw any conclusions regarding the association
between microcirculatory perfusion disturbances and mortality
after cardiac surgery.13 However, earlier research suggested
that in high-risk cardiac procedures with prolonged CPB time,
microcirculation is better maintained and may even be
improved by pulsatile flow when compared with nonpulsatile
flow,13,25,30 potentially due to the reduction of the systemic
inflammatory response.16,17 Despite the vast literature, it
remains uncertain if pulsatile flow during CPB is superior to
nonpulsatile flow.13 Table 1 summarizes several studies that
have investigated microcirculatory changes in on- and off-
pump cardiac surgery and pulsatile versus nonpulsatile flow
during cardiopulmonary bypass.5,13
Endothelial Glycocalyx During Cardiac Surgery
The endothelial glycocalyx has a significant role in main-
taining vascular homeostasis.14,21,22 Situated between the
endothelium and the circulation, the endothelial glycocalyx
3
largely controls essential physiologic functions such as shear
stress mechanotransduction, antiinflammatory and anticoagu-
lative responses, and vascular permeability.5 Cardiopulmonary
bypass results in the breakdown of the glycocalyx, which is an
early indicator of endothelial injury.22,26 This enables circulat-
ing red blood cells to contact endothelial cells more frequently,
resulting in increased vascular flow resistance.14,22 Addition-
ally, endothelial glycocalyx breakdown leads to a significant
decrease in nitric oxide production and an alteration of micro-
circulatory perfusion patterns,13,14,21 including perfusion
heterogeneity, reduction of functional capillaries, and micro-
vascular shunt, which are all associated with impaired tissue
oxygenation.12 Therefore, targeting glycocalyx protection and
restoration to optimize postoperative organ function is impor-
tant (Fig 2).5,13-15,22
Anesthetic Drugs
The effects of anesthetic drugs on macrohemodynamics
have been studied extensively during the last decades.44 How-
ever, their impact on microcirculation, including capillary
blood flow and oxygenation, is still not understood fully.44
Although anesthetics might affect microcirculatory perfu-
sion,10 the evidence is minor and only transient.12,13 Therefore,
further research is needed to elucidate the specific effects of
anesthetics on microcirculatory parameters.44
Previous studies investigated the impact of different types of
anesthesia on microcirculation.1,5,9,10,12,31,44 It is interesting to
note that only the study of De Backer et al. discovered that
anesthesia significantly reduced microcirculatory perfusion
but that this effect was only transitory.12 However, no such
results were found in any of the other trials.10
Intravenous Hypnotics
Propofol causes vasodilation by increasing the production of
nitric oxide.1,12 This might result in microvascular shunting,
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Table 1
Summary of Several Studies Investigating Microcirculatory Alterations in both On- and Off-Pump Cardiac Surgery and Pulsatile Versus Nonpulsatile Flow During
Cardiopulmonary Bypass5,13

First Author, Year Type of Surgery No. of Method, Microcirculatory Primary Findings
Participants Variables

On-pump versus off-pump CPB

Atasever et al., 201131 ONCAB and OPCAB 48 patients SDF imaging; FCD, RBC Decreased PVD after initiation of CPB with signs of
surgery velocity, sublingual oxygen decreased oxygen extraction, minor
saturation microcirculatory changes despite severe
macrohemodynamic impairment during cardiac
surgery
Atasever et al., 201239 OPCAB surgery 39 patients SDF imaging; FCD, RBC Decreased RBC velocity, sublingual oxygen
velocity, sublingual oxygen saturation, and cerebral oxygen index during
saturation, cerebral NIRS cardiac positioning
Koning et al., 201440 ONCAB and OPCAB 31 patients SDF imaging; RBC velocity, Increased microcirculatory flow heterogeneity after
surgery HI initiation of CPB with additional increase after
admission in ICU in ONCAB group; no
microcirculatory alterations in the OPCAB group
Koning et al., 201432 ONCAB and OPCAB 26 patients MFI, TVD, PVD Persistent decrease of PVD and PPV after initiation
surgery of CPB, decrease of MFI at the end of surgery in
CPB group, no microcirculatory changes in
OPCAB group
Bienz et al., 201637 ONCAB and OPCAB 32 patients SDF imaging, small vessel Unspecific minor microcirculatory alterations
surgery count, vessel count with during ONCAB and OPCAB surgery
continuous flow, TVD,
PVD, small vessel density
Pulsatile versus non-pulsatile flow during CPB
Elbers et al., 201141 ONCAB or aortic 16 patients SDF imaging, PVD, PPV, HI, No major differences in microvascular variables
valve repair surgery PVD, MFI between pulsatile and nonpulsatile flow
Koning et al., 201222 ONCAB surgery 36 patients SDF imaging; TVD, PVD, Temporary decrease of PVD and MFI in pulsatile
MFI CPB group; persistent decrease PVD and MFI in
nonpulsatile CPB group
O’neil et al., 201230 High-risk ONCAB 20 patients OPS imaging; PPV for each Decreased PPV in both groups with more severe
surgery flow score (0-4) decrease in PPV and increased signs of
heterogeneous flow in nonpulsatile CPB group,
recovery to baseline values only in the pulsatile
CPB group
Yuruk et al., 201242 ONCAB surgery with 20 patients SDF imaging; PVD Minor microcirculatory alterations during
conventional or miniaturized CPB, decrease of PVD during
miniaturized CPB conventional CPB
system
O’neil et al., 201843 High-risk ONCAP 20 patients OPS imaging; PPV separated Decreased PPV in both groups, with more severe
surgery for each flow score (0-3); decrease in PPV and increased signs of
vessel density, NIRS, heterogeneous flow in nonpulsatile CPB group;
vascular occlusion test recovery to baseline values only in the pulsatile
CPB group; steeper reperfusion slope in the
pulsatile CPB group

Abbreviations: CPB, cardiopulmonary bypass; FCD, functional capillary density; HI, heterogeneity index; ICU, intensive care unit; MFI, microcirculatory flow
index; NIRS, near-infrared spectroscopy; ONCAB, on-pump coronary artery bypass; OPCAB, off-pump coronary artery bypass; OPS, orthogonal polarization
spectral; PPV, proportion of perfused vessels; PVD, perfused vessel density; RBC, red blood cell; SDF, sidestream dark field; TVD, total vessel density.

decreased capillary density, increased blood flow heterogene- Inhalation Anesthetics

ity, and decreased tissue oxygen supply.5,10,13,28 In 2016, Liu
et al. found that dexmedetomidine, a highly selective alpha-2
agonist,causesvasodilationanddownregulationoftheinflamma-
tory response, decreases leukocyte-endothelial interactions, and
produces mild hypocoagulation.1,45 Therefore, it might be better
to improve microcirculation in cardiac surgerypatientsduring the
early postoperative period compared with propofol.1,28 The key
mechanisms of anesthetic-induced tissue perfusion changes
include, presumably, changes in microvascular responsiveness,
nitricoxidepathways,andcytokinerelease.1,44
There is still a lot of debate about the effect of inhalation
anesthetics on patient outcomes after cardiac surgery.13 Halo-
genated anesthetics induce peripheral vasodilation and reduce
vascular permeability, thus favoring microvascular recruitment
and tissue oxygen diffusion,10,44 as indicated by increases of
€
TVD and PVD.15 Ozarslan et al. found that sevoflurane signifi-
cantly reduced microcirculatory perfusion during cardiac sur-
gery compared with isoflurane and desflurane, as evidenced by
a significantly lower proportion of perfused vessels in small
 ARTICLE IN PRESS
H. De Cuyper and J. Poelaert / Journal of Cardiothoracic and Vascular Anesthesia 00 (2023) 110
Fig 2. Red blood cell flow patterns before (left) and after (right) cardiopulmonary bypass.
vessels during CPB.13,35 This effect was only temporary
because it vanished by the time surgery was ended.
Nevertheless, both balanced anesthesia and total intravenous
anesthesia were associated with the overall maintenance of
microvascular perfusion and tissue oxygenation.10 Both propo-
fol and sevoflurane were demonstrated to exert a protective
effect against ischemia/reperfusion injury by modulating the
inflammatory response, reducing oxidative stress, and promot-
ing tissue apoptosis.3,10,12,28
Vasoactive Drugs
The goal of vasopressors is to achieve a perfusion pressure
above the lower autoregulation threshold, enabling tissue per-
fusion while evading undue vasoconstriction.2 Increasing per-
fusion pressure with vasopressor use may not improve
microcirculation but rather impair it. However, at the same
time, it should be considered that increasing perfusion pressure
was reported to be beneficial for the perfusion of other organs,
such as the kidney.9 Maier et al. investigated the effect of
phenylephrine, an alpha-1-adrenoreceptor agonist, on micro-
circulation during CPB.11 Raising systemic vascular resistance
greatly enhanced perfusion pressure during constant systemic
blood flow, but did not affect systemic oxygen transport fac-
tors or the acid-base state. Alpha-1-adrenergic receptor activa-
tion also resulted in a reduction of sublingual microcirculatory
tissue oxygen delivery due to a decrease in small vessel blood
flow despite unchanged systemic parameters.5,9,11 A formerly
continuous capillary blood flow pattern transitioned into a
more sluggish flow pattern, with a significant percentage of
capillaries exhibiting the “stop and go” phenomenon.13 Based
on these findings, it is believed that the use of phenylephrine
for perfusion pressure enhancement during hypothermic CPB
should be considered carefully because of its possible damag-
ing effect on tissues or even organs, particularly in those with
a preexisting flow reduction in the arteriole.11 After phenyl-
ephrine administration discontinuation, sublingual tissue oxy-
gen uptake reduces and reverts to prephenylephrine levels.11
Norepinephrine administration is linked to impaired micro-
vascular perfusion in controlled conditions, although this
effect is not observed when the agent is used to restore blood
pressure in shock.2,12 After cardiac surgery, an elevation in
mean arterial pressure through norepinephrine infusion
prompted a rise in splanchnic oxygen extraction without
5
affecting intestinal mucosal perfusion. This phenomenon is
conceivably attributed to autoregulation.10
Previous studies have shown conflicting results regarding
epinephrine’s impact on the splanchnic microcirculation after
cardiac surgery.46,40 In general, evidence is limited in suggest-
ing improved regional perfusion with epinephrine use, but it
may lead to increased myocardial workload, oxygen consump-
tion, and lactate production.28,47,48
Vasopressin seemed to have a lower impact on microcircu-
latory blood flow compared with other vasoactive medications
when administered for reversing vasoplegia related to systemic
inflammatory response syndrome.28,49
Inotropic Agents
The increase in cardiac output elicited by inotropes might go
together with increases in microvascular perfusion.2 For
instance, De Backer et al. demonstrated that intravenous infu-
sion of dobutamine at a rate of 5 mg/kg/min enhanced sublin-
gual microcirculation in patients with septic shock.6,12
Notably, this improvement in microcirculation was notcon-
nected to variations in cardiac output and blood pressure, and
was directly linked to the reduction in lactate concentrations.
The microcirculatory impact of dobutamine was not discern-
ible via conventional macrocirculatory parameters.9 Neverthe-
less, additional research is required to gain a complete and
improved understanding of the effects of dobutamine on sub-
lingual microcirculation during cardiac surgery.5,28
Fluids
Fluids can improve convective microvascular flow by
increasing cardiac output and blood pressure.19 Numerous
experimental studies have demonstrated the advantageous
effect of starches on the microcirculatory system.19,27
However, the administration of these therapies is contraindi-
cated due to their adverse effects on critically ill
patients.2,12,19,20,25,39,44 It should be noted that excessive intra-
vascular volume expansion can impede diffusional microvas-
cular oxygen transport due to tissue edema, and has the ability
to damage the glycocalyx layer, thereby promoting endothelial
dysfunction.50 This may cause a reduction in the area available
for gas exchange and an increase in diffusional distance and
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PVD.15 Moreover, reduced capillary flow and hematocrit
could result from lower viscosity levels.2
Transfusion
In patients undergoing cardiac surgery, perioperative red
blood cell transfusion is applied routinely to treat anemia
induced by blood loss and CPB-induced hemodilution.5,14,15,51
Blood transfusion improves systemic circulation and oxygen-
carrying capacity by increasing systemic hemoglobin, filling
previously empty capillaries, and reducing diffusion distances
between oxygen-carrying red blood cells and parenchymal
cells, resulting in increased medium-sized vascular density
and oxygen delivery in the sublingual microcirculation regard-
less of systemic hemodynamic parameters or volume
status.27,39,51 In contrast, red blood cell (RBC) transfusion
may result in adverse effects, such as transfusion-related acute
lung injury, volume overload, and immunomodulation.50,52
Furthermore, numerous authors have proposed that RBC trans-
fusion, particularly aged, stored RBCs, may compromise endo-
thelial function and, subsequently, microcirculatory blood flow
due to the nitric oxide and L-arginine scavenging effects
of cell-free plasma hemoglobin and arginase-1 activity,
respectively.50,53,54
Extracorporeal Membrane Oxygenation
Extracorporeal membrane oxygenation assists organ func-
tion by providing blood flow support and supplying oxygen-
ated blood to tissues in critically ill patients.37,55,56 However,
it can disrupt the integrity of red blood cells, leading to the
release of hemoglobin from excessive contact with foreign sur-
faces and mechanical stress.37,56 Hemolysis can have severe
effects on the microcirculation, where plasma hemoglobin can
scavenge nitric oxide, cause oxidation, produce reactive oxy-
gen species, and lead to inflammatory responses.16 A restricted
number of studies have examined the impact of extracorporeal
membrane oxygenation on microcirculation. However, further
investigations are required to mitigate the diminished micro-
circulatory perfusion and consequential oxygenation caused
by extracorporeal membrane oxygenation.37,54,42
Fig 3. Sublingual microcirculation images of a healthy patient (left) and a fluid-resuscitated shock patient (right).
Hand-Held Video Microscopes to Assess Sublingual
Microcirculation
Recently, hand-held video microscopes (HVMs) have been
introduced into clinical practice, enabling real-time bedside
analysis of microcirculatory variables, which could result in
a more individualized approach.4,6,9,20,26 Hand-held video
microscopes could provide information on the hemodynamic
status of the patient, such as the classification of shock or
adjustment of the dosage of vasopressors or inotropes based on
demand.3,5 They also could aid in guidance for fluid therapy
and red blood cell transfusions, as well as the evaluation of
treatment response.5,7 However, HVMs are not yet considered
a standard of care, as there is a shortage of controlled studies
demonstrating its benefits in terms of outcomes,13 inter-
observer variability, and technical limitations for its clinical
implementation (Fig 3).3,7
The current review focuses on the use of HVMs to quantify
and visualize microcirculatory perfusion. Other indicators,
such as Doppler-derived techniques, mixed and central venous
oxygen (O2) saturations, tissue spectrophotometry, tissue car-
bon dioxide partial pressure, transcutaneous oxygen partial
pressure electrodes, the venous-arterial carbon dioxide tension
difference, clinical biomarkers, and assessments4-6,9,19,24 exist
within clinical practice and are beyond the scope of this
review.
Cytocam Incident Dark Field
Cytocam Incident Dark Field (IDF) imaging is a third-gen-
eration HVM that offers real-time visualization of the in vivo
microcirculation.3,9,10 Based on the objective principle of IDF
illumination, this hand-held computer-controlled device has
been developed to overcome the technical limitations of its
predecessors, namely orthogonal polarization spectroscopy
and sidestream dark field imaging.4,8,13,15,20,26,28 For instance,
the Cytocam IDF device has a high-resolution imaging sensor
that is synchronized to short-pulsed illumination, resulting in
sharper and higher contrast images with a larger field of
view.2,6,9,13,15,20,26,27 The most frequently examined regional
site for HVMs is the sublingual area, which may be a helpful
surrogate for critical organ microcirculation.5 This imaging
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H. De Cuyper and J. Poelaert / Journal of Cardiothoracic and Vascular Anesthesia 00 (2023) 110
method could help guide goal-directed fluid therapy in the
postoperative management of cardiac surgery patients, poten-
tially resulting in better outcomes (Fig 4).4,6
Working Mechanism2,5,6,10,13,16
1. Gently remove saliva and other fluids and place the probe
on the sublingual mucosa.
2. Record 3 different 10-second videos with adequate focus
and contrast
3. Avoid pressure artifacts, which may impede microcircula-
tory flow.
4. Perform offline video analysis with the assistance of spe-
cialized software.
Although HVMs do not directly assess tissue oxygenation,
they can evaluate microcirculatory perfusion and convective
and diffusive oxygen transfer.9 They offers significant data on
the patient’s hemodynamic status and facilitate the adjustment
of vasopressor or inotrope dosage as necessary.7 They estab-
lish secure limits, guide fluid therapy, and RBC transfusion,
and assess treatment response.5,15
Microcirculatory Variables
Hand-held video microscopes allow the identification of
flow heterogeneity, defined as the variability of blood flow
within a specific area of interest.5,28 Flow heterogeneity can
help to differentiate among different types of shock.4,13,15 The
heterogeneity index can be determined using the microvascu-
lar flow index or the PPV variation within the field of view,
and is calculated using the variance in red blood cell velocity
across all arteries in the area of interest.2,4,13 It is recom-
mended that data from at least 3 different sites be averaged to
quantify microcirculatory flow at a given time point. The
microvascular flow index can be used to calculate the convec-
tive capacities of the microcirculation, such as erythrocyte
Fig 4. Cytocam Incident Dark Field enabling noninvasive real-time imaging of the capillary bed and assessment of sublingual microcirculatory perfusion. IDF,
Incident Dark Field.
7
velocity. It is a semiquantitative assessment of RBC velocity
per image quadrant or an average of individual vessel flow. In
addition, PPV, defined as a binomial determinant of perfusion
(“flow” or “no flow”), can provide information on the convec-
tive characteristics of microcirculatory perfusion.2,5,9,13,17,20
Diffusive capacities can be quantified through the calcula-
tion of TVD, defined as the sum of all capillaries containing
red blood cells divided by the field of view.2,9,13 The De
Backer score, which is based on a grid, can be employed to
approximate the TVD.5,13 The PVD provides an estimate for
the functional capillary density, and reflects both convective
and diffusive components.13 Perfused vessel density considers
only vessels with blood flow, and is computed as PPV multi-
plied by TVD. The PVD is regarded as the most reliable
technique for experimental research. However, absolute meas-
urements of PVD can be subject to methodologic differences
and observer dependence, leading to variations of up to 30%.
As a less-subjective alternative, the functional capillary den-
sity was introduced based on automated blood cell flow analy-
sis in each vessel using the space-time diagram.2,4,5,13,17,20
Table 2 summarizes the most common microcirculatory var-
iables and their definitions.5,9,13
Limitations
Although monitoring the sublingual microcirculation
appears to be an attractive variable for monitoring critically ill
patients as a prognostic tool and target for resuscitation, signif-
icant barriers remain:
1. This technique is highly operator-dependent. An experi-
enced user is needed for data acquisition from these videos
to segment the videos into still images, where the vessels
are then individually traced before evaluating the quality of
the microcirculation. It is recommended that HVM users
receive theoretical and practical training to avoid pressure
artifacts caused by the unnecessary force of the probe on
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8 H. De Cuyper and J. Poelaert / Journal of Cardiothoracic and Vascular Anesthesia 00 (2023) 110

Table 2
Microvascular Variables5,9,13

Variable Unit Definition

PPV % Percentage of perfused vessels per total vessels

Based on binominal determinant of perfusion: “flow” or “no flow” (convective property)
TVD mm/mm2 Total vessel area per surface area
Surrogate for capillary distance (diffusive property)
PVD mm/mm2 PPV £ TVD
Determinant of capillary distance (diffusive property) and red blood cell velocity (convective property)
FCD mm/mm2 Measure of PVD based on individual vessel STD
MFI Au Grid-based score per quadrant:
0 = no flow
1 = intermittent flow, 2 = sluggish flow
3 = normal flow
Quick, semiquantitative assessment of the red blood cell velocity by “eyeballing”
HI au Coefficient of variation, expressed as (maximum  minimum value) / average; determinant of heterogeneity of blood
flow
De Backer score n/mm The number of vessels crossing a grid (3 horizontal and vertical equidistance lines drawn on the screen) divided by the
total length of the gridlines
Surrogate for TVD applicable to different vessel types
STD mm/s Measurement of exact red blood cell velocity

Abbreviations: au, arbitrary unit; FCD, functional capillary density; HI, heterogeneity index; MFI, microvascular flow index; PPV, proportion of perfused vessels;
PVD, perfused vessel density; TVD, total vessel density; STD, space-time diagram.

the mucosa, which can restrict microcirculatory flow and
lead to inaccurate measurements.2,5,8
2. After obtaining video fragments, semiautomated video anal-
ysis (AVA 3.2 software, MicroVision Medical, Amsterdam,
The Netherlands) takes place.2,5,18,26 This method is limited
in its applicability to guide real-time treatment decisions of
critically ill adults despite its excellent intraobserver reli-
ability and good-to-moderate interobserver reliability.18,20
Thus, an equally reliable and precise automated software
that integrates video quality evaluation is imperative.18 Fur-
thermore, analysis of a single video can take up to 20
minutes by an experienced operator.5 This complex and
time-consuming process is still a major limitation.
3. In addition to this already lengthy and laborious process,
the 2018 consensus guidelines from the European Society
of Intensive Care Medicine for microcirculation image
analysis also require a detailed assessment of video quality
using the Microcirculation Image Quality Score.20
Acquired videos are scored on an ordinal scale of 0 (opti-
mal quality), 1 (acceptable quality), and 10 (unacceptable
quality), ranking videos across 6 domains. This manual
process has limited feasibility in the dynamic critical care
setting. Thus, an equally reliable and precise automated
software that integrates video quality evaluation is impera-
tive. Recently, an algorithm has been proposed for fully
automated video analysis that can provide instant results
and avoid observer bias during analysis.5,18
4. There is a lack of controlled studies showing benefits in
terms of outcomes and technical limitations for its clinical
implementation, making this technique mainly a research
tool.2,5
5. It remains difficult to standardize variables to describe the
sublingual microcirculation. This is an important step
toward bedside monitoring, as automated real-time analysis
of microvascular videos is essential in the development of
research protocols and clinical algorithms incorporating
point-of-care microvascular analysis.5,20
Future Aspects
Hand-held video microscopes have improved the com-
prehension of hemodynamic processes during and after car-
diac surgery. More research is necessary that explores the
influence of CPB, anesthesia, and other medications on
microcirculation, as the consequences of microcirculatory
alterations on perioperative complications and patient out-
comes remain ambiguous.13
The development of automated, real-time analysis for
microcirculatory videos may expand the reach of HVMs and
facilitate their use at the point of care and for bedside diagnosis
of microcirculatory changes. Nevertheless, a debate regarding
the potential of microcirculatory monitoring to enhance patient
outcomes is ongoing.5,18,24
There is a need to develop treatment goals, strategies, and
target values for microcirculatory variables and integrate them
into protocolized hemodynamic therapy algorithms.1,5
If these steps are completed, patients undergoing cardio-
vascular surgery could benefit from using HVMs for
microcirculatory monitoring. Hemodynamic treatment that
is guided by microcirculatory measurements may help
to improve patient outcomes by reducing perioperative
complications.5
Conclusions
Cardiac surgery, particularly when using CPB, has been
shown to have a negative impact on microcirculation and
 ARTICLE IN PRESS
H. De Cuyper and J. Poelaert / Journal of Cardiothoracic and Vascular Anesthesia 00 (2023) 110
tissue oxygenation, which could lead to higher postoperative
morbidity and mortality rates. Although the macrohemody-
namic goals of the surgery may be achieved, the microcircula-
tion may still be compromised. Direct observation of the
microcirculation via HVMs is a crucial and secure noninvasive
technique used in cardiac surgery. It permits an accurate
assessment of the impact of cardiovascular surgery, and has
significant potential value in enhancing and personalizing
hemodynamic management. In the future, therapy may con-
centrate on restoring normal microcirculation and optimizing
macrocirculatory characteristics. Therefore, there is a need to
enhance microcirculatory monitoring in the medical field to
support physicians in managing cardiac surgery patients thera-
peutically. This potentially could enhance hemodynamic man-
agement and postoperative outcomes by facilitating goal-
directed fluid therapy and identifying signs of systemic inflam-
matory response syndrome, which may contribute to postoper-
ative multiple organ dysfunction. Although technologic
advancements may help overcome certain methodologic limi-
tations, it is crucial to establish therapeutic goals to success-
fully incorporate microcirculatory monitoring into regular
clinical procedures rather than only using it for experimental
investigations. Further investigation is required to analyze the
impact of perioperative interventions, including fluid adminis-
tration, catecholamines, and other medication, on microcircu-
lation. Finally, randomized controlled studies aimed at
illustrating the favorable effects of a microcirculation-focused
resuscitation on results would produce ample evidence to jus-
tify its clinical application.
Declaration of competing interest
None.
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