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Abstract
Microcirculation£¨visualize the
microcirculation at the bedside,clinical
microcirculation£©plays an important role both in physiological
and pathophysiological states. Early recognition of changes in
microcirculation is crucial for starting early therapeutic
intervention and reversing the organ failure. Orthogonal
polarization spectral (OPS) and Sidestream dark field imaging (SDF) £¨visualize the microcirculation at
the
bedside,clinical microcirculation£©are relatively new noninvasive methods that allow direct visualisation of the microcircu¬lation at the bedside and
analysis using semi-quantitative scores. In human medicine,
these optical devices have been so far carried out in critically
ill adult patients (sepsis, shock, cardiac arrest etc.). To
date, only a few medical papers have been published on the use
of the technique in children, in particular in preterm neonates.
Although it has been the sublingual region commonly used for the
observation in adults, the most frequently used site for
assessment in newborns is the skin or buccal mucosa. The studies
published on the use of OPS/SDF imaging £¨Sidestream dark field imaging (SDF),visualize
the microcirculation at the bedside,clinical
microcirculation£©in the newborns show
them as a potentially important addition to hemodynamic
monitoring in neonatal intensive care.
Key words: microcirculation, neonates, Orthogonal
polarization spectral imaging, Sidestream dark field imaging,
functional capillary density in physiological and
pathophysiological
Abbreviations
states. [1-3] The microvascular perfusion is OPS Orthogonal
polarization spectral controlled locally in health and is main-SDF
Sidestream dark field tained despite changes in arterial blood
pres-FCD Functional capillary density sure. The local
autoregulation mechanisms ECMO Extracorporeal membrane oxygena-are
very individual, vary depending on ortion gans, diseases,
metabolic activity or even PDA patent ductus arteriosus each
patient.
Arterial blood pressure is considered as a main marker of tissue
perfusion.
However Introduction there is no absolute threshold blood
pressure that would define adequate perfusion.
Mi-Microcirculation£¨Sidestream dark field imaging (SDF),visualize
the microcirculation at the bedside,clinical
microcirculation£© is an important part of the crovascular
blood flow measurement as a di¬cardiovascular system. It ensures
the tissue rect oxygen supply indicator would be an oxygen
supply and has a crucial role in the important additional tool
to hemodynamic interaction between blood and tissue, both
assessment in intensive care. Early detection of abnormalities
in the tissue perfusion al¬lows early intervention and better
clinical outcome in critically ill patients. [4] Orthog¬onal
polarization spectral (OPS) [2] and its improved successor
Sidestream dark field (SDF) imaging£¨visualize
the microcirculation at the bedside,clinical
microcirculation£© are relatively new noninva¬sive handheld devices for bedside observa¬tion of the
microcirculation. [5]
OPS/SDF imaging (Sidestream dark field imaging (SDF),visualize
the microcirculation at the bedside,clinical
microcirculation
)
The development of new technologies for microvascular
observation enabled studying various pathophysiological states
at the cap¬illary level. The techniques were validated in animal
studies with great effort to implement them to clinical
research. For many years, capillary microscopy had been the only
method for observation of the microcircula¬tion in humans.
Capillary microscopes can be used only on easily accessible
surfaces (skin, nailfold, lip or bulbar conjunctiva) and
therefore have significant limitations in clini¬cal
applications. OPS imaging technology and its validation against
conventional capil¬lary microscope provide new possibilities for
further clinical research in microcirculation.
[5] The most frequently used place for direct visualisation of
the microcirculation in adults is the sublingual area. Clinical
studies are fo¬cused mainly on critically ill patients (in
sep¬sis, shock, cardiac arrest). [3, 5] The device is based on
the principle that green polarized light (548 nm) illuminates
the tissue sur¬rounding the capillaries and is absorbed by
hemoglobin within the erythrocytes. The backscattered light
passes through the ana¬lyzer that filters out surface
reflections creat¬ing a high-contrast image of flowing
erythro¬cytes in capillaries.
Despite visualizing the blood flow alter¬ations in critically
ill patients, several limita¬tions in OPS imaging still remain,
in particu¬lar movement and pressure artefacts. [4, 5] SDF
imaging£¨Sidestream dark field imaging (SDF),visualize
the microcirculation at the bedside,clinical
microcirculation£©, a new improved device based on OPS technology, provides
a better image quality. In this technique a light guide is sur¬rounded by light emitting diodes (LED) of wavelenght 530 nm
to provide sidestream dark field illumination. The lens system
of the light guide is optically isolated from the ring of LEDs
to prevent images from contam¬ination by tissue surface
reflections. In the videosequence red blood cells are imaged as
dark flowing structures against white/grayish background. To
provide a high quality image diodes are emitting the light in
sychrony with the frame rate of the CCD camera. This
stro¬boscopic imaging prevents from artefacts while capturing
flowing structures (erythro¬cytes). For the purpose of SDF
imaging the Microscan videomicroscope was developed (Microvision
Medical, Amsterdam, Nether¬lands). The probe with a sterile
disposable cap is placed on the organ/tissue surface and allows
the observation of the microcirculation£¨Sidestream dark field imaging (SDF),visualize
the microcirculation at the bedside,clinical
microcirculation£© morphology and
perfusion in various clinical states. The videosequence is
visu¬alised on a monitor. Digitally recorded im¬ages are stored
on a hard-drive and the analysis is performed off-line. [5]
However, the analysis of videosequences is time-con¬suming and
requires certain training period. There are several software
systems and scor¬ing scales available for the analysis. A round
table conference in 2006 focused on key points for optimal
visualisation of the micro¬circulation as well as on various
scoring sys¬tems. The participants proposed recommen¬dations for
the image acquisition and further analysis which include
investigating mini¬mum 3-5 sites per organ, each videose¬quence
at least of 20 s. The scores consist of functional capillary
density (FCD) ¨C a param¬eter of perfusion and an indirect index
of tis¬sue oxygen supply measured in cm/cm², pro¬portion of
perfused vessels (PPV) and semi¬quantitative microcirculatory
flow index (MFI) based on predominant type of flow in four
quadrants (0 = no flow, 1 = intermit¬tent, 2 = sluggish, 3 =
normal). [6]
Orthogonal Polarization Spectral (OPS)/Sidestream dark field (SDF)
imaging £¨Sidestream dark field imaging (SDF),visualize
the microcirculation at the bedside,clinical
microcirculation£©
Microcirculation in clinical research
In clinical research methods for visualisation of the
microcirculation have been widely ap¬plied in critically ill
adult patients (in sepsis or other forms of distributive shock).
The key point is to undestand the changes of the
mi¬crocirculation at the molecular level. The most frequently
used site for assessment in clinical research is the sublingual
mucosal surface. Recent studies have shown patho¬physiological
changes at the sublingual level in the development of organ
failure in septic patients that can be observed already at
ear¬ly stages of the disease. There are dearrange¬ments in the
blood flow at the capillary lev¬el, de Backer et al. [7]
described reduced vessel density and reduced proportion of the
perfused small (<20 µm) vessels in patients with sepsis. These
alterations are more re¬markable in patients with a worse
outcome. In survivors, the perfusion improves with ad¬equate
therapy but just if treated at early stages of the sepsis.
Microvascular impair¬ment can be observed also in patients with
severe heart failure and cardiogenic shock. In comparison with a
control group, there was a lower proportion of small vessels
per¬fused in cardiac failure. [8]
Microcirculation in pediatrics/neonatology
Microcirculatory changes in various patho¬physiological states
can be observed also in neonates.
Recently there have been several medical papers focused on the
investigation of the microcirculation in newborns, especially in
preterm infants. [4, 9-15] With regard to the fact that there
are significant differences in children (different body
proportions, higher metabolic rate, lack of compensatory
respira¬tory and cardiovascular reserve) as well as different
pathophysiological response to ill¬ness, children cannot be
regarded as small adults and deserve own clinical research to
provide age related parameters. Before OPS/SDF imaging£¨Sidestream dark field imaging (SDF),visualize
the microcirculation at the bedside,clinical
microcirculation£© the
assessment of the mi¬crocirculation was performed by
videopho¬tometric microscopy or laser Doppler. In the last 10
years, the field of interest has been fo¬cused on OPS/SDF
imaging£¨Sidestream dark field imaging (SDF),visualize
the microcirculation at the bedside,clinical
microcirculation£©, the studies have shown alterations at microcirculatory
level in various pathophysiological states in neonates. Although
it is the sublingual re¬gion commonly used for observing of the
mi¬crocirculation in adults, the most frequently used site for
assessment in pediatric patients is the skin [9, 10, 15] or
buccal mucosa. [4, 11-14] Genzel-Boroviczeny et al. focused on
observing the microcirculation transcuta¬neously, provided first
quantitative microvas¬cular parameters in neonates using OPS
im¬aging and proved its use as a safe noninva¬sive tool in
children. The study group has al¬so published data on changes in
erythrocyte blood flow according to hemoglobin levels in the
first days after birth [9], further re¬search showed changes in
microcirculation after therapeutic transfusion. [10] The
obser¬vation of the sublingual area that is the most frequently
used for the assessment of the mi¬crocirculation in adult
patients is however not easy to do in children. The sublingual
re¬gion is difficult to access due to the size of the probe, the
examination itself is not very well tolerated and there are also
sequence artefacts because of the great amount of sali¬va in the
mouth. Transcutaneous observation of the microcirculation using
OPS/SDF imaging£¨Sidestream dark field imaging (SDF),visualize
the microcirculation at the bedside,clinical
microcirculation£© is only possible to be performed in new¬borns
and infants, in older children the measurement is limited
because the skin is thicker and the microcirculation has a more
adult pattern. [11] Top et al. have published studies on the use
of the technique in criti¬cally ill neonates as well as in
infants and older children. They have observed the buc¬cal
mucosa which shares the common em¬bryogenic origin with the
splanchnic mu¬cosa, the group focused on children up to 15 years
and reported that there are similar al¬terations on buccal
mucosa in septic pedi¬atric patients. [11] The microvascular
re¬sponse to extracorporeal membrane oxy¬genation (ECMO) of
critically ill infants with respiratory distress was
investigated in fur¬ther studies and proved microcirculatory
al¬terations (reduced FCD) in ill infants in com¬parison with a
control group. [12] In a more recent paper Top et al. showed the
effect of inhaled NO in infants with persistent pul¬monary
hypertension and proved that in¬haled NO positively affects the
microcirculation£¨Sidestream dark field imaging (SDF),visualize
the microcirculation at the bedside,clinical
microcirculation£©. [13] Hiedl et al. investigated the
differ¬ences in microcirculatory parameters in preterm infants
with hemodynamically sig¬nificant persistent ductus arteriosus
(PDA) in comparison with preterm infants without PDA and found
that these changes disap¬peared after therapeutic intervention.
[14]
Conclusion
Tissue oxygenation and homeostasis are es¬sential for every
living cell and depend on microvascular perfusion. OPS/SDF
imaging£¨Sidestream dark field imaging (SDF),visualize
the microcirculation at the bedside,clinical
microcirculation£© allow direct visualisation of the microcircula¬tion and
even though the studies have so far focused mainly on adult
patients, there have been several medical papers lately that
showed its use in pediatric intensive care, in particular in
neonatology. The main differ¬ence for the observation in
pediatrics is the area for the investigation. Most study groups
observed the microcirculation of the skin, only Top et al. used
the buccal mucosa. There have been published data mainly on
microcirculatory parameters of preterm in¬fants with
pre-existing disease but physiolog¬ical microvascular parameters
have not been widely reported yet. The physiology of the
microcirculation in neonates might have an importance for
further studies. The field of the clinical research in
microcirculation is open and suggests several new directions.
The methods have some limitations but if the development of
technology enables online analysis, OPS/SDF imaging£¨Sidestream dark field imaging (SDF),visualize
the microcirculation at the bedside,clinical
microcirculation£© might help
the clinicians to start early and effectively target¬ed therapy.
Acknowledgements
The research was funded by the Institutional program of the
University Hospital Hradec Kr¨¢lov¨¦.
References
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