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920 March 2013 Volume 41 Number 3

This work and investigation sure to follow will undoubtedly
provide new insights into the pathophysiology of sepsis and
the potential for a novel therapeutic target.
1. Martin GS, Mannino DM, Eaton S, et al: The epidemiology of sepsis in the
United States from 1979 through 2000. N Engl J Med 2003; 348:1546
2. Dellinger RP, Levy MM, Carlet JM, et al: Surviving Sepsis Campaign:
International guidelines for management of severe sepsis and septic
shock. Crit Care Med 2008; 36:295327
3. Vincent JL, Opal SM, Marshall JC: Ten reasons why we should NOT
use severity scores as entry criteria for clinical trials or in our treat-
ment decisions. Crit Care Med 2010; 38:283287
4. Pierrakos C, Vincent JL: Sepsis biomarkers: A review. Crit Care 2010;
5. Janz DR, Bastarache JA, Peterson JF: Association Between Cell-Free
Hemoglobin, Acetaminophen, and Mortality in Patients With Sepsis:
An Observational Study. Crit Care Med 2013; 41:784790
6. Larsen R, Gozzelino R, Jeney V, et al: A central role for free heme in
the pathogenesis of severe sepsis. Sci Transl Med 2010; 2:51ra71
7. Reiter CD, Wang X, Tanus-Santos JE, et al: Cell-free hemoglobin lim-
its nitric oxide bioavailability in sickle-cell disease. Nat Med 2002;
8. Boutaud O, Moore KP, Reeder BJ, et al: Acetaminophen inhibits
hemoprotein-catalyzed lipid peroxidation and attenuates rhabdomyol-
ysis-induced renal failure. Proc Natl Acad Sci USA 2010; 107:2699
9. Rivers E, Nguyen B, Havstad S, et al; Early Goal-Directed Therapy
Collaborative Group: Early goal-directed therapy in the treatment of
severe sepsis and septic shock. N Engl J Med 2001; 345:1368
10. Gaieski DF, Mikkelsen ME, Band RA, et al: Impact of time to antibiot-
ics on survival in patients with severe sepsis or septic shock in whom
early goal-directed therapy was initiated in the emergency depart-
ment. Crit Care Med 2010; 38:10451053
11. Lee BH, Inui D, Suh GY, et al; Fever and Antipyretic in Critically ill pa-
tients Evaluation (FACE) Study Group: Association of body tempera-
ture and antipyretic treatments with mortality of critically ill patients
with and without sepsis: Multi-centered prospective observational
study. Crit Care 2012; 16:R33
e Backer et al describe the value of assessing sublin-
gual microcirculation for estimating the outcome in
patients with severe sepsis in this issue of Critical Care
Medicine (1). Microvascular dysfunction seems to be the key
element of the pathogenesis of septic shock. The causes of this
dysfunction may lie in the occurrence of generalized micro-
vascular thrombosis (2). This thrombosis may prevent bacteria
in the tissues from trafcking to the systemic circulation via
the capillaries. However, when this microvascular thrombo-
sis is generalizing, microvascular dysfunction with extensive
tissue ischemia may result in organ failure and even death.
On the other hand, global hemodynamic parameters are de-
ranged in patients suffering from septic shock (3). The ques-
tion is whether these global hemodynamic measures are as-
sociated with regional hemodynamics and vice versa. Indeed,
hemodynamic monitoring of septic patients is impeded by the
discrepancy between the macrohemodynamics and the mi-
crocirculation of internal organs. Microcirculation dysfunc-
tion does not correlate with the internal organs circulation
because of the highly heterogeneous micro circulation struc-
ture and function in different sites (4). Furthermore, despite
therapeutic correction of systemic oxygen delivery variables,
regional hypoxia and oxygen extraction decits persist. The
determination of microvascular dysfunction may not only
be a prognostic parameter but also help guiding therapeutic
measures in patients with septic shock.
The development of new technologies such as capillary
microscopy, laser Doppler, intravital videomicroscopy, or-
thogonal polarization spectral (OPS), and sidestream darkeld
imaging (SDF) enabled microcirculation monitoring. The lat-
ter two have been used in the study by De Backer et al (1).
Overall, physicianscientists using one of these possibilities try
to connect micro circulatory imbalance with global hemody-
namic dysfunction and outcome. For instance, tissue oxygen
saturation (StO
) in septic shock patients as measured by tissue
spectroscopy was signicantly lower in the nonsurvivors than
in the survivors. In detail, StO
values < 78% were associated
with increased mortality at day 28 (5). Interestingly, StO
relates with central venous saturation (ScvO
) in normotensive
patients with severe sepsis or septic shock (6). ScvO
with the cardiac index in patients suffering from septic shock
(7). Thus, we can seemingly derive an association between
the microcirculation and a parameter from global hemo-
dynamics from this study. Besides the oxygen tension, tissue
hypercarbia as measured in the ear lobe has also been shown
Has the Cat Got Your Tongue? Evaluation of
Circulation by Microcirculation*
Martijn van Griensven, MD, PhD
Department of Trauma Surgery
Klinikum rechts der Isar
Technical University Munich
Munich, Germany
*See also p. 791.
Key Words: hemodynamics; microcirculation; sepsis; shock; tissue
The author has not disclosed any potential conflicts of interest.
Copyright 2013 by the Society of Critical Care Medicine and Lippincott
Williams & Wilkins
DOI: 10.1097/CCM.0b013e3182770e61
Critical Care Medicine 921
to be correlated with microcirculatory alterations in septic
patients (8). Sublingual capnometry resulted in similar
results (9). Regional microcirculatory blood ow is the main
determinant of sublingual carbon dioxide partial pressure.
No association with systemic carbon dioxide partial pressure
could be detected. Furthermore, during the early phase of re-
suscitated severe sepsis and septic shock, there appears to be
no correlation between sublingual microcirculatory alterations
and the central-to-toe temperature differences (10).
All of the above mentioned methods represent simple,
noninvasive methods to monitor microcirculatory alterations
in septic patients. Most of the studies underline the idea of
a dispersive nature of blood ow under conditions of sepsis
between microcirculatory and systemic hemodynamics. This
is corroborated by the study of De Backer et al (1) using OPS
and SDF sublingual microcirculation imaging. They presented
a large cohort of patients having undergone measurements
of their microcirculation. Unfortunately, the patients were
included in different studies, and the measurements presented
were only performed at the start of the respective studies during
an extended period of time. Therefore, the outcome may not
only depend on early microcirculatory function but also on
interventions performed. Nevertheless, the measurements
are very valuable as pathologic values are shown upon
admission to the ICU. Thus, these methods may be helpful in
determining the status of the patients. Two different methods
of measurement have been usedOPS and SDFwhich can
be discussed as being a disadvantage as well as an advantage.
It may be argued that the results are obtained by different
methods and cannot be compared completely. On the other
hand, although two different methods were used, overall
valid conclusions could be drawn. Thus, it would not make
a difference which method is being used in a clinical setting.
The ndings indicate that microcirculation is dysfunctional
in severe sepsis despite relatively normal global hemodynamic
parameters. Especially the proportion of perfused small vessels
(PPVs) was the most strongly associated with outcome (area
under the curve = 0.818) (1). PPV and lactate levels were
independent determinants of the outcome of severe sepsis in
the early phase. The authors also investigated 48 patients 48 hrs
after onset of severe sepsis. In these patients, PPV alterations
were not as pronounced anymore. Therefore, it is important
to determine the microcirculatory status as early as possible
to be able to prioritize therapy. Microcirculatory recruitment
is needed to ensure adequate microcirculatory perfusion
and the oxygenation of tissue cells. Therapy must include
focused recruitment of hypoxic-shunted microcirculatory
It has been shown that clinical application of these devices is
feasible. It is important that the measurements are readily avail-
able and interpretable without the need of extensive calcula-
tions. In that case, this tool of determining the microcirculatory
status in the sublingual or thenar area will be a valuable piece
in diagnosing and in the prognosis of (severe) sepsis. Especially,
as the microcirculatory status is not reected by global hemo-
dynamic parameters.
1. De Backer D, Donadello K, Sakr Y, et al: Microcirculatory Alterations
in Patients With Severe Sepsis: Impact of Time of Assessment and
Relationship With Outcome. Crit Care Med 2013; 41:791799
2. Dixon B: The role of microvascular thrombosis in sepsis. Anaesth In-
tensive Care 2004; 32:619629
3. Quezado ZM, Natanson C: Systemic hemodynamic abnormalities
and vasopressor therapy in sepsis and septic shock. Am J Kidney
Dis 1992; 20:214222
4. Bateman RM, Sharpe MD, Ellis CG: Bench-to-bedside review: Micro-
vascular dysfunction in sepsishemodynamics, oxygen transport, and
nitric oxide. Crit Care 2003; 7:359373
5. Leone M, Blidi S, Antonini F, et al: Oxygen tissue saturation is lower in
nonsurvivors than in survivors after early resuscitation of septic shock.
Anesthesiology 2009; 111:366371
6. Mesquida J, Masip J, Gili G, et al: Thenar oxygen saturation measured
by near infrared spectroscopy as a noninvasive predictor of low cen-
tral venous oxygen saturation in septic patients. Intensive Care Med
2009; 35:11061109
7. Perner A, Haase N, Wiis J, et al: Central venous oxygen saturation
for the diagnosis of low cardiac output in septic shock patients. Acta
Anaesthesiol Scand 2010; 54:98102
8. Valle F, Mateo J, Dubreuil G, et al: Cutaneous ear lobe Pco at 37C
to evaluate microperfusion in patients with septic shock. Chest 2010;
9. Creteur J, De Backer D, Sakr Y, et al: Sublingual capnometry tracks
microcirculatory changes in septic patients. Intensive Care Med
2006; 32:516523
10. Boerma EC, Kuiper MA, Kingma WP, et al: Disparity between skin
per fusion and sublingual microcirculatory alterations in severe sepsis
and septic shock: A prospective observational study. Intensive Care
Med 2008; 34:12941298