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REVIEW

CURRENT
OPINION Lactate and microcirculation as suitable targets
for hemodynamic optimization in resuscitation
of circulatory shock
Michael E. Kiyatkin a and Jan Bakker b,c,d,e

Purpose of review
A discussion of recent research exploring the feasibility of perfusion-guided resuscitation of acute
circulatory failure with a focus on lactate and microcirculation.
Recent findings
Upon diagnosis of shock, hyperlactemia is associated with poor outcome and, under appropriate clinical
circumstances, may reflect inadequate tissue perfusion. Persistent hyperlactemia despite resuscitation is
even more strongly correlated with morbidity and mortality. Importantly, there is minimal coherence
between lactate trends and static hemodynamic measures such as blood pressure, especially after the
initial, hypovolemic phase of shock. During this early period, lactate guided-resuscitation is effective and
possibly superior to hemodynamic-guided resuscitation. Similar to hyperlactemia, impaired microcirculation
is ubiquitous in shock and is evident even in the setting of hemodynamic compensation (i.e., occult shock).
Moreover, persistent microcirculatory derangement is associated with poor outcome and may reflect
ongoing shock and/or long-lasting damage. Although the wait continues for a microcirculation-guided
resuscitation trial, there is progress toward this goal.
Summary
Although questions remain, a multimodal perfusion-based approach to resuscitation is emerging with
lactate and microcirculation as core measures. In this model, hyperlactemia and microcirculatory
derangement support the diagnosis of shock, may help guide resuscitation during the initial period, and
may reflect resuscitation efficacy and iatrogenic harm (e.g., fluid overload).
Keywords
lactate, microcirculation, shock

INTRODUCTION compensation. Second, resuscitation aimed at nor-

In spite of decades of research, treatment of acute malization of MAP, CO, and central venous pressure
circulatory failure remains challenging. This is due (CVP) is increasingly recognized as contributory to
&&

in large part to the inability to clearly monitor tissue
perfusion. As inadequate perfusion is pathogno-
monic of shock, this limitation is a major obstacle
in patient care. Traditionally, therapeutic interven-
tions such as fluid resuscitation were targeted to
improve static, global hemodynamic parameters
such as mean arterial pressure (MAP) and cardiac
output (CO). These parameters are relatively easy to
measure with good accuracy and precision and were
considered the primary determinants, and therefore
good surrogates, of organ perfusion. This reliance on
&
MAP and CO continues to this day [1 ]. There is a
growing consensus; however, that macrohemody-
namic parameters are in fact poorly reflective of
tissue perfusion [2]. First, changes in hemodynamic
values may be masked by catecholamine-driven
harmful fluid overload [3 ]. In place of these
a
Department of Anesthesiology, bDivision of Pulmonary, Allergy, and
Critical Care Medicine, Department of Medicine, Columbia University
Medical Center, NewYork-Presbyterian Hospital, cDepartment of Pul-
monary and Critical Care, Langone Medical Center-Bellevue Hospital,
New York University, New York, New York, USA, dDepartment of Intensive
Care Adults, Erasmus MC University Medical Center, Rotterdam, The
Netherlands and eFacultad de Medicina, Pontificia Universidad Catolica
de Chile, Santiago, Chile
Correspondence to Jan Bakker, Division of Pulmonary, Allergy, and
Critical Care Medicine, Department of Medicine, Columbia University
Medical Center, NewYork-Presbyterian Hospital, 622 West 168th St.,
Room PH 8109, New York, NY 10032, USA. Tel: +1 917 208 7648;
e-mail: jb3387@cumc.columbia.edu
Curr Opin Crit Care 2017, 23:000000
DOI:10.1097/MCC.0000000000000423

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KEY POINTS
 Persistent hyperlactemia and microcirculatory
derangement are characteristic of acute circulatory
failure and are associated with poor outcome.
 During resuscitation of shock and especially after the
initial, hypovolemic phase, there is minimal coherence
between static hemodynamic measures such as blood
pressure and serum lactate or
peripheral microcirculation.
 Studies continue to demonstrate efficacy of lactate
guided-resuscitation during the initial 68-h period after
diagnosis of shock.
 Although the wait continues for a microcirculation-
guided resuscitation trial, there is progress toward
this goal.
traditional parameters, there is growing interest in
more direct measures of tissue perfusion such serum
lactate and peripheral tissue microcirculation. In
this review, we highlight recent studies that support
multimodal perfusion-guided resuscitation of acute
circulatory failure, with a focus on lactate and
microcirculation monitoring.
HYPERLACTEMIA IN EARLY SHOCK IS
ASSOCIATED WITH POOR OUTCOME AND
MAY REFLECT INADEQUATE TISSUE
PERFUSION
There continues to be no question that hyperlacte-
mia more than 2 and especially more than 4 mmol/l
at the time of shock diagnosis is associated with
increased morbidity and mortality [49]. This
association may reflect inadequate perfusion. This
also supports hyperlactemia as an important warn-
ing sign of shock that should prompt expanded
resuscitation.
Persistent hyperlactemia, despite several hours
of resuscitation, is even more strongly associated
with poor outcome. Many groups have demon-
strated in septic and cardiogenic shock that persist-
ent hyperlactemia more than 2 mmol/l after 624 h
of resuscitation, rather than initial hyperlactatemia,
was associated with elevated morbidity and
mortality. During resuscitation of either form of
shock, a reduction in lactate levels of more than
2060% by 624 h predicted lower mortality [10
15]. Even in studies in which admission hyperlacte-
mia more than 24 mmol/l was indeed associated
with higher mortality, persistent hyperlactemia
beyond 24 h had an even stronger association with
poor outcome [4,8]. Exploring this further, a post-
hoc analysis of the FINNAKI trial revealed greater
2 www.co-criticalcare.com
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mortality with an admission lactate more than
2 mmol/l only in univariate but not multivariate
analysis, with a clear association between mortality
and persistent hyperlactemia for more than 72 h
&
[16 ]. A meta-analysis of various forms of circulatory
shock similarly demonstrated a survival benefit of
&
improved hyperlactemia over 624 h [17 ]. These
and previous studies have contributed to the incorp-
oration of hyperlactemia more than 2 mmol/l
despite adequate fluid resuscitation into the
Sepsis-3 diagnostic criteria [18].
HYPERLACTEMIA IS CORRELATED
WITH ABNORMAL HEMODYNAMIC
PARAMETERS ONLY DURING THE INITIAL
PHASE OF SHOCK
The relationship between lactate and systemic
hemodynamic parameters during circulatory shock
is puzzling. On the one hand, they appear to be
incoherent. For example, whereas a reduction in
lactate during treatment of septic shock is associated
with improved mortality, an elevation in MAP, CVP,
and ScvO2 are not [10]. In fact, secondary analysis of
the ARISE trial for the treatment of septic shock
revealed that isolated hyperlactemia more than
4.0 mmol/l without hypotension, but not vice versa,
was associated with increased morbidity and
&
mortality [19 ]. Moreover, there was no difference
in lactate concentrations in septic shock patients
resuscitated to either normodynamic or hyperdy-
namic states [14]. On the other hand, others have
noted that both hyperlactemia more than
2.0 mmol/l and MAP less than 65 mmHg at the onset
of septic shock and after 24 h of resuscitation were
independent predictors of mortality, although cor-
relation between the two was not explored [4].
Several explanations have been put forth for
& && && &
these discrepancies [20 ,21 ,22 ,23 ]. It appears
that during the initial, hypovolemic phase of shock,
hyperlactemia does indeed parallel poor systemic
hemodynamics. In these circumstances, fluid resus-
citation improves both. However, this hemody-
namic coherence and fluid sensitivity rapidly
disappears, severely limiting the utility of hemody-
&
namic-based resuscitation protocols [23 ].
RESUSCITATION OF SHOCK TARGETING
AN INCREMENTAL DECREASE IN LACTATE
IS EFFECTIVE, AT LEAST DURING THE
EARLY PHASE
Given the above, it is clear why lactate is an attrac-
tive clinical parameter for guiding resuscitation.
Randomized control trials incorporating lactate
are continuing with encouraging results. One such
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Lactate and microcirculation as suitable targets Kiyatkin and Bakker
trial in septic shock patients compared early goal-
directed therapy with a modified protocol replacing
ScvO2 monitoring with a graded venous lactate
reduction protocol (10% by 2 h, 20% by 4 h, and
30% by 6 h). Although patients in the lactate-guided
group received more fluid, they experienced lower
&&
morbidity and mortality over 60 days [24 ]. This
parallels the findings of previous lactate-guided
&& &&
resuscitation trials [25 ,26 ]. Studies have so far
limited lactate-guided resuscitation to the initial,
acute phase of shock, typically 68 h after diagnosis.
The reasons for this are multiple. As discussed above,
the correlation between persistent hyperlactemia
and mortality is strongest during the initial period.
As clarified later in this article, in the subacute phase
of shock, lactate normalization slows and becomes
multifactorial, with continued lactate-guided resus-
citation potentially leading to fluid overload
& && && &
[20 ,21 ,22 ,23 ].
IMPAIRED MICROCIRCULATION IS
UNIVERSAL IN SHOCK AND IS PRESENT
EVEN WHEN GLOBAL HEMODYNAMICS
ARE COMPENSATED
With the onset of shock, the microcirculation shows
clear evidence of dysfunction even in the absence of
any changes in static hemodynamic parameters (i.e.,
occult shock). For example, during the first 6 h of
septic shock resuscitation, it was noted that the
severity of sublingual microcirculatory impairment
was not correlated with any decreases in MAP, CO,
or mixed venous oxygen saturation (SmvO2) [27].
Furthermore, after 24 h of resuscitation, patients
with normodynamic septic shock were found to
have equivalent, abnormal microcirculation as
patients in a hyperdynamic state [14]. In an animal
model of septic shock, a dobutamine infusion
during the first 2 h of resuscitation significantly
improved sublingual and small bowel mucosal
microcirculation with a parallel decrease in lactate
but had no change in CO, MAP, CVP, or SmvO2 [28].
In patients with hemorrhagic shock, blood trans-
fusion within 12 h likewise improved microcircula-
tory parameters without affecting MAP, CO, or
lactate [29]. In cardiogenic shock, there were no
significant differences in hemodynamics or lactate
at the time of initiation of mechanical support
between survivors and nonsurvivors despite signifi-
cant differences in their microcirculatory profiles
[30]. In certain circumstances, however, hemody-
namic coherence is indeed observed. For example, it
was demonstrated that fluid challenge in septic
shock patients improved microcirculation together
with CO and hyperlactemia but only within the first
24 h of resuscitation [31,32]. In an animal model of
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hemorrhagic shock, sublingual microcirculatory
abnormalities developed rapidly and were associ-
ated with low CO and MAP as well as elevated
lactate. Over a 3-h resuscitation course, however,
CO and MAP gradually normalized despite the
persistence of aberrant microcirculation and
hyperlactemia [33]. In summary, microcirculatory
derangement may parallel abnormal hemodynam-
ics in the initial period, is an exquisitely sensitive
marker of acute circulatory failure, and should lower
the threshold for expanding resuscitation.
PERSISTENT MICROCIRCULATORY
DERANGEMENT IN SHOCK IS
ASSOCIATED WITH POOR OUTCOME
As with persistent hyperlactemia, evidence contin-
ues to mount that persistent microcirculatory
derangement is associated with increased morbidity
and mortality. In septic shock patients, for example,
persistent abnormalities in capillary perfusion of
skin and sublingual mucosa 2472 h after the
initiation of resuscitation was found to be associated
with elevated sequntial organ failure (SOFA) scores,
a more positive fluid balance, greater vasopressor
use, higher lactate concentrations, and increased
mortality [14,34]. This is consistent with an earlier
study in pediatric septic shock patients that revealed
equally impaired microcirculation in survivors
and nonsurvivors after 24 h of resuscitation but
improved microcirculation only in survivors by
Day 2 and especially by Day 3, with nonsurvivors
exhibiting persistent impairments in their micro-
circulation [35]. Comparing lactate and microcircu-
lation, both of which are excellent prognostic
markers, a recent study in septic shock patients
revealed that combined hyperlactemia more than
4 mmol/l and hypoperfusion after 24 h was associ-
ated greater morbidity and mortality than equival-
ent hyperlactemia but normal peripheral perfusion
&
[36 ]. In adult cardiogenic shock patients, abnormal
sublingual microcirculation at the initiation of
veno-arterial Extra Corporeal Membrane Oxygen-
ation support was likewise found to be a strong
predictor of mortality [30]. This further supports
the value of microcirculation monitoring.
PERSISTENT MICROCIRCULATORY
ABNORMALITIES DESPITE EFFECTIVE
RESUSCITATION MAY REFLECT
LONG-LASTING INJURY
Although microcirculatory derangement is ubiqui-
tous, ominous, and may on occasion mirror abnor-
mal hemodynamics during the initial hypovolemic
phase of shock, the microcirculation becomes more
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difficult to interpret in the subacute period (>24 h).
Systemic hemodynamics typically normalize,
whereas microcirculatory parameters either normal-
ize concurrently reflecting shock resolution [37] or
persist for several days indicating long-lasting ische-
mic damage, continued shock, or iatrogenic injury
& &&
(e.g., fluid overload) [23 ,38,39 ]. For example, in
one study in septic shock, abnormal skin micro-
circulation was correlated with elevated lactate
but only at the time of diagnosis, losing correlation
2472 h after initiation of resuscitation with lactate
largely normalizing, suggesting shock resolution,
whereas microcirculation remained abnormal [34].
Conversely, in another group of septic shock
patients with persistent hyperlactemia despite
48 h of treatment, fluid loading improved hemody-
namic parameters but had no effect either on lactate
levels or the microcirculation, suggesting continued
shock [32]. Some have argued that this late, fluid-
insensitive state makes microcirculation better
suited for evaluating organ dysfunction than guid-
&&
ing resuscitation [39 ]. Others have countered that
because microcirculation monitoring is uniquely
able to distinguish patterns of shock such as gener-
alized low flow state or heterogeneous capillary
blood flow, this technique may caution against
further fluid administration and suggest more tar-
geted therapies such as nitroglycerin and inotropes
[38,40]. Moreover, as noted above, when microcir-
culation is paired with other perfusion parameters
such as lactate, this fluid-insensitivity may in fact
argue against any further fluid administration,
which may only improve vital signs while causing
harmful fluid overload. In other words, microcircu-
latory monitoring can help diagnose occult shock
and both guide and limit resuscitation in the acute
as well as subacute periods.
CONTINUED WAIT FOR A
MICROCIRCULATION-GUIDED
RESUSCITATION TRIAL
Although lactate-guided resuscitation has already
been evaluated in multiple randomized controlled
trials, we are still waiting for an equivalent study
incorporating microcirculation. Without such a
study, postulating about grand resuscitation strat-
egies will remain in the realm of research rather than
at the bedside in which it desperately belongs. A
microcirculation trial is inevitable as dark field
microscopes become more widespread and auto-
mated analyses improve. Although we eagerly await
this trial, progress continues toward this goal. One
promising, ongoing study is the MICROSHOCK
trial, which recently demonstrated the feasibility
and safety of sublingual imaging in traumatic
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hemorrhagic shock patients presenting to the emer-
&
gency room [41 ]. Although not utilizing dark field
microscopy, other measures of peripheral perfusion
such as capillary refill time (CRT) were recently
compared against traditional hemodynamics in a
goal-directed trial for septic shock. Less morbidity
was noted when fluid resuscitation was guided by a
combination of peripheral perfusion measures
&&
[42 ].
CAVEATS TO LACTATE-GUIDED AND
MICROCIRCULATION-GUIDED
RESUSCITATION
With respect to monitoring serum lactate, studies
continue to highlight the complexity of lactate
metabolism and the need to interpret hyperlactemia
with caution. In a septic shock sheep model, for
example, esmolol and dexmedetomidine infusions
during resuscitation lowered endogenous lactate
levels and enhanced clearance of exogenous lactate
without affecting CO [43]. This agrees with a previous
clinical study showing lower admission lactate con-
centrations in septic shock patients on -blocker
&
therapy [44 ]. This cautions against the common
misconception that lactate is simply a metabolic
byproduct of glycolysis, and thus a marker of dysoxia.
In reality, hyperlactemia is not clearly associated with
decreased delivery of oxygen; rather, it is a key glu-
coneogenic precursor whose production is enhanced
by adrenergic drive and exogenous catecholamines,
and its serum concentration may be elevated from
reduced hepatic clearance due to ischemia or even
the sepsis toxicosis itself [45].
Although a clearer picture of microcirculatory
changes during shock is emerging, there remain a
number of concerns. Perhaps the Achilles Heel of this
technique, rapid and reliable quantification of dark
field microscopy, the most modern technique for
measuring microcirculation, remains challenging.
The latest generation of automated algorithms for
analyzing data remain unreliable and inaccurate
compared with traditional, manual evaluation
[46,47]. However, this will surely improve as the
algorithms are developed further. Another possibility
is the development of a simpler grading system, for
example, the 5-point point of care microcirculation
score, which requires only 2 min for calculation
with good interrater consistency and agreement with
traditional 45-min-long analysis [48 ]. Conversely,
&
this may prove irrelevant and microcirculation
monitoring may evolve into a multipurpose tech-
nique akin to echocardiography, with minimally
skilled operators deducing basic yet important infor-
mation and highly skilled able to obtain more
detailed data. Another continued concern is the
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Lactate and microcirculation as suitable targets Kiyatkin and Bakker
FIGURE 1. A putative triangular basis of circulatory shock.
As hypothesized by Vincent et al. in their tribute to Prof Max
Harry Weil [55], the full clinical picture of shock includes
three features: hypotension, altered tissue perfusion, and
hyperlactatemia, all of which originate from underlying
microcirculatory disturbances. However, this presentation is
often incomplete. Adapted from [55].
relevance of the most common monitoring site the
sublingual region. This is commonly monitored
because it is readily accessible and the bulk of data,
including recent studies [49,50], support a close cor-
relation of sublingual, intestinal mucosal, and con-
junctival microcirculation, suggesting a common
sympathetic vasoconstrictor mechanism.
Other concerns that should be addressed before
adopting lactate-guided and/or microcirculation-
guided resuscitation include significant study hetero-
geneity and the relationship of these promising strat-
egies with other perfusion-based techniques such as
CRT. As illustrated above, the literature is unfortu-
nately riddled with heterogeneity, including failure
to distinguish hyperdynamic from normodynamic
septic shock, evaluation of shock at different stages of
resuscitation, use of different animal models, and use
of nonstandardized diagnoses and resuscitation pro-
tocols [51]. Moreover, there are other promising,
technically simpler perfusion parameters, including
CRT and tissue Pv-aCO2, a combination of which
& &&
may prove highly informative [36 ,42 ,5254].
CONCLUSION
Acute circulatory failure remains difficult to treat [18].
Because shock is defined by inadequate tissue per-
fusion, lactate and microcirculation hold great
promise as resuscitation monitors. Progress continues
in this direction, and an era of perfusion-guided
resuscitation may be near (Fig. 1). Specifically, hyper-
lactemia and microcirculatory derangement may
support the diagnosis of shock and guide resuscita-
tion during the initial period. By 24 h, persistent
hyperlactemia and abnormal microcirculation may
indicate continued shock and prompt expanded
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treatment. Microcirculation monitoring may
additionally provide information about the mechan-
ism of shock. This, of course, must be paired with
treatment of the underlying cause. Moreover, no
protocol, however well supported, can fully replace
the judgement and repeated re-evaluation of an
experienced and skeptical clinician.
Acknowledgements
None.
Financial support and sponsorship
None.
Conflicts of interest
There are no conflicts of interest.
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6 www.co-criticalcare.com
Copyright 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
26. Jansen TC, van Bommel J, Schoonderbeek FJ, et al. Early lactate-guided
&& therapy in intensive care unit patients a multicenter, open-label, randomized
controlled trial. Am J Respir Crit Care Med 2010; 182:752761.
This is an early and important lactate-guided resuscitation trial in a mixed cohort of
circulatory shock patients. Morbidity and mortality were significantly lower when
the therapeutic algorithm targeted a reduction in lactate versus an improvement in
static hemodynamic parameters.
27. Ospina-Tascon GA, Umana M, Bermudez WF, et al. Can venous-to-arterial
carbon dioxide differences reflect microcirculatory alterations in patients with
septic shock? Intensive Care Med 2016; 42:211221.
28. Ospina-Tascon GA, Garcia Marin AF, Echeverri GJ, et al. Effects of dobutamine
on intestinal microvascular blood flow heterogeneity and oxygen extraction
during septic shock. J Appl Physiol (1985) 2017. [Epub ahead of print]
29. Tanaka S, Escudier E, Hamada S, et al. Effect of RBC transfusion on
sublingual microcirculation in hemorrhagic shock patients: a pilot study. Crit
Care Med 2017; 45:e154e160.
30. Kara A, Akin S, Dos Reis Miranda D, et al. Microcirculatory assessment of
patients under VA-ECMO. Crit Care 2016; 20:344.
31. Pottecher J, Deruddre S, Teboul JL, et al. Both passive leg raising and intravas-
cular volume expansion improve sublingual microcirculatory perfusion in severe
sepsis and septic shock patients. Intensive Care Med 2010; 36:18671874.
32. Ospina-Tascon G, Neves AP, Occhipinti G, et al. Effects of fluids on
microvascular perfusion in patients with severe sepsis. Intensive Care Med
2010; 36:949955.
33. Hutchings SD, Naumann DN, Watts S, et al. Microcirculatory perfusion shows
wide inter-individual variation and is important in determining shock reversal
during resuscitation in a porcine experimental model of complex traumatic
hemorrhagic shock. Intensive Care Med Exp 2016; 4:17.
34. Sturm T, Leiblein J, Schneider-Lindner V, et al. Association of microcirculation,
macrocirculation, and severity of illness in septic shock: a prospective observa-
tional study to identify microcirculatory targets potentially suitable for guidance
of hemodynamic therapy. J Intensive Care Med 2016. [Epub ahead of print]
35. Top AP, Ince C, de Meij N, et al. Persistent low microcirculatory vessel density in
nonsurvivors of sepsis in pediatric intensive care. Crit Care Med 2011; 39:813.
36. Alegria L, Vera M, Dreyse J, et al. A hypoperfusion context may aid to interpret
& hyperlactatemia in sepsis-3 septic shock patients: a proof-of-concept study.
Ann Intensive Care 2017; 7:29.
This is a very informative retrospective study in septic shock patients comparing
the prognostic ability of hyperlactemia with and without hypoperfusion defined by
ScvO2 less than 70% or Pc(v-a)CO2 at least 6 mmHg. The presence of hypo-
perfusion in addition to hyperlactemia predicted greater vasopressor requirement,
prolonged mechanical ventilation, longer ICU stay, more rescue therapies, and
greater mortality. This study highlights both the complexities of interpreting
hyperlactemia in isolation and the utility of additional perfusion monitors, possibly
together as a multimodal monitoring strategy.
37. Hernandez G, Luengo C, Bruhn A, et al. When to stop septic shock resuscita-
tion: clues from a dynamic perfusion monitoring. Ann Intensive Care 2014; 4:30.
38. Ince C, Guerci P. Why and when the microcirculation becomes disassociated
from the macrocirculation. Intensive Care Med 2016; 42:16451646.
39. Hernandez G, Teboul JL. Is the macrocirculation really dissociated from the
&& microcirculation in septic shock? Intensive Care Med 2016; 42:16211624.
This is a thought-provoking editorial questioning the clinical relevance of micro-
circulatory abnormalities. The authors argue that in the acute phase of shock,
microcirculatory changes frequently parallel and are redundant to standard of care
macrohemodynamic parameters. In the subacute phase, however, persistent
microcirculatory changes are often resistant to fluid administration. The authors
argue that these observations call into question the utility of microcirculation
monitoring in everyday clinical practice. These valid concerns are addressed by an
excellent response [38].
40. Ince C. Hemodynamic coherence and the rationale for monitoring the micro-
circulation. Crit Care 2015; 19 (Suppl 3):S8.
41. Naumann DN, Mellis C, Smith IM, et al. Safety and feasibility of sublingual
& microcirculation assessment in the emergency department for civilian and
military patients with traumatic haemorrhagic shock: a prospective cohort
study. BMJ Open 2016; 6:e014162.
This is a preliminary report on the feasibility of a major ongoing clinical trial
evaluating the utility of microcirculation monitoring in the resuscitation of traumatic
hemorrhagic shock. Sublingual monitoring of microcirculation was shown to be
safe and practical even in an emergency situation.
42. van Genderen ME, Engels N, van der Valk RJ, et al. Early peripheral perfusion-
&& guided fluid therapy in patients with septic shock. Am J Respir Crit Care Med
2015; 191:477480.
This is a very important proof-of-concept clinical trial in septic shock patients
comparing standard hemodynamic-directed therapy with a multimodal perfusion
evaluation-directed protocol incorporating capillary refill time, peripheral perfusion
index, forearm-to-fingertip body temperature gradient, and tissue oxygenation
saturation. Patients who were resuscitated according to peripheral perfusion
markers received less fluid and had shorter hospital stays and lower SOFA scores.
Although not evaluating the more advanced and informative sublingual microcir-
culation dark-field microscopy technique, this study supports the utility of perfusion
monitoring and provides a framework for future microcirculation studies.
43. Hernandez G, Tapia P, Alegria L, et al. Effects of dexmedetomidine and
esmolol on systemic hemodynamics and exogenous lactate clearance in early
experimental septic shock. Crit Care 2016; 20:234.
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Lactate and microcirculation as suitable targets Kiyatkin and Bakker
44. Contenti J, Occelli C, Corraze H, et al. Long-term beta-blocker therapy
& decreases blood lactate concentration in severely septic patients. Crit Care
Med 2015; 43:26162622.
This very interesting retrospective study in septic shock patients revealed an
association between lower blood lactate concentration and -blocker therapy
regardless of a particular patients SOFA score. Although there was heterogeneity
between the two patient groups (e.g., less heart failure in the -blocker group), this
study clearly highlights the important metabolic role of lactate and the danger of
simplistically associating hyperlactemia with dysoxia.
45. Garcia-Alvarez M, Marik P, Bellomo R. Sepsis-associated hyperlactatemia.
Crit Care 2014; 18:503.
46. Arnemann PH, Hessler M, Kampmeier T, et al. Comparison of an automatic
analysis and a manual analysis of conjunctival microcirculation in a sheep
model of haemorrhagic shock. Intensive Care Med Exp 2016; 4:37.
47. Carsetti A, Aya HD, Pierantozzi S, et al. Ability and efficiency of an automatic
analysis software to measure microvascular parameters. J Clin Monit Comput
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48. Naumann DN, Mellis C, Husheer SL, et al. Real-time point of care micro-
& circulatory assessment of shock: design, rationale and application of the point
of care microcirculation (POEM) tool. Crit Care 2016; 20:310.
This is an interesting article addressing one of the major limitations of microcirculation
monitoring the labor-intensive interpretation of microscopy videos. This is often cited
as the major hindrance to the incorporation of this technique into everyday clinical
practice. Although one approach is to automate this process [46,47], another approach
is to develop faster and simpler data interpretation tools, as explored in this article.
1070-5295 Copyright 2017 Wolters Kluwer Health, Inc. All rights reserved.
Copyright 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
49. Yin L, Yang Z, Yu H, et al. Changes in sublingual microcirculation is closely
related with that of bulbar conjunctival microcirculation in a rat model of
cardiac arrest. Shock 2016; 45:428433.
50. de Bruin AF, Kornmann VN, van der Sloot K, et al. Sidestream dark field
imaging of the serosal microcirculation during gastrointestinal surgery. Color-
ectal Dis 2016; 18:O103O110.
51. Kavanagh BP, Nurok M. Standardized intensive care. Protocol misalign-
ment and impact misattribution. Am J Respir Crit Care Med 2016;
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52. Ospina-Tascon GA, Bautista-Rincon DF, Umana M, et al. Persistently
high venous-to-arterial carbon dioxide differences during early resusci-
tation are associated with poor outcomes in septic shock. Crit Care
2013; 17:R294.
53. Jakob SM, Groeneveld AB, Teboul JL. Venousarterial CO2 to arterial
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54. Mesquida J, Saludes P, Gruartmoner G, et al. Central venous-to-arterial
carbon dioxide difference combined with arterial-to-venous oxygen
content difference is associated with lactate evolution in the hemody-
namic resuscitation process in early septic shock. Crit Care 2015;
19:126.
55. Vincent JL, Ince C, Bakker J. Clinical review: circulatory shock an update: a
tribute to Professor Max Harry Weil. Crit Care 2012; 16:239.
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