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

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Cardiovascular system

mortality with an admission lactate more than


KEY POINTS 2 mmol/l only in univariate but not multivariate
 Persistent hyperlactemia and microcirculatory analysis, with a clear association between mortality
derangement are characteristic of acute circulatory and persistent hyperlactemia for more than 72 h
&
failure and are associated with poor outcome. [16 ]. A meta-analysis of various forms of circulatory
shock similarly demonstrated a survival benefit of
 During resuscitation of shock and especially after the &
improved hyperlactemia over 624 h [17 ]. These
initial, hypovolemic phase, there is minimal coherence
between static hemodynamic measures such as blood and previous studies have contributed to the incorp-
pressure and serum lactate or oration of hyperlactemia more than 2 mmol/l
peripheral microcirculation. despite adequate fluid resuscitation into the
Sepsis-3 diagnostic criteria [18].
 Studies continue to demonstrate efficacy of lactate
guided-resuscitation during the initial 68-h period after
diagnosis of shock.
HYPERLACTEMIA IS CORRELATED
 Although the wait continues for a microcirculation- WITH ABNORMAL HEMODYNAMIC
guided resuscitation trial, there is progress toward PARAMETERS ONLY DURING THE INITIAL
this goal. PHASE OF SHOCK
The relationship between lactate and systemic
hemodynamic parameters during circulatory shock
traditional parameters, there is growing interest in is puzzling. On the one hand, they appear to be
more direct measures of tissue perfusion such serum incoherent. For example, whereas a reduction in
lactate and peripheral tissue microcirculation. In lactate during treatment of septic shock is associated
this review, we highlight recent studies that support with improved mortality, an elevation in MAP, CVP,
multimodal perfusion-guided resuscitation of acute and ScvO2 are not [10]. In fact, secondary analysis of
circulatory failure, with a focus on lactate and the ARISE trial for the treatment of septic shock
microcirculation monitoring. revealed that isolated hyperlactemia more than
4.0 mmol/l without hypotension, but not vice versa,
was associated with increased morbidity and
HYPERLACTEMIA IN EARLY SHOCK IS &
mortality [19 ]. Moreover, there was no difference
ASSOCIATED WITH POOR OUTCOME AND in lactate concentrations in septic shock patients
MAY REFLECT INADEQUATE TISSUE resuscitated to either normodynamic or hyperdy-
PERFUSION namic states [14]. On the other hand, others have
There continues to be no question that hyperlacte- noted that both hyperlactemia more than
mia more than 2 and especially more than 4 mmol/l 2.0 mmol/l and MAP less than 65 mmHg at the onset
at the time of shock diagnosis is associated with of septic shock and after 24 h of resuscitation were
increased morbidity and mortality [49]. This independent predictors of mortality, although cor-
association may reflect inadequate perfusion. This relation between the two was not explored [4].
also supports hyperlactemia as an important warn- Several explanations have been put forth for
ing sign of shock that should prompt expanded
& && && &
these discrepancies [20 ,21 ,22 ,23 ]. It appears
resuscitation. that during the initial, hypovolemic phase of shock,
Persistent hyperlactemia, despite several hours hyperlactemia does indeed parallel poor systemic
of resuscitation, is even more strongly associated hemodynamics. In these circumstances, fluid resus-
with poor outcome. Many groups have demon- citation improves both. However, this hemody-
strated in septic and cardiogenic shock that persist- namic coherence and fluid sensitivity rapidly
ent hyperlactemia more than 2 mmol/l after 624 h disappears, severely limiting the utility of hemody-
of resuscitation, rather than initial hyperlactatemia,
&
namic-based resuscitation protocols [23 ].
was associated with elevated morbidity and
mortality. During resuscitation of either form of
shock, a reduction in lactate levels of more than RESUSCITATION OF SHOCK TARGETING
2060% by 624 h predicted lower mortality [10 AN INCREMENTAL DECREASE IN LACTATE
15]. Even in studies in which admission hyperlacte- IS EFFECTIVE, AT LEAST DURING THE
mia more than 24 mmol/l was indeed associated EARLY PHASE
with higher mortality, persistent hyperlactemia Given the above, it is clear why lactate is an attrac-
beyond 24 h had an even stronger association with tive clinical parameter for guiding resuscitation.
poor outcome [4,8]. Exploring this further, a post- Randomized control trials incorporating lactate
hoc analysis of the FINNAKI trial revealed greater 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- hemorrhagic shock, sublingual microcirculatory
directed therapy with a modified protocol replacing abnormalities developed rapidly and were associ-
ScvO2 monitoring with a graded venous lactate ated with low CO and MAP as well as elevated
reduction protocol (10% by 2 h, 20% by 4 h, and lactate. Over a 3-h resuscitation course, however,
30% by 6 h). Although patients in the lactate-guided CO and MAP gradually normalized despite the
group received more fluid, they experienced lower persistence of aberrant microcirculation and
&&
morbidity and mortality over 60 days [24 ]. This hyperlactemia [33]. In summary, microcirculatory
parallels the findings of previous lactate-guided derangement may parallel abnormal hemodynam-
&& &&
resuscitation trials [25 ,26 ]. Studies have so far ics in the initial period, is an exquisitely sensitive
limited lactate-guided resuscitation to the initial, marker of acute circulatory failure, and should lower
acute phase of shock, typically 68 h after diagnosis. the threshold for expanding resuscitation.
The reasons for this are multiple. As discussed above,
the correlation between persistent hyperlactemia
and mortality is strongest during the initial period. PERSISTENT MICROCIRCULATORY
As clarified later in this article, in the subacute phase DERANGEMENT IN SHOCK IS
of shock, lactate normalization slows and becomes ASSOCIATED WITH POOR OUTCOME
multifactorial, with continued lactate-guided resus- As with persistent hyperlactemia, evidence contin-
citation potentially leading to fluid overload ues to mount that persistent microcirculatory
& && && &
[20 ,21 ,22 ,23 ]. derangement is associated with increased morbidity
and mortality. In septic shock patients, for example,
persistent abnormalities in capillary perfusion of
IMPAIRED MICROCIRCULATION IS skin and sublingual mucosa 2472 h after the
UNIVERSAL IN SHOCK AND IS PRESENT initiation of resuscitation was found to be associated
EVEN WHEN GLOBAL HEMODYNAMICS with elevated sequntial organ failure (SOFA) scores,
ARE COMPENSATED a more positive fluid balance, greater vasopressor
With the onset of shock, the microcirculation shows use, higher lactate concentrations, and increased
clear evidence of dysfunction even in the absence of mortality [14,34]. This is consistent with an earlier
any changes in static hemodynamic parameters (i.e., study in pediatric septic shock patients that revealed
occult shock). For example, during the first 6 h of equally impaired microcirculation in survivors
septic shock resuscitation, it was noted that the and nonsurvivors after 24 h of resuscitation but
severity of sublingual microcirculatory impairment improved microcirculation only in survivors by
was not correlated with any decreases in MAP, CO, Day 2 and especially by Day 3, with nonsurvivors
or mixed venous oxygen saturation (SmvO2) [27]. exhibiting persistent impairments in their micro-
Furthermore, after 24 h of resuscitation, patients circulation [35]. Comparing lactate and microcircu-
with normodynamic septic shock were found to lation, both of which are excellent prognostic
have equivalent, abnormal microcirculation as markers, a recent study in septic shock patients
patients in a hyperdynamic state [14]. In an animal revealed that combined hyperlactemia more than
model of septic shock, a dobutamine infusion 4 mmol/l and hypoperfusion after 24 h was associ-
during the first 2 h of resuscitation significantly ated greater morbidity and mortality than equival-
improved sublingual and small bowel mucosal ent hyperlactemia but normal peripheral perfusion
&
microcirculation with a parallel decrease in lactate [36 ]. In adult cardiogenic shock patients, abnormal
but had no change in CO, MAP, CVP, or SmvO2 [28]. sublingual microcirculation at the initiation of
In patients with hemorrhagic shock, blood trans- veno-arterial Extra Corporeal Membrane Oxygen-
fusion within 12 h likewise improved microcircula- ation support was likewise found to be a strong
tory parameters without affecting MAP, CO, or predictor of mortality [30]. This further supports
lactate [29]. In cardiogenic shock, there were no the value of microcirculation monitoring.
significant differences in hemodynamics or lactate
at the time of initiation of mechanical support
between survivors and nonsurvivors despite signifi- PERSISTENT MICROCIRCULATORY
cant differences in their microcirculatory profiles ABNORMALITIES DESPITE EFFECTIVE
[30]. In certain circumstances, however, hemody- RESUSCITATION MAY REFLECT
namic coherence is indeed observed. For example, it LONG-LASTING INJURY
was demonstrated that fluid challenge in septic Although microcirculatory derangement is ubiqui-
shock patients improved microcirculation together tous, ominous, and may on occasion mirror abnor-
with CO and hyperlactemia but only within the first mal hemodynamics during the initial hypovolemic
24 h of resuscitation [31,32]. In an animal model of phase of shock, the microcirculation becomes more

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difficult to interpret in the subacute period (>24 h). hemorrhagic shock patients presenting to the emer-
&
Systemic hemodynamics typically normalize, gency room [41 ]. Although not utilizing dark field
whereas microcirculatory parameters either normal- microscopy, other measures of peripheral perfusion
ize concurrently reflecting shock resolution [37] or such as capillary refill time (CRT) were recently
persist for several days indicating long-lasting ische- compared against traditional hemodynamics in a
mic damage, continued shock, or iatrogenic injury goal-directed trial for septic shock. Less morbidity
& &&
(e.g., fluid overload) [23 ,38,39 ]. For example, in was noted when fluid resuscitation was guided by a
one study in septic shock, abnormal skin micro- combination of peripheral perfusion measures
&&
circulation was correlated with elevated lactate [42 ].
but only at the time of diagnosis, losing correlation
2472 h after initiation of resuscitation with lactate
largely normalizing, suggesting shock resolution, CAVEATS TO LACTATE-GUIDED AND
whereas microcirculation remained abnormal [34]. MICROCIRCULATION-GUIDED
Conversely, in another group of septic shock RESUSCITATION
patients with persistent hyperlactemia despite With respect to monitoring serum lactate, studies
48 h of treatment, fluid loading improved hemody- continue to highlight the complexity of lactate
namic parameters but had no effect either on lactate metabolism and the need to interpret hyperlactemia
levels or the microcirculation, suggesting continued with caution. In a septic shock sheep model, for
shock [32]. Some have argued that this late, fluid- example, esmolol and dexmedetomidine infusions
insensitive state makes microcirculation better during resuscitation lowered endogenous lactate
suited for evaluating organ dysfunction than guid- levels and enhanced clearance of exogenous lactate
&&
ing resuscitation [39 ]. Others have countered that without affecting CO [43]. This agrees with a previous
because microcirculation monitoring is uniquely clinical study showing lower admission lactate con-
able to distinguish patterns of shock such as gener- centrations in septic shock patients on -blocker
&
alized low flow state or heterogeneous capillary therapy [44 ]. This cautions against the common
blood flow, this technique may caution against misconception that lactate is simply a metabolic
further fluid administration and suggest more tar- byproduct of glycolysis, and thus a marker of dysoxia.
geted therapies such as nitroglycerin and inotropes In reality, hyperlactemia is not clearly associated with
[38,40]. Moreover, as noted above, when microcir- decreased delivery of oxygen; rather, it is a key glu-
culation is paired with other perfusion parameters coneogenic precursor whose production is enhanced
such as lactate, this fluid-insensitivity may in fact by adrenergic drive and exogenous catecholamines,
argue against any further fluid administration, and its serum concentration may be elevated from
which may only improve vital signs while causing reduced hepatic clearance due to ischemia or even
harmful fluid overload. In other words, microcircu- the sepsis toxicosis itself [45].
latory monitoring can help diagnose occult shock Although a clearer picture of microcirculatory
and both guide and limit resuscitation in the acute changes during shock is emerging, there remain a
as well as subacute periods. number of concerns. Perhaps the Achilles Heel of this
technique, rapid and reliable quantification of dark
field microscopy, the most modern technique for
CONTINUED WAIT FOR A measuring microcirculation, remains challenging.
MICROCIRCULATION-GUIDED The latest generation of automated algorithms for
RESUSCITATION TRIAL analyzing data remain unreliable and inaccurate
Although lactate-guided resuscitation has already compared with traditional, manual evaluation
been evaluated in multiple randomized controlled [46,47]. However, this will surely improve as the
trials, we are still waiting for an equivalent study algorithms are developed further. Another possibility
incorporating microcirculation. Without such a is the development of a simpler grading system, for
study, postulating about grand resuscitation strat- example, the 5-point point of care microcirculation
egies will remain in the realm of research rather than score, which requires only 2 min for calculation
at the bedside in which it desperately belongs. A with good interrater consistency and agreement with
traditional 45-min-long analysis [48 ]. Conversely,
&
microcirculation trial is inevitable as dark field
microscopes become more widespread and auto- this may prove irrelevant and microcirculation
mated analyses improve. Although we eagerly await monitoring may evolve into a multipurpose tech-
this trial, progress continues toward this goal. One nique akin to echocardiography, with minimally
promising, ongoing study is the MICROSHOCK skilled operators deducing basic yet important infor-
trial, which recently demonstrated the feasibility mation and highly skilled able to obtain more
and safety of sublingual imaging in traumatic detailed data. Another continued concern is the

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Lactate and microcirculation as suitable targets Kiyatkin and Bakker

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


FIGURE 1. A putative triangular basis of circulatory shock. None.
As hypothesized by Vincent et al. in their tribute to Prof Max
Harry Weil [55], the full clinical picture of shock includes Conflicts of interest
three features: hypotension, altered tissue perfusion, and There are no conflicts of interest.
hyperlactatemia, all of which originate from underlying
microcirculatory disturbances. However, this presentation is
often incomplete. Adapted from [55].
REFERENCES AND RECOMMENDED
READING
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relevance of the most common monitoring site the been highlighted as:
& of special interest
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because it is readily accessible and the bulk of data,


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& patients with hyperlactatemia than with refractory hypotension. Shock 2017. This is a very informative retrospective study in septic shock patients comparing
[Epub ahead of print] the prognostic ability of hyperlactemia with and without hypoperfusion defined by
This is a post-hoc analysis of the multicenter ARISE trial comparing outcomes in ScvO2 less than 70% or Pc(v-a)CO2 at least 6 mmHg. The presence of hypo-
septic shock patients with isolated, significant hyperlactemia (>4 mmol/l) versus perfusion in addition to hyperlactemia predicted greater vasopressor requirement,
isolated, fluid-refractory hypotension. Isolated hyperlactemia was associated with prolonged mechanical ventilation, longer ICU stay, more rescue therapies, and
higher morbidity and mortality. This emphasizes the greater clinical relevance of greater mortality. This study highlights both the complexities of interpreting
significant hyperlactemia compared with static hemodynamic parameters in the hyperlactemia in isolation and the utility of additional perfusion monitors, possibly
setting of septic shock resuscitation. together as a multimodal monitoring strategy.
20. Bakker J, de Backer D, Hernandez G. Lactate-guided resuscitation saves 37. Hernandez G, Luengo C, Bruhn A, et al. When to stop septic shock resuscita-
& lives: we are not sure. Intensive Care Med 2016; 42:472474. tion: clues from a dynamic perfusion monitoring. Ann Intensive Care 2014; 4:30.
One of three excellent editorials on the current state of lactate-guided resuscita- 38. Ince C, Guerci P. Why and when the microcirculation becomes disassociated
tion. This article emphasizes the complicated physiology of lactate metabolism and from the macrocirculation. Intensive Care Med 2016; 42:16451646.
the need to take this into account when interpreting study results. The authors 39. Hernandez G, Teboul JL. Is the macrocirculation really dissociated from the
recommend a multimodal perfusion monitoring strategy to best treat circulatory && microcirculation in septic shock? Intensive Care Med 2016; 42:16211624.
failure, whereas minimizing the impact of confounders of any one strategy. This is a thought-provoking editorial questioning the clinical relevance of micro-
21. Bloos F, Zhang Z, Boulain T. Lactate-guided resuscitation saves lives: yes. circulatory abnormalities. The authors argue that in the acute phase of shock,
&& Intensive Care Med 2016; 42:466469. microcirculatory changes frequently parallel and are redundant to standard of care
One of three excellent editorials on the current state of lactate-guided resuscita- macrohemodynamic parameters. In the subacute phase, however, persistent
tion. This article summarizes evidence supporting hyperlactemia and particularly its microcirculatory changes are often resistant to fluid administration. The authors
persistence as a predictor of morbidity and mortality. argue that these observations call into question the utility of microcirculation
22. Monnet X, Delaney A, Barnato A. Lactate-guided resuscitation saves lives: no. monitoring in everyday clinical practice. These valid concerns are addressed by an
&& Intensive Care Med 2016; 42:470471. excellent response [38].
One of three excellent editorials on the current state of lactate-guided resuscita- 40. Ince C. Hemodynamic coherence and the rationale for monitoring the micro-
tion. This article emphasizes the complicated metabolic role of lactate and the circulation. Crit Care 2015; 19 (Suppl 3):S8.
current scarcity of randomized controlled trials, evaluating lactate reduction as a 41. Naumann DN, Mellis C, Smith IM, et al. Safety and feasibility of sublingual
resuscitation guide. & microcirculation assessment in the emergency department for civilian and
23. Bakker J. Lactate levels and hemodynamic coherence in acute circulatory military patients with traumatic haemorrhagic shock: a prospective cohort
& failure. Best Pract Res Clin Anaesthesiol 2016; 30:523530. study. BMJ Open 2016; 6:e014162.
An excellent review of the current state of lactate-guided resuscitation with an This is a preliminary report on the feasibility of a major ongoing clinical trial
emphasis on the utility of multimodal perfusion monitoring strategies to better evaluating the utility of microcirculation monitoring in the resuscitation of traumatic
evaluate resuscitation and limit the impact of weaknesses inherent to each tool. hemorrhagic shock. Sublingual monitoring of microcirculation was shown to be
24. Zhou X, Liu D, Su L, et al. Use of stepwise lactate kinetics-oriented hemo- safe and practical even in an emergency situation.
&& dynamic therapy could improve the clinical outcomes of patients with sepsis- 42. van Genderen ME, Engels N, van der Valk RJ, et al. Early peripheral perfusion-
associated hyperlactatemia. Crit Care 2017; 21:33. && guided fluid therapy in patients with septic shock. Am J Respir Crit Care Med
This is a single-center, randomized controlled trial in septic shock patients 2015; 191:477480.
comparing outcomes with early goal-directed therapy versus a modified This is a very important proof-of-concept clinical trial in septic shock patients
protocol incorporating graded venous lactate reduction (i.e., 10% by 2 h, comparing standard hemodynamic-directed therapy with a multimodal perfusion
20% by 4 h, and 30% by 6 h) in place of the SvO 2 and transfusion arms. This evaluation-directed protocol incorporating capillary refill time, peripheral perfusion
builds on earlier lactate-guided resuscitation trials [25 &&,26&&] and likewise index, forearm-to-fingertip body temperature gradient, and tissue oxygenation
demonstrates reduced morbidity and mortality when lactate is used to direct saturation. Patients who were resuscitated according to peripheral perfusion
resuscitation. markers received less fluid and had shorter hospital stays and lower SOFA scores.
25. Jones AE, Shapiro NI, Trzeciak S, et al. Lactate clearance vs central venous Although not evaluating the more advanced and informative sublingual microcir-
&& oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. culation dark-field microscopy technique, this study supports the utility of perfusion
JAMA 2010; 303:739746. monitoring and provides a framework for future microcirculation studies.
This is an early and important randomized controlled trial that demonstrated 43. Hernandez G, Tapia P, Alegria L, et al. Effects of dexmedetomidine and
noninferiority of lactate-guided compared with hemodynamically guided treatment esmolol on systemic hemodynamics and exogenous lactate clearance in early
of septic shock. 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 49. Yin L, Yang Z, Yu H, et al. Changes in sublingual microcirculation is closely
& decreases blood lactate concentration in severely septic patients. Crit Care related with that of bulbar conjunctival microcirculation in a rat model of
Med 2015; 43:26162622. cardiac arrest. Shock 2016; 45:428433.
This very interesting retrospective study in septic shock patients revealed an 50. de Bruin AF, Kornmann VN, van der Sloot K, et al. Sidestream dark field
association between lower blood lactate concentration and -blocker therapy imaging of the serosal microcirculation during gastrointestinal surgery. Color-
regardless of a particular patients SOFA score. Although there was heterogeneity ectal Dis 2016; 18:O103O110.
between the two patient groups (e.g., less heart failure in the -blocker group), this 51. Kavanagh BP, Nurok M. Standardized intensive care. Protocol misalign-
study clearly highlights the important metabolic role of lactate and the danger of ment and impact misattribution. Am J Respir Crit Care Med 2016;
simplistically associating hyperlactemia with dysoxia. 193:1722.
45. Garcia-Alvarez M, Marik P, Bellomo R. Sepsis-associated hyperlactatemia. 52. Ospina-Tascon GA, Bautista-Rincon DF, Umana M, et al. Persistently
Crit Care 2014; 18:503. high venous-to-arterial carbon dioxide differences during early resusci-
46. Arnemann PH, Hessler M, Kampmeier T, et al. Comparison of an automatic tation are associated with poor outcomes in septic shock. Crit Care
analysis and a manual analysis of conjunctival microcirculation in a sheep 2013; 17:R294.
model of haemorrhagic shock. Intensive Care Med Exp 2016; 4:37. 53. Jakob SM, Groeneveld AB, Teboul JL. Venousarterial CO2 to arterial
47. Carsetti A, Aya HD, Pierantozzi S, et al. Ability and efficiency of an automatic venous O2 difference ratio as a resuscitation target in shock states? Intensive
analysis software to measure microvascular parameters. J Clin Monit Comput Care Med 2015; 41:936938.
2016. [Epub ahead of print] 54. Mesquida J, Saludes P, Gruartmoner G, et al. Central venous-to-arterial
48. Naumann DN, Mellis C, Husheer SL, et al. Real-time point of care micro- carbon dioxide difference combined with arterial-to-venous oxygen
& circulatory assessment of shock: design, rationale and application of the point content difference is associated with lactate evolution in the hemody-
of care microcirculation (POEM) tool. Crit Care 2016; 20:310. namic resuscitation process in early septic shock. Crit Care 2015;
This is an interesting article addressing one of the major limitations of microcirculation 19:126.
monitoring the labor-intensive interpretation of microscopy videos. This is often cited 55. Vincent JL, Ince C, Bakker J. Clinical review: circulatory shock an update: a
as the major hindrance to the incorporation of this technique into everyday clinical tribute to Professor Max Harry Weil. Crit Care 2012; 16:239.
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.

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