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2021 Blood Lactate Levels in Sepsis in 8 Questions
2021 Blood Lactate Levels in Sepsis in 8 Questions
2021 Blood Lactate Levels in Sepsis in 8 Questions
REVIEW
CURRENT
OPINION Blood lactate levels in sepsis: in 8 questions
Jean-Louis Vincent a and Jan Bakker b,c,d,e
Purpose of review
Blood lactate concentrations are frequently measured in critically ill patients and have important prognostic
value. Here, we review some key questions related to their clinical use in sepsis.
Recent findings
Despite the metabolic hurdles, measuring lactate concentrations remains very informative in clinical
practice. Although blood lactate levels change too slowly to represent the only guide to resuscitation, serial
lactate levels can help to define the patient’s trajectory and encourage a review of the therapeutic strategy
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a
Question 1: Does hyperlactatemia always Department of Intensive Care, Erasme Hospital, Université libre de
Bruxelles, Brussels, Belgium, bDepartment of Intensive Care, Erasmus
reflect anaerobic metabolism in sepsis? MC – University Medical Center, Rotterdam, The Netherlands, cDepart-
ment of Pulmonology and Critical Care, New York University NYU
Answer: No. Langone Medical Center, dDepartment of Pulmonology and Critical Care,
Columbia University Medical Center, New York, USA and ePontificia
Under physiological conditions, lactate is a normal Universidad Católica de Chile, Department of Intensive Care, Santiago,
end-product of glucose metabolism via two main Chile
pathways: glycolysis and oxidative phosphoryla- Correspondence to Jean-Louis Vincent, MD, PhD, Department of Inten-
tion. Glycolysis is a process that generates small sive Care, Erasme Hospital, Route de Lennik 808, 1070 Brussels,
amounts of adenosine triphosphate (ATP), but Belgium. E-mail: jlvincent@intensive.org
because of its speed, can create significant energy. Curr Opin Crit Care 2021, 26:000–000
Oxidative phosphorylation is the process that DOI:10.1097/MCC.0000000000000824
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Cardiopulmonary monitoring
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as being due to cellular alterations alone; reduced especially when the evolution of the patient’s con-
tissue perfusion is an important factor. dition is uncertain. Some people have used the term
‘lactate clearance’ to describe the decrease in lactate
concentrations over time, but this is inappropriate,
Question 4: Can lactate concentrations because hyperlactatemia is determined more by
predict outcome? increased production than by decreased elimination
[16]. A recent study showed that increased produc-
Answer: Yes, definitely. tion and decreased elimination can coexist also in
Numerous studies have shown that lactate concen- malaria [17]. Reference to lactate clearance can also
trations are associated with patient survival and/or lead to confusion when a patient is receiving renal
organ failure in both adult and pediatric sepsis replacement therapy. Moreover, an increase in lac-
&
[1,3,4,5 ]. Importantly, even early measurements tate concentrations over time would represent ‘neg-
are predictive of outcome [3]. ative clearance’ [6]. To separate the effects of
decreased lactate elimination from increased pro-
duction would require infusion of a highly concen-
Question 5: Should we combine lactate and trated lactate solution or the administration of
SvO2 concentrations? &
radiolabeled lactate [18 ], which, although poten-
tially of interest to study the mechanisms of lactate
Answer: Yes and no. kinetics, would be of little practical use in routine
Patient management should never be based on one patient care.
variable alone, and adding mixed (SvO2) or central Lactate concentrations change relatively slowly,
(ScvO2) venous oxygen saturation values, a marker of because lactate metabolism takes time. The first
inadequate oxygen delivery,to lactate concentrations study on serial lactate concentrations in 1993 [13]
can help identify tissue hypoperfusion and may lead showed that in the best case scenario of a rapid
to beneficial clinical interventions. However, one response to fluid therapy, lactate concentrations
cannot expect lactate and S(c)vO2 to be correlated decreased by 10% in one hour; higher rates of
[14]. During resuscitation, changes in S(c)vO2 during decline are therefore unlikely. Therefore, measure-
an increase in DO2 (e.g., with fluids or dobutamine ment of lactate concentrations every one or two
administration) are much faster than changes in lac- hours is recommended [6]. Some monitoring sys-
tate concentrations, so that the relationship between tems may allow more frequent assessment of blood
the two is difficult to interpret [15]; combining these lactate concentrations, but it is unclear whether this
two variables is therefore not straightforward. holds any advantage over hourly measurements.
It may be attractive to consider that a high SvO2 Importantly, because the majority of lactate is
(or ScvO2 when only a central venous catheter is metabolized in the liver, evaluating the time course
available) in the presence of elevated lactate con- in patients with advanced liver dysfunction is
centrations could reflect a severe alteration in cellu- more complex.
lar function, wherein the cells can no longer use
oxygen (a process sometimes called ‘cytopathic hyp-
oxia’). Unfortunately, a high SvO2 can also be due to Question 7: Can assessment of serial lactate
microvascular alterations. One may consider that an concentrations be used to guide therapy?
increase in DO2 will increase cellular metabolism in
the presence of hemodynamic alterations and not in Answer: Yes and no.
the presence of cellular alterations. The former is Jansen et al. [19] showed that evaluating lactate
indeed what characterizes VO2/DO2 dependency in kinetics over time could be used to influence therapy,
shock states. Unfortunately, these measurements but, as already stated, one should not focus on a single
are not easily applied at the bedside. variable to guide therapy, and this applies to lactate as
well as to other variables. Because changes in lactate
concentrations over time are slow and variable, they
Question 6: Is it valuable to repeat the
are of little use alone to guide therapy in the critically
measurement of blood lactate
ill patient in whom rapid therapeutic decisions are
concentrations?
often needed as hemodynamic status alters quickly.
In a post hoc analysis of the ANDROMEDA-SHOCK
Answer: Yes, definitely. study, resuscitation guided by blood lactate levels in
Following the time course of blood lactate concen- patients with normal capillary refill time, a much
trations can provide valuable information, more rapid indicator of tissue perfusion than lactate,
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Cardiopulmonary monitoring
FIGURE 1. A pragmatic approach to help guide therapy in critically ill patients by measuring lactate concentrations.
&&
was associated with more organ dysfunction [20 ]. administration of hypertonic lactate. In experimen-
Nevertheless, trends in lactate concentrations in tal sepsis, it was suggested that hypertonic lactate
combination with other variables can help indicate infusion could improve the microcirculation [26],
response to treatment. A pragmatic approach to use but in a larger animal model of hyperdynamic sepsis,
of lactate concentrations to help guide therapy in Su et al. [27] observed harmful effects.
critically ill patients is proposed in Fig. 1. The goal of therapy should not per se be to
decrease lactate concentrations, but to intervene
Question 8: Is lactate toxic? in the process that leads to increased lactate con-
centrations if this process is likely to be harmful to
the patient, for example, tissue hypoxia.
Answer: Not really.
Lactate in and of itself is not a toxic molecule and is
used as a fuel for cells via the mono-carboxylate trans- CONCLUSION
porters; it may even have important beneficial regu- Measuring lactate concentrations in sepsis provides
&
latory properties [21 ]. When lactate concentrations important and useful information in terms of prog-
increase in the blood, they increase also in the cells nosis and a patient’s response to treatment. Serial
and influence their function. Lactate increases T lactate concentrations may not help directly guide
helper 1 cell differentiation and the production of acute changes in therapy, but may help orient the
interferon-g and modifies macrophage function. overall therapeutic strategy. Hyperlactatemia should
These effects may also have some immunosuppres- not be considered as a problem in itself but as a
sive action [22], and may therefore contribute to the reflection of altered cell function where the cause
acquired immunosuppression (sometimes called of this alteration relates to the clinical actions needed
‘immunoparalysis’) of sepsis, although the implica- to improve the patient’s condition and outcome.
tions of this possible effect in patients with sepsis are
not well-defined. Acknowledgements
It is unclear whether improving lactate metabo-
None.
lism can improve outcome. The administration of
dichloroacetate can decrease lactate concentrations,
but this was not associated with improved hemody- Financial support and sponsorship
namics or survival [23]. There was no correlation None.
between thiamine, a co-factor in aerobic metabolism,
and lactate concentrations [24] and thiamine supple- Conflicts of interest
mentation was not associated with improved out- J.L.V. is Editor-in-Chief of Current Opinion in Critical
comes in a small pilot study of patients with septic Care. He has no other conflicts of interest to declare.
shock [25]. There has been some recent interest in the J.B. has no conflicts of interest to declare.
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