Review: Lactate & Sepsis - PulmCCM
Jan 172016

15419185_sOn this snowy, Stockholm Sunday, I look out from my quarters on the Mälardrottningen across the still, icy waters and I think about a cirrhotic patient for whom I recently cared.  She presented with significant dyspnea as she had stopped taking her diuretics.  Instead, she was using excessive doses of her friend’s albuterol inhaler to treat her shortness of breath.  Additionally, she had been drinking alcohol heavily for seven days prior to admission.  Her venous pH was 7.38, and her lactate concentration was over 7.0 mmol/L – a sepsis alert was called.


In a very recent and fantastic review by Suetrong and Walley, the mechanisms of lactate formation are revisited.  Notably, a distinction is made between hyperlactatemia – an elevated concentration of lactate in the blood – and lactic acidosis, which is comprised of both hyperlactatemia and systemic acidosis.

The authors discuss the mechanisms by which lactate is formed and aptly detail that many of these processes do not result in acid formation.  Notably, while the generation of pyruvate from glucose does generate [H+], the conversion of pyruvate to lactate consumes an equimolar amount of [H+] such that the production of lactate does not result in a net gain of protons [i.e. acidosis].  So where does the acidosis – with which we are so familiar – come from?  The excess protons are the result of an impaired Kreb’s Cycle.  In states of true tissue oxygen debt, intracellular protons can no longer be consumed during the Kreb’s Cycle; consequently, intracellular acidosis and acidemia ensue.  It is this latter means of hyperlactatemia to which we attach the label ‘type A’ or lactic acidosis with clinical evidence of tissue hypoxia.

However, as described 40 years ago, excessive lactate may come from clinical states where there is no evidence of tissue hypoxia – the so-called B-type lactate.  As clearly and concisely surveyed in their review, Suetrong and Walley explain that increased glycolytic flux [e.g. from sepsis itself, from beta-agonists, from increased muscle activity], a poisoned pyruvate dehydrogenase complex [e.g. from thiamine deficiency or other toxins/medications], an elevated NADH/NAD+ ratio [e.g. from ethanol intoxication] and impaired lactate clearance [e.g. from severe hepatic or even renal insufficiency] may all result in hyperlactatemia.  Within this litany of causes, to the extent that mitochondrial, and therefore the Kreb’s Cycle function remains intact, there can be little-or-no acidosis despite elevations in serum lactate.

Lactate concentration in sepsis

The authors go on to explain the underlying reasons for hyperlactatemia and lactic acidosis in sepsis which include impaired oxygen delivery in early, under-resuscitated sepsis [a mechanism common to all types of shock], but also regional cytopathic tissue hypoxia.  This latter entity occurs due to microcirculatory unrest and embarrassed mitochondrial function.  While tissue can maximally extract up to 70% of its received oxygen supply, in sepsis, this ability may be diminished to 50% extraction or less.  Thus, when total body – or even organ – oxygen delivery is optimized [or exceeded], localized oxygen debt can occur.  In addition to the aforementioned states of A-type lactate, increased B-type lactate is a common entity within the sphere of severe sepsis and septic shock.  B-type lactate can and will occur because resting adrenergic state is increased, exogenous catecholamines are administered and lactate clearance is impaired.  Importantly, the provision of beta-agonists such as epinephrine are known to raise serum lactate levels secondary to hepatic stimulation of glycogenolysis/glycolysis [i.e. increased B-type lactate]; ostensibly, this effect is counterbalanced by epinephrine’s ability to augment cardiac output and, therefore, tissue oxygen delivery [i.e. attenuated A-type lactate].

Clinical implications of lactate measurement

Whether obtained from an arterial or venous sample, if measured quickly following phlebotomy, serum lactate elevation is a strong prognosticator in sepsis.  Significantly, this is irrespective of the underlying pathophysiology of lactate elevation [i.e. A versus B-type above].  Thus, regardless of the reason for lactate elevation, it speaks to tissues and organs under hemodynamic and/or metabolic duress; whatever its underpinnings, hyperlactatemia should be heeded.  Arguably, this is why there is no true inflection point in the relationship between lactate level and prognosis in septic patients.

While elevated lactate predicts untoward clinical outcomes, using its clearance as a marker of successful resuscitation has revealed mixed results.  As the authors highlight, this may be the result of the aforementioned competing effects of beta-agonists such as epinephrine on serum lactate concentrations.  Indeed, in the CATS trial, epinephrine infusion significantly increased serum lactate, but did not impair clinical outcome in severely septic patients.  Conversely, the use of esmolol in a similar patient population reduced oxygen delivery, and serum lactate levels, but improved clinical end-points.  The use of lactate clearance is equivalent, or perhaps superior, to central venous oxygen saturation; however, this debate is nuanced and muddied.  In summary, changes in lactate concentration, alone, cannot solely and definitively be used as a resuscitative end-point, but must be integrated into a clinical gestalt which should include other indices of hemodynamic success such as improved urine output, mentation, etc.

Treating lactic acidosis in sepsis

As described in this excellent post, hyperlactatemia, like sinus tachycardia, may be an adaptive response to sepsis.  Therefore, treatment should focus on the underlying fire rather than the smoke.  Source control and timely, appropriate antibiotics are clearly paramount.  Beyond these interventions, expeditious restoration of global hemodynamic parameters without excessive fluid administration is indicated.  If lactate levels continue to rise, the clinician must consider impaired organ perfusion [e.g. gut or limb ischemia] and microcirculatory dysfunction as underlying etiologies.  Excessive beta-agonists should be avoided and hepatic insults such as medications or venous congestion should be appreciated and rectified in an attempt to augment lactate clearance.  Finally, there is little or no role for the use of sodium bicarbonate in lactic acidosis.  As well, renal replacement therapy and dichloroacetate provision have both been shown to treat lactic acidosis, but without clear improvement in survival.

Happy New Year and belated-birthday, Mum!


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  7 Responses to “Review: Lactate & Sepsis”

  1. Like steroids and so many others, lactate is one of those things that just won’t die.

    If we had nothing else to go on, no HR, BP, cool extremities, oliguria, altered mentation,abdominal pain out of proportion to examination, none of those things, then lactate might (might) help us identify patients who need some more attention in terms of resuscitation. But we do have all of those things.

    Lactate is a test, and it holds the false promise of simplifying clinical decision making to a numerical value, one that you can order, even from afar. But it cannot replace clinical acumen, and until somebody makes a credible study of its use to guide therapy, it is just a superfluous test in ICU patients, much as BNP and troponin are.

    We must be very careful about getting sexed up over physiology and biochemistry. While it is very good to understand these things (heck as a resident and aspiring pulmonologist, I could draw from memory the entire steroid synthesis pathway, or a diagram of a nephron with dozens of ion channels) it is just as important to understand their limitations in terms of helping make good clinical decisions. Most often in critical illness, minutiae of physiology and biochemistry are just a bunch of distracting noise, and they have a notorious history of misguiding us and causing harm (Gattinoni and superphysiological targets, Rivers and EGDT, everyone using a ventilator to chase ABGs with high tidal volumes for decades, swan ganz catheters, balloon pumps and many other examples of being oversexed by physiology and hurting patients with it).

  2. Nice information

  3. Outstanding review
    In contrast to ,many of the other surrogates suggested in the first reply, as data points to guide resuscitation, lactate level are a much more reliable indicator of tissue oxygen delivery and metabolism, than HR, BP or other suggested parameters, all of which can be influenced by so many numerous other factors..
    Clearly, assessing fluid responsiveness is a complex question, requiring incorporating many data points into the analysis
    Lactate levels, particularly how they evolve, in response to treatment, is very helpful in deciding if one is doing the correct thing,IE: lactate levels improving, versus lactate levels increasing, which in my opinion suggests the patient is not responding, either because the treatment is incorrect or the patient is terminally ill.


    • To my knowledge there are no credible data that support the above contentions. Do tou have references to support them?

      Paul Marik has convincingly demonstrated that there is NO SUCH THING as lactic acidosis it is stoichiometrically not possible, and that the notion that lactate levels replect the tissue level things you are referring to is farce and fantasy.

      it is high time that we cease and desist with trying to apply what we presume is an inderstanding of biochemistry to intact organisms.

      my guess is that lactate is leading many people to injure patients with excessive fluids.

      thats only a guess but it is my point – without creduble data suggesting that lactate driven strategies are beneficial, you are basing that strategy on a guess.

      Cliffords principles warn us that our beliefs should be strong in proportion to the evidence supporting them.

      It is good advice.

  4. Here is an article by Paul Marik illustrating Scott’s point. Required reading for all intensivists, fellows, residents, and CMS bureaucrats designing sepsis core measures:

  5. Nice information sir

  6. Nice information sir ,

    Many patients on ventilator receive Nebulization with Beta 2 agonist, we should stop unnecessary Nebulization

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