EMCrit Wee – Is Lactate Clearance a Flawed Paradigm?

low-clearance

A listener, Øyvind S Holen, and the PrecordialThumper both alerted me to an article recently published by Paul Marik and Rinaldo Bellomo:
Lactate clearance as a target of therapy in sepsis: a flawed paradigm

In the paper, they discuss many of the misunderstandings re: lactate and lactate clearance. This wee is my response. I’d love to hear your opinions.

This Post was by

Now on to the Wee…

Play

You finished the 'cast,
Now get CME credit

Not a subcriber yet? Why the heck not?
By subscribing, you can...

  • Get CME hours
  • Support the show
  • Write it off on your taxes or get reimbursed by your department

Sign Up Today!

.

Subscribe Now

If you enjoyed this post, you will almost certainly enjoy our others. Subscribe to our email list to keep informed on all of the ED Critical Care goodness.

This Post was by , MD, published 2 years ago. We never spam; we hate spammers! Spammers probably work for the Joint Commission.

Comments

  1. rfdsdoc says:

    thanks Scott. interesting stuff.
    My immediate question on hearing your thoughts is ” if the lactate was going down and you did the echo just for teachng purposes and it looked crappy, would you still put up inotropes or be reassured by the lactate and sit tight?”

  2. Hi Dr. Weingart,

    I read the article by Dr. Marik and Dr. Bellomo last week and was happy to see that it caught your eye. It is an excellent review on lactate physiology and brings up some interesting theories why we do or do not clear our lactate burden. What it does not do is provide a convincing argument in changing how we use lactate in every day practice. From the Jones study (2) we know that people who clear their lactate levels do better than those who do not. Whether this is a prognostic factor or an evaluation of our resuscitation efforts is unclear. Even how well lactate predicts poor outcomes is unclear. In a 2005 study published by Shapiro et al. (3) the AOC of laboratory lactate, as a predictor of “badness”, was 0.67.

    In their final paragraph Dr. Marik and Dr. Bellomo cites two trials as evidence why lactate should not be used as a guide for resuscitation (4,5). Both are articles from the NEJM published in the 1990s. Interestingly they are both attempts of goal directed therapy in the ICU. In the first, the goals of cardiac index and oxygen deliver are utilized to guide care (4). If, after proper fluid resuscitation, these goals were not met, dobutamine was added. The second trial (5) randomized patients to one of 3 groups. In each respective group they used cardiac index, oxygen delivery or standard care to guide their resuscitation. If you look at the methods of this study it was very similar to the EGDT protocol in Dr. Rivers landmark trial (6). Obviously both trials were negative. As we’re all the trials of goal directed therapy before Dr. Rivers utilized its concepts in the ED. This is more a comment on the importance of early, aggressive care and maybe, the lack of utility of dobutamine. The leap to using this as evidence that we should not use lactate to guide our care is weak at best.

    There is an argument to be made (Jerry Hoffman makes a rather convincing one) that lactate adds very little to your resuscitative efforts. In the Shapiro study cited previously (3) the sensitivity and specificity of a serum lactate level of 2.5 at predicting death were 59% and 71% respectively. Even at low levels you will miss a large quantity of very sick patients if you use it as your single screening tool.

    I hope this adds something of substance to the discussion. I am a big fan and love what you do,

    Sincerely,
    Rory

    1. Marik PE, Bellomo R, Demla V. Lactate clearance as a target of therapy in sepsis: A flawed paradigm. OA Critical Care 2013 Mar 01;1(1):3.
    2. Jones AE, Shapiro NI, Trzeciak S, Arnold RC, Claremont HA, Kline JA. Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA 2010 Feb;303(8):739-46.
    3. Nathan I. Shapiro, Michael D. Howell, Daniel Talmor, Larry A. Nathanson, Alan Lisbon, Richard E. Wolfe, J. Woodrow Weiss Serum Lactate as a Predictor of Mortality in Emergency Department Patients with Infection . Annals of Emergency Medicine – May 2005 Vol. 45, Issue 5, Pages 524-528
    4. Hayes MA, Timmins AC, Yau E, Palazzo M, Hinds CJ, Watson D. Elevation of systemic oxygen delivery in the treatment of critically ill patients. N Engl J Med 1994 Jun;330(24):1717-22.
    5. Gattinoni L, Brazzi L, Pelosi P, Latini R, Tognoni G, Pesenti A. A trial of goal-oriented hemodynamic therapy in critically ill patients. N Engl J Med 1995 Oct;333(16):1025-32.
    6. 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(19):1368-1377

  3. Biju John says:

    Hi Scott,
    Definitely, a very interesting discussion, but I feel that Dr. Marik and yourself are saying essentially the same thing……that there is more to Sepsis than meets the eye!. It is essential we understand that the so called ‘Oxygen debt’ may not exist in every patient with a high lactate….the latter may just be reflecting the ton of badness that is already in progress. I don’t think Dr. Marik is implying that high lactate does not have a prognostic implication at all.
    You said that you would not be averse to trying inotropes if you found the heart to be crappy on echo….but this is exactly what Marik is saying as well! If the lactate was high as a result of increased catecholamine stimulation of metabolism, then wouldn’t you also expect to see the same effect on the heart? I mean, wouldn’t the heart be hyperdynamic as well?
    If you find a lazy heart on ECHO, in the presence of a high lactate, perhaps there might be some element of oxygen debt at play , and I think we are justified in trying to improve Oxygen delivery .

    John

    • Biju,

      I think we disagree on the intent of the article, which is to debase the concept of using lactate clearance as a resuscitation goal. All the rest that you mention is just a lead-up to that. I agree with most of what Dr. Marik has said up until the point where they then conclude b/c of these things, serial lactates can not be used to guide a severe sepsis resuscitation.

  4. Iwan Dierckx says:

    I accept that (endogenous) catecholamines are responsible for elevated lactate in many cases and as such represents a stress state and “badness”.
    But what does this mean for patients we start exogenous catecholamines on ?
    Logically, this would prevent us from using lactate clearance as a marker for effective resuscitation because you would expect lactate to go up instead of down.
    For epinephrine we know this to be true, at least for the first day after starting epinephrine infusion (CAT study)

    • Absolutely, this is why I don’t use epi as a primary pressor if I want to use lactate clearance. Albuterol will also mess with lactate’s value.

  5. Here is a quick search strengthening what Iwan Dierckx posted.
    http://www.ncbi.nlm.nih.gov/pubmed/18323749
    http://www.ncbi.nlm.nih.gov/pubmed/11901313

    I believe we are continuing to misunderstand the Kreb-Cycle and its mechanism. There are several way Lactate is formed to Lactate Dehydrogenase then converted back to a usable form for the cells. For Example, if pyruvic acid was converted by fermentation then we would be thinking more about elevated Ethanol levels in shock states.

  6. Stephanie Chan says:

    Did a lit search and way back in ’99 this was published in the Lancet: http://www.ncbi.nlm.nih.gov/pubmed/10465191

    A redux perhaps?

  7. Len Ulan says:

    Scott, I just listened to this Wee again after having to endure an IHI presentation touting CVP and ScVO2 and slamming lactate clearance. I totally agree with your points. My question to you (topic for a separate Wee), What is the evidence that ScVO2 predicts survival in Severe Sepsis? The Surviving Sepsis Campaign and IHI seem to think the evidence is stronger for ScVO2 than lactate clearance. I would like your perspective.

    • Len,

      The Jones trial established lactate clearance as equivalent if not superior to ScvO2. CVP is laughable and has been debunked by 2 separate meta-analyses by Paul Marik et al. If you meet a staunch defender of CVP and ScvO2, you may want to ask if there is anything in their academic career that biases them to that viewpoint.

  8. I have to contend a bit with Marik and Bellomo’s argument that lactate is disproportionately driven by catecholamine stimulation via beta-receptors. While the citation of adrenergic blockers blunting lactate rise in hemorrhagic shock is somewhat pertinent, the evidence they cite by Levy et al. to extrapolate this model to sepsis is flawed. They claim that beta-receptor agonists are a main driver of lactate production based on an experiment in which ouabain (a Na/K/ATPase pump inhibitor) was given to septic patients with a resultant decrease in lactate production (given that catechoamine beta-agonists drive lactate production through simulation of the Na/K/ATPase pump). However, they fail to acknowledge that by inhibiting the pump, ATP levels in the cell will markedly increase (since the Na/K/ATPase pump is the major consumer of ATP, using anywhere from 25 to 70% of available cytoplasmic ATP for its purpose) resulting in allosteric feedback on phosphofructokinase (the rate limiting enzymatic step in glycolysis), thus decreasing glycolysis and also reducing lactate production without much regard to the aerobic (or anaerobic) state of the cell, assuming that ATP levels remain in adequate supply inside a poisoned and paralyzed cell.

    This is not to say that hyperlactatemia in sepsis is an due to oxygen debt, short of a mixed venous saturation of 5%. I think it is very complicated and is likely mostly attributable to intrinsic mitochondrial dysfunction in the setting of a hyperinflammatory state (which is likely ameliorated with crystalloid infusions, vasodilators and perhaps blood transfusions with absolutely nothing to do with achieving goal ScvO2 levels or lactate clearance directly, but that’s for another post all together).

    Thanks Scott for the chance to rant and use the small part of my brain reserved for biochemistry so long ago…
    Dustin

    • Absolutely grand comment Dustin. I have always thought of the lactate of sepsis as a mixed bag of stuff just as you say. The one conclusion I always come back to in my septic and my trauma patients is that when it comes to lactate, if its not getting better things are probably getting worse.

  9. Forgot to add that the evidence using dichloroacetate as a simulator of oxidative metabolism to drive down lactate levels reinforces the mitrochondrial dysfunction hypothesis and further negates the oxygen debt argument- yes epinephrine may accelerate glycolysis and lactate production, but it is the failure of the mitrochondia to keep up in the septic state that is the real trouble, and which will eventually lead to multi-organ failure via mitochondrial shutdown. Septic cardiomyopathy is only a proxy for this process, which is unlikely to be ameliorated with pro-inflammatory beta-agonists.
    And so I’ve pretty much typed myself into the same conclusion as Marik and Bellomo…ok, I’m done!

  10. Lactate not clearing (or increasing), SvO2> 70, Hbg >10, No evidence of LV dysfunction on bedside echo, fluid resuscitation appears adequate (however you prefer to determine that), ABx and source control done (you think, at least) -> Give esmolol trial?

    CZ

Trackbacks

  1. […] provoked a short sharp retort from Dr Scott Weingart on his Emcrit podcast (much shorter than our longish dissection!)  Have a listen to his thoughts then carry on to our […]

  2. […] For a more extensive discussion on the role of lactate in the sepsis patient – please check out my recent podcast with Dr Seth Trueger and Dr Weingarts’s response to the Marik / Bellomo paper […]

  3. […] Is Lactate Clearance a Flawed Paradigm? We know a high lactate is a bad sign in a sick patient, but do we really understand lactate? It seems the debate is on! […]

Speak Your Mind (Along with your name, job, and affiliation)