Evidence for Monitoring Lactate in Critical Illness

Created on Sat, 07/11/2015 - 18:34
Last updated on Wed, 04/25/2018 - 21:03

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In July 2015, I wrote that though this topic has never been examined before, "it would be worthwhile to apparoach it in a "critically evaluate lactate monitoring" sort of way". Then, in Question 8 from the first paper of 2016 the college asked the candidates to "critically evaluate the role of monitoring blood lactate levels in the critically ill". It was easy to guess that this was going to come up at some stage. Probably the best published resource for a quick overview of this topic is this review article by Bakker et al (2013).

Rationale for lactate monitoring in critical illness

  • Lactate is a product of anaerobic metabolism
  • Anaerobic metabolism in human tissues is an abnormal physiological state, be it of poor tissue perfusion or impaired oxygen utilisation.
  • Lactate clearance is rapid in the presence of normal hepatic function
  • Serum lactate may therefore be useful as a biomarker, a measure of anaerobic metabolism.
  • Conditions which result in a raised lactate may not be easy to identify in critically ill patients (eg. ischaemic gut, ischaemic limbs, sepsis, etc) and so lactate levels may be the only feature of such conditions

Advantages of lactate monitoring in critical illness

  • A simple test, widely available, and can be performed as a part of blood gas analysis
  • Venous and arterial lactate levels correlate conveniently
  • Lactate is cheap to test - there may be a saving in healthcare costs
  • Its clearance by kidneys and dialysis is proportionally poorer than hepatic clearance, which means as a biomarker it is neither obscured by dialysis nor falsely elevated in the presence of renal failure.
  • It offers a quantitative marker to evaluate the success of resuscitation
  • It is thus an effective surrogate endpoint in the evaluation of therapies aimed to improve tissue perfusion

Errors of lactate measurement

  • Storage delay: metabolism by blood cells can cause an elevated lactate
  • Collection error: A sample accidentally mixed with compound sodium lactate will cause a spuriously elevated lactate level.
  • Measurement error: a "lactate gap" is generated when the lactate-sensing electrode in the b;lood gas machine confuses lactate with ethylene glycol

Errors of lactate interpretation

  • Tissue perfusion may be normal, and lactate clearance may be impaired (as in liver disease)
  • Lactate may be raised due to poor tissue oxygen utilisation, rather than poor perfusion (eg. in septic shock)
  • Lactate may be raised in the absence of acidosis (eg. exogenous compound sodium lactate administration).
  • Lactate may be raised because of increased production by abnormal metabolic processes in neoplastic tissue

Evidence for and against the use of lactate as a biomarker

In the college answer to Question 8 from the first paper of 2016, various statements were made regarding the evidence for lactate monitoring. Below, I have tried to track down the references from where those statements came from.

Lactate as a prognostic marker:

  • It correlates well with mortality in sepsis: patients with a presenting lactate over 4.0mmol/L were almost five times more  likely to die (Mikkelsen et al, 2009)
  • High levels may reveal underlying "occult" sepsis in otherwise stable patients (Rivers et al, 2001).
  • It is associated with a poor prognosis in trauma. Specifically, failure to normalise the lactate over the first 2 days is associated with worse organ failure and increased mortality (Manikis et al, 1995)
  • It predicts poor recovery from cardiac arrest. Survivors and patients with good neurological outcome had lower lactate levels at 0, 12 and 24 hours (Donnino et al, 2015 is the 100-patient study mentioned by the college)
  • It acts as a trigger for liver transplatation: lactate predicts non-survivors from paracetamol toxicity earlier than the King's College Criteria (Bernal et al, 2002). However, somehow the effect of adding lactate to the King's College Criteria actually decreases their diagnostic odds ratio slightly, from about 27 to about 26. (Craig et al, 2010)

Lactate as a guide to therapy:

  • It is non-inferior to mixed venous saturation as a goal of early sepsis therapy (Jones et al, 2010).
  • It can be used to guide therapy in cardiac surgical patients (though neither Pölönen et al in 2000 nor Shrestha et al in 2015 were able to demonstrate a statistcially significant mortality benefit, owing to underpowered study design)

 

References

Jansen, Tim C., Jasper van Bommel, and Jan Bakker. "Blood lactate monitoring in critically ill patients: A systematic health technology assessment*." Critical care medicine 37.10 (2009): 2827-2839.

Okorie, Okorie Nduka, and Phil Dellinger. "Lactate: biomarker and potential therapeutic target." Critical care clinics 27.2 (2011): 299-326.

Mikkelsen, Mark E., et al. "Serum lactate is associated with mortality in severe sepsis independent of organ failure and shock*." Critical care medicine 37.5 (2009): 1670-1677.

Manikis, Panagiotis, et al. "Correlation of serial blood lactate levels to organ failure and mortality after trauma." The American journal of emergency medicine 13.6 (1995): 619-622.

Bernal, William, et al. "Blood lactate as an early predictor of outcome in paracetamol-induced acute liver failure: a cohort study." The Lancet 359.9306 (2002): 558-563.

Jones, Alan E., et al. "Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial." Jama 303.8 (2010): 739-746.

Fuller, Brian M., and R. Phillip Dellinger. "Lactate as a hemodynamic marker in the critically ill." Current opinion in critical care 18.3 (2012): 267.

Rivers, Emanuel, et al. "Early goal-directed therapy in the treatment of severe sepsis and septic shock." New England Journal of Medicine 345.19 (2001): 1368-1377.

Donnino, Michael W., et al. "Initial lactate and lactate change in post-cardiac arrest: a multi-center validation study." Critical care medicine 42.8 (2014): 1804.

Craig, Darren George Norman, et al. "Systematic review: prognostic tests of paracetamol‐induced acute liver failure." Alimentary pharmacology & therapeutics 31.10 (2010): 1064-1076.

Bakker, Jan, Maarten WN Nijsten, and Tim C. Jansen. "Clinical use of lactate monitoring in critically ill patients." Annals of intensive care 3.1 (2013): 1.

Shrestha, K. R., B. Pradhan, and B. Koirala. "A prospective randomized study of goal oriented hemodynamic therapy in cardiac surgical patients." Journal of Institute of Medicine (2015).

Pölönen, Pekka, et al. "A prospective, randomized study of goal-oriented hemodynamic therapy in cardiac surgical patients." Anesthesia & Analgesia 90.5 (2000): 1052-1059.