Critically evaluate the role of monitoring blood lactate levels in the critically ill

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ollege Answer

Introduction:

Lactate measurement is easy, widely available and accurate. High blood lactate levels may represent increased production from tissues and/or decreased metabolic clearance.

Uses

  • End-point of resuscitation – lactate clearance.
  • Diagnosis of inadequate tissue oxygenation / ischaemia.
  • Risk stratification in ED and ICU – predictor of non-survival.
  • Prognostication and assessment of severity in liver disease.
  • Prognosis post cardiac arrest.
  • Lactate gap (lactate value from POC analyser – lactate value from lab) assists diagnosis in ethylene glycol toxicity.

Evidence:

  • Lactate levels proportional to mortality – lactate ≥ 4 is associated with poorer outcome.
  • Poor lactate clearance in trauma patients associated with bad prognosis.
  • High lactate levels may indicate underlying sepsis in patients who otherwise appear stable (in Rivers EGDT in sepsis trial, 50% patients with MAP >100 had high lactate).
  • Multi-centre study of 100 patients post cardiac arrest showed lower lactate levels in first 24 hours and increased lactate in first 12 hours post arrest were associated with survival and good neurological outcome.
  • Sustained high levels of lactate in paracetamol toxicity related ALF may be a trigger for need for transplantation.

Three studies have looked at lactate-directed versus non-lactate-directed therapy in: 

  • Post-cardiac surgery patients – showed reduction in morbidity but not powered to look at mortality.
  • Septic patients in the ED – testing non-inferiority with ScvO2 showed no difference in outcomes although some limitations of study.
  • ICU patients with raised lactate levels – used GTN when ScvO2 normalised but lactate remained high. Showed statistically significant reduction in morbidity and trend to reduction in mortality but course of lactate levels in both groups was similar.

Practical points:

Monitoring alone does not improve outcome and treatment needs to target the underlying disease. Adequate understanding of the anaerobic and aerobic mechanisms of production and clearance is essential to correctly interpret the significance of raised lactate levels. Lactate levels should be interpreted with clinical correlation.

Lactate levels not useful in:

  • Elevated lactate levels with beta agonist therapy (increased lactate production from increased glycolytic flux).
  • Post seizures.

Overall: 

  • Lactate levels in critical illness not fully understood.
  • Lack of high-level evidence showing use of lactate monitoring improves outcomes.

Summary statement:

For example: Lactate appears to be an epiphenomenon and marker of severity in the critically ill. My practice is to use it as an end-point of resuscitation and an indicator of possible underlying tissue ischaemia in the shocked patient but not necessarily to react in patients who are otherwise haemodynamically stable with adequate tissue O2 delivery.

Additional comments:

Candidates were given credit for including valid points not included in the template. The detail of the studies given in the above template was not required for a pass mark.

Satisfactory answer for a pass mark was expected to include:

  • The uses of lactate monitoring 
  • Some reference to the supporting evidence
  • Limitations of lactate monitoring

Discussion

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.

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

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:

  • In sepsis, it is non-inferior to mixed venous saturation as a goal of early sepsis therapy (Jones et al, 2010).
  • Following cardiothoracic surgery, it can be used to guide therapy in haemodynamically unstable patients (though neither Pölönen et al in 2000 nor Shrestha et al in 2015 were able to demonstrate a statistically significant mortality benefit, because their studies were underpowered)
  • To target the use of GTN when ScvO2 normalised but lactate remained high : The literature on the subject is somewhat mixed. As an example, in 2010 Janssen et al used GTN to optimise the microcirculation along with several other EGDT-era manoeuvres (eg. the use of CVP to guide fluid responsiveness). GTN infusion was commenced if the lactate levels did not fall with conventional therapy even after the ScvO2 had returned to normal. Eight hours of such lactate-guided therapy produced a mortality reduction from 43.5% to 33.9%, which is weird because there was no difference in the lactate levels between the groups.  Ther practice is also mentioned in the review by Bakker et al (2013, where one of the et als was Janssen), where an (unpublished?) study by Lima et al (2012) is discussed, using GTN to normalise lactate . Bakker (also a co-author of Lima et al, 2012) was critical of this technique in his later review article, saying that the evidence did not support this use of lactate monitoring (or GTN infusion). 

References

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.

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.

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).

Lima A, van Genderen M, Van Bommel J, Bakker J: "Nitroglycerine dose-dependent improves peripheral perfusion in patients with circulatory shock: results of a prospective cross-over study". Intensive Care Med 2012, 38(Suppl 1):S127.- cited in Bakker et al, 2013

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.

Jansen, Tim C., et al. "Early lactate-guided therapy in intensive care unit patients: a multicenter, open-label, randomized controlled trial." American journal of respiratory and critical care medicine 182.6 (2010): 752-761.