Sepsis is something that is generating an impressive amount of research in Pediatric Emergency Medicine right now. From recognition, to electronic monitoring and care bundles we are doing our best to recognize and manage children in and at risk for sepsis as early as possible. The purpose of this post is to discuss one lab test that is helpful in the stratification of risk in children with SIRS, sepsis, septic shock, severe sepsis – basically the whole gamut. That lab is…

Lactate

First, some definitions

SIRS Criteria

≥ 2 meets SIRS definition, 1 of which must be abnormal temperature or leukocyte count

  • Temp >38.5°C (101.3°F) or < 36°C (96.8°F)
  • Tachycardia (or Bradycardia if <1 year)
  • Tachypnea or Mechanical Ventilation Needed
  • Abnormal leukocyte count or >10% bands

Sepsis

  • SIRS + a suspected or known source of infection

Severe Sepsis

Sepsis + ≥ 1 of the following (Click here for organ dysfunction criteria)
  • Cardiovascular Dysfunction
    or
  • ARDS
    or
  • ≥ 2 Other Organ Dysfunction

Septic Shock Criteria

Sepsis + Cardiovascular Dysfunction

  • Cardiovascular Dysfunction despite adequate fluid resuscitation

A tiny bit of biochemistry

For the purposes of this post lactic acid = lactate. It is more complicated than that – but I don’t want to go too deep into the weeds. And, just so that your memory is jostled ever so slightly…

With NORMAL perfusion

  • Aerobic metabolism
  • Pyruvate is converted to acetyl CoA

With ABNORMAL perfusion

  • Anaerobic metabolism
  • pyruvate is converted to lactate (less ATP)

Lactic acid is basally produced in muscle, brain, RBCs and the kidneys. Normally it is <1 mmol/L. But, it can be increased after:

  • Seizure
  • Heavy exercise
  • Shivering
  • Shock

The well perfused body clears it readily. But, in the ill child, anaerobic metabolism predominates, and the lactate that builds up can’t be cleared. So, in a way, lactate is a marker of strained metabolism.

Lactate and mortality

The evidence

Early studies (on rats) showed that lactate elevation was associated with mortality Weil, Circulation, 1970. Then, (still before I was born) human studies noted that “the case fatality rate in patients in whom blood lactate exceeded 2.7 mM was 50%. The fatality rate was 5% when lactate was less than 2.7 mM.” Cady, Crit Care Med, 1973. This certainly peaked the interest of researchers who were looking for a way to quantify mortality risk in severely ill patients in whom the clinical assessment was mired in uncertainty.
In the ensuing decades research in adults has outstripped that in children (as is usually the case). For example:
Shapiro, Ann Emerg Med, 2005
  • Mortality rate of lactate <2.5 mmol/L = 4.9%
  • Lactate ≥ 4 mmol/L = 28.4%
  • Furthermore ≥ 4 was 36% sensitive and 92% specific for any death
Howell, Intensive Care Med, 2007
  • Lactate >4 increased mortality in normotensive patients

Mikkelson, Crit Care Med, 2009

  • In adults with severe sepsis/septic shock a lactate >4 is associated with mortality with an OR=4.87

Puskarich, Acad Emerg Med, 2012

  • Lactate mortality risk scales with incremental increases
  • Mortality is 6% for lactate <1 but up to 39% for 19-20

Evidence in kids

Wow, that’s a lot of evidence on grown ups. But what about kids? Well, here you go…

Scott, Acad Emerg Med, 2012

  • High lactate increased the risk of organ dysfunction, need for IV fluids, antibiotics and ICU admission

Jat, Indian J Crit Care Med, 2011

  • A lactate >5 mmol/L at various times after PICU admission had increased odds of mortality
    • 0–3 hours: OR=6.7, PPV=38%, NPV=80%
    • 12 hours: OR=12.5, PPV=71%, NPV=83%
    • 24 hours: OR=8.6, PPV=64%, NPV=83%

Bai, BMC Pediatrics, 2014

  • A high lactate level upon admission was associated with mortality (OR = 1.17; 95% CI, 1.07-1.29; p = 0.001)
  • The sensitivity of 61% and a specificity of 86%, and positive and negative likelihood ratios of  4.5 and 0.45 respectively were at a cut-off value of >5.55 mmol/L

What about just using the anion gap?

According to Rivers, NEJM, 2001 an elevated AG (>12) is 52.8% sensitive and 81.0% specific with a negative predictive value of 89.7% for the prediction of lactic acidosis. A normal bicarb in 22% and normal AG are seen in 25% of patients with a lactate 4-6.9 mmol/L. So therefore, just because the gap is “normal” it doesn’t mean the lactate is.

Don’t I have to get an arterial sample?

Getting an art-stick on a kid is hard. Is a venous lactate fine? Klein, Acta Med Austriaca, 1976 noted that the correlation coefficient between venous and arterial samples for blood lactate was 0.94. No matter what send it as one of the first labs if there’s a tourniquet. Also, the sample will be OK for 15 minutes at room temp.

Are there any false positive that I should worry about?

Generally a lactate >4 is bad if you are worried about the kid. Be aware that patients using beta agonists (asthma) can have a high lactate too. Other conditions with elevated lactate include:

  • Liver failure (poor clearance)
  • Exercise (marathon runner with heat exhaustion/stroke)
  • Post-seizure

In summary

  • >4 is bad and associated with increased odds of mortality
  • Don’t let it be the only thing you use to make the sick vs not-sick differentiation
  • A venous sample is fine
  • It is not inferior to more invasive early-goal directed therapy monitoring resources
  • Clearance may be an important prognostic factor as therapeutic response is monitored