Nam K. Tran, PhD, HCLD (ABB), FACB, Director of Clinical Chemistry and Point-of-Care Testing
Kelly Lima, BS, PhD Student
Rachel Caynak, BS, Medical Student

Background

Lactate testing plays a critical role in sepsis management.1 Previously, a blood lactate level of >4 mmol/L was used to help identify patients with severe sepsis and septic shock. SEPSIS-3 guidelines proposed in 2016 have suggested moving the blood lactate cut off to >2 mmol/L.2,3 This lower lactate cut off is reflected in Centers for Medicare and Medicaid Services (CMS) “Sepsis Bundles”.4 Unfortunately, lactate testing has several limitations which may impact clinical interpretation.

Lack of Standardization of Lactate and Pre-Analytical Factors

Prior studies conducted at the UC Davis Health Clinical Laboratory suggest lactate measurements may be off by as much as 1.5 mmol/L for values >2 mmol/L and potentially causing misclassification of sepsis severity.5 Unlikely other common analytes such as electrolytes (e.g., sodium or potassium), or metabolites such as creatinine and glucose, lactate testing is not standardized. Standardization of chemistry tests ideally requires a traceable reference material for calibration. For example, serum creatinine is standardized to a higher order testing method known as isotope dilution mass spectrometry (IDMS).6 IDMS techniques measure exact concentrations of creatinine which help align everyday laboratory testing platforms used for routine patient care. Standardization enables results from one platform to another to be more comparable. In contrast, no reference method or traceable material exists for lactate—resulting in non-standardized testing.7 This issue is further complicated by pre-analytical factors leading to inaccurate results. Pre-analytical factors include testing delays and interfering substances. Delays in sample testing can result in falsely high lactate levels. Inhibition of erythrocyte metabolism by sodium fluoride preservatives (“gray top tubes”) is neither immediate nor complete, while placement on ice only slows cellular metabolism.8 Other pre-analytical factors include the presence of interfering medications and physiologic factors that may alter lactate measurements.9

Lab Best Practice

Trending of lactate measurements should be performed using a single platform. Mixing and matching results from multiple platforms could result in inappropriate result interpretation. Pre-analytical error may be minimized by ensuring rapid transportation of specimens, and as needed, using ice. Point-of-care lactate measurements has also been suggested to improve analytical performance by minimizing the time from collection to actual testing.5 Caution is advised in adopting any point-of-care lactate testing since not all devices, like glucose meters, are created equal.

References

  1. Surviving Sepsis Campaign website: http://www.survivingsepsis.org/SiteCollection Documents/ Bundle-3-Hour-Step1-Measure-Lactate.pdf, Accessed on August 1, 2018
  2. Singer M, Deutschman C, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA 2016;315:801-810.
  3. Sartelli M, Kluger Y, Ansaloni L, et al. Raising concerns about sepsis-3 definitions. World J Emerg Surg 2018;13:6.
  4. Raschke RA, Groves RH, Khurana HS, et al. A quality improvement project to improve the Medicare and Medicaid Services (CMS) sepsis bundle compliance rate in a large healthcare system. BMJ Open Quality 2017;6:e00080.
  5. Lima K, Caynak R, Tran NK. Lactate monitoring for severe sepsis and septic shock: are all lactate measurements the same? Crit Care Med 2016;44:443.
  6. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) website: https://www.niddk.nih.gov/health-information/communication-programs/ nkdep/laboratory-evaluation/glomerular-filtration-rate/creatinine-standardization/recommendations, Accessed on August 1, 2018.
  7. Ridenour RV, Gada RP, Brost BC, Karon BS. Comparison of lactate values between point-of-care and central laboratory analyzers. Am J Clin Pathol 2007;128:168-171.
  8. Rako I, Mlinaric A, Dozelencic M, et al. Effect of different pre-analytical conditions on plasma lactate concentration. Biochem Med 2018;28:020701.
  9. Godwin Z, Lima K, Greenhalgh DG, et al. A retrospective analysis of clinical laboratory interferences caused by frequent administration of medications. J Burn Care Res 2016;37:e10-e17.