Utility of Obtaining a Lactate Measurement in the ED

Authors: Tyler Hurst, DO and Christopher Doty, MD

(Residency Physician and Program Director, respectively, for University of Kentucky Emergency Medicine Residency Program)

Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Stephen Alerhand, MD

Background

Lactate was first proposed as a prognostic biomarker in 1964 by Broder and Weil who observed that a lactate excess of >4 mmol/L was associated with poor outcomes in patients with undifferentiated shock (1).

After the Rivers Trial, the majority of medical studies regarding lactate have examined its use as a biomarker and resuscitation endpoint in patients with sepsis and septic shock.

An elevated lactate is not specific to septic shock. Any process that causes tissue hypoperfusion and subsequent anaerobic metabolism can lead to an elevated lactate.

There are many conditions other than shock that may lead to an elevated lactate: mesenteric ischemia, liver failure, DKA, and certain medications/toxicological causes.

The Basics

Lactate is the byproduct of anaerobic metabolism. It is cleared primarily by hepatic metabolism and to a lesser extent by renal excretion. The half-life of lactate is approximately 20 min.

Lactate is generally measured in mmol/L with the normal value considered to be < 2 mmol/L and an abnormal value is generally considered > 4 mmol/L.

Lactic acidosis is a common cause of metabolic anion gap acidosis. The blood lactate level in mmol/L contributes to elevating the anion gap in a 1:1 ratio.

Lactic acidosis is broken down into two subtypes Type A lactic acidosis is seen in states of hypoperfusion or poor oxygenation. Type B lactic acidosis is seen in states of high metabolism, organ dysfunction, and toxins .



Blood samples should be processed within < 15-30 min after being drawn. Samples are run on a blood gas analyzer with results obtained in 2-3 min.

Venous lactate levels are equivalent to arterial lactate levels, which negates the need for an arterial puncture when obtaining a lactate measurement (2).

Trauma

Advanced trauma life support is heavily reliant on vital sign abnormalities to identify patients in shock. Tissue hypoperfusion, usually from blood loss, is common in trauma patients and will not always be apparent from vital sign abnormalities. For this reason most trauma protocols include a lactate measurement.

In trauma, a lactate >4 mmol/L is associated with a mortality of nearly 20%. Amongst patients with an initial lactate > 4mmol/L, clearance at 6 hours is associated with increased survival (3).

Septic Shock

One-half of patients with severe sepsis will have a systolic BP >90mmHg and one-fifth will have a normal blood pressure with a MAP of > 100mmHg. This has led experts to propose lactate as a screening tool on any patient meeting SIRS criteria (4).

Normotensive patients with a lactate >4 mmol/L have a mortality rate of 30% (5).

Amongst septic patients with a lactate greater than 4 mmol/L, clearance at 6 hours is associated with increased survival (6). Studies comparing lactate clearance and SVO2 monitoring as a guide to adequate resuscitation have shown lactate clearance to be non-inferior to SVO2 in terms of in-hospital mortality (7).

Cardiogenic/Obstructive shock

Fewer studies have been performed studying lactate in cardiogenic and obstructive shock. In patients with ST-segment myocardial infarction, a lactate clearance of <10% at 12 hours identified a subset of patients at higher risk for death (8).

Patients with pulmonary embolism and a lactate level ≥ 2 mmol/L had a mortality of nearly 20% (9).

Regional tissue ischemia

Mesenteric ischemia is a potentially difficult condition to diagnose. Lactate has a high sensitivity (96%) but low specificity (38%) when studied as a biomarker for acute mesenteric ischemia (10). In a patient with abdominal pain, an elevated lactate should raise the concern for mesenteric ischemia.

An elevated lactate can also be seen in acute limb ischemia, compartment syndrome, and necrotizing fasciitis.

Other causes

Acute or chronic liver failure can lead to an elevated lactate, as the liver is the primary organ responsible for its metabolism. In critically ill patients with chronic liver disease, an elevated lactate is still associated with increased risk of mortality (11).

In patients with diabetic ketoacidosis, lactate is commonly found to be elevated. The mechanism is not completely understood, but is thought to be due to hypoperfusion as well as altered glucose metabolism. An elevated lactate in patients with DKA does not correlate with increased mortality or increased ICU length of stay (12).

Toxicology

Common drugs/toxins associated with an elevated lactate are: alcohols, stimulants, carbon monoxide, cyanide, linezolid, nucleoside reverse transcriptase inhibitors, Metformin, Propofol, and acetaminophen.

Hypermetabolic states

Any state of prolonged vigorous muscular activity can lead to an elevated lactate. Commonly seen examples in an ED population are: patients who just suffered a seizure, those who are restrained and are straining against restraints, and athletes recently engaged in intense physical activity.

Asthmatics may have elevated lactate both from greatly increased muscular work of breathing and the fact that beta-agonists like albuterol can increase lactate levels.

Additional Editor Pearls

Elderly patients may not necessarily produce lactate levels corresponding to their level of illness severity. Do not disregard an elderly sick patient simply based on a low-normal lactate.

An elevated lactate in a patient with otherwise normal vital signs may be a harbinger of coming vital sign instability and/or SIRS, as shown by the Rivers trial (above).

Lactate may only be a late finding in acute mesenteric ischemia.

So I’ve obtained a lactate, now what?

A normal lactate does not exclude dangerous conditions, just as a high lactate does not always correlate with increased mortality.

In a patient with a lactate >4 mmol/L or even >2 mmol/L, this should raise your concern for a potentially dangerous condition. If this patient is clinically stable and without deranged vital signs, it is reasonable to judiciously resuscitate them with fluids and recheck a lactate level in 2 hours. If the patient is unstable or has vital sign abnormalities suggestive of shock, this patient is likely critically ill and in need of emergent intervention.

In the clinically stable patient whose lactate remains elevated despite adequate resuscitation, the clinician must consider that this patient could be seriously ill and look for possible confounding sources such as: mesenteric ischemia, occult hemorrhage, or untreated infection.

Bottom line

A venous lactate is an easy-to-obtain and quick-to-result biomarker for mortality in critically ill patients.

One of the main responsibilities of an ER doctor is to identify those patients who are at highest risk for mortality. Unfortunately, not all critically ill patients will present with abnormal vital signs or obvious blood loss. Obtaining a lactate can potentially identify those patients in occult shock and reduce mortality by expediting definitive treatment.

References / Further Reading

1.) Broder G, Weil MH. Excess Lactate: An Index of Reversibility of Shock in Human Patients. Science. 1964; 143:1457–1459.

2.) Younger JG, Falk JL, Rothrock SG. Relationship between arterial and peripheral venous lactate levels. Acad Emerg Med 1996; 3:730-4.

3.) Odom SR, Howell MD, Silva GS, et al. Lactate clearance as a predictor of mortality in trauma patients. The journal of trauma and acute care surgery 2013; 74(4):999–1004.

4.) Singer AJ, Taylor M, Domingo A, Ghazipura S, Khorasonchi A, Thode, HC, Shapiro NI. Diagnostic characteristics of a clinical screening tool in combination with measuring bedside lactate level in emergency department patients with suspected sepsis. Academic emergency medicine 2014; 21:853–857

5.) Shapiro NI, Howell MD, Talmor D, et al. Serum lactate as a predictor of mortality in emergency department patients with infection. Annals of emergency medicine 2005; 45(5):524–528.

6.) Arnold RC, Shapiro NI, Jones AE, et al. Multicenter study of early lactate clearance as a determinant of survival in patients with presumed sepsis. Shock 2009; 32(1):35–39.

7.) Jones AE, Shapiro MI, Trzeciak S, et al. Lactate clearance vs. central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA 2010; 303:739–46.

8.) Attana P, Lazzeri C, Chiostri M, Picariello C, Gensini GF, Valente S. Lactate clearance in cardiogenic shock following ST elevation myocardial infarction: a pilot study. Acute cardiac care 2012; 14(1):20–26.

9.) Vanni S, Viviani G, Baioni M, et al. Prognostic value of plasma lactate levels among patients with acute pulmonary embolism: the thrombo-embolism lactate outcome study. Annals of emergency medicine 2013; 61(3):330–338.

10.) Lange H, Toivola A. Warning signals in acute abdominal disorders. Lactate is the best marker of mesenteric ischemia. Lakartidningen 1997; 94(20):1893–1896.

11.) Kruse JA, Zaidi SA, Carlson RW. Significance of blood lactate levels in critically ill patients with liver disease. The American journal of medicine 1987; 83(1):77–82.

12.) Cox, KC.; NC; Carney, EE.; Howell, MD.; Donnino, MW. Prevalence and significance of lactic acidosis in diabetic ketoacidosis. Journal of Critical Care 2012; 27(2):132–137.

13.) http://www.ncbi.nlm.nih.gov/pubmed/25186838

14.) http://www.ncbi.nlm.nih.gov/pubmed/25450570

15.) http://www.ncbi.nlm.nih.gov/pubmed/25432592

16.) http://www.ncbi.nlm.nih.gov/pubmed/25466313

17.) http://www.ncbi.nlm.nih.gov/pubmed/25325409

18.) http://www.ncbi.nlm.nih.gov/pubmed/25124137

19.) http://www.ncbi.nlm.nih.gov/pubmed/24776606

20.) http://www.ncbi.nlm.nih.gov/pubmed/24079682