Elevated Lactate – Not just a marker for sepsis and septic shock

LACTATE_Short.pngAs nurses working at the bedside, most of us are familiar with the common lab test, lactate. We know that when cells become hypoxic, lactate levels increase. While working in the intensive care unit, checking a lactate level was routine. Unfortunately, an elevated lactate level is typically a bad sign for the patient, often related to increased organ dysfunction and mortality. In recent years, the blood lactate level has gained wide acceptance as an important marker in the diagnosis of sepsis and septic shock and is useful in evaluating response to fluid resuscitation. An elevated lactate is not only a marker for sepsis and septic shock – it may signal other important clinical conditions as well. So, what is lactate and what exactly does it tell us?

Lactate is an organic molecule produced by most tissues in the human body, with the highest production found in muscle.1 Here’s a quick and basic review of how lactate is produced. The body normally produces energy by way of aerobic metabolism, which requires oxygen to break down carbohydrates, amino acids, and fats. Via glycolysis, glucose is converted into pyruvate, which enters the Krebs cycle to produce oxygen and adenosine triphosphate (ATP) or energy. If oxygen isn’t available to body cells, anaerobic metabolism kicks in to produce energy. In this pathway, pyruvate is metabolized by the enzyme lactate dehydrogenase (LDH) into lactate.2 Lactate leaves the cells, enters the bloodstream, and transports to the liver, where it is oxidized back to pyruvate and then converted to glucose via the Cori cycle.1,2  Lactate is cleared from the blood, primarily by the liver and, to a lesser extent, by the kidneys and skeletal muscles.2

A normal blood lactate level is 0.5-1 mmol/L. Hyperlactatemia is defined as a persistent, mild to moderately elevated (2-4 mmol/L) lactate level without metabolic acidosis.2 This can occur with adequate tissue perfusion and tissue oxygenation. A level > 4 mmol/L defines lactic acidosis3, a level high enough to tip the acid-base balance, which may result in a serum pH < 7.35 in association with metabolic acidosis. Lactate can be measured from both venous and arterial blood.  Serum samples should be processed within 15 minutes to avoid falsely elevated results. If processing cannot occur within this time frame, the sample should be kept on ice.

Hyperlactatemia and lactic acidosis may occur with an increase in lactate production, a decrease in lactate clearance, or a combination of both.3 An increase in lactate production is typically caused by impaired tissue oxygenation, either from decreased oxygen delivery or a disorder in oxygen use, both of which lead to increased anaerobic metabolism.3 Most causes of lactic acidosis are due to significant, systemic tissue hypoperfusion, referred to as type A lactic acidosis. Alternately, in Type B lactic acidosis, the etiology may be related to toxic-induced impairment of cellular metabolism, local hypoperfusion (i.e. regional ischemia) or in many instances, the mechanism is unknown. Below are some common causes of lactic acidosis:

Type A:
  • Sepsis and septic shock: dysfunction in the microcirculation (where oxygen is exchanged) leads to lactate production, while decreased oxygen delivery contributes to a decrease in lactate clearance.3
  • Cardiogenic, obstructive and hemorrhagic shock: may cause decreased oxygen delivery and hypoperfusion.
  • Cardiac arrest: ischemia and inflammation following cardiac arrest may cause an increase in lactate.
  • Severe lung disease, respiratory failure or pulmonary edema: excessive work of breathing causes anaerobic muscle activity.
  • Trauma: hypoperfusion due to blood loss is common in trauma patients and may lead to elevated lactate levels.

Type B:
  • Seizures: depending on the type, seizures can produce a significant increase in lactate, but the effect is short-term; once the seizure has resolved, lactate levels typically return to baseline.
  • Excessive muscle activity: lactate increases with strenuous exercise due to anaerobic metabolism and may be seen in rhabdomyolysis.
  • Regional ischemia: mesenteric ischemia, bacterial peritonitis, acute pancreatitis, extremity compartment syndrome, gangrene and other types of soft tissue infections may elevate lactate.
  • Burns and smoke inhalation: smoke inhalation victims are at risk of elevated lactate due to potential inhalation of cyanide and/or carbon monoxide.
  • Diabetic ketoacidosis (DKA): due to a change in metabolism; elevated lactate in DKA is not necessarily associated with worse outcomes.
  • Thiamine deficiency: low thiamine levels result in anaerobic metabolism and increased lactate production; risk factors for thiamine deficiency include poor nutrition, chronic liver disease, alcoholism, hyperemesis gravidarum, anorexia nervosa, and gastric bypass surgery.
  • Malignancy: tumors may cause production of glycolytic enzymes, impaired liver clearance and malnutrition leading to thiamine deficiency.
  • Liver dysfunction: the liver is the primary organ responsible for lactate clearance; injury or failure results in decreased lactate clearance.
  • Genetic: inborn disorders of metabolism, particularly in the pediatric population, may cause elevated lactate levels.
  • Drugs and Toxins that may cause increased lactate:
    • Metformin (biguanide)
    • Acetaminophen
    • (Nucleoside reverse transcriptase inhibitors (NRTI)
    • Linezolid
    • Beta-2 agonists
    • Propofol
    • Epinephrine
    • Theophylline
    • Alcohols (ethanol, propylene glycol and methanol)
    • Cocaine
    • Carbon monoxide
    • Cyanide
Treatment of elevated lactate levels should be determined by the underlying cause. If hypoperfusion or hypoxemia is the culprit, focus on improving perfusion to the affected tissues. In shock, treatments include fluid administration, vasopressors, or inotropes. In regional ischemia, surgery may be needed to restore circulation or remove damaged tissue.1 If drugs, seizures, malignancy, or thiamine deficiency is the cause, stop, reverse, and treat the offending agent.1 Multiple conditions can contribute to lactic acidosis, therefore it is critical to carefully evaluate the patient’s complete medical history, conduct a thorough physical assessment, and assess other laboratory or diagnostic tests before beginning treatment.

Myrna B. Schnur, RN, MSN 

1. Anderson, L.W., Mackenhauer, J., Roberts, J.C., Berg, K.M., Cocchi, M.N., and Donnino M.W. (2013, October). Etiology and therapeutic approach to elevated lactate. Mayo Clinic Proceedings, 88(10), 1127- 1140.
2. Lactic acidosis. (2017, January) Retrieved on 1/31/2017 from http://emedicine.medscape.com/article/167027-overview
3. Causes of lactic acidosis. (2017, January) Retrieved on 1/17/2017 from https://www.uptodate.com/contents/causes-of-lactic-acidosis?source=search_result&search=plasma%20lactate%20concentration&selectedTitle=1~150

More Reading & Resources
Laboratory signs of sepsis [Infographic]
The Subtle Signs of Sepsis [Infographic]
Making Sense of the Updated Sepsis Definitions
Focus On: Sepsis


Posted: 3/17/2017 7:59:23 AM by Lisa Bonsall, MSN, RN, CRNP | with 0 comments

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