Rich Greene, PA-C
You pick up the charts to begin your shift…
- 37 yo male doing roofing (or marathon runner) and the outside temperature is in the 90s with 70% humidity…elevated temperature and also feels dehydrated
- 83 yo female sent by nursing home…doesn’t appear right and also has a fever
- 25 yo male, known diabetic has been vomiting and doesn’t feel good, fingerstick glucose was also above 500
- 21 yo female following an overdose and Narcan revival. EMS states mother was on scene doing compressions when they arrived.
- 43 yo male, known seizure history and non-compliant with medications presents following 3 seizures today and is actively seizing on the EMS stretcher
After obtaining initial lab studies, you receive multiple phone calls from your lab and nursing staff informing you that due to elevated WBC and elevated lactic acid ALL of your patients now also meet sepsis alert criteria. What do you do now?!?
Better yet, our clinical question to answer is, “What do I do with an elevated lactic acid?”
If you are currently practicing in emergency medicine, critical care, or hospitalist settings you are no doubt familiar with the “Surviving Sepsis Campaign.” This campaign was started in 2002 by the Society of Critical Care Medicine to use evidence-based guidelines to reduce the relative risk of death by 25% in severe sepsis and septic shock. One of the critical markers put forth was lactic acid level and, consequently, this lab test is now drawn on a very routine basis. But not all elevated lactic acid lab values indicate a septic patient. It may also signal other important conditions as well. Before we delve into the clinical implications of this lab test, let’s answer what is lactic acid and what does it tell us?
QUICK REVIEW: KREB’S CYCLE AND CORI CYCLE
Lactate (or lactic acid) is a byproduct of anaerobic cellular respiration. In summary, our body normally produces energy from glucose through a process described by the Kreb’s cycle. During the glycolysis phase, glucose is reduced to pyruvate. In the presence of oxygen (an aerobic process), pyruvate enters the Kreb’s cycle to produce energy. When oxygen is absent (the anaerobic process), the pyruvate enters the Cori cycle to produce energy. In the Cori cycle, the pyruvate is metabolized by lactate dehydrogenase (LDH) into lactate/lactic acid. Lactate then leaves the cells, enters the bloodstream, and is transported to the liver. In the liver, it is oxidized back to pyruvate and then back to glucose. Lactate is primarily cleared by the liver and also by skeletal muscle and the kidneys.
CLINICAL IMPLICATIONS OF LACTIC ACIDOSIS:
Clinically, a normal lactic acid level is 0.5-1 mmol/L. An elevate value above 2 mmol/L is the threshold to show impaired organ function and also generate a “sepsis alert”. Any elevated value is the result of overproduction of lactate, impaired clearance of lactate, or also a combination of both. Because this indicates an anaerobic process, we must understand that this is from impaired tissue oxygenation (decreased oxygen delivery or disorder of oxygen use).
PATHOPHYSIOLOGIC CLASSIFICATION OF LACTIC ACIDOSIS
|Ischemia: Shock, sever anemia, cardiac arrest||Delayed Clearance: renal or hepatic dysfunction|
|Global Hypoxia: carbon monoxide poisoning||Pyruvate Dehydrogenase dysfunction: sepsis, thiamine deficiency, alcoholic or diabetic ketoacidosis, catecholamine excess|
|Respiratory failure: severe asthma, COPD, asphyxia||Uncoupling of Oxidative Phosphorylation: cyanide, salicylates, methanol and ethanol, anti-retroviral drugs, valproic acid, biguanides, INH|
|Regional hypoperfusion: limb or mesenteric ischemia||Acclerated aerobic glycolysis: increased effort, sepsis, seizure, malignancy, large fructose load|
However, we must differentiate between two terms: Hyperlactatemia and lactic acidosis. Hyperlactatemia is a mild elevation of lactate values (2-4 mmol/L) without also developing a metabolic acidosis. Lactic acidosis has higher lactate levels (>4 mmol/L) in association with a metabolic acidosis resulting in a serum pH <7.35. Hyperlactatemia can occur in the setting of adequate tissue perfusion, intact buffering systems, and adequate tissue oxygenation. On the other hand, lactic acidosis is associated with major metabolic dysfunction, tissue hypoperfusion, and the effects of certain drugs or congenital abnormalities with carbohydrate metabolism. Likewise, numerous etiologies may be responsible for the presence of lactic acidosis, most commonly circulatory failure and hypoxia. Most causes of lactic acidosis are due to tissue hypoperfusion (Type A lactic acidosis). In Type B lactic acidosis, there are many etiologies and in many instances the cause is unknown.
|TYPE A||TYPE B|
|Sepsis and Septic shock: dysfunction of microcirculation leads to lactate production, while decreased oxygen delivery contributes to a decrease in lactate clearance||Seizure: can produce a significant increase in lactate. This is only short term and once seizure resolves, levels typically return to baseline|
|Cardiogenic, obstructive, or hemorrhagic shock: decreased oxygen delivery and hypoperfusion||Excessive muscle activity: lactate increases with strenuous activity due to anaerobic metabolism or rhabdomyolysis|
|Cardiac arrest: ischemia and inflammation following cardiac arrest increases lactate||Regional ischemia: mesenteric ischemia, pancreatitis, compartment syndrome, gangrene or other soft tissue infections|
|Severe lung disease, respiratory failure, or pulmonary edema: excessive work of breathing causes anaerobic muscle activity||Diabetic ketoacidosis: change in glucose metabolism increases lactate levels|
|Trauma: hypoperfusion due to blood loss leads to increased lactate levels||Drugs and Toxins|
Back to the question…
“What do I do with an elevated lactic acid?” As we have stated, not every elevated lactic acid level is caused by sepsis. The short answer is, treat the underlying cause. The longer answer is that based on our history and physical exam, we also should have a clinical gestalt of what the clinical picture entails. Additionally, clinicians should order testing to rule-in or rule-out conditions. Why did we order the lactate level to begin with? Again, this will be based on our clinical picture and history.
If the underlying cause is hypoperfusion or hypoxemia, treatment should focus on improving perfusion to the affected tissues using fluids or pressors. In cases of regional ischemia, there may be a need to consult a vascular surgeon. If drugs, toxins, or seizures are the cause, treat the appropriate toxidrome with the reversal agent or also abortive medication. In general, many conditions can create a lactic acidosis. Regardless, treat the underlying cause based on your history, physical exam, and other lab values.
- Kreb’s and Cori cycle photo: https://acutecaretesting.org/en/articles/lactate-and-lactic-acidosis/
- Pathophysiologic Classification of Lactic Acidosis: Gunnerson, Kyle. “Lactic Acidosis,” https://emedicine.medscape.com/article/167027-overview
- Type A and Type Designations of Lactic Acidosis: Schnur, Myrna. “Elevated Lactate—Not just a marker for sepsis and septic shock,” https://www.nursingcenter.com/ncblog/march-2017/elevated-lactate-–-not-just-a-marker-for-sepsis-an
- Marshall, John. “The Survivng Sepsis Campaign: a history and perspective,” https://pubmed.ncbi.nlm.nih.gov/20524900/
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