Usefulness of lactate measurement in practice

Plasma lactate, a by-product of cellular anaerobic metabolism, has been used in human intensive care units alongside other clinical parameters to guide fluid therapy as well as providing prognostic information.

Recent years have seen an increasing interest in its use in veterinary medicine, particularly in critical patients where it can be used to guide therapy as well as being a prognostic indicator.

Cellular biology and lactate metabolism

An understanding of cellular biology and normal lactate metabolism is important to understand the possible use of measuring lactate in practice.

Glycolysis, the metabolic pathway in which glucose is converted to pyruvate for energy, is an important aspect of cellular biology. Energy released in this process is used to form the high-energy compounds adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH). For glycolysis to continue the NADH must be oxidised back to nicotinamide adenine dinucleotide (NAD). Under low oxygen conditions pyruvate alone is responsible for the regeneration of NAD and in the process is converted to lactate. Lactate can therefore be considered a by-product of anaerobic metabolism.

All cells can produce lactate under anaerobic conditions, but certain tissues produce excess lactate under normal conditions. These are the red blood cells, gastrointestinal tract, skeletal muscle, heart, brain and skin. Excess lactate is removed predominantly by the liver, as well as the kidneys and heart (Dugdale, 2010).

The normal reference range for lactate for healthy dogs has been reported as 0.3mmol/L to 2.5mmol/L (Hughes et al, 1999). Feline reference ranges are considered to be wider; values up to 5.33mmol/L have been reported in clinically healthy cats (Tynan et al, 2015).

Lactic acidosis is defined as elevated lactate with associated metabolic acidosis. Hyperlactataemia and lactic acidosis can be divided into two main types – A and B – with various subtypes (Table 1).

Type A lactic acidosis, as a result of tissue hypoxia, is the most common cause of hyperlactataemia (Lagutchik et al, 1998). It commonly occurs as a result of hypoperfusion or anaemia. Additionally, excessive consumption of tissue oxygen under certain conditions, such as during seizure activity and hypermetabolic states, leads to type A lactic acidosis. Type B lactic acidosis occurs under conditions of adequate tissue oxygen delivery, but altered mitochondrial function. Type B lactic acidosis has three subdivisions: type B1, a defect in production or decreased lactate clearance; type B2, interference of oxidative phosphorylation by drugs and toxins; and type B3-mitochondrial defects (Allen and Holm, 2008). Systemic diseases and sepsis are common causes of type B lactic acidosis.

Use in clinical practice

Assessment of hypovolaemia

Hypovolaemia leads to increased sympathetic tone and vasoconstriction and subsequently results in hypoperfusion and tissue hypoxia. Anaerobic metabolism ensues, leading to the production of lactate and type A hyperlactataemia (Dugdale, 2010). Blood lactate concentration is strongly correlated with other indicators of hypovolaemia, including heart rate and blood pressure. Higher blood lactate concentration has been shown in patients with systolic pressure less than 90mmHg (Reinke et al 2015).

Lactate measurement in patients showing signs of shock can therefore be considered a useful objective measure of tissue perfusion alongside blood pressure to guide fluid therapy. Moreover, due to the neural, hormonal and biochemical mechanisms employed during the initial phase of shock to maintain systemic blood pressure, lactate measurement can be considered a more sensitive measure of tissue perfusion than systolic blood pressure early in shock (Dugdale, 2010).

Prognosis information

There has been interest in the use of lactate levels as a predictor of outcome. Blood lactate concentration has been shown to be negatively associated with systolic blood pressure and survival probability; hypotensive dogs without hyperlactataemia had a better prognosis and chance of surviving to hospital discharge than hypotensive dogs with hyperlactataemia (Ateca et al, 2015).

Particular discussion in veterinary literature has been about use of lactate as a prognostic indicator for patients with gastric dilatation and volvulus.

Gastric dilatation leads to impaired venous return and decreased stroke volume, resulting in subsequent tissue hypoxia. Gastric dilatation and volvulus can also result in gastric necrosis, which has been associated with poor outcome. Plasma lactate concentrations >7.4mmol/L at presentation have been strongly correlated with gastric necrosis and worse prognosis (Beer et al, 2013).

Furthermore, persistent hyperlactataemia in patients with gastric dilatation and volvulus despite adequate fluid resuscitation has been shown to correlate with reduced survival (Green et al, 2011). Lactate measurements in this situation may alert the clinician to the severity of the disease prior to surgery, which can be communicated to the owners to make them aware of potential findings at surgery and risk.

Measuring the trends in lactate is considered more useful than single readings in evaluating prognosis. Serial plasma lactate levels in the first 6 to 12 hours of hospitalisation are crucial in guiding therapy. Dogs with lactate concentrations greater than the reference interval at 6 hours are more likely not to survive, compared with dogs with lactate concentrations within the reference interval (Stevenson et al, 2007).

Presence of persistent hyperlactataemia has been correlated with reduced survival in patients with idiopathic immune-mediated haemolytic anaemia and in predicting development of multiple organ failure in patients presenting in septic shock (Bakker et al, 1996; Holahan et al, 2010).

Use in diagnosis

Lactate is also a metabolite of bacterial fermentation. Concentrations of lactate in peritoneal fluid may be useful as a bedside test for diagnosis of septic peritonitis. Lactate levels of abdominal effusions >2.5mmol/L are considered to be strongly suggestive of septic effusion and a blood-to-fluid lactate difference <-2.0 mmol/L has been shown to be 100 per cent sensitive and specific for a diagnosis of septic peritoneal effusion (Bonczynski et al, 2004; Garrett et al, 2004). Lactate measurement of abdominal fluid is quick and easy to perform and should be considered a useful adjunctive to cytology for diagnosis of septic peritonitis.

Measurement of lactate in practice

Many point of care lactate measurement devices are available. Tabletop devices include the i-STAT¹, the EPOC², The EDGE³, Accutrend⁴ Lactate Pro⁵ and Lactate Scout⁶. These all have acceptable agreement with the laboratory analyser (Acierno et al, 2008). A small volume of blood (0.3ml) is required and the blood can be venous or arterial. However, venous sampling better reflects tissue perfusion than arterial samples. The sample needs to be run immediately and one must be efficient in sampling as prolonged use of a tourniquet can lead to localised increase in lactate.

Conclusion

Lactate, a by-product of anaerobic metabolism and measured in venous blood is a useful tool in the emergency patient. Lactate is considered a sensitive marker of tissue perfusion and therefore measuring it provides a guide for fluid resuscitation in shocked patients. Changes in lactate concentrations over time in response to therapy may also provide prognostic information and guide decision-making.

It is important to be aware of other causes of hyperlactataemia, including the effect of local tourniquets and systemic disease to ensure correct interpretation and subsequent action based on the results.

Acknowledgement

The author thanks Dominic Barfield, BSc, BVSc, MvetMed, DACVECC, DECVECC for reviewing this article.

Manufacturers

• 1. i-STAT Portable Handheld, Abbott Point of Care, Illinois, US.
• 2. EPOC, Woodley Equipment Company, UK.
• 3. The EDGE Handheld Lactate Analyser, Woodley Equipment Company, UK.
• 4. Accutrend Plus system, Cobas, US.
• 5. Lactate Pro 2, portable blood lactate analyser, Australia.
• 6. Lactate Scout, EKF Diagnostics, Germany.