The Use of Lactate as a Biomarker

Abstract

Lactate is the base of lactic acid, first isolated by the Swedish chemist Carl Wilhelm Scheele in 1780. Since that time, lactate has been the focus of much attention in prominent scientific research, playing a role in the work of Nobel Prize laureates Otto Meyerhof, Archibald Hill, Carl Cori, Gerty Cori, and Hans Krebs. Huckabee was the first to detail hyperlactatemia and associated acidosis as a distinct clinical entity. Contemporary investigations have evaluated the use of lactate to assist in measuring the severity of acute illness, diagnosing disease states, predicting mortality, and assessing response to resuscitation. As with all biomarkers of disease, an understanding of the underlying physiology informs clinicians of the potential strengths and weaknesses of the use of serum lactate. Furthermore, clinical research seeks to define the role of serum lactate at the point of care. At one end of the spectrum, we can review a biochemistry text and understand the stoichiometric relationship between glucose and lactate in aerobic and anaerobic conditions; at the other extreme, we can correlate lactate levels with outcome in acutely ill patients. Between the bench and the bedside, it is necessary to refine our thinking, to organize our approach to serum lactate in a way that is both consistent with the basic science and optimally useful in the clinical setting. Classically, this link was provided by the division of lactic acidosis as type ‘‘A’’ or ‘‘B.’’ This classification scheme identifies ‘‘Type A’’ lactic acidosis as occurring in the setting of decreased perfusion or tissue oxygenation, whereas ‘‘Type B’’ lactic acidosis is concordant with underlying organ dysfunction, toxins, or metabolic errors. Of note, there is controversy that extends beyond semantics with regard to ‘‘lactic acidosis’’ and its relationship to metabolic acidosis. Some authors propose that there is no evidence to support the notion that lactate production causes acidosis. Rather, the acidosis is caused by ATP hydrolysis. Simply put, these authors propose that the term and concept of ‘‘lactic acidosis’’ should be rejected as the construct is not biochemically valid. More accurately, in a clinical context, lactate accumulation may coexist with an acidosis, such that the rise in lactate and the fall in pH occur concomitantly but not necessarily in a causal fashion. Thus, describing and analyzing serum lactate independent of changes in acid-base status may be the more sound physiologic paradigm. In this issue of the Journal of Intensive Care Medicine, Drs Kjelland and Djogovic propose a new approach to lactate accumulation based on precellular, cellular, and postcellular mechanisms. The authors review and grade the current body of literature organized by 3 patient presentations corresponding to their classification scheme. The authors conceptualize hyperlactatemia in a logical way, without relying on the controversial notion of ‘‘lactic acidosis.’’ Their proposed classification and grading of the evidence summarizes an otherwise broad topic in an intuitive way that acute care physicians may find useful. Moreover, this rigorous review helps to identify the gaps in our understanding of serum lactate and carries implications for future efforts. Unfortunately, their classification scheme may fail the clinician at times because increases in serum lactate can occur clinically due to several causes at the same time. Thus, patients in early septic shock may have increases in lactate due to poor perfusion as a consequence of hypovolemia and cardiac dysfunction (precellular cause as enumerated by the authors), impaired mitochondrial respiration (cellular cause), and altered clearance due to liver dysfunction (postcellular). Consequently, the approach advocated by the authors may be insufficient at times to help guide the management of the patient. Several areas of lactate research are poised for further development.