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When oxygen delivery falls below a critical threshold, the anaerobic threshold, the amount of oxygen available for consumption is not able to meet the needs of cells. These imbalances result in cellular hypoxia, resulting in failure of mitochondrial oxidative phosphorylation, and as a result energy metabolism becomes wholly dependent upon anaerobic glycolysis1. Anaerobic glycolysis sharply increases the production of cellular lactate, which diffuses into the blood during prolonged cell ischemia. Elevated circulating lactate concentration thus often indicates widespread inadequate tissue oxygenation due to inadequate oxygen delivery and/or consumption 2. In this issue of Anesthesiology, Regnier et al present a prospective cohort analysis of the utility of lactate and lactate clearance measurements in the setting of the acutely traumatized patients3.
Numerous previous studies have documented the utility of lactate as a prognostic indicator in shock states 2;4. The use of lactate measurements is gaining recognition in critical care settings as a potential indicator of tissue hypoperfusion5;6. Furthermore, lactate screening as a method of risk stratification and prognosis has been shown to be beneficial in hemodynamically stable patients with suspected infection 5;7. Underscoring the importance of these data is the fact that point-of-care testing performed at the patient’s bedside is becoming more common 8, 9.
There are many evidence based, data-driven and logical arguments why lactate clearance monitoring is a superior therapeutic target than oxygen derived variables. First, the published experimental (randomized trial) evidence supporting the use of lactate clearance as a therapeutic target is more robust in terms of the number of multi-center studies10;11. Unlike oxygen derived variables, the ability to clear lactate has consistently predicted better survival in published studies of resuscitation12-15. Second, elevated lactate levels reflect the total picture of energy metabolism in the acutely stressed patient. Elevated blood lactate has long been known to reflect anaerobic metabolism from tissue hypoxia in critically ill patients2. However, besides these anaerobic processes, aerobic (metabolic) mechanisms that affect the host’s efficiency of energy transfer also contribute to lactate production. Cytokine mediated glucose uptake and catecholamine stimulated Na-K pump over-activity both can result in increased pyruvate production that eventually will overwhelm the catalytic capacity of pyruvate dehydrogenase and result in increased lactate due either to mass effect, sepsis induced pyruvate dehydrogenase dysfunction, or both. Additionally, reduced lactate clearance may reflect globally impaired metabolic function by the liver and kidney, both of which normally contribute to systemic lactate disposal through anaplerosis, a mechanism that carboxylates lactate and delivers it to the tricarboxylic acid cycle independent of the action of pyruvate dehydrogenase 16. Thus, lactate clearance biologically reflects more of the general homeostasis of the host and provides more meaningful data about the overall adequacy of the resuscitative processes.
Lactate clearance has previously been shown to be of value in monitoring several critically ill populations including sepsis10;12 and cardiac arrest17. With the present publication by Regnier et al we now have important evidence of the utility of lactate clearance in the acutely traumatized population3. There are several important conclusions that can be drawn from this interesting report. First, the early clearance of lactate provides additional important prognostic information beyond what is available from just single lactate measurements or severity of illness scores, particularly in the setting of patients who died early deaths. This additional information can assist the clinician to understand the adequacy of the resuscitative process that has been undertaken, the severity of the potentially ongoing insult, and the physiological responses to the insult-resuscitation interaction. Second, the data clearly support the paradigm of evaluating lactate clearance early in the clinical course, underscoring the rapidity with which the body identifies and reacts to lactate production. In fact, the reported data confirm that much of the clearance will take place in the first 2 hours and that there appears to be a plateau of the clearance effect at later time points (2 to 4 hours). This is likely due to the decrease in production with resuscitation and increase in clearance resulting in flattening of the relationship as depicted in Figure 2 of the report. Third, there appears to be an important threshold for achieving a lactate clearance of 20% per hour. This level is associated with a sharp drop in mortality, particularly among subjects with initial lactate levels between 2 and 10 millimoles/liter. Identification of this threshold is important inasmuch as it provides a numeric target for clinicians to consider as an important target to achieve. Additionally, this target is similar to those reported as important thresholds in other disease states10;11. Fourth and finally, an important finding by Regnier et al is that among normotensive subjects, neither initial lactate or lactate clearance contributed additional prognostic value beyond what was available in standard scoring systems. This suggests that lactate may have limited value in detecting occult hypoperfusion in the acutely traumatized patient. This finding is an important distinction to the established utility of lactate for identifying occult hypoperfusion in sepsis5;6;18.
As with any report, the report by Regnier et al has some important limitations which should be considered. First, this is an observational study and can only provide associative interactions rather than cause and effect interactions. Thus, the present observations are not adequate to change practice; however, they are important observations that could be carried forward in therapeutic experimental trials. And second, this study took place in France which has a different organized pre-hospital medical care system as compared to many other regions of the world. This effect could not be controlled and thus it is not clear if this had a confounding effect on the reported results.
In conclusion, the report by Regnier et al provides important new information suggesting that early lactate clearance in the setting of acute traumatic injury, particularly clearance rates of 20% per hour, provide important additional prognostic information beyond what is presently available from single lactate measurements and scoring systems. These observations support the continually emerging evidence that clearing lactate is always good, probably never bad and should be strongly considered as important information in the armamentarium of caring for the critically ill and injured.
Disclosure Dr Jones has received funding from the National Institutes of Health to study lactate clearance in sepsis resuscitation. Dr Jones has never been assigned patents, received patent royalties, honoraria, consulting fees, or other monetary or non-monetary payments at any time related to the use of lactate or lactate clearance.
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