Lactate is GOOD for the patient and not BAD

It would appear that despite intense scientific inquiry most clinicians still believe that the Earth is flat and that an increased serum lactate is the result of impaired tissue oxygen delivery and anaerobic metabolism. This concept is perpetuated by The Surviving Sepsis Campaign who state “we suggest targeting resuscitation to normalize lactate in patients with elevated lactate levels AS A MARKER OF HYPOPERFUSION.” These concepts are WRONG.

The understanding of Lactate is shrouded with misconceptions and myths. These are briefly reviewed below.

Humans are not yeast and rarely produce lactate anaerobically. It is widely regarded (and likely incorrect) that in the setting of sepsis, an increased lactate is a marker of impaired microcirculatory flow and anaerobic metabolism. There is however convincing clinical and experimental data that the increased lactate is as a result of increased B2 adrenergic activation (as part of the stress response) with greater production of pyruvate than can enter the Krebs cycle. Hence lactate accumulates aerobically (analogous situation to increased lactate production during exercise). B2 adrenergic stimulation increases glycogenolysis with increased production of glucose, which is then metabolized to pyruvate at a rate that exceeds its metabolic conversion in the Krebs cycle. This results in stress hyperglycemia and stress hyperlactemia. Both are evolutionary preserved responses which are designed to enhance survival during stress (and provide the vital organs with a source of fuel). Blocking these survival responses increases the risk of death during stress. It is likely that thiamine deficiency and decreased activity of pyruvate dehydrogenase (due to cytokines) further increase the likelihood of developing stress hyperlactemia. It has been demonstrated that the GLOBAL anaerobic threshold of adults is about 4mls/kg/min (JAMA 1993; 270;1724) and this threshold does not change with sepsis. In adults this translates into a hemoglobin of 4g/dl and a cardiac index of just over 1 L/minM2. This degree of impaired oxygen delivery is quite uncommon in critical illness and usually a pre-terminal event. From the above it is clear that the level of lactate is a measure of the degree of activation of the stress response (and serum catecholamine levels) and a prognostic marker. LACTATE IS GOOD FOR THE PATIENT AND NOT BAD. As a consequence of Myth No 1, it is widely believed that clinicians should increase oxygen delivery (DO2) in response to a high lactate. WRONG. The notion of increasing oxygen delivery to achieve some “magical target” DO2 or to achieve a certain central venous/mixed venous oxygen saturation or lactate concentration (or lactate clearance) has universally failed to improve patient outcomes. Gattonni et al demonstrated this over 20 years ago (NEJM 1995;333:1025). It is striking that in the b-blocker in sepsis study, treatment with a B1 antagonist (esmolol) decreased CI and DO2 was this associated with a more rapid clearance of lactate (JAMA 2013;310:1683). The only intervention that I am aware of that can actually decrease blood lactate level (and improve patient outcome) is the administration of thiamine (Crit Care Med 2016;44;360). Attempting to “titrate” therapy to a lactate level is as absurd as titrating treatment to a White Blood Cell count (WBC). However, in patients with localized lactate production (e.g ischemic bowel, ischemic limb etc) fixing the plumbing will reduce lactate levels and improve patient outcome. Probably one of the most remarkable of the Myths is the notion that the act of measuring lactate in and of itself improves patient outcomes. This concept is promoted by the Surviving Sepsis Campaign and is a core requirement of the SEP-1 Federal mandate. This concept is as absurd as suggesting that measuring a WBC improves the outcome of sepsis. While it is true that some studies have shown a lower mortality in patients in whom the lactate is measured within 3 hours (as opposed to later or never); this is not because measuring lactate improves outcome. It is simply a marker of better care. Measuring a blood lactate within 3 hours is a marker of more timely recognition of sepsis, receipt of antibiotics and earlier treatment. Lactate causes an acidosis. The conversion of pyruvate to lactate consumes rather than produces a hydrogen ion. Therefore lactate production retards, not causing an acidosis (Am J Physiol 2004;287: R502). The presence of an acidosis in many (not all) patients with an increased lactate is once again an association and not causal. The cause of the acidosis in these patients is not exactly clear; the hydrolysis of ATP has been one explanation that has been proposed. “Medical Fables” suggest that Ringers Lactate is contraindicated in patients with liver disease as this will cause a severe lactic acidosis. This is not correct; lactate is given as the base and not the acid and cannot cause an acidosis, rather, the opposite is true. The lactate is metabolized in the liver either by gluconeogenesis or oxidation with both reactions consuming a hydrogen ion. This has been demonstrated in both experimental models and clinical studies (even in presence of severe liver disease). In a murine model of acetaminophen toxicity LR has been demonstrated to improve liver recovery.(BMC Gasstroenerol 2011;11;125) In a hemorrhagic shock model LR as compared to NS was associated with less hepatic, renal and pulmonary injury (shock 2012;39268). Furthermore, LR has been reported to be safe in patients undergoing hepatectomy. Most specifically Goldstein evaluated the ability of dogs to handle a rapid infusion of Ringers lactate solution in the presence of severe hepatic injury. (Can J Surg 1972; 15:318). In this study they failed to demonstrate that exogenous lactate caused a prolonged or progressive elevation of arterial lactate in animals with a severe disturbance of hepatic function.