Lactate in critical illness

Lactate measurement in the critically ill has been traditionally used to stratify patients with poor outcome. However, plasma lactate levels are the result of a finely tuned interplay of factors that affect the balance between its production and its clearance. When the oxygen supply does not match its consumption, organisms such as man who are forced to produce ATP for their integrity adapt in many different ways up to the point when energy failure occurs. Lactate, being part of the adaptive response, may then be used to assess the severity of the supply/demand imbalance. In such a scenario, the time to intervention becomes relevant: early and effective treatment may allow the cell to revert to a normal state, as long as the oxygen machinery (i.e. mithocondria) is intact. Conversely, once the mithocondria are deranged, energy failure occurs even in the presence of normoxia. The lactate increase in critically ill patients may therefore be viewed as an early marker of a potentially reversible state. Lactate in critical illness The normal reference values for lactate are traditionally considered 1 ± 0.5 mmol/l in normal patients and <2 mmol/l in critically ill patients [1]. Since 1975, values above 2 mmol/l but lower than 5 mmol/l have been separated from values above 5 mmol/l, associated with acidemia, as different clinical entities – referring to hyperlactatemia states in the former situation as opposed to lactic acidosis in the latter situation [2]. A further stratification, initially proposed by Cohen in 1976 [3], has been subsequently used according to the presence (type A) or absence (type B) of ‘evident’ causes of tissue hypoxia to explain the underlying cause of increased lactate. Over the years, however, more sophisticated means of assessing regional and even local perfusion have changed the aforementioned classification into a more perfusionoriented vision. In fact, our increased ability to assess tissue oxygenation clearly implies that measured plasma lactate concentration is only a small window of a much more complicated scenario. Lactate as a clinical marker of hypoxia As will be described, lactate is one of the intermediate products that increase as a consequence of the rearrangement of metabolism during hypoxia. As such, lactate has been widely considered a marker of tissue hypoxia. There are several examples of the increase of lactate in hypoxic conditions [4,5]. Figure 1 shows our own experimental results. The lactate increase is very fast, a matter of minutes, and is proportional to the defect in the oxidative metabolism [6]. However, measured plasma lactate is the balance between production and clearance. Liver failure does in fact influence the kinetics of lactate increase [7]. It is also worth note that lactate is an intermediate compound of normal metabolism. Erythrocytes, for instance, which are equivalent to an organ weighing approximately 2500 g, are obligatory anaerobes and ‘breathe’ via the lactate they produce that is recycled from fatty acid oxidation in the liver. Lactate, in this case, may be considered an energy shuttle rather than a waste compound [8]. Outcome and stratification of severity Lactate has been used as a marker in critically ill patients since 1964 [9]. In 1970, Weil and Afifi clearly showed the relationship between lactate concentration and outcome [10]. Several authors have subsequently confirmed those results [11-15]. Interestingly, lactate measurements have also been used to stratify patients. In fact, plasma lactate may be used as Review Lactate as a marker of energy failure in critically ill patients: hypothesis Franco Valenza, Gabriele Aletti, Tommaso Fossali, Giorgio Chevallard, Francesca Sacconi, Manuela Irace and Luciano Gattinoni Istituto di Anestesia e Rianimazione, Università degli Studi di Milano, Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena – Fondazione IRCCS di Natura Pubblica, Milan, Italy Corresponding author: Franco Valenza, [email protected] Published online: 28 September 2005 Critical Care 2005, 9:588-593 (DOI 10.1186/cc3818) This article is online at http://ccforum.com/content/9/6/588 © 2005 BioMed Central Ltd See related commentary by Leverve in this issue, page 622 [http://ccforum.com/content/9/6/622]