Effect of high-dose dexamethasone on perioperative lactate levels and glucose control

Introduction: Blood lactate levels are increasingly used to monitor patients. Steroids are frequently administered to critically ill patients. However, the effect of steroids on lactate levels has not been adequately investigated. We studied the effect of a single intraoperative high dose of dexamethasone on lactate and glucose levels in patients undergoing cardiac surgery. Methods: The Dexamethasone for Cardiac Surgery (DECS) trial was a multicenter randomized trial on the effect of dexamethasone 1 mg/kg versus placebo on clinical outcomes after cardiac surgery in adults. Here we report a pre-planned secondary analysis of data from DECS trial participants included at the University Medical Center Groningen. The use of a computer-assisted glucose regulation protocol—Glucose Regulation for Intensive care Patients (GRIP)—was part of routine postoperative care. GRIP aimed at glucose levels of 4 to 8 mmol/L. Primary outcome parameters were area under the lactate and glucose curves over the first 15 hours of ICU stay (AUC15). ICU length of stay and mortality were observed as well. Results: The primary outcome could be determined in 497 patients of the 500 included patients. During the first 15 hours of ICU stay, lactate and glucose levels were significantly higher in the dexamethasone group than in the placebo group: lactate AUC15 25.8 (13.1) versus 19.9 (11.2) mmol/L × hour, P <0.001 and glucose AUC15 126.5 (13.0) versus 114.4 (13.9) mmol/L × hour, P <0.001. In this period, patients in the dexamethasone group required twice as much insulin compared with patients who had received placebo. Multivariate and cross-correlation analyses suggest that the effect of dexamethasone on lactate levels is related to preceding increased glucose levels. Patients in the placebo group were more likely to stay in the ICU for more than 24 hours (39.2%) compared with patients in the dexamethasone group (25.0%, P = 0.001), and 30-day mortality rates were 1.6% and 2.4%, respectively (P = 0.759). Conclusions: Intraoperative high-dose dexamethasone increased postoperative lactate and glucose levels in the first 15 hours of ICU stay. Still, patients in the dexamethasone group had a shorter ICU length of stay and similar mortality compared with controls. Trial registration: ClinicalTrials.gov NCT00293592. Registered 16 February 2006. * Correspondence: t.h. ottens@umcutrecht.nl Department of Anesthesiology and Intensive Care, University Medical Center Utrecht, Mail stop Q.04. 2.313, PO Box 85500, Utrecht 3508 GA, The Netherlands Full list of author information is available at the end of the article © 2015 Ottens et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Ottens et al. Critical Care (2015) 19:41 Page 2 of 13 Introduction High doses of corticosteroids are often administered to attenuate the inflammatory response to cardiac surgery and cardiopulmonary bypass (CPB) [1]. Administration of a corticosteroid such as methylprednisolone or dexamethasone during cardiac surgery is associated with a reduced duration of postoperative mechanical ventilation and intensive care unit (ICU) and hospital stay, probably because of a lower risk of postoperative pulmonary complications [1-4]. Still, controversy regarding their use remains because of potential important adverse effects. Corticosteroids increase insulin resistance and may increase hyperglycemia and blood glucose variability. The pronounced inflammatory response following cardiac surgery and CPB contributes to decreased insulin secretion and increased insulin resistance. Although too rigid a regulation of blood glucose may increase the risk of hypoglycemia, inadequate glucose control is associated with increased ICU morbidity and mortality [5,6]. Studies on the influence of corticosteroids on lactate levels are scarce, and their results are contradictory [7,8]. Dexamethasone effectively reduces the production of pro-inflammatory cytokines during cardiac surgery and thus may reduce lactate production [7,9] on the one hand, but increases the amount of substrate for lactate formation (pyruvate from glucose) by increasing hepatic glucose release and insulin resistance on the other. Furthermore, dexamethasone increases catecholamine production in the adrenal medulla via its stimulating effect on phenylethanolamine-M-methyltransferase [10]. Catecholamines affect splanchnic perfusion as well as muscle Na-K-ATP-ase activity, Both of which may also lead to increased lactate production [11,12]. Because blood glucose [5,13,14] and lactate levels [15-20] are both well-established and important clinical outcome predictors in ICU patients, including those after cardiac surgery, we investigated the effect of a single intraoperative high dose of dexamethasone on glucose control and lactate levels after cardiac surgery. We studied a subset of patients included in the Dexamethasone for Cardiac Surgery (DECS) trial, a multicenter randomized trial recently carried out in The Netherlands [3]. This trial found a reduced risk of respiratory failure and infections and reduced ICU and hospital length of stay in patients who received dexamethasone. We assessed the effect of dexamethasone on postoperative lactate and glucose levels.