A comparison of postoperative blood lactate concentrations and kinetics in cardiac surgical patients being and not being administered metformin
Keywords:Metformin, Lactate, Lactate clearance, cardiac surgery
Aim. Early discontinuation of metformin before cardiac surgery is advised by several national societies, although no hard evidence exist supporting this practice. This precaution is mostly extrapolated by data on different clinical settings. The aim of this study is to investigate the impact of preoperative metformin use on lactate concentrations and lactate clearance during the first postoperative day following cardiac surgery.
Methods. Among 367 consecutive patients who underwent elective on-pump cardiac surgery from January 2019 to October 2019, 109 were diabetics, 74 of whom were treated with metformin. Data on lactate concentrations and clearance during the first postoperative day were prospectively collected on arrival in the ICU, as well as after H6, H12 and H24 in the ICU and subsequently compared. A subgroup analysis focusing only on the diabetic patients was also performed. Repeated measures multivariate analysis of variance (MANOVA) was used to investigate the data on the basis of the group, time and their interaction effects.
Results. Lactate concentrations were the same for both groups upon arrival in the ICU. Interestingly, metformin users presented lower lactate concentrations than non-users on the following measurements (p = 0.003 at 6 h and p = 0.01 at 24 h). No significant interaction was found between the two groups (p = 0.76). No difference was found between the two groups in terms of lactate clearance (p = 0.53). In the subgroup analysis no difference was observed between metformin users and non-users, either on lactate concentrations (p = 0.61), or on lactate clearance (p = 0.86).
Conclusions. In the intensive care unit setting following heart surgery, the use of metformin up until the night before surgery was not associated with increased postoperative lactate concentrations or impaired lactate clearance.
Bailey CJ, Turner RC: Metformin. N Engl J Med 1996; 334: 574-579. DOI: https://doi.org/10.1056/NEJM199602293340906
Park, Joongmin; Hwang, Sung Yeon; Jo, Ik Joon; Jeon, Kyeongman; Suh, Gee Young; Lee, Tae Rim; Yoon, Hee; Cha, Won Chul; Sim, Min Seob; Carriere, Keumhee Chough; Yeon, Seungmin; Shin, Tae Gun Impact of Metformin Use on Lactate Kinetics in Patients with Severe Sepsis and Septic Shock SHOCK: May 2017 - Vol 47: 5 - p 582–587 DOI: https://doi.org/10.1097/SHK.0000000000000782
Lee EY, Hwang S, Lee YH, et al. Association between Metformin Use and Risk of Lactic Acidosis or Elevated Lactate Concentration in Type 2 Diabetes. Yonsei Med J. 2017;58(2):312– 318. DOI: https://doi.org/10.3349/ymj.2017.58.2.312
De Fronzo R et al. Metformin-associated lactic acidosis: Current perspectives on causes and risk Metabolism. 2016 Feb;65(2):20-9 DOI: https://doi.org/10.1016/j.metabol.2015.10.014
National Institute for Health and Clinical Excellence, Type 2 Diabetes Clinical Guideline 87. Available from: http://www.nice.org.uk/cg87
The Electronic Medicines Compendium Metformin summary of product characteristics Available from medicine/23244/SPC#CLINICAL_PRECAUTIONS
Cheisson G., Jacqueminet S., Cosson E., Ichai C., Leguer A-M , Nicolescu-CatargiB. Perioperative management of adult diabetic patients. Preoperative period Anaesthesia Critical Care & Pain Medicine2018;37:9-19 DOI: https://doi.org/10.1016/j.accpm.2018.02.020
Kapoor P, Mandal B, Chowdhury U, et al. Changes in myocardial lactate, pyruvate and lactate-pyruvate ratio during cardiopulmonary bypass for elective adult cardiac surgery: early indicator of morbidity. J Anaesthesiol Clin Pharmacol 2011; 27(2): 225–232 DOI: https://doi.org/10.4103/0970-9185.81819
Ranucci M, De Toffol B, Isgrò G, et al. Hyperlactatemia during cardiopulmonary bypass: determinants and impact on postoperative out-come. Critical Care 2006; 10: R167 DOI: https://doi.org/10.1186/cc5113
Zhang Z., Xu X. Lactate Clearance Is a Useful Biomarker for the Prediction of All-Cause Mortality in Critically Ill Patients: A Systematic Review and Meta-Analysis Crit Care Med2014; 42:2118–2125 DOI: https://doi.org/10.1097/CCM.0000000000000405
Bakker J, Nijsten MW, Jansen TC. Clinical use of lactate monitoring in critically ill patients. Ann Intensive Care. 2013;3(1):12 DOI: https://doi.org/10.1186/2110-5820-3-12
Lopez-Delgado JC, Esteve F, Javierre C, Torrado H, Rodriguez-Castro D, Carrio ML, et al. Evaluation of serial arterial lactate levels as a predictor of hospital and long-term mortality in patients after cardiac surgery. J Cardiothorac Vasc Anesth. 2015;29:1441–53 DOI: https://doi.org/10.1053/j.jvca.2015.04.024
Vincent, J., Quintairos e Silva, A., Couto, L. et al. The value of blood lactate kinetics in critically ill patients: a systematic review. Crit Care 20, 257 (2016) DOI: https://doi.org/10.1186/s13054-016-1403-5
Levy B, Desebbe O, Montemont C, Gibot S. Increased aerobic glycolysis through beta2 stimulation is a common mechanism involved in lactate formation during shock states. Shock 2008; 30: 417–21 DOI: https://doi.org/10.1097/SHK.0b013e318167378f
Eppenga W.L., Lalmohamed A., Geerts A.F., Derijks H.J., Wensing M., Egberts A., et al. Risk of lactic acidosis or elevated lactate concentrations in metformin users with renal impairment: a population-based cohort study. Diabetes Care. 2014; 37: 2218-2224 DOI: https://doi.org/10.2337/dc13-3023
Glucophage (metformin hydrochloride) and Glucophage XR (extended-release) prescribing information. Bristol-Myers Squibb, Bristol, NJ2009
Graham G.G., Punt J., Arora M., Day R.O., Doogue M.P., Duong J.K., et al. Clinical pharmacokinetics of metformin. Clin Pharmacokinet. 2011; 50: 81-98 DOI: https://doi.org/10.2165/11534750-000000000-00000
Nazer RI, Alburikan KA. Metformin is not associated with lactic acidosis in patients with diabetes undergoing coronary artery bypass graft surgery: a case control study. BMC Pharmacol Toxicol. 2017;18(1):38. DOI: https://doi.org/10.1186/s40360-017-0145-6
Bano T, Mishra SK, Kuchay MS, et al. Continuation of Metformin Till Night Before Surgery and Lactate Levels in Patients Undergoing Coronary Artery Bypass Graft Surgery. Indian J Endocrinol Metab. 2019;23(4):416–421 DOI: https://doi.org/10.4103/ijem.IJEM_114_19
Doenyas-Barak K, Beberashvili I, Marcus R, Efrati S. Lactic acidosis and severe septic shock in metformin users: a cohort study. Crit Care. 2016; 20:10 DOI: https://doi.org/10.1186/s13054-015-1180-6
Minton J, Sidebotham DA. Hyperlactatemia and Cardiac Surgery. J Extra Corpor Technol. 2017;49(1):7-15
Maillet J. M., Le Besnerais P., Cantoni M., et al. . Frequency, risk factors, and outcome of hyperlactatemia after cardiac surgery. Chest. 2003;123:1361–6 DOI: https://doi.org/10.1378/chest.123.5.1361
Hajjar LA, Almeida JP, Fukushima JT, et al. High lactate levels are predictors of major complications after cardiac surgery. J Thorac Cardiovasc Surg. 2013;146(2):455-460 DOI: https://doi.org/10.1016/j.jtcvs.2013.02.003
Mustafa I, Roth H, Hanafiah A, et al. Effect of cardiopulmonary bypass on lactate metabolism. Intensive Care Med. 2003;29(8):1279-1285 DOI: https://doi.org/10.1007/s00134-003-1860-6
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