ORIGINAL ARTICLE Original Article Perioperative metabolic therapy improves redox status and outcomes in cardiac surgery patients: A randomised trial Jee-Yoong Leong, MBBS a , Juliana van der Merwe, RN a , Salvatore Pepe, PhD a , Michael Bailey, PhD b , Anthony Perkins, PhD c , Robyn Lymbury, PhD c , Donald Esmore, FRACS a , Silvana Marasco, MS a and Franklin Rosenfeldt, MD, FRACS a,b,∗ a Cardiac Surgical Research Unit, Alfred Hospital, Department of Surgery Monash University, Baker IDI Institute, Melbourne, Australia b Department of Epidemiology & Preventive Medicine, School Public Health & Preventive Medicine, Monash University Alfred Hospital, Melbourne, Australia c Heart Foundation Research Centre, School of Medical Science, Griffith University Gold Coast Campus, Queensland, Australia Objective: Perioperative therapy with antioxidants and metabolic substrates has the potential to reduce oxidative stress and improve recovery from cardiac surgery, particularly in elderly and high risk cases. The aim of this study was to assess the effect of perioperative metabolic therapy at a biochemical, clinical and economic level in cardiac surgical patients. Methods: Patients (n = 117, mean age 65 ± 1.0 years, 74% male) undergoing elective coronary artery bypass graft (CABG) and/or valve surgery in 2004–2006 were randomised to receive in double blinded fashion, while on the waiting list for surgery (approximately two months) and one month after surgery, either metabolic therapy (coenzyme Q 10 , magnesium orotate, lipoic acid, omega-3 fatty acids and selenium) or placebo. Biochemical and clinical outcomes were assessed. Results: Cardiac surgery increased oxidative stress and decreased plasma levels of key antioxidants. Metabolic therapy for a mean of 76 ± 7.5 days increased antioxidant levels preoperatively so that the adverse effect of surgery on redox status was attenuated. Metabolic therapy reduced plasma troponin I, 24 hours postoperatively from 1.5 (1.2–1.8) (geometric mean 95% CI) g/L, to 2.1 (1.8–2.6) g/L (P = 0.003) and shortened the mean length of postoperative hospital stay by 1.2 days from 8.1 (7.5–8.7) to 6.9 (6.4–7.4) days (P = 0.004) and reduced hospital costs. Metabolic therapy was inexpensive and had no clinically significant side effects. Conclusions: Perioperative metabolic therapy for cardiac surgery is safe and inexpensive and is associated with improved redox status, reduced myocardial damage, and shortened length of postoperative hospital stay. (Heart, Lung and Circulation 2010;19:584–591) © 2010 Australasian Society of Cardiac and Thoracic Surgeons and the Cardiac Society of Australia and New Zealand. Published by Elsevier Inc. All rights reserved. Keywords. Perioperative therapy; Antioxidants; Metabolic therapy; Cardiac surgery; Oxidative stress; Coenzyme Q10 Introduction A n increasing proportion of patients presenting for car- diac surgery in the present era are elderly, with a high incidence of co-morbidities such as diabetes, heart failure, previous myocardial infarction and renal impair- ment. Advanced age and significant co-morbidities are associated at a biochemical level with an enhanced degree of oxidative stress [1] and clinically with higher rates of postoperative complications and an increased length of hospital stay [2]. We postulated that by the periopera- Received 14 May 2010; accepted 7 June 2010; available online 2 August 2010 ∗ Corresponding author at: Cardiac Surgical Research Unit, The Alfred Hospital, PO Box 315, Prahran, NSW 3181, Australia. Tel.: +61 3 9076 3684, fax: +61 3 9076 2317. E-mail address: f.rosenfeldt@alfred.org.au (F. Rosenfeldt). tive use of metabolic agents we could favourably influence myocardial metabolism and improve clinical outcomes. The term “metabolic agent” is used to describe a natu- rally occurring substance that when administered to the body can produce a beneficial effect on metabolism [3]. The following metabolic agents have been clearly demon- strated to have beneficial effects on the heart and were therefore included in our regimen of cardiac metabolic therapy: coenzyme Q 10 (CoQ 10 ) [4–6], lipoic acid [7], selenium [8,9], orotic acid [10,11], and omega-3 polyun- saturated fatty acids [12–15]. Following a promising pilot study [3] we evaluated the efficacy of this regimen in the current prospective randomised clinical trial in patients having elective cardiac surgery. The aims of the study were to determine in patients undergoing elective cardiac surgery, the effect of periop- erative metabolic therapy on oxidative stress, antioxidant © 2010 Australasian Society of Cardiac and Thoracic Surgeons and the Cardiac Society of Australia and New Zealand. Published by Elsevier Inc. All rights reserved. 1443-9506/04/$36.00 doi:10.1016/j.hlc.2010.06.659