Oral β-blockade in relation to energy expenditure in clinically stable patients with liver cirrhosis: A double-blind randomized cross-over trial Wai Gin Lee a , John L. McCall b , Edward J. Gane c , Rinki Murphy d , Lindsay D. Plank a, ⁎ a Department of Surgery, University of Auckland, Private Bag 92019, Auckland, New Zealand b Department of Medical and Surgical Sciences, Section of Surgery, University of Otago, Dunedin, New Zealand c New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand d Department of Medicine, University of Auckland, Private Bag 92019, Auckland, New Zealand ARTICLE INFO ABSTRACT Article history: Received 14 October 2011 Accepted 2 April 2012 Elevated resting energy expenditure (REE) is seen in liver cirrhosis and is associated with reduced transplant-free survival. Non-selective β-blockers reduce REE in acute hypermetabolic conditions. We examined whether non-selective β-blockers reduce REE in patients with stable liver cirrhosis. Twenty-two stable cirrhotic patients (Child–Pugh grading: 19A, 2B, 1C) were randomized to 3-month treatment with nadolol (titrated to decrease resting pulse rate by 20%) or placebo and after a 1-month washout period crossed to the alternative treatment for a further 3 months. REE was measured by indirect calorimetry and total body protein by neutron activation analysis at the beginning and end of each 3-month period of treatment. A predicted REE was calculated for each patient based on total body protein. A measured to predicted REE ratio > 1.22 indicated significantly elevated REE. The primary outcome was REE at the end of 3-month treatment with nadolol compared with placebo. Elevated REE was seen in one patient at study entry. After 3 months on placebo REE was 1506 ± 40 (SEM) kcal/d and on nadolol, 1476 ± 40 kcal/d, a mean reduction of 31 ± 16 kcal/d (P= .076). Total body protein changes were not significant. Nadolol was well tolerated with no increase in the rate of adverse events. In stable cirrhotic patients, nadolol was not associated with reduction in REE. A larger, longer-term study with different eligibility criteria is required to investigate whether this treatment offers benefits additional to its use for prevention of variceal hemorrhage. © 2012 Elsevier Inc. All rights reserved. Keywords: Hypermetabolism Indirect calorimetry Malnutrition Total body protein Neutron activation 1. Introduction Hypermetabolism occurs when resting energy expenditure (REE) is elevated above normal levels and is seen in up to one- third of patients with liver cirrhosis [1–4] where it is associated with reduced overall and transplant-free survival [1,5–7]. Earlier work from our group showed that lower REE was associated with improved survival even for patients within the normal range of REE [1]. In addition, patients taking β- blockers to prevent variceal bleeding were three times less METABOLISM CLINICAL AND EXPERIMENTAL 61 (2012) 1547 – 1553 Abbreviations: CI, confidence interval; CRP, C-reactive protein; MELD, model for end-stage liver disease; REE, resting energy expenditure; TBP, total body protein. Australian Clinical Trials Registry number: ACTRN12607000546459. ⁎ Corresponding author. Tel.: +64 9 923 6949; fax: +64 9 377 9656. E-mail address: l.plank@auckland.ac.nz (L.D. Plank). 0026-0495/$ – see front matter © 2012 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.metabol.2012.04.001 Available online at www.sciencedirect.com Metabolism www.metabolismjournal.com