Oral β-blockade in relation to energy expenditure in clinically stable patients with liver cirrhosis: A double-blind randomized cross-over trial

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.