Oxygen kinetics and energy expenditure in fulminant hepatic failure and during liver transplantation

• Main Author: Walsh, Timothy Simon
• Published: University of Edinburgh 1999
• Subjects: 616.3
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.663428

The purpose of this thesis was to examine aspects of oxygen transport and uptake in patients with acute chronic liver disease with specific reference to the management of fulminant hepatic failure (FHF) and the intraoperative management of patients undergoing liver transplantation. A prospective randomised controlled study was carried out in patients with FHF with two major objectives: first to compare the reverse Fick method of calculating oxygen consumption (VO<SUB>2</SUB>) with a gas exchange method. Second, to evaluate the effect of the drug N-acetylcysteine in patients with FHF which previous work suggested may improve DO<SUB>2</SUB>, VO<SUB>2</SUB>, and tissue oxygen extraction in this condition. These studies showed that the reverse Fick method is inaccurate in patients with FHF because of propagation of measurement errors. Mathematical coupling could explain the apparent dependence of VO<SUB>2</SUB> on DO<SUB>2</SUB> when the Fick method was used to calculate VO<SUB>2</SUB>. The factors which increase the likelihood of mathematical coupling in oxygen kinetics studies were considered. With the gas exchange method of measuring VO<SUB>2</SUB> no clinically significant relationship was found between DO<SUB>2</SUB> and VO<SUB>2 </SUB>during N-acetylcysteine infusion, and no improvement in oxygen extraction by tissues was found. Variable effects on cardiovascular parameters were found, but overall no differences from the control group were demonstrated. No relationship was found between plasma N-acetylcysteine concentrations and clinical response. Energy expenditure and the acute phase response was investigated in patients with FHF. Energy expenditure was increased by approximately 20-25% in FHF in comparison with spontaneously breathing healthy volunteers and physically anhepatic patients with chronic liver disease studied during liver transplantation. Plasma TNFα, IL-6, and C-reactive protein were measured. These were significantly elevated in comparison with healthy controls in keeping with a significant acute phase response. Studies were carried out in patients undergoing liver transplantation using indirect calorimetry. Significant changes in metabolic rate, oxygen transport, and acid-base balance were demonstrated following graft reperfusion and the factors which influence these changes were discussed.