This thesis examines aspects of oxygen transport and uptake in patients with
acute and 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 evaluating the effect of the drug N- acetylcysteine on DO2, VO2, and tissue
oxygen extraction. A previous study showed that this drug increased all of these
oxygen kinetic variables, which was considered of therapeutic benefit. The present
study showed that this earlier finding was an artifact related to the method of
calculating oxygen consumption (the Fick method). This method produced unreliable
results in patients with FHF because it was inaccurate, non -reproducible, the the
relation between DO2 and VO2 was subject to mathematical couplig error. No
clinically significant improvements in any oxygen kinetic variables were observed after
N- acetylcysteine administration, even when followed for a prolonged period. Variable
effects on cardiovascular parameters were found, but overall no differences from the
control group were demonstrated. No relationship was found between plasma Nacetylcysteine concentrations and clinical response.
A prospective study examining energy expenditure and the acute phase
response was carried out 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 TNFa, 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. The study indicated hypermetabolism during severe
FHF despite the loss of functioning liver cell mass and the effects of sedation,
analgesia, and mechanical ventilation. This was most likely attributable to a systemic
inflammatory response.
In patients undergoing liver transplantation indirect calorimetry was used to
examine changes in metabolic rate and pulmonary physiology following graft
reperfusion. Significant changes in metabolic rate, oxygen transport, and acid -base
balance were demonstrated the factors which influence these changes were discussed.
The use of the piggyback surgical technique was associated with greater metabolic
stability than the use of venovenous bypass.
A prospective observational study compared the two methods for managing
the anhepatic phase of liver transplantation, namely venovenous bypass or the
piggyback surgical technique. This study demonstrated higher cardiac output, VO2,
and blood temperature during the anhepatic phase with the piggyback surgical
technique. This suggested better preservation of tissue oxygenation with this
approach, which may translate into improved postoperative function.
Two techniques of graft reperfusion, namely via the portal vein or the hepatic
artery, were compared in another prospective observational study. This study
indicated that the increase in VO2 after reperfusion occurred more slowly when the
hepatic artery was used, but was accompanied by a slower release of acid load into
the circulation and less requirement for vasopressor support. Reperfusion via the
hepatic artery may therefore be preferable in the patient at risk of haemodynamic or
cerebral decompensation following reperfusion, although further studies are required
to ensure graft outcome is equivalent with both techniques.
