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

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WalshTS_1999redux.pdf (28.59Mb)
Date
1999
Author
Walsh, Timothy Simon
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Abstract
 
 
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.
 
URI
http://hdl.handle.net/1842/27613
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