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Sepsis syndrome in patients requiring intensive therapy: The role of the anti-endotoxic agent Taurolin

Willatts, Sheila Margaret; (1994) Sepsis syndrome in patients requiring intensive therapy: The role of the anti-endotoxic agent Taurolin. Doctoral thesis (M.D), UCL (University College London). Green open access

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Abstract

Sepsis syndrome is the clinical manifestation of endotoxaemia in which bacteraemia may occur. Sepsis is increasing in importance as a cause of multiple organ failure and death in patients requiring intensive therapy. Such patients are at increased risk of infection and are often immunocompromised. It is likely that endotoxaemia initiates release of a cascade of cytokines which mediate inflammatory damage to tissues. Treatment is aimed at maintaining tissue oxygen delivery and minimising further damage. Whilst there have been major advances in intensive therapy and antibiotic development, there has been little change in mortality from gram-negative sepsis in the last twenty years. The recent introduction of anti-endotoxic agents may prove to be a therapeutic advance. This thesis evaluates an anti-endotoxic agent, taurolidine, in patients with sepsis syndrome who were managed by a standard protocol in the Intensive Therapy Unit at Bristol Royal Infirmary. An effective anti-endotoxic agent should reduce endotoxaemia, its systemic effects, the onset of organ failure and mortality. Taurolidine is an amino-acid derivative made up with 5% povidine in water for intravenous use. It was used in a randomised, double-blind placebo controlled study in 100 patients with sepsis syndrome after a pilot study in 30 patients reviewed the incidence and severity of endotoxaemia in a variety of conditions. The effects of taurolidine compared to placebo were assessed by measuring changes in plasma endotoxin, cytokine and acute phase protein concentrations. Physiological and biochemical assessments were also made and a daily assessment of organ failure, clinical and bacteriological response was recorded. Results of the pilot study failed to confirm an association between endotoxin and outcome. There was no difference in outcome in the controlled study between those treated with taurolidine and those given placebo. No major adverse reactions occurred in those patients treated with taurolidine nor in either group as a result of the increased fluid load of the infusions. The incidence of bacteraemia in these patients at admission to the Intensive Therapy Unit was low probably because of prior administration of antibiotics in all cases. It seems unlikely that anti-endotoxic agents such as taurolidine administered on admission to the ITU will have a substantial effect on the outcome of sepsis syndrome in this country.

Type: Thesis (Doctoral)
Qualification: M.D
Title: Sepsis syndrome in patients requiring intensive therapy: The role of the anti-endotoxic agent Taurolin
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Health and environmental sciences; Sepsis; Taurolin
URI: https://discovery.ucl.ac.uk/id/eprint/10104789
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