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Modulating the stress response in critical illness

Khaliq, W; (2017) Modulating the stress response in critical illness. Doctoral thesis , UCL (University College London).

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Abstract

OBJECTIVES: 1. To temporally characterize the stress response to critical illness in intensive care patients 2. To develop a translational animal model of critical illness in which the stress response can be studied further in a laboratory setting 3. To examine whether pharmacological manipulation with beta-blockade can modify the stress response to critical illness and improve survival DESIGN: A prospective observational cohort study was undertaken in critically ill adult patients admitted to the adult critical care unit of a London teaching hospital. Physiological, pharmacological and diagnostic data were collected and blood samples analysed for a wide range of biological stress response markers. Patients were studied until ICU discharge or death. A simultaneous study was performed using a rat model of faecal peritonitis. Physiological variables were recorded in these animals, as in the human patients, and blood samples were similarly processed. Additional study of cardiovascular variables, immune, inflammatory, metabolic, neuroendocrine, organ injury and metabolomic markers was performed. The stress response could be characterized in survivors and non-survivors of critical illness in both the animals and the patients. The animal model of faecal peritonitis was also used to study the impact of the beta-blocker, esmolol, on both survival and the stress response to critical illness. RESULTS: The stress response in both patients and the rat faecal peritonitis model could be used to distinguish eventual survivors and non-survivors of sepsis. Many of these changes occurred early during the course of illness. Treatment with esmolol improved survival in rats predicted to die, but worsened mortality in those predicted to survive. Esmolol improved some markers of the stress response, such as pro- and antiinflammatory cytokines, in addition to modifying cardiovascular physiological variables. However, it did not alter the critical illness stress response in its entirety. CONCLUSIONS: These studies have helped to characterize the stress response to critical illness in far greater detail than previously shown, including cardiovascular, immune, metabolic, biochemical, hormonal and metabolomic changes. Although beta-blockade may improve outcomes in those predicted to die from sepsis, they may be detrimental in those who would have otherwise survived.

Type: Thesis (Doctoral)
Title: Modulating the stress response in critical illness
Event: UCL (University College London)
Language: English
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/1531999
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