Natural History and Determinants of Changes in Physiological Variables after Ischaemic Stroke.

Andrew Wong (2008). Natural History and Determinants of Changes in Physiological Variables after Ischaemic Stroke. PhD Thesis, School of Medicine, The University of Queensland.

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Author Andrew Wong
Thesis Title Natural History and Determinants of Changes in Physiological Variables after Ischaemic Stroke.
School, Centre or Institute School of Medicine
Institution The University of Queensland
Publication date 2008-09-01
Thesis type PhD Thesis
Supervisor Dr Stephen Read
Prof Philip Schluter
Dr Jon Chalk (deceased)
Total pages 114
Total colour pages 9
Total black and white pages 105
Subjects 11 Medical and Health Sciences
Abstract/Summary Abstract Background The prognosis after an ischaemic stroke is determined largely by how much damage is done to the brain. Currently physicians possess only a few therapies that can improve outcome. Early changes in common physiological variables, such as blood pressure, temperature and blood glucose levels, represent a potential therapeutic target, and manipulation of these variables may eventually yield an effective and potentially widely applicable range of therapies for optimising stroke recovery. However, the natural history and determinants of physiological change require clarification before the effects of manipulating physiology can be assessed. Previous research suggests that blood pressure and glucose falls over the first few days and temperature rises over this time. Some of the determinants of this change have been identified, for example stroke severity, but their influence has not been accurately quantified. The lack of detail in previous attempts to characterise these relationships is partly due to a reliance on traditional cross-sectional statistical techniques. My aims were to use the most apposite statistical technique, namely mixed-effects modelling, to accurately characterise the temporal patterns of post-stroke blood pressure, temperature and glucose, and to identify baseline factors that represent determinants of change in these three physiological variables. Methods A cohort of ischaemic stroke patients was recruited within 48 hours of stroke onset, and their blood pressure, temperature and glucose was recorded at least every 4 hours until 48 hours post-stroke. Factors representing potential determinants of change in these physiological variables were also recorded, including stroke severity and the presence of infection. There were no protocols dictating the treatment of these physiological variables, but if this occurred, those treatments were also recorded. In each analysis, mixed-effects models were generated with serial measures of physiology as the outcome factors and the potential determinants of physiological change as the explanatory factors. These determinants included time, representing the temporal patterns of change. Patients with diabetes were excluded from the analysis of glucose, for several reasons including the excessive impact on glycaemia made by dietary intake in patients with diabetes. Results There were 157 eligible patients overall. The analysis of blood pressure (n=157) revealed a linear systolic blood pressure fall of 14.9 mmHg (95% Confidence Interval (CI) 6.2, 22.6 mmHg) and a diastolic blood pressure fall of 6.1 mmHg (95%CI 1.6, 10.5 mmHg) over the first 48 hours after stroke. Patients with post-stroke infection exhibited a slight rise in systolic blood pressure of about 4 mmHg. Higher systolic blood pressures were seen in older patients and in those with pre-existing or previously treated hypertension, previous strokes or transient ischaemic attacks, in regular alcohol users and in those with mild to moderately severe stroke. Systolic blood pressures were 4.6 mmHg (95%CI 2.35,6.85 mmHg) lower in current smokers than in non-smokers. Of the 156 patients eligible for the temperature analysis, temperature rose by 0.17 deg C in patients with mild stroke (National Institutes of Health Stroke Score (NIHSS)≤6) and 0.35 deg C in patients with moderate to severe stroke (NIHSS≥6) over the first 48 hours after stroke. Temperatures were higher in those who required paracetamol. Temperatures were 0.33 deg C (95%CI 0.07, 0.58) higher in patients with infection and the effect was fixed during the 48 hour observation period. Blood glucose remained static in the 124 patients without diabetes during the first 48 hours after stroke. Glucose levels where higher in those requiring glucose lowering therapy, and in those with more severe stroke. Conclusions I have quantified the amount by which blood pressure falls and temperature rises over the first 48 hours after stroke. In addition, I have shown that mean glucose levels remain static during this time, suggesting that previous reports of acutely resolving post-stroke hyperglycaemia may have represented misinterpretation of regression to the mean. Several determinants of change in post-stroke physiological variables were identified, with unexpected findings in several cases. Higher systolic blood pressures were seen with stroke of moderate severity but not mild or severe stroke. This relationship was fixed during the first 48 hours after stroke, but while more severe stroke was also associated with higher temperatures, the latter effect became more marked as time passed. Conversely, infection was associated with a fixed elevation in temperature, but was associated with systolic blood pressures that rose slightly during the observation period. These apparent inconsistencies require clarification in future work, for example studies of whether markers of the inflammatory or neuroendocrine stress responses evolve in parallel with the changes in physiological variables. This work provides fundamental information regarding the natural history and determinants of changes in physiological variables post-stroke, and will improve the design of future studies investigating the prognostic significance of untreated and treated physiological variables after stroke. This will ultimately lead to the refinement of clinical guidelines for the management of physiological variables post-stroke and to better outcomes for stroke patients.
Keyword cerebrovascular disease
Cerebral Ischemia
blood pressure
body temperature
blood sugar
medical statistics
Additional Notes Colour: 51, 53, 57, 66, 67, 70, 79, 80, 83 A3: Nil Landscape: 35

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Created: Fri, 09 Oct 2009, 21:39:59 EST by Dr Andrew Wong on behalf of Library - Information Access Service