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Title: Myocardial and microvascular physiology in septic shock and response to volume expansion treatment
Author: Obonyo, Nchafatso Gikenyi
ISNI:       0000 0004 9355 1839
Awarding Body: Open University
Current Institution: Open University
Date of Award: 2020
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Despite being common clinical practice, volume expansion for septic shock resuscitation has been challenged by emerging evidence showing increased case-fatality. I hypothesised that volume expansion treatment in septic shock did not alter cardiac and microvascular physiologic functions. I conducted a systematic review on effects of volume expansion on the microcirculation in lipopolysaccharide-induced endotoxaemic shock; collaboratively developed of a large animal model of endotoxaemic shock and subsequently conducted a pre-clinical trial on volume expansion using either a fluid bolus or blood transfusion in the model; and finally, a longitudinal clinical observational study on volume resuscitated paediatric septic shock. The main findings were: (a) In the systematic review, 11 studies were included in which I found there were several different models with variations in definitions of endotoxaemic shock, timing of volume expansion resuscitation in relation to induction of endotoxaemia, duration of resuscitation, volume of fluid administered, methods used to assess the microcirculation and overall duration of the models. These differences precluded meta-analysis; (b) in the pre-clinical model, endotoxin infusion led to a reduction in mean arterial pressure, MAP from 85 ± 12.8 to 49 ± 8.0 mmHg (difference in means 36 mmHg; 95%CI 17.5 to 46.5; p<0.001) and fluid bolus treatment was associated with a higher cumulative median (IQR) noradrenaline requirement 68.9mg [19.3-140.0] to maintain a target MAP of 60-65mmHg compared to non-bolus sham 39.6mg [20.3-65.4] or healthy control (10mg [3-20]) (ꭓ2(2df) 11.04; p=0.004); (c) in the clinical observational study, mortality was higher among children presenting with WHO shock and managed with a fluid bolus (WHO guideline) compared to those with non-WHO shock receiving maintenance fluid only (100% versus 12.5%; risk difference, 0.67; 95%CI, 0.36-0.97; p= 0.007). Fluid bolus treatment was associated with elevated levels of circulating atrial natriuretic peptide, ANP and increased vasopressor requirements (pre-clinical study) and mortality outcome (clinical study).
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral