Identification and detection of haematological markers for the diagnosis of sepsis in major burn patients

Briddon, Nicholas Robert Thomas (2023) Identification and detection of haematological markers for the diagnosis of sepsis in major burn patients. Masters by Research thesis (MSc), Manchester Metropolitan University.

File will be available on: 21 June 2025. Available under License Creative Commons Attribution Non-commercial No Derivatives. Download (2MB)

Abstract

Major burns are a global issue that are difficult to treat, in-part due to the complications that can arise as a result of the compromised nature of the patients’ immune system. The most important and frequent complication is sepsis, given that the body’s first line of defence against invading pathogens, the skin, is severely compromised in such patients and given that the nature of the severe injury has resulted in the deregulation of my physiological processes that make the patient more vulnerable to the effects of a systemic infection. The RE-ENERGIZE clinical trial has generated the largest ever dataset available for the study of major burns patients. The present study has utilised this dataset to examine the effectiveness of current scoring and assessment criteria for predicting patient outcome in major burns, and for identifying those patients at risk of death from sepsis. The work has verified the utility of current scoring systems (BAUX, TBSA, APACHE II) for prognostication, and, more importantly, has identified other factors with strong prognostic capacity, including levels of urea, bilirubin and creatinine in the blood, as well as requirement for mechanical ventilation and the number of days spent on ventilation, requirement for renal replacement therapy and the highest SOFA score during the patient’s hospital stay. However, the work has also shown that many of these factors do not hold their predictive capacity for sepsis-related mortality, demonstrating that further research is needed to provide a new system to identify those at risk of death from sepsis. This has been historically difficult to do as many of the usual identifiable features that present during sepsis, are present during a major burn injury, regardless of the presence or absence of sepsis. The present work indicates that routine testing of newer sepsis biomarkers needs to be introduced into burn patient care to allow early identification of infection and sepsis, thereby improving survival rates. Given the above, the present study also focused on the development of a novel screen-printed-electrode (SPE)-based sensor for the rapid detection of a known sepsis biomarker, procalcitonin (PCT). This biomarker was chosen because it displays a high sensitivity and specificity for detecting sepsis, as well as having the important ability to differentiate between a systemic bacterial infection from the usual systemic inflammatory response system that becomes activated during major burn pathology. Prior research by the wider team at Manchester Metropolitan University had already proven that such an approach could be used for the detection of the inflammatory marker, Interleukin-6 (IL-6). This thesis is the first report in the literature for the use of antibodies in conjunction with the SPEs to detect PCT, but the results show that further work is required to fully optimize this technology to provide an acceptable reproducibility.