BJA/RCoA Project Grants

University of Birmingham

Title
Could characterising different phenomes associated with hyperlactaemia allow better targeted therapy for patients in shocked states?

Amount
£14,938

Scientific Abstract
Serum lactate is widely used as a predictor of poor prognosis in shocked patients. In sepsis particularly, hyperlactaemia correlates with mortality. It is additionally used to prognosticate other conditions - including major trauma and diabetic ketoacidosis (DKA).

Hyperlactaemia represents imbalance between lactate production and clearance. Classical biochemistry considers lactate a waste product of anaerobic respiration; recent evidence suggests a physiological role for lactate, and that its catabolism may operate in other cell types - including the brain. Though all lactate biochemically derives from pyruvate, the physiological pathway leading to hyperlactaemia may differ between patients.

We propose a research programme investigating the biosynthetic pathways leading to hyperlactaemia in different diseases - sepsis, trauma, and DKA. Following an epidemiological study investigating the prevalence and outcomes of hyperlactaemia, we will use Ultra Performance Liquid Chromatography-Mass Spectrometry to analyse the metabolic profiles of patients according to diagnosis and lactate level. Data will be correlated against biochemical and clinical information to derive associations between hyperlactaemia and its metabolic causes.

Elucidating the physiological origin of lactate in acutely unwell patients may offer a means to tailor and titrate therapy to individual patient metabolic profiles - this project tests the feasibility of this hypothesis, and builds a platform for future research.

University of Nottingham

Title
Cerebrovascular accident and Acute coronary syndrome and Peri-operative Outcomes study (CAPO)

Amount
£69,999

Scientific Abstract
Stroke and acute coronary syndrome (ACS) are recognised risk factors for adverse outcomes following surgery. It is not clear how long this risk exists and whether it is modified by characteristics of the stroke or ACS (treatment, pathophysiological effect) or by the type of surgery. Previous work by our group and others has demonstrated an association between both stroke and ACS, and adverse perioperative outcomes following major orthopaedic surgery; the effects were less evident for patients undergoing major vascular surgery.

Building on previous work, we propose a database linkage study between the Myocardial Ischaemia National Audit Project (MINAP), the Sentinel Stroke National Audit Programme (SSNAP), Hospital Episode Statistics (HES) and the Office for National Statistics (ONS). We will examine a cohort of patients undergoing surgery between 2007 and 2017, linking these to data on presentation, treatment and recovery from previous stroke and ACS. Our endpoints will be mortality, postoperative ACS, prolonged length of stay, and emergency readmission rates.

Expected outputs are robust estimates of time-dependent risks associated with stroke and ACS, stratified by surgical type and characteristics of stroke and ACS. These will inform patient-centred decision-making and possible future clinical trials to reduce risk.

The University of Edinburgh

Title
Traumatic Brain Injury Associated Radiological Deep Venous Thrombosis Incidence and Significance (TARDIS)

Amount
£69,454 (£20,000 part-funded by NACCSGBI)

Scientific Abstract
Significant uncertainty exists about the optimal timing of pharmacological prophylaxis (PT) following moderate to severe traumatic brain injury (TBI). Concerns over the risks of contusion enlargement, and haemorrhage tend to delay PT. Paradoxically however, evidence of harm associated with the presence of DVT is not strong. Possible associations with an increase in ventilator days and poor functional outcome are only suggested by the existing literature. A randomised controlled trial (RCT) to investigate the safety and efficacy of early PT following TBI is difficult to justify.

We will conduct a prospective pilot study to define the incidence of proximal DVT following TBI using compression ultrasound. Evidence of associated harms will be sought. These include, acute lung injury and ventilator associated pneumonia, the number of ventilated days, ICU and hospital length of stay. Functional outcomes will be measured using the modified Oxford handicap scale and extended Glasgow outcome scale at 6 months.

The output of this study could be used to justify and power a definitive study to determine if proximal DVT complicating TBI is associated with clinical and functional harms. An RCT of early verses late PT with end points derived from these observational studies might then be warranted.

Imperial College, London

Title
Novel preservative strategy in protecting lung graft

Amount
£69,173

Scientific Abstract
Lung transplantation is a cost-effective treatment for patients with end-stage lung disease. Despite the demonstrated advantages of transplantation, the full potential of these benefits cannot be obtained due to the severe shortage of donated lungs. The proposed project aims to investigate Novel preservative strategy in protecting lung graft, using a rat lung ex vivo preservation model. Mechanistic study will encompass various approaches to elucidate the cellular and molecular mechanisms contributing to lung graft hypothermia-ischaemia injury, for example, profiling of inflammatory cytokines and DAMPs (e.g. Histone), and qualitative and quantitative analyses of necroptosis-related death pathway. Finally, the therapeutic potential of a2 adrenoceptor agonist Dexmedetomidine, a routinely used anaesthetic adjuvant, against such injuries will be determined. It is likely that findings from the proposed study could be used to provide the biological rationale for clinical studies, and ultimately guiding clinical trials and practices to enhance the donor lung graft quality.