Title: Development of microdialysis online sensor technology for use in critical care of acute brain trauma patients
Funder: Department of Health and Social Care

Abstract: Design The proposed study contains two primary components; product development and the clinical study. Within these components there are distinct work packages; the objectives and deliverables are highlighted in the research plan. The product development component involves the design and manufacturing of the product together with ensuring any intellectual property is protected appropriately and that the product is adherent to current safety requirements. The clinical trial element will take the form of an observational study comparing the new product to that of the current clinical standard, ISCUS (M Dialysis AB, Stockholm, Sweden). The clinical component will comprise 3 stages; an in vitro analysis where the samples will be collected using the sterile collection vial and analysed using the new product in a laboratory setting. Once calibrated appropriately, the device will then be used to measure microdialysis fluid concurrently with the ISCUS analysis. This will initially be performed using 2 microdialysis catheters and then finally using a single catheter. Target population The study focuses on adult patients with a severe traumatic brain injury confirmed with cranial imaging. - Inclusion criteria: 1. Adults aged 16 or older with a TBI confirmed on cranial imaging. 2) Severe injury requiring ventilation on the critical care unit. 3) Patients requiring invasive monitoring of ICP and ABP. - Exclusion criteria: 1. Where a patient is unlikely to survive for longer than 24 hours. Health technologies being assessed A novel analytical device that incorporates an integrated surface-enhanced Raman spectroscopy (SERS) microfluidic chip that is suitable for measuring continuous microlitre flow. This technology is compatible with the existing microdialysis brain catheter, pump, tubing and clinically determined flow rates. Enrolment Recruitment rate has been estimated at 10 patients per month. On the basis of hospital episode statistics (HES), approximately 100 patients with a severe TBI are admitted to the Addenbrookes NCCU per year. Research Output The expected output from the research is that we will have a new device that provides rapid, real-time analysis of brain chemistry with minimal labour requirements and a low-cost disposable chip as the only consumable. The clinical and research benefits are detailed in the Expected Output of Research/Impact section. Patient & Public Involvement, and Dissemination We intend to disseminate the findings of our study via high impact factor journals, the Health Technology Assessment (HTA) journal and presentation at national and international meetings. In addition to meetings orientated around neurosurgery, we will target conferences organised for the different health professionals who care for patients with traumatic brain injury, including those in emergency medicine, paediatric intensive care, rehabilitation medicine and medical technology.

Lay abstract: Aim: Development of a low-cost &ldquo;real-time&rdquo; brain chemistry online sensor for use in critical care of acute brain trauma patients. Background: Head injury is the largest single cause of death in those aged under 40 years in the developed world. After the initial traumatic event, the greatest clinical challenge is to limit secondary insults to the brain. After injury, complex, dynamic changes occur in the brain s chemistry. Managing these dynamic events can vastly improve patient outcome. Currently, we monitor pressure in the brain and oxygen levels with &ldquo;real-time&rdquo; analyses, which allows us to respond rapidly to any dangerous changes in these parameters. The analysis of brain chemistry is performed using a technique called microdialysis, which collects samples of brain fluid. These have to be manually transferred to the bedside analyzer every hour, for several days. Design & Methods: We have established proof-of-concept in the laboratory for a novel sensor for glucose, lactate and pyruvate, the three most important substances monitored hourly by the existing bedside equipment. The importance of these three substances in clinical monitoring is recognised in the Consensus Statement produced from the International Microdialysis Forum 2014 (Hutchinson et al., 2015). The new sensor utilises a technique called surface-enhanced Raman spectroscopy, and does not require the expensive consumables used in existing bedside microdialysis analysers. Further laboratory work will optimise the sensor, which will then be trialled and ultimately utilised online at the bedside. Patient & Public Involvement, and Dissemination: The new technology will create opportunities for improvements in patient management and therapy. Development of this sensor will assist in the deployment of microdialysis monitoring of brain-injury patients to many more hospitals critical-care units and paediatric critical-care units. Patients, carers and relevant members of the public will also be involved, including through the charity Headway.

Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: INJURIES AND ACCIDENTS