Title: First-in-man evaluation of a rapid, real-time continuous arterial PO2 sensor in the critically ill.
Funder: Department of Health and Social Care

Abstract: Research questions The principal question is: how do dynamic real-time PaO2 signals (the PaO2 signature ) reflect individual changes in ventilator-settings and therapy in critically-ill patients? A secondary question is whether specific PO2 signatures correspond to specific outcome trajectories in individual patients. Background We have developed an arterial PO2 sensor which has a rapid response-time and can detect oscillations in PO2 within a single breath. In animal models of ARDS, the sensor can detect cyclical atelectasis and cyclical blood-flow redistribution within the ventilatory cycle. Aims and Objectives The key aim is to determine the utility and potential of dynamic PaO2 measurement in critically-ill patients with ARDS. The objective whereby this is to be realised is to undertake a 'First-in Man' observational patient study to determine the relationship between PaO2 signature and patient phenotype . Methods In a cohort of ICU patients with ARDS, we will measure each individual s PaO2 signature via continuous real-time dynamic PaO2 sensing. We will compare signature changes with a) any changes in clinical condition and ventilator setting as occur during routine clinical care, and b) a variety of mechanical parameters traditionally associated with the development of ventilator-induced lung-injury, and which are routinely collected via the automated high-fidelity physiological data-logger at St Thomas Hospital. Timelines for delivery We aim to have to necessary approvals in place by month 12, before which time the sensor, canula and optical components will be refined and adapted ready for human use. The clinical study will take place between months 12 and 30. Data analysis will take place throughout the study. Anticipated Impact and Dissemination If our sensor can detect a biomarker of lung injury, as it has done in animal models, the device could have a significant impact on clinical care in critically-ill patients. A formal commercialisation plan could then follow this study.

Lay abstract: We plan to evaluate a novel oxygen sensor, with potential to detect important features of severe lung disease in critical illness, and to influence treatment. Many critically ill patients in Intensive Care Units (ICUs) require artificial ventilation (by a mechanical ventilator, aka 'life-support machine') to breathe effectively. This is often the case even if the reason for their admission to ICU was not primarily a lung problem. Unfortunately however, artificial/mechanical ventilation often itself causes further lung injury. This is known as Ventilator-Induced Lung Injury (VILI). This problem is a major financial burden to the NHS. 35-50% of patients with this condition will die as a result of it, and survivors may be left with significant chronic lung disease, and post traumatic stress. During mechanical ventilation, some of the lung's tiny air-sacs may collapse completely when the patient breathes out, and pop open again as they breathe in. This repetitive process (cyclical atelectasis, or CA) can cause injury to the air-sacs, and causes the oxygen concentration in the blood to vary within each breath; rising when breathing in as the air-sacs pop open, and falling when breathing out as they collapse again. Mechanical-ventilation may also overstretch parts of the lung and impair the circulation of blood to these regions. This also causes blood oxygen concentration to vary within each breath. So this varying (oscillating) oxygen concentration in the blood is potentially a sign that harmful events are occurring in the lung, and also that mechanical ventilation is not being applied in the safest and best way. Our current NIHR-funded project has successfully resulted in the invention of a sensor with a rapid response-time of less than 0.1s. It can be placed in an artery, via a canula. We have made the device simple and safe to use and it needs no special user skill. In separate animal tests, we confirmed that the presence of oxygen oscillations in arterial blood is indeed a sign of CA and overstretching. These oscillations could therefore potentially guide the clinician to optimise the ventilator settings to minimise VILI in a way tailored to each individual patient. This would be a significant step to improving outcome in this condition. In this application, we propose for the first time to bring this technology from the lab to the patients' bedside. We plan to study the oscillating oxygen signal or 'signature' in a series of patients with severe lung injury undergoing routine care, to establish the links between an individual s oxygen signature and any changes in their care (particularly changes in ventilator setting) and outcomes. This research work will bring our technology to the point where it is ready for marketing and clinical trials in patients.

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