Association of Anaesthetists/Barema Joint Research Grants

Background: If patients become very ill they often cannot breathe for themselves and need mechanical ventilation where oxygen and air is blown into their lungs. This requires a procedure called intubation where a breathing tube is passed into the patient's windpipe under anaesthesia. Although lifesaving it may cause complications including;
• Pneumonia caused by the patient inhaling bacteria from their throat as they are
unable to cough due to the sedation and the breathing tube.
• A life-threatening condition called Acute Respiratory Distress Syndrome caused by
pressure stretching their lungs resulting in widespread inflammation.
It is therefore important to get patients breathing without the help of the ventilator as soon as they have recovered sufficiently. Stopping mechanical ventilation involves removing the breathing tube in the patient's windpipe. Unfortunately, some patients may have become very weak after a critical illness so they may not manage to breathe without the ventilator and will need re-intubation then treatments and time on the ventilator to build up the strength of their breathing muscles. Re-intubation is associated with an increased risk of death and prolonged intensive care stay. We try to identify patients who are ready to be extubated by performing a spontaneous breathing trial (SBT) during which the patient breathes without the full support of the ventilator for thirty minutes. If the patient copes with this without becoming exhausted they will be extubated. Measurements can be made during the SBT to predict if extubation will be successful. Despite these actions a proportion of patients will need re-intubation. When deciding whether to extubate a patient doctors must balance the potential benefits of reducing a patient's duration of mechanical ventilation against the risks of re-intubation.

Aims: This study aims to use cardiopulmonary exercise testing (CPET) equipment in a new way. CPET is already used to assess how patients tolerate exercise in order to predict poor outcomes from major surgery. We plan to investigate how CPET measurements change during an SBT, and whether these changes can be used to predict the possibility of failed extubation.

Methodology: This is a purely observational study of intensive care patients who have been mechanically ventilated for over forty-eight hours. Patients will receive normal care except for being connected to the CPET equipment which will make measurements before and during their SBT. Other than using the CPET equipment no additional tests will be required from these patients, but we will collect the results of tests gathered as part of their normal care. We will see if our CPET measurements can predict the success of the SBT or relate to other traditional measures of readiness for extubation.

Expected Outcome: If this study establishes that CPET equipment can be used to predict the outcome of SBTs this could potentially increase options that clinicians can use to reduce failed extubation, an event that is associated with increased likelihood of death and longer stays on intensive care.

Implications: Given the observational nature of the study there will be negligible risk to participating patients.

Background
Mechanical ventilation is used to support respiration in patients who are otherwise unable to breathe. It is used in patients undergoing general anaesthesia for surgery, and patients with significant lung disorders in the Intensive Care Unit. A large body of evidence suggests that, whilst unavoidable, mechanical ventilation also has the potential to cause harm.

One harmful mechanism is cyclical atelectasis, the collapsing and re-expanding of the small balloon-like air-filled structures within the lung within the course of a single breath. Normally, the lung transfers oxygen from air into the blood continuously. However, if parts of the lung collapse within the course of a breath, they do not contain oxygen, and are temporarily unable to transfer oxygen to the blood until they reopen again. Unfortunately, measuring cyclical atelectasis is challenging and clinicians are often only able to institute therapies that they know will help a proportion of patients, uncertain whether the individual patient they are treating will be one of these.

If it were possible to continuously measure blood oxygen levels during the course of a single breath, their degree of swing would provide a way to measure cyclical atelectasis. Armed with such knowledge, clinicians could then alter the mechanical ventilator settings and see in real time if the alteration was beneficial. We have recently developed a monitor that can measure these swings in oxygen levels, and that we propose to test on blood sampled from Intensive Care patients.

Aims
We shall employ two complementary techniques to demonstrate the presence of blood oxygen oscillations in patients receiving mechanical ventilation.

Methodology
We propose two observational studies of critically unwell patients in the Intensive Care Unit. First, we shall rapidly sample small volumes of blood from a patient and analyze them using standard, clinically available equipment to determine the oxygen levels within them. Being able to sample these volumes quickly enough, we expect to be able to see the oxygen level change within the course of a single breath. Second, we plan to slowly draw arterial blood over our newly developed oxygen sensor outside of the patient's body, via a plastic tube inserted into the artery as part of usual care. We shall perform this second experiment at two different mechanical ventilatory settings and then compare the size of the oscillations seen in each case. We need to study 30 patients, and shall only visit each patient on one occasion to conduct both studies involving the sampling of approximately 30 mL of blood.

Expected Outcomes
We expect to demonstrate oscillations in oxygen levels within the timeframe of a single breath, with the smallest oscillations associated with the ventilator settings causing the least cyclical atelectasis.

Implications
Our ultimate aim is to develop an indwelling sensor that allows mechanical ventilatory settings to be individualised for the sickest patients. This approach would reduce harm to patients and the burden on Intensive Care Units throughout the country.