Carbon dioxide insufflation and brain protection during open-heart surgery
Funder: National Institute for Health Research Efficacy and Mechanism Evaluation
Sponsor: University Hospitals Bristol and Weston NHS Foundation Trust
Status: In set up
Brain injury is a common complication after open heart surgery and affects 6 out of every 10 people. For most of those affected, symptoms will be mild such as short-term confusion or memory problems. Although rare, symptoms of brain injury can be more serious such as a stroke and it has been suggested that brain injury may also trigger dementia.
It is thought that blowing carbon dioxide over the heart when it is being operated (insufflation) on can reduce the amount of these tiny air bubbles getting into the blood stream, because carbon dioxide is heavier than air. We are running the CO2 study to find out if this is true.
In this study, we will compare carbon dioxide with medical air. Medical air is the same as the air around you and does not have any effects, medical air will be used as a placebo in the CO2 study.
The CO2 Study will randomise 704 participants from across the UK who are having open heart valve surgery to receive either carbon dioxide insufflation (IMP) or medical air insufflation (placebo). Neither the participant, Surgical Team or Research Team will be aware of which intervention is being given, however, the Perfusionist who will operate the cylinder will know which gas the participant is receiving.
Insufflation with the allocated intervention will be delivered at a flow rate of 5L/min from just before cannulation for cardiopulmonary bypass until 10 minutes after cardiopulmonary bypass.
One-hundred study participants from the Bristol centre will be asked to take part in the CO2 mechanistic sub-study. Sub-study participants will undergo a transcranial doppler (TCD) ultrasound of the middle cerebral artery during their surgery to monitor intraoperative air microemboli load and CBF. Participants will also undergo near-infrared spectroscopy (NIRS) to monitor the TOI of the frontal lobes during surgery.
All participants will undergo neurocognitive and functional assessments and quality of life; National Institute of Health Stroke Scale, Confusion Assessment Method, Barthel Index, Addenbrooke’s Cognitive examination and Oral Trail Making Test, SF-12, before surgery, whilst an inpatient (National Institute of Health Stroke Scale and Confusion Assessment Method only), and three months after surgery.
All participants will have diffusion-weighted MRI 2-10 days post-surgery, before discharge, which will be reviewed for radiographic evidence of brain injury.
The primary outcome is acute ischemic brain injury within 10 days post-surgery based on new brain lesions identified with DW MRI or clinical evidence of permanent brain injury according to the updated definition of stroke for the 21st century.
Secondary outcomes include
- Number and volume of DWI brain lesions
- Objective quantification of the impairment caused by new ischemic brain injury assessed using the National Institutes of Health Stroke Scale
- Delirium assessed using the 3-minute diagnostic interview for Confusion Assessment Method
- Functional status assessed using the Barthel Index score
- Neurocognitive function in 6 domains (verbal memory, visual memory, executive functioning, visuospatial or constructional praxis, attention, and information processing speed), assessed using Addenbrooke’s Cognitive Examination III and Trail making Tests A and B
- Quality of life assessed using the physical and mental subscales of the 12-Item Short-Form Health Survey
- Composite of all-cause mortality, clinical stroke, or acute kidney injury within 30 days of surgery
- Serious adverse events to 3 months
- Survival to 3 months
Frequently Asked Questions
Chief Investigator: Associate Professor Umberto Benedetto
Trial Manager: Ms Rachel Todd