Efficacy and safety of carbon dioxide insufflation for brain protection for patients undergoing planned left-sided open heart valve surgery: protocol for a multicentre, placebo-controlled, blinded, randomised controlled trial (the CO2 Study).

Introduction: Brain injury is common following open heart valve surgery. Carbon dioxide insufflation (CDI) has been proposed to reduce the incidence of brain injury by reducing the number of air microemboli entering the bloodstream in surgery. The CO2 Study will evaluate the efficacy and safety of CDI in patients undergoing planned left-sided open heart valve surgery.
Methods and Analysis: The CO2 Study is a multicentre, blinded, placebo-controlled, randomised controlled trial. Seven-hundred and four patients aged 50 years and over undergoing planned left-sided heart valve surgery will be recruited to the study, from at least eight UK National Health Service hospitals, and randomised in a 1:1 ratio to receive CDI or medical air insufflation (placebo) in addition to standard de-airing. Insufflation will be delivered at a flow rate of 5 L/min from before the initiation of cardiopulmonary bypass until 10 min after cardiopulmonary bypass weaning. Participants will be followed up until 3 months post-surgery. The primary outcome is acute ischaemic brain injury within 10 days post-surgery based on new brain lesions identified with diffusion-weighted MRI or clinical evidence of permanent brain injury according to the current definition of stroke.
Ethics and Dissemination: The study was approved by the East Midlands-Nottingham 2 Research Ethics Committee in June 2020 and the Medicines and Healthcare products Regulatory Agency in May 2020. All participants will provide written informed consent prior to undertaking any study assessments. Consent will be obtained by the principal investigator or a delegated member of the research team who has been trained in the study and undergone Good Clinical Practice training. Results will be disseminated through peer-reviewed publications and presentations at national and international meetings. Study participants will be informed of results through study notifications and patient organisations.
Trial Registration Number: ISRCTN30671536.
Competing Interests: Competing interests: CR, GDA and BG received support from the National Institute for Health and Care Research for the project associated with this manuscript, which was paid to the University of Bristol. RT, MP, LC, ML and SK received support from the National Institute for Health and Care Research for the project associated with this manuscript, which contributed to their salary. PP, NV and RS received support from the National Institute for Health and Care Research for the project associated with this manuscript, which was paid to the University of Oxford. EA received support from the National Institute for Health and Care Research for the project associated with this manuscript, which was paid to the RS reports ad hoc payments for providing expert testimony for the Parliamentary & Health Service Ombudsman. RS is the director and shareholder of Oxford Heart Surgery, chairs the Intercollegiate Speciality Board on Cardiothoracic Surgery, and is a member of the Special Advisory Committee in Cardiothoracic Surgery for the Royal Surgery Colleges. RS is an honorary secretary of the Society for Cardiothoracic Surgery in Great Britain and Ireland. No other conflicts were reported.
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