title: Perfusion Pressure Cerebral Infarct (PPCI) trial - the importance of mean arterial pressure during cardiopulmonary bypass to prevent cerebral complications after cardiac surgery: study protocol for a randomised controlled trial.
abstract: BACKGROUND
  Debilitating brain injury occurs in 1.6-5 % of patients undergoing cardiac surgery with cardiopulmonary bypass. Diffusion-weighted magnetic resonance imaging studies have reported stroke-like lesions in up to 51 % of patients after cardiac surgery. The majority of the lesions seem to be caused by emboli, but inadequate blood flow caused by other mechanisms may increase ischaemia in the penumbra or cause watershed infarcts. During cardiopulmonary bypass, blood pressure can be below the lower limit of cerebral autoregulation. Although much debated, the constant blood flow provided by the cardiopulmonary bypass system is still considered by many as appropriate to avoid cerebral ischaemia despite the low blood pressure.
  
  
  METHODS
  The Perfusion Pressure Cerebral Infarct trial is a single-centre superiority trial with a blinded outcome assessment. The trial is randomising 210 patients with coronary vessel and/or valve disease and who are undergoing cardiac surgery with the use of cardiopulmonary bypass. Patients are stratified by age and surgical procedure and are randomised 1:1 to either an increased mean arterial pressure (70-80 mmHg) or 'usual practice' (40-50 mmHg) during cardiopulmonary bypass. The cardiopulmonary bypass pump flow is fixed and set at 2.4 L/minute/m(2) body surface area plus 10-20 % in both groups. The primary outcome measure is the volume of the new ischaemic cerebral lesions (in mL), expressed as the difference between a baseline, diffusion-weighted, magnetic resonance imaging scan and an equal scan conducted 3-6 days postoperatively. Secondary endpoints are the total number of new ischaemic cerebral lesions, postoperative cognitive dysfunction at discharge and 3 months postoperatively, diffuse cerebral injury evaluated by magnetic resonance spectroscopy and selected biochemical markers of cerebral injury. The sample size will enable us to detect a 50 % reduction in the primary outcome measure in the intervention compared to the control group at a significance level of 0.05 and with a power of 0.80.
  
  
  CONCLUSIONS
  This is the first clinical randomised study to evaluate whether the mean arterial pressure level during cardiopulmonary bypass influences the development of brain injuries that are detected by diffusion-weighted magnetic resonance imaging.
  
  
  BACKGROUND
  ClinicalTrials.gov, NCT02185885 . Registered on 7 July 2014.
authors.affiliation: Department of Cardiothoracic Anaesthesiology, Heart Centre, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100, Copenhagen, Denmark. ppci@vedel.dk.
authors.forename: Anne G
authors.initials: AG
authors.lastname: Vedel
authors.affiliation: Department of Cardiothoracic Anaesthesiology, Heart Centre, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100, Copenhagen, Denmark.
authors.forename: Frederik
authors.initials: F
authors.lastname: Holmgaard
authors.affiliation: Department of Anaesthesia, Centre of Head and Orthopaedics, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100, Copenhagen, Denmark.
authors.forename: Lars Simon
authors.initials: LS
authors.lastname: Rasmussen
authors.affiliation: Neurobiology Research Unit, Neuroscience Centre, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100, Copenhagen, Denmark.
authors.forename: Olaf B
authors.initials: OB
authors.lastname: Paulson
authors.affiliation: Department of Radiology, Diagnostic Centre, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100, Copenhagen, Denmark.
authors.forename: Carsten
authors.initials: C
authors.lastname: Thomsen
authors.affiliation: Department of Radiology, Diagnostic Centre, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100, Copenhagen, Denmark.
authors.forename: Else Rubæk
authors.initials: ER
authors.lastname: Danielsen
authors.affiliation: Department of Radiology, Diagnostic Centre, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100, Copenhagen, Denmark.
authors.forename: Annika
authors.initials: A
authors.lastname: Langkilde
authors.affiliation: Department of Clinical Biochemistry, Diagnostic Centre, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100, Copenhagen, Denmark.
authors.forename: Jens P
authors.initials: JP
authors.lastname: Goetze
authors.affiliation: Department of Biostatistics, University of Copenhagen, Øster Farimagsgade 5, DK-2100, Copenhagen, Denmark.
authors.forename: Theis
authors.initials: T
authors.lastname: Lange
authors.affiliation: Department of Cardiothoracic Anaesthesiology, Heart Centre, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100, Copenhagen, Denmark.
authors.forename: Hanne Berg
authors.initials: HB
authors.lastname: Ravn
authors.affiliation: Department of Cardiothoracic Anaesthesiology, Heart Centre, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100, Copenhagen, Denmark.
authors.forename: Jens C
authors.initials: JC
authors.lastname: Nilsson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D062186:Arterial Pressure; D006348:Cardiac Surgical Procedures / Q000009:adverse effects; D002315:Cardiopulmonary Bypass / Q000009:adverse effects / Q000379:methods*; D002544:Cerebral Infarction / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D002560:Cerebrovascular Circulation; D002985:Clinical Protocols; D003072:Cognition Disorders / Q000209:etiology / Q000517:prevention & control; D003718:Denmark; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D006706:Homeostasis; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D010477:Perfusion / Q000009:adverse effects / Q000379:methods*; D012107:Research Design; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
keywords: Cardiac anaesthesia; Cardiopulmonary bypass surgery; Embolic stroke; Ischaemic stroke; Postoperative cognitive dysfunction