TY - JOUR

T1 - Perfusion Pressure Cerebral Infarct (PPCI) trial - the importance of mean arterial pressure during cardiopulmonary bypass to prevent cerebral complications after cardiac surgery

T2 - study protocol for a randomised controlled trial

AU - Vedel, Anne G.

AU - Holmgaard, Frederik

AU - Rasmussen, Lars Simon

AU - Paulson, Olaf B.

AU - Thomsen, Carsten

AU - Danielsen, Else Rubæk

AU - Langkilde, Annika

AU - Goetze, Jens P

AU - Lange, Theis

AU - Ravn, Hanne Berg

AU - Nilsson, Jens C.

PY - 2016/5/17

Y1 - 2016/5/17

N2 - 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/design: 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/m2 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.Discussion: 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.Trial registration: ClinicalTrials.gov, NCT02185885. Registered on 7 July 2014.

AB - 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/design: 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/m2 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.Discussion: 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.Trial registration: ClinicalTrials.gov, NCT02185885. Registered on 7 July 2014.

KW - Cardiopulmonary bypass surgery

KW - Cardiac anaesthesia

KW - Ischaemic stroke

KW - Embolic stroke

KW - Postoperative cognitive dysfunction

UR - https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-016-1753-y

U2 - 10.1186/s13063-016-1373-6

DO - 10.1186/s13063-016-1373-6

M3 - Journal article

C2 - 27189028

VL - 17

SP - 1

EP - 11

JO - Trials

JF - Trials

SN - 1745-6215

M1 - 247

ER -