Perfusion Pressure Cerebral Infarction Trial (PPCI)

Rigshospitalet

Status: Completed

Conditions: Embolic Stroke; Postoperative Cognitive Dysfunction

Treatments: Procedure: Increased bloodpressure during CPB.

Study type: Interventional

Funder types: Other

Identifiers

NCT02185885

4142, PPCI (Other Identifier)

E-22329-01 (Other Identifier)

H-3-2013-110

Details and patient eligibility

About

STUDY HYPOTHESIS

In cardiac surgery the volume of perioperative cerebral infarctions can be reduced by increasing mean arterial pressure (MAP) during the cardiopulmonary bypass procedure.

BRIEF STUDY SUMMARY

Heart surgery using cardiopulmonary bypass (CPB) can be complicated by injury to the brain. Previous studies using brain scans have reported small stroke-like lesions in up to 51% of patients after cardiac surgery. However, only 1-6 % of patients have permanent symptoms of severe brain damage.

The majority of brain lesions seem to be caused by particulate matter (emboli) that wedge in blood vessels of the brain thereby compromising flow. In addition, insufficient blood flow to areas of the brain supplied by narrowed, calcified vessels may contribute. MAP during CPB usually stabilizes below the lower limit of cerebral autoregulation, which is accepted since sufficient total blood flow is guaranteed during CPB.

The aim of the PPCI trial is to investigate if increased MAP during CPB can prevent or reduce the extent of brain injury after cardiac surgery. A beneficial effect could result from reduced embolic injury through increased blood flow in collateral vessels and/or by increased blood flow in calcified arteries.

180 patients scheduled for cardiac surgery will be randomly allocated to increased MAP (70-80 mm Hg) or 'usual practice' (typically 45-50 mm Hg) during CPB, whereas CPB blood flow is intended equal and fixed in the two groups. Patients are examined before and 3-6 days after surgery with magnetic resonance imaging (MRI) brain scans, mental tests and by blood borne markers of brain injury.

If higher MAP during CPB is beneficial, a change of practice can easily be implemented in the clinical routine.

Full description

TRIAL DESIGN

The PPCI trial is a randomized, controlled, outcomes assessor and patient blinded, single-center superiority trial with two parallel groups in a 1:1 allocation ratio. The randomization will be stratified according to age (stratum 1 < 70 years; stratum 2 ≥ 70 years) and type of surgery (stratum 1 - surgery involving the aortic and/or mitral valve; stratum 2 - surgery not involving these valves).

Enrollment: 197 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• ≥ 18 years of age.
• scheduled elective or subacute cardiac surgery with the use of CPB.
• type of surgery either coronary artery bypass grafting (CABG) and/or heart valve surgery (provided that the valve prosthesis used is MRI compatible).

Exclusion criteria

• a history of stroke.
• a history of reversible ischemic deficits (duration of symptoms 24-72 hours)
• a history of transitory ischemic attacks (duration of symptoms < 24 hours)
• diagnosis of neurodegenerative disorders such as Alzheimers, Multiple Sclerosis etc.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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197 participants in 2 patient groups

Increased bloodpressure during CPB

Experimental group

Description:

The cardiopulmonary bypass (CPB) procedure is conducted according to department guidelines with the modification that MAP is kept between 70 and 80 mm Hg. This is achieved by refract intravenous doses of phenylephrine to a total maximum of 2.0 mg, and after that continuous intravenous infusion of norepinephrine up to 0.4 μg/kg/min if necessary.

Treatment:

Procedure: Increased bloodpressure during CPB.

Regular bloodpressure during CPB

No Intervention group

Description:

The cardiopulmonary bypass (CPB) procedure is conducted in accordance with departmental guidelines, where MAP is sought to be ≥ 45 mm Hg. This is achieved by refract intravenous doses of phenylephrine to a total maximum of 2.0 mg, and after that continuous intravenous infusion of norepinephrine up to 0.4 μg/kg/min if necessary.