Neuroprotection With Erythromycin in Cardiac Surgery

First Version: Study Protocol Authors: Thomaidou E., Vretzakis G., Argiriadou E., Stamatiou G., et al.

Perioperative administration of erythromycin and brain protection

Study Setting: On-pump, planned cardiac surgery. Randomized, double blinded clinical trial of two parallel groups. Group A: control group. Group B: erythromycin group (dose 25mg/kg intravenously).

Purpose:

Neurological complications occur in open heart surgery with a frequency of 40% and they range from major neurological deficits (due to a stroke) to neurocognitive and behavioral disorders. This study aims to determine if erythromycin, a worldwide known antibiotic, protects the brain from damage when given in high doses before and during open heart surgery.

Hypothesis:

The investigators consume that high dose of erythromycin will protect the brain with a pharmacological preconditioning against the global ischemia during the perioperative period of heart surgery.

The aims of this study are:

• To determine the effect of high-dose perioperative erythromycin administration on neurological outcome in patients undergoing cardiac surgery
• To determine the relationship of neurological monitoring, specifically NIRS, to neurological outcomes and to determine if erythromycin affects this relationship.

Preoperative Period

Patient Exclusion Criteria: patients > 80 years old, cerebrovascular disease with residual deficits, stroke, alcoholism, psychiatric disease.

Preoperative patient neurocognitive status assessment from the same clinical psychologist in all patients:

at least one day before surgery, perform neurocognitive tests.

Patients of group A: 25mg/kg erythromycin intravenously 12 hours before surgery.

Intraoperative Period

Cerebral monitoring: continuous measurement and registration of cerebral oximetry data (NIRS - INVOS), record of frequency and duration of desaturation episodes (a fall >20% compared to baseline values) and record of interventions to correct desaturation.

Anaesthesia depth monitoring: continuous measurement of bispectral index (BIS).

Registration of: duration of CPB and cross clamp time, mean arterial pressure, heart rate, temperature and ETCO2.

Anesthesia Procedures: anesthesia induction with fentanyl 10-15μg/kg, propofol 2gm/kg and rocuronium 0,6mg/kg. Anesthesia maintenance with propofol.

Postoperative Period - ICU

Postoperative patient neurocognitive status assessment from the same clinical psychologist in all patients:

On discharge, and 3 months later perform neurocognitive tests.

Patients of group A: will receive high dose of erythromycin 12 hours after the end of surgery.

Registration of:

Post operative blood loss, duration of ICU stay, mechanical ventilation duration, duration of hospital stay, inotropic support, postoperative myocardial infarction, re-operation, dialysis, neurocognitive decline, other complications.

BIOCHEMICAL INDEX

Blood samples will be taken from all patients for the detection of tau protein, IL-1 and IL-6,

• preoperatively
• 12 hours after surgery
• the 6th day after surgery

Inclusion criteria

• patients < 80 years old scheduled for elective cardiac surgery coronary artery bypass grafting, good cooperation with the clinical psychologist

Exclusion criteria

• patients > 80 years old
• cerebrovascular disease with residual deficits
• stroke
• alcoholism
• psychiatric disease