Clinical trial NCT01274754: Neuroprotection With Erythromycin in Cardiac Surgery
Official title: Perioperative Administration of Erythromycin and Brain Protection
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Functional Disturbances Following Cardiac Surgery
Keywords: neuroprotection
erythromycin
neurocognitive assessment
Lead sponsor: AHEPA University Hospital
Sponsor class: OTHER
Collaborators: name: University of Thessaly
First posted: 2011-01-12
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: patients scheduled for elective cardiac surgey coronary artery bypass grafting

Brief summary: 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.

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.

Detailed description: 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:

1. To determine the effect of high-dose perioperative erythromycin administration on neurological outcome in patients undergoing cardiac surgery
2. 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,

1. preoperatively
2. 12 hours after surgery
3. the 6th day after surgery

Eligibility criteria: 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

Primary outcomes:
measure: biochemical markers of brain ischemia and intraoperative cerebral oxymetry data
timeFrame: September 2010
Secondary outcomes:
measure: better neurocognitive outcome in Erythromycin group
timeFrame: November 2010
Other outcomes:
Locations:
city: Thessaloniki
country: Greece
facility: Ahepa University Hospital
state: Hotmail
city: Thessaloniki
country: Greece
facility: Ahepa University Hospital
Study officials:
affiliation: University of Thessaly
name: George Vretzakis, Prof.
role: STUDY_DIRECTOR
References:
citation: Thomaidou E, Argiriadou H, Vretzakis G, Megari K, Taskos N, Chatzigeorgiou G, Anastasiadis K. Perioperative Use of Erythromycin Reduces Cognitive Decline After Coronary Artery Bypass Grafting Surgery: A Pilot Study. Clin Neuropharmacol. 2017 Sep/Oct;40(5):195-200. doi: 10.1097/WNF.0000000000000238.