Intravenous Fish Oil in Critically Ill Cardiac Patients

Study Overview
=================
Brief Summary
-----------------
A large body of evidence has accumulated showing that n-3 PUFAs exert extensive cardiac effects. The development of commercial solutions of FO opens perspectives for therapeutic applications in patients with acute cardiac conditions.the 3 following hypotheses will be addressed in patients requiring cardiac surgery under cardiopulmonary bypass or after myocardial infarction:perioperative /post-PTCA intravenous fish oil modifies the composition of membrane phospholipids in platelets and cardiac cells, blunts the physiological response to cardiac surgery/myocardial infarction, and reduces the incidence of arrhythmias, and reduces the occurrence of systolic dysfunction.

Detailed Description
-----------------
A. Randomized trial in 40 cardiac surgery patients Early rapid infusion of fish oil (3 times in 24 hours) in cardiac surgery patients. B. Randomized trial 20 myocardial infarction patients (abandonned) Continuous infusion of the same dose over 24hrs in the myocardial infarction patients Additional trial in healthy volunteers (investigating physiological changes after cardiac study): -Open trial in 8 healthy lean volunteers to investigate the impact of the same 0.6 g/kg FO dose IV (Week 1: 3hrs), and then orally on week 2, on platelet n-3 PUFA incorporation, platelet function, heart rate and peak flow response to stress test.

Official Title
-----------------
Effects of Intravenous n-3 Polyunsaturated Fatty Acid Administration in Critically Ill Cardiac Surgery and Myocardial Infarction Patients

Conditions
-----------------
Coronary Artery Disease

Intervention / Treatment
-----------------
* Drug: Fish oil emulsion
* Drug: Saline


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Coronary artery disease requiring elective surgical repair under cardiopulmonary bypass Acute myocardial infarction requiring ICU management Exclusion Criteria: Absence of consent Ventricular ejection fraction < 35% Beating heart surgery or emergency surgery Hypercholesterolemia > 5 mmol/l Thrombolysis Chronic steroid therapy Acute or chronic renal failure prior to surgery (plasma creatinine > 150 umol/l) Chronic coagulation disorder Premenopausal female Consumption of more than 3 times fish per week

Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Saline (No lipid emulsion) | Drug: Saline<br>* 3 infusions, perioperative or post-PTCA<br>|
| Experimental: Fish oil emulsion<br>3 infusions of 0.2 g/kg omega-3 PUFA within 24 hours in cardiac surgery (continuous infusion post-PTCA) | Drug: Fish oil emulsion<br>* 0.2 g/kg FO, 3 times in 24 hours, infused over 3 hours each in cardiac surgery, or continuous infusion of 0.6 g/kg post PTCA<br>* Other names: Omegaven,Fresenius Kabi AG;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incorporation of n-3 PUFA into platelet cell membrane and myocardial tissue | The primary outcome is the determination of magnitude of the incorporation and the time required for incorporation of omega-3 fatty acid cell membrane composition after short intravenous infusions was unknown until the present study (HPLC determination of fatty acid membrane composition in all patients) | 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inflammatory and metabolic response | cytokine determination, CRP, glucose control (blood levels and insulin requirements) in all patients | From operation to ICU discharge (maximum 28 days) | 
| Global clinical outcome | length of mechanical ventilation, length of ICU and hospital stay in all patients | From operation to hospital discharge (maximum 28 days) | 
| Myocardial recovery after surgery | Holter monitoring during cardiac surgery or for 72 hours | From operation to hospital discharge (maximum 28 days) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Fish oil supplement, n-3 PUFA, Cardiac function, Membrane incorporation, Inflammation, Clinical outcome