Investigation Into the Role of GTN & RIPC in Cardiac Surgery (ERIC-GTN)

The Effect of Remote Ischaemic Preconditioning and Glyceryl Trinitrate on Peri-operative Myocardial Injury in Cardiac Bypass Surgery Patients (ERIC-GTN Study)

The purpose of this study is to determine whether Glyceryl Trinitrate (GTN) reduces injury to the heart during heart-lung bypass surgery in combination with the newer technique of remote ischaemic preconditioning (RIPC).

Ischaemic heart disease is a leading cause of mortality in the western world. A number of patients undergo coronary artery bypass graft (CABG) surgery as treatment for ischaemic heart disease. With the rise of interventional procedures, patients who are coming to have CABG surgery are higher risk1. Remote ischaemic preconditioning (RIPC) has been shown to reduce perioperative myocardial injury (PMI) in patients having CABG even when cold blood cardioplegia or intermittent cross clamp fibrillation is used as cardioprotective measures. These patients have a general anaesthetic with multiple infusions including Glyceryl Trinitrate (GTN). The use of GTN in these patients is based on theoretical assumptions of coronary vasodilation pre operatively along with maintaining graft potency postoperatively. We intend to investigate the effect of GTN in patients undergoing cardiac surgery being subjected to RIPC in its role as a Nitric Oxide (NO) donor. Exogenous NO has been shown to be cardioprotective in animal models.

Patients administered a Remote Ischaemic preconditioning protocol (three-5 min cycles of simultaneous inflation to cuffs placed on upper arm and thigh) prior to surgery and IV normal saline 2-5 mL/h during surgery.

Patients administered sham simulated Remote Ischaemic Preconditioning protocol prior to surgery and IV Glyceryl Trinitrate 2-5ml/h during surgery.

Patients administered Remote Ischaemic Preconditioning protocol and IV Glyceryl Trinitrate during surgery

Normal saline IV started prior to knife to skin at a rate of 2-5 mls/h and stopped just after weaning off bypass.

IV GTN given during surgery started prior to knife to skin and stopped after weaning off cardiopulmonary bypass.

Troponin T area under the curve will be calculated using blood samples collected at 0,6,12,24,48 and 72 hours plotting it against time to calculated AUC.

The inotrope score will be calculated as follows: Dosages (in μg/kg/min) of [Dopamine + Dobutamine] + [(Adrenaline + Noradrenaline + Isoproterenol + Isoproterenol) x 100] + [(Enoximone + Milrinone) x 15]

The duration of endotracheal intubation will be noted in hours. Re-intubation rates will be calculated by noting down the number of patients requiring re-intubation and comparing this amongst the 4 groups.

Serum creatinine levels will be noted in the first 3 days postoperatively. If a patient requires renal replacement therapy, this will be recorded and comparisons made amongst the groups. Hourly urine output and daily urine volumes for the duration of ITU stay will be recorded.

Atrial fibrillation will be diagnosed using ECG. A record of the number of patients developing AF post operatively, the intervention used to treat it and whether or not the patient reverted to sinus rhythm prior to ITU discharge will be documented

Inclusion Criteria: Age > 18 years all patients admitted for on- pump CABG and/or valve surgery Able to give consent Exclusion Criteria: Allergies to excipients of IMP and placebo Chronic Renal failure (eGFR<30 ml/min/kg) Severe liver disease Peripheral arterial disease Pregnant or lactating women

Hamarneh A, Sivaraman V, Bulluck H, Shanahan H, Kyle B, Ramlall M, Chung R, Jarvis C, Xenou M, Ariti C, Cordery R, Yellon DM, Hausenloy DJ. The Effect of Remote Ischemic Conditioning and Glyceryl Trinitrate on Perioperative Myocardial Injury in Cardiac Bypass Surgery Patients: Rationale and Design of the ERIC-GTN Study. Clin Cardiol. 2015 Nov;38(11):641-6. doi: 10.1002/clc.22445. Epub 2015 Sep 28.