A new treatment on the way to improve brain and kidney health outcomes after heart surgery

Key points

Heart surgery requiring the heart-lung machine (cardiopulmonary bypass) saves lives but can cause brain and kidney problems in many patients.
Florey researchers are teaming up with clinical specialists at hospitals across Victoria and South Australia to test a Florey-patented treatment with the goal of reducing brain and kidney injuries.
The Australian Government’s Medical Research Future Fund (MRFF) will provide $4.9 million to support the research over 5 years.

MEGA-HEART project receives funding

The MRFF has selected a research project led by The Florey and University of Melbourne to reduce brain and kidney injury after cardiac surgery. Florey critical care researchers will lead a multi-site study to test a treatment which could prove a game changer for patients undergoing heart surgery.

The MEGA-HEART project has received a $4.9 million grant from the Australian Government’s MRFF.

Lead investigator Professor Yugeesh Lankadeva said up to half of all heart surgery patients experience postoperative delirium and 30 per cent of patients have acute kidney injury.

“Many people wake from life-saving heart surgery in a confused, forgetful and disturbed state. And many experience minor to severe kidney problems,” Professor Lankadeva said.

These issues can lengthen or complicate recovery or may even prove fatal in some cases – yet no therapies are available.

Professor Lankadeva said the project centres on administering a “mega-dose” of a novel formulation of sodium ascorbate that was recently developed and patented by The Florey to treat heart surgery patients in operating theatres and intensive care units.

He said for the past 3 years the team, with experts in many fields – cardiologists, endocrinologists, cardiac anaesthetists, cardiac surgeons, clinical perfusionists, intensive care physicians, nephrologists and neuropsychiatrists – had developed methods for studying the effects of heart surgery and cardiopulmonary bypass on brain and kidney health in sheep.

“Our compelling preliminary data in sheep undergoing cardiopulmonary bypass suggests our formulation of sodium ascorbate reduces neuroinflammation, which may prevent delirium. It also appears to reduce kidney inflammation, hypoxia and cell death in the inner region of the kidney – the renal medulla – which may prevent acute kidney injury.”

The funding will enable a 3-stage multidisciplinary research program:

Identifying the optimal dose of sodium ascorbate to prevent or reduce inflammation in the brain and prevent inflammation, hypoxia and cell death in the kidneys in sheep.
Determining the physiological and immunological mechanisms by which a mega-dose of sodium ascorbate exerts its effects of vital benefit to organs.
Establishing safety and efficacy of the optimal dose of sodium ascorbate in patients undergoing heart surgery in hospital-based trials.

“We aim to follow this project with larger scale clinical trials to transform the management of patients undergoing heart surgery to improve brain and kidney health outcomes,” Professor Lankadeva said.

The clinical trial will recruit patients and involve perioperative and critical care physicians from Austin Health, the Victorian Heart Hospital, The Alfred, Royal Melbourne Hospital and Royal Adelaide Hospital.

Austin Health Head of Anaesthesia Research and clinical lead of the MEGA-HEART project, Associate Professor Lachlan Miles, said delirium and acute kidney injury after heart surgery can make an already challenging recovery considerably more difficult.

Brain and kidney injury do not discriminate and can happen to anyone undergoing one of these life-saving heart surgical procedures.

“Developing a therapy that prevents these common complications could be the biggest development in peri-operative heart surgical care in the last 25 years. It’s a tremendously exciting time to be working in this space, and a privilege to be able to help move this therapy from the bench to the bedside.”

Professor Lankadeva receives funding through an Emerging Leader Investigator Grant from the National Health and Medical Research Council of Australia and a Future Leader Fellowship from the National Heart Foundation of Australia.

Heart Foundation Chief Medical Advisor Professor Garry Jennings said: ”Many people have short term medical problems during their recovery including poor kidney function, heart arrythmias and chest complications. Anecdotally, people often complain that their mental faculties are ‘not quite right’.”

He said the Heart Foundation offers patients and their families the free ‘MyHeart MyLife’ support program to help navigate these issues and he welcomed MEGA-HEART which also addresses these concerns.

“The Heart Foundation has contributed to funding the research that has made a large-scale clinical trial possible. We look forward to seeing people recover from successful cardiac surgery more quickly and fully return to their activities at work or recreation.”

MEGA-HEART involves researchers and clinicians from The Florey, University of Melbourne, Austin Health, Monash Health, Royal Adelaide Hospital, Alfred Health, Monash University, St Vincent’s Hospital Melbourne and The Victorian Heart Hospital.

A cardiac patient’s experience: “After surgery, you’re a different person for a while.”

Dr Simon Iles is an intensive care doctor at one of Melbourne’s busiest hospitals and knows first-hand what it’s like to recover from cardiopulmonary bypass.

Now in his 40s, Dr Iles (right) was aged 28 and on cardiology rotation at a New Zealand hospital when he collapsed. He’d been summoned to resuscitate a cardiac patient and raced to get there in time.

“I ran up 5 flights of stairs and I was first to arrive. I was pretty fit back then, and I blacked out. I’d gone into a very fast heart rate – effectively my pulse rate was 300 beats per minute.”

While the other patient was being resuscitated, the team also had to deliver a shock to Dr Iles to restore cardiac rhythm.

“I woke up half an hour later completely bamboozled.”

Dr Iles’ condition was due to an undetected congenital abnormality that caused fluid to collect in his lungs. The only solution was surgery a few weeks later.

“I was really anxious. The operation involves sawing through the sternal bone so they can access your heart, and your heart being stopped – you don’t have a heartbeat for a couple hours while they fix the underlying problem.”

Dr Iles was hooked up to a cardio-pulmonary bypass circuit which acted as his heart and lungs, pumping and oxygenating his blood for him.

It’s a weird experience waking up after an operation of that size. You are very disorientated, your brain’s not clicking. You wonder ‘What has happened, where am I?’. I was in the ICU for a couple of days and then moved to a ward. I was young, fit and strong, but the post operative pain was the worst I have experienced in my life.

Dr Iles says the first 4 days were a blur. He suffered short-term memory loss, even forgetting close friends’ names.

“It wasn’t confusion, it was just this bizarre space. You just blank. After surgery, you’re a different person for a while. Some people fly through and notice absolutely nothing. But I had 6 weeks of quite significant personality change. I was withdrawn and took antidepressants for about 3 months because I just couldn’t see the world favourably and couldn’t get any enthusiasm for anything. I recovered completely – but not without challenges.”

Dr Iles is sharing his personal story to support the MEGA-HEART project that aims to resolve the kinds of problems he suffered post-surgery.

“Meeting some of the people involved in this research has been uplifting and they’ve offered me some amazing insights – to see their enthusiasm and the excitement with scientists collaborating with clinical staff. It’s infectiously uplifting,” he said.