Life was tough for those guys. Each resident was on call alternate nights and lucky to escape the hospital before 7 pm the following evening. And I discovered the hard way that you always had to be clean-shaven before the boss turned up in the morning. He did not tolerate sloppy or tired, even though the residents were perpetually exhausted. It was all part of the training.
As I drew closer to the group I could overhear the conversation. Kirklin wanted to know why a new resident had used a particular drug to slow a rapid heart rate. Having recently joined the service, the young man was not up to speed with the boss’s strictly regimented protocols for post-operative care. He responded to the onslaught by saying that he had called Kirklin the previous night and he’d told him to use the drug.
‘I don’t remember that,’ Kirklin replied, steam billowing out of his ears. ‘I must have been sleeping. Don’t you ever take an order from me again while I’m asleep.’
As I strode past the gathering, the boss concluded his tirade and turned to abandon the wobbly residents. My eyes met his, and I froze in his steely gaze.
‘You’re Westaby, aren’t you? I’ve seen your picture. I was expecting you last week.’
This was a testing remark deliberately aimed at putting me on the back foot. I simply said in my best English accent, ‘No sir, you are mistaken. Last week was Christmas.’
The chief resident, who’d remained at his shoulder, looked at the ceiling and rolled his eyes, anticipating a thunderbolt. Instead a broad grin broke through and Kirklin’s tired eyes wrinkled behind his horn-rimmed spectacles. Englishman had contradicted the living legend and scored a touchdown in the process.
‘I’ve been told you are difficult,’ he said. ‘So Bentall sent you to reform school. Come along to the office.’
Eugene ‘Gene’ Blackstone was there waiting for him. Blackstone had trained as a surgeon at the university but then moved over into full-time cardiovascular research. His role was to analyse the departments’ data output and use it to shape day-to-day clinical practice. Some referred to Blackstone as Kirklin’s auxiliary brain, and even Kirklin acknowledged him as a genius.
My own lowly title was ‘international clinical fellow’. There were always several of us there at a time and we came right at the bottom of the pecking order, lab rats who helped in the operating room. But that was OK. Just to be there was special. Everyone had to start from the first rung in this environment, and we all hoped to be involved in some great research project, a ground-breaking endeavour where we could publish important papers with our names alongside the master, Kirklin, and the wizard, Blackstone. We all saw this as the ticket to success back in our own countries.
Kirklin opened by inviting me to talk about myself. Apparently the phrase ‘outstanding technical surgeon but a nightmare to work with’ had appeared in my references. Although I was more than content to hear that, Kirklin quite reasonably wondered what I had done to warrant the second part of the description. Was I one of those bullish public schoolboy types from Eton or Harrow? I soon disabused him of that notion. I told him about growing up in the north of England in a steel town just like Birmingham, Alabama, then watching my grandfather die from heart failure when nothing could be done to help him. I mentioned that I had worked in the steelworks and as a hospital porter to support myself through medical school. Not that any of this made me difficult – I blamed all that on the head injury. This struck a chord with Kirklin, who was an American football fan. He was intrigued that rugby was just as violent but we didn’t wear helmets.
The fact that I managed to hold their attention for twenty minutes was very satisfying. It was an animated exchange and I repeatedly made them laugh. This impromptu meeting was like winning the lottery. A list of new projects had been drawn up for the year but the formal meeting to allocate the research would be later that week.
While Kirklin caught up with his secretary, Blackstone engaged with me directly. ‘I’ve read your curriculum vitae,’ he said. ‘You have a degree in biochemistry. I think you can help us with something.’
Jet lagged, I smiled at him but my spirits sank. I didn’t want to do fucking biochemistry. I was there to operate and show them what I was made of. So I said nothing.
Then Kirklin returned. ‘I want you to work with my son on a project,’ he said. ‘Jim has just joined us as chief resident from Boston.’
Then I started to listen. If the boss wanted his own son involved it had to be important. As he left the office for the operating room his departing remark to me was, ‘Come and join me when Gene has explained everything.’
I’d been accepted into the fold. But no more bullshit. I would never get away with it. For once I had to be a team player, not the prima donna.
The schedule in the unit was unrelenting. The residents’ morning rounds began at 5 am and Kirklin was called at precisely 6 o’clock with a progress report. A minute too soon and he would put the phone down on you; a minute too late and you were in trouble when he arrived in the hospital. Surgery began after breakfast at 7 o’clock and often went on well into the evening. Morbidity and mortality were simply unacceptable, particularly through human error. Then there were the evening rounds. Full departmental academic meetings where research updates were presented took place on both Wednesday and Saturday mornings at 8 o’clock. Topic presentations or journal reviews had to be flawless. On Sunday morning at 7 o’clock Kirklin and Blackstone held academic business meetings to review progress in the various research projects and finalise scientific manuscripts for publication. Kirklin usually went riding on Sunday afternoons, while Blackstone went to church.
When the residents foolishly dared to complain of sleep deprivation following long nights in intensive care, Kirklin replaced them with clinical nurse practitioners. For the fellows like me, laboratory research would alternate with operating theatre sessions. Patient follow-up for published papers had to be exhaustive, complete with telephone calls to the coroner’s office, prisons and overseas embassies until all patients had been located. One fellow working alongside me spent two years following up 5,000 coronary bypass patients to produce one single manuscript. That was the Kirklin work ethic.
The system I had to adapt to was all about perfection – the best outcomes, the lowest death rates. In the mid-1960s the surgical mortality rate for blue babies with a condition called tetralogy of Fallot exceeded 50 per cent. By 1970 in Birmingham it was 8 per cent. Come 1981, Kirklin’s exacting protocols and meticulous surgery meant that any death was considered a disaster. Children simply no longer died from technical errors, and those who experienced life-threatening problems usually did so because of their exposure to the heart–lung machine. There was therefore an ongoing battle against the post-perfusion syndrome and it was time to drill down to the cause. This was to be my research. I had the appropriate background to dig deep and discover the biochemical triggers for these damaging effects. Right place, right time, right project.
So what was already known? With certainty, it was the contact between the patient’s own blood and the myriad of plastics and metals in the bypass circuit that initiated the reaction. Most tissues of the body seemed to be affected by it, and the full-blown syndrome was always accompanied by a swinging temperature that persisted for two or three days, together with a rise in white blood cell count. These were also the features of a blood-borne infection or septicaemia. So my hypothesis was that we were investigating whole-body inflammation, in contrast to the local inflammatory response that occurs in pneumonia, appendicitis or a boil.
When the syndrome proved fatal, the autopsy findings often supported that generalised inflammatory concept. Just as occurred with an infected cut, fluid – known as oedema – leaked into the tissues, causing them to swell. In the lungs this caused laboured breathing, low blood-oxygen levels and sometimes frank bleeding into the bronchial tubes. Similar swelling in the brain caused what was known as post-pump delirium – agitation
and confusion, making the patient difficult to control. Then kidney function would deteriorate, causing even more fluid to be held in the body. The whole process tended to be self-limiting and disappeared within a week, but the frail or sicker patients did not survive it.
To improve our clinical response to the syndrome we needed to know its cause. Gene Blackstone had made it clear that there were substantial resources to support the project and that I would be expected to work out what could be done about it. As the new chief resident, Jim Kirklin would help with patient studies, and I even had laboratory technicians assigned to assist me. They were giving me every opportunity to change cardiac surgery.
I started the detective work by devouring the literature on inflammation. What was it that stimulated white blood cells to come together and attack bacteria or foreign bodies such as splinters in the skin? What caused infected tissues to accumulate fluid and weep serum? Tipped off by Blackstone, I read that kidney dialysis patients suffered lung problems too. The dialysis and heart–lung machines had much in common – plastic tubing and synthetic membranes in broad contact with blood. The dialysis machine exchanges toxic chemicals, the heart–lung machine exchanges gases, but the materials at the blood–foreign surface interface were similar.
Scientists and kidney physicians at the University of Minnesota had already found some clues. They showed that a little-known chain of proteins in the blood called the complement system was activated by contact with the dialysis membrane and that toxins released by the reaction caused white blood cells to adhere to the lining of the blood vessels in the lungs. What’s more, the Scripps Research Institute in San Diego had developed a chemical assay to measure the amounts of toxin circulating in the blood. I was so excited and energised by reading all this that I rushed straight from the library to Blackstone’s office to inform him of my line of investigation.
Mildly amused by the eccentric Englishman, Gene swivelled around in his chair and responded in a Deep Southern drawl. ‘I wondered how long it would take you to uncover that paper. Get on and call Scripps. Ask if they will take blood samples from us, then come back to me with your protocol. Have a good day!’
I suggested that we should take serial blood samples from a consecutive series of Kirklin’s patients who were having operations both with and without the bypass machine. Then we would carefully record the severity of the post-perfusion syndrome by assessing brain, lung and kidney function, together with blood clotting during their recovery. The object of the exercise was to determine whether blood levels of the toxins could be linked to the degree of post-operative organ dysfunction in the patient.
It was a great project for me because I could spend all day in the operating theatre watching or assisting with the operations, then learn more about intensive care as I collected the blood samples overnight. These were the places I wanted to be, not in some boring laboratory washing test tubes, although I had my fair share of that while preparing the blood samples to be dispatched to California. It was when I was bold enough to tell Kirklin that I wanted to scrub in with the surgery, not just to watch, that another technician was allocated to work with me. This was my reward for staying in the hospital around the clock and not being as troublesome as Bentall had predicted.
Having Jack assigned to work with me brought further opportunities and suggested an obvious plan. If the blood–foreign surface interaction was the trigger, it would be great to find out which of the many synthetic materials were problematic and whether the temperature within the bypass circuit made a difference. Going off piste again, I set up my own little biochemistry lab and, with Jack’s help, spirited away expensive bypass equipment from the perfusionists’ storeroom. We broke down the various polymers and plastic tubes into pieces small enough to fit into a test tube, then incubated them with fresh human blood. We just paid students for an armful, no big deal in those days.
I eventually collected samples from 116 patients on cardiopulmonary bypass and from a dozen who’d had shunt operations or vascular repairs without the machine. None of the non-bypass operations showed a rise in toxin levels, telling us that neither the anaesthetic nor the surgery itself triggered a significant inflammatory reaction. Now the exciting bit – all the cardiopulmonary bypass patients had shedloads of toxins released in their blood, and the longer the patient remained on the heart–lung machine, the higher the levels rose. Moreover, the higher the level of toxins, the more likely the patient was to suffer lung, kidney and brain dysfunction afterwards. Even post-operative heart failure seemed to be related to high levels of toxin release. Eleven of the bypass patients died, and there was a close correlation between elevated toxin levels and risk of death.
Huge amounts of data were generated during these experiments. Consequently, it took weeks of detailed analysis by Gene Blackstone to unravel the findings. In essence, we had finally identified the mechanism of the post-perfusion syndrome. The toxins released by blood–foreign surface interaction stuck to the patient’s white blood cell membranes, causing them to aggregate and initiate inflammation in the vital organs. Using strategically placed catheters in the operating theatre, I showed that virtually half of the body’s circulating white blood cells became trapped in the patient’s lungs at the end of cardiopulmonary bypass when we allowed blood to flow back into them again. It was oxygen free radicals and protein digestive enzymes released from the trapped white cells that damaged the delicate tissue membranes. I remember presenting these extraordinary findings to the research meeting and the stunned silence they caused. Silence – followed by great excitement. But what was the point of discovering all this if nothing could be done about it? That’s where my covert efforts in the laboratory bore fruit.
The hours in the operating theatre were long, then I would join Jack in the laboratory to work on the synthetic materials. What we heard from Scripps was a complete revelation. Medical-grade nylon, which was widely approved for use in dialysis and heart–lung machines, strongly activated the complement system. Other materials did too, but to a lesser degree. Before we demonstrated this, nylon’s propensity to release damaging chemicals did not feature in any assessment of biocompatibility. I could now see the way forward. We could clearly make a difference. I explained my tinkering in the background to Gene Blackstone and then to Kirklin. The results from our materials testing were shown to the companies who manufactured the oxygenators and blood reservoirs for the bypass machines. Presented with the evidence, they worked a way to remove the nylon and substitute more blood-compatible materials. Then we waited to see whether this would make a difference.
With a successful project under my belt, I spent more and more time scrubbing in with the surgeons. Kirklin was regimented and fastidious. He took his time and did nothing without a good reason. Every move was based on measurement, algorithms and protocol. The incision had to be a certain length, the patch a certain diameter, the valve a particular size, all carefully correlated with the patient’s body weight. Nothing was ever left to chance, and he was easily irritated when onlookers asked too many questions during a case. Yet he seemed to take a shine to the eccentric Englishman, and wrote kind and encouraging letters when I was back in London.
In the adjacent theatre was Al Pacifico, the complete antithesis to Kirklin and the swiftest and most spontaneous surgeon I’d ever watched. By 1981 it was Pacifico who was operating on the most complex congenital heart disease cases, the twisted, contorted hearts full of holes or obstructed ventricles. Everything he did looked straightforward, effortless and second nature. I would step back from the operating table and write down or draw every critical step. This became my ‘play book’ of congenital heart surgery, an invaluable resource when I inaugurated my own paediatric programme in Oxford.
Often there would be just Pacifico, with me across the table and a physician’s assistant at my side. Although physician assistants, universally known as PAs, were not doctors, they were trained to remove leg veins for coronary bypass
operations, to open and close chests, and to assist the surgeon with parts of other operations. Experienced PAs did these things just as well as the surgical residents; in turn, their presence eventually enabled the residents to cover the intensive care unit and post-operative wards, making their long days manageable. A nurse anaesthetist, again without medical training, would primarily look after an adult case, while a medically qualified anaesthesiologist would supervise two or three operating rooms.
I was intrigued by this approach, but I doubted whether operating PAs or nurse anaesthetists could ever be sanctioned in the NHS. The British medical profession was far too arrogant and self-interested to acknowledge that any aspect of their work could be undertaken without the statutory six years at medical school. In reality, PAs were trained in half that time and were far more cost-effective. I remembered thinking that I would do this when I got a consultant job back home. Bugger the establishment.
We soon found that oxygenators and circuits without nylon were indeed making a difference – patients spent less time on the ventilator and in the intensive care unit because their lungs were better, and fewer died. In addition, there was a decrease in post-operative blood transfusion and the need for kidney dialysis fell away. This had massive economic implications and that fundamental piece of research saved many thousands of lives, indeed infinitely more than I saved over my whole surgical career. I started to get invitations to lecture throughout North America, and Blackstone was happy for me to do this. The name Westaby became known to the great and the good of US cardiac surgery, as well as those in the cardiovascular industry.
In the midst of this success I heard that Dr Cooley had implanted a total artificial heart in Houston, only the second ever attempted. It was a Friday morning. Audaciously, that same evening I set out for Houston on the ‘red eye’, determined to meet the great man and see the remarkable technology for myself. I felt like one of the wise men making my way to Bethlehem to meet the baby Jesus. Like me, Dr Cooley had trained at the Brompton, so I had an opening gambit. I accosted him out of the blue at 6.30 am at the entrance of St Luke’s Hospital and was kindly received. He took me to see the patient in their 120-bed intensive care unit and later that night I was called back to watch the heart transplant. The artificial heart was rubbish, the overall experience sensational. This visit began my long association with the Texas Heart Institute and mechanical circulatory support.
The Knife's Edge Page 10