Calne flew to Basel, Switzerland, to convince the executives at Sandoz to commit to the production of cyclosporine. After much discussion, they “somewhat reluctantly agreed, believing that developing cyclosporine would be regarded as an ethical and humanitarian gesture but would probably be a money loser. They had no idea that this compound would revolutionize organ transplantation, create a huge new market, and become a gigantic source of revenue for their company.”
Initial human trials, begun in 1978, were somewhat disappointing; high doses of the drug were toxic to the kidneys. Nevertheless, five of seven patients left the hospital with functioning grafts. Calne then performed transplants in thirty-four more patients using cyclosporine alone, and his results showed high patient mortality. Five patients had died, three had developed cancers, and almost none had normal kidney function.
Despite initial concerns about Calne’s results, Starzl commenced, with his usual vigor, his own trial using cyclosporine. As he did with azathioprine before, he combined cyclosporine with steroids, which allowed him to decrease toxicity to the kidneys. Between December 1979 and September 1980, he treated sixty-six patients in a non randomized trial. Shortly thereafter, he moved to Pittsburgh and hit the ground running. In 1981, sixty-five more kidneys were transplanted using a prednisone-cyclosporine combination. The outcomes were unmistakably positive, with a one-year graft survival of 90 percent.
By 1983, cyclosporine had received FDA approval for kidney, liver, and heart transplant. The discovery of this drug was a huge step forward for the field of organ transplantation—perhaps on par with the major firsts that took place in the 1960s. Transplantation had arrived.
Part III
Expanding
the Horizon
Beyond the
Simplicity of
the Kidney
Only those who will risk going too far can possibly find out how far one can go.
— T.S. ELIOT
6
Open Heart
The Invention of Cardiopulmonary Bypass
This assemblage of metal, glass, electric motors, water baths, electrical switches, electromagnets, etc. looked for all the world like some ridiculous Rube Goldberg apparatus. Although the apparatus required infinite attention to detail it served us well and we were very proud of it. The heart-lung machines in use today bear as little resemblance to that early model as the jet plane of today bears to that magnificent conglomeration of wires, struts, and canvas that sailed into the air in 1905 from the dunes of Kitty Hawk with one of the Wright brothers at the controls.
— JOHN GIBBON JR., IN A DREAM OF THE HEART, BY HARRIS B. SHUMACKER
The path to kidney transplantation in humans followed a chronology from Carrel to Kolff to Medawar to Murray. Years before Murray and his colleagues unlocked the puzzle of kidney transplantation, entering the chest was anathema to most surgeons, and operating on a beating heart was a guaranteed massacre. The story of extrarenal transplants, starting with the heart, requires us to jump back in time, when a few brave souls thought they might be able to solve the mystery of the cardiovascular system.
My own story also returns to a time when my bravery was about to be tested for the first time.
University of Chicago, Internship and Residency
Internship was absolute chaos. I had arrived in Chicago after four years of medical school in New York with the official label of “doctor” but no actual skills, other than skinning dead people and cutting sutures in the OR. Aside from giving me a bunch of book knowledge about physiology and biochemistry, medical school had done very little to prepare me for what came next.
My first task as an intern was to gain experience taking care of sick people. The other interns and I covered so many patients and so many attendings that we could never get on top of the work. The more efficient I got with my tasks, the less I looked at patients as human beings and the more I looked at them as a list of boxes to check off. I inflicted so much pain on patients by sticking in needles and tubes, pulling out needles and tubes, cutting and sewing and draining, that I became desensitized to their experience. I would say, “Just relax, take a deep breath. You’re gonna feel some pressure,” but I wasn’t really listening or paying attention. Patients would squirm around as I drained their abscesses, and I would just keep going. In fact, it got to the point where I regarded the patients as standing in the way of my accomplishing these tasks. I remember going into one patient’s room to pull out a chest tube. He was sitting at a table with his food tray in front of him, but rather than get him back in the bed first, I pulled the tube out while he was sitting there. Box checked.
As uncaring as this sounds, some element of detachment is necessary in surgery. Once an operation starts, I completely disconnect from the fact that there is a person on the table, with a life and a family. Indeed, part of the reason a surgeon’s training is so long and difficult is that you have to reach the point where you can do what needs to be done every day without becoming overly attached to, and therefore emotionally drained by, each case.
A couple of months into my training, I killed my first patient. My task was to place a central line in an elderly woman who needed IV antibiotics, a procedure I had done many times before. Placing a central line, also known as a central venous catheter, involves sticking a big needle into a vein in the neck or chest, and threading a catheter in fifteen to twenty centimeters so it sits in a vein right outside the heart, to administer medicines or fluids or withdraw blood. The patient was in her eighties, chronically on a ventilator, and with a tracheotomy in her neck. She didn’t speak or interact in any appreciable way. And she was folded up like a pretzel. What was the point? I called the attending at home, and he said to put the line in. I gathered the kit and all the fixings and then called the patient’s son. I explained that every procedure had risks, but this was relatively minor and shouldn’t be a big deal. He thanked me.
I poured the betadine on the patient’s chest, put on my sterile gloves, and took out the needle. I then put my thumb on her clavicle and plunged the needle into the skin below it. I hit the tip of the needle into the clavicle and then walked it down so I could advance it just below the clavicle and toward her chest, pulling back on the plunger the whole time. I advanced all the way in and didn’t get any blood back. This meant I hadn’t hit the vein. But I didn’t get any air, either, so I figured I hadn’t hit her lung, which was good. I pulled back, changed my angle, and advanced again. This time I got that sweet rush of dark red blood. I was in. I pulled off the plunger, and blood slowly poured back. I then advanced the wire and removed the needle. I threaded the triple lumen catheter over the wire and made sure to grasp the wire as it came out the back end, so it wouldn’t get sucked into the patient due to the negative pressure going to the heart. I advanced the line about fifteen centimeters and removed the wire. All the ports drew blood.
I was just getting ready to sew the line in when the sat monitor, which keeps track of a patient’s oxygen saturation, started to sound its alarm. I looked over at it: the level of oxygen in her blood was at only 40 percent. That’s not good. It should be in the nineties at least. I quickly started sewing the line in, hoping that the monitor’s alarm was going off because the sensor had slipped off her finger. Still, her saturation level kept dropping. Then her blood pressure cuff’s alarm started sounding, and the sat monitor showed that her heart rate had dropped down into the twenties. She was about to code.
I realized that I must have nailed her lung on that first pass. As I finished tying the stitch in the line, I turned to the medical student who was observing this and said, “Open your book to ‘tension pneumothorax’ and tell me what gauge needle to poke in her chest and where to put it.” At this point, I was listening to the patient’s chest with a stethoscope; I couldn’t hear any breath sounds. Not good.
The medical student yelled out, “Fourteen-or sixteen-gauge needle, second rib space.”
I ran out of the room to the storage cart, yelling to a nurse,
“Call a code!” From the cart, I grabbed a handful of big needles, ran back to the patient, and squirted some more betadine on her chest. Then I uncapped the biggest needle I had and plunged it into her chest, not far below her clavicle. A bunch of air rushed out. Good sign, I hoped. But the patient’s sat monitor was picking up nothing.
I heard the overhead page in the background announcing the code. I knew within minutes that a bunch of people would pour into the room and ask me what I’d done. I plunged a second needle next to my first. More air. No other changes on the monitor. As I started doing chest compressions, people began coming into the room.
They stood there for a second, wondering what the hell I was doing. Then one of the medical residents went up to the head of the bed to start pumping breaths into the patient’s trach tube with an Ambu bag.
I heard my chief resident, Charlie, behind me. “What happened?”
“I think I nailed her lung putting the line in.”
“Shit. Let’s just throw a big chest tube in and see if it works.”
We both knew it wouldn’t. He handed me a knife he always carried in his pocket—don’t worry; it was sterile—and walked me through the tube insertion, since it was one of my first. We cut down over the rib in the fifth intercostal space. I poked through the muscle in between her ribs with a big clamp, and more air came out. We threaded the tube in the space between her rib cage and her lungs. During all this, the medicine team was performing CPR. We hooked the tube up to the suction canisters that the nurses had prepared. None of it made a difference.
About twenty minutes into the code, we all agreed to call it. She was dead. I had killed her. We call this a clean kill. No doubt who was responsible.
Charlie put his arm around me and said, “Don’t worry about it. It’s probably for the best.”
One of the attending surgeons who happened to be around had come in the room. He came up to me and said, “She was probably dead already.”
I knew she wasn’t. I called her medical attending and let him know what had happened. He thanked me and apologized all at the same time. I offered to call the family, and he said that was a good idea.
I called the son who had given me his consent an hour before. “Hi, this is Dr. Mezrich, whom you talked to before about that line placement? I have some bad news about your mother. Unfortunately, there was a complication. Her lung was under a lot of pressure, and unfortunately the line nicked the lung—”
He cut in. “Did she die?”
“Yes. I’m so sorry.”
He was quiet for a few seconds. Then he said, “Okay, thanks. We’ll be in soon. Thanks for trying. She can rest now.” He was trying to make it okay for me. I felt pissed off that I had been put in this situation but also incredibly guilty. I just had killed someone. That’s not a feeling you get used to very quickly.
Toward the end of the second year of my residency, I worked for a particularly malignant chief resident—Charlie was his name (but not the same Charlie who helped me with the chest tube). At this point I was considered one of the best residents in the hospital, but what no one realized was that I had no idea how to do any operations. I was a likable guy, always comfortable telling jokes and interacting with the staff. Typically, the attending would conduct the operation, and I would assist, keeping everyone laughing. No one really focused on my lack of progress, and I figured at some point I would just start understanding how to do things. The reality is, it doesn’t work that way.
One day, one of the staff told Charlie to take me through a case. It was something simple, like an inguinal hernia. Once the patient was prepped and draped and ready to go, Charlie just stood there and said, “Do it.” But I hadn’t read up on the procedure and had no idea what to do.
The next two hours were incredibly painful for me—at every step, Charlie demonstrated to me that I had no idea how to operate. And then, in an act of brutal honesty that actually changed the course of my training for the next decade, he said, “Wow, Mezrich, you really have no idea what you’re doing in here. Everyone thinks you are this good resident, but I don’t think you’ve learned anything about operating in the last two years. You are way behind everyone in your class.”
I knew he was right, and deep down, his words made me nervous. So, I took them to heart. After that, no matter how late I got home or how early I had to get up the next morning, I prepared for the next day’s cases. I bought a surgical atlas and went over the steps of each case. I tried to perform each operation in my mind. I was also more aggressive about trying to get in the OR, and I stopped joking around once there. Also, I honestly assessed how well I understood the cases after we were done. Surgical learning needs to be active. As much as I (and everybody else) feared Charlie, I owe him a big debt of gratitude. He woke me up to what it means to learn how to be a surgeon. If you are reading this, thanks, Charlie. Though you’re still an asshole.
WHEN CONSIDERING ALL the services I rotated through as a resident, none was as crazy or as memorable as cardiac surgery. I often make fun of heart surgeons for the small area they operate on, and the simplicity of the heart as an organ, but the reality is I was very close to choosing cardiac surgery as a profession.
Cardiac surgery, to me, is very black and white. If you do a good job, the patients do fine. If you don’t, they die. We used to say if the operation went well, you could stick the patients out in the woods and they would do fine. But if something went wrong, it didn’t matter how hard you worked, you could never pull them through. This is an oversimplification, but it rings true in my mind. During my first cardiac rotation, as a second-year resident, the other resident who was supposed to be with me had just quit. So, I did the rotation alone, working upward of 130 hours a week.
I have so many crazy stories from those days and nights: opening chests in the middle of the night, placing huge lines and tubes, transfusing so many units of blood. When it comes to self-reliance, I think I built more of mine on that cardiac rotation than on any other service.
One particular surgeon stands out in my memory: Bob Karp. I learned more about physiology, patient care, accountability, and endurance from Karp than from anyone else in my training. A supremely well-trained heart surgeon, Karp got his medical degree back in 1958. He had a special interest in congenital heart surgery on babies and children, and he grew a large program in Chicago. Normally, a surgeon with the prestige of Karp would have fellows that would scrub in with him or her, but Dr. Karp did not have fellows, so the residents got to scrub in, even when he was doing crazy cases on babies, reconstructing their hearts, taking them from dysfunctional malformed bags and turning them into life-sustaining pumps. The operating room under Dr. Karp was kept silent, with the exception of barely audible classical music and his quiet commands to the technicians running the bypass pump. Karp was quite calm in the OR, but if you annoyed him he could absolutely destroy you.
Every night at 9:00 p.m. and every morning at 6:00 a.m. we residents were expected to make the “Karp call,” during which we ran through our patient cases with him. You could never go home at night before making that call, and always had to be back in the next morning well in advance of the morning call. For twenty minutes before the call, we would scamper around the unit gathering our patients’ big wall charts listing their vitals, labs, inputs and outputs, pressors, and meds. The nurses knew about the Karp call, and if they liked you, they’d have the charts ready, filled in, and maybe even stacked and good to go. If a chart was missing, the call was guaranteed to be a disaster. Each time I dialed Karp’s number, my heart would be pounding.
“Hello,” he would say quietly, almost as if he didn’t know who was calling.
At first I tried a little small talk, but quickly realized this was not to be tolerated.
“Vitals! Output!” he would scream. He didn’t want my editorializing.
At that point, I’d start hammering out the patients’ numbers: blood pressure, heart rate, chest tube output, urine, pressors, labs.
At so
me point, he’d cut me off. “Give this, do that, transfer him out, give blood. Next.” And I would move on.
Over time, Karp got to know me well. After about a month, he even let me give my opinion.
“Mr. Smith looks great, I’m not worried about him.”
“Next.”
Gaining Karp’s trust was one of the proudest accomplishments of my life. By the end of my second month with him, I had decided I wanted to go into cardiac surgery. Stopping and starting hearts, reconstructing misshapen pumps in little babies, the pure technical demand, the black-and-whiteness of it—it was all so intoxicating. Once Karp realized I was interested in the field, he would call me to his office for teaching sessions, where we’d review articles, talk about physiology, or he would ask me what my questions were. He knew everything about the heart, knew why some operations worked and some didn’t, and he had no problem admitting when he’d made an error.
Though I didn’t choose it in the end, I remain fascinated with the field of cardiac surgery, and much of that fascination is driven by the people who made open-heart surgery a reality. There is nothing cooler, more beautiful, really, than the perfectly orchestrated dance of going on bypass and shutting the heart off. When you open the chest and expose that pumping muscle that makes everything work, that bag of worms performing frenetic, cacophonic movements that are actually much more coordinated than you would first think; when you insert the various catheters that fill with blood and listen to the back-and-forth between the cardiac surgeon and the pump techs, working together perfectly in a give-and-take that seems so simple; when the cardiac surgeon says those fateful words, “On bypass,” and runs the cardioplegia in, stopping the heart in its tracks; when you hear nothing other than the whir of the machine taking over the role of the heart and lungs—the mystery of the heart is now gone; it is just this bag of blood, so simple and easy to manipulate.
How Death Becomes Life Page 10