by I. Douglas McLaren, MD
When I came over to Ann Arbor from Manchester, England in December 1985, the liver transplantation program here at the U-M had been running for four months. We were still at the old Main Hospital in those days, but in February of 1986 the huge new University of Michigan Medical Center opened, and we all moved across. Dr. Fred White of our department had set up the liver transplant program with the surgeons, and after training with him, I was persuaded to join the team. That first year only half a dozen transplants were performed. Progress followed the usual learning curve. The patients were very sick and mortality was high.
Gradually, as donor availability and our experience increased, outcome improved. I was sent off to the liver Mecca at Pittsburgh for a few days to see how the big shots did things, they were conducting more than 700 cases per year. I remember standing in the OR in the middle of the night surrounded by five donor livers, waiting for their recipients, in coolers dotted around the room. Back in Ann Arbor, Dr. White and I were on call for livers every other night, for two years. When we whined, Dr. Allan Brown told us that he had been in Denver in the 1970s when the now famous surgeon Dr. Starzl was operating. Starzl did the first successful human orthotopic liver transplant in 1963. When Dr. White described his department-made rapid blood infusion system, Dr. Brown would counter with stories of four strong medical students squeezing blood by hand through four IVs, one in each limb. Gradually, a couple of other tough (deranged?) hombres were coaxed onto the team and things started looking up.
Through the late 1980s, cases changed from desperate 24-hour marathons on comatose patients with 200-unit blood losses, to semi-elective eight hour skin-to-skin procedures with zero- to 10-unit blood losses on relatively well patients. The introduction of the immunosupressant cyclosporin A in 1976 and its combination with prednisone had already improved graft survival. In 1988, after the clinical effectiveness of monoclonal antibodies was established, OKT3 supplanted ALG. The next improvement we saw came in the late 1980s with the introduction of the preservative perfusate U.W. solution in place of Euro-Collins solution. This lengthened the cold ischemia time of the donor liver from 10 to 24 hours. Some of the pressure to operate, often throughout the night, was relieved and cases were scheduled more as semi-elective 7:00 am starts. We liked this a lot. No longer were the surgeon, perfusionist, anesthesiologist and nurse standing in the OR all night. The U.W. solution also seemed to improve graft and patient survival statistics.
For bloody cases, we very much relied on Dr. White’s homemade 'Power Infuser' to pour fluid into exsanguinating patients. This large invention basically consisted of two three-liter cardiotomy reservoirs, a roller-head pump from the heart room, a 40-micron filter, and a countercurrent blood warmer which propelled blood and plasma into the patient at over a liter per minute through two 8.5 French cannulae, one in the antecubital fossa and one in the right IJ. It was definitely a lifesaver. Unfortunately, to initiate infusion one had to remove a sturdy clamp, crank up the beast, and then reapply the clamp to stop the infusion. Any distraction during infusion, especially at a busy time like reperfusion, could lead to a very large volume of fluid being delivered inadvertently. We also needed air detectors to spot potential emboli. So when Dr. White moved away we opted for the HaemoneticsŪ Rapid Infusion System (RIS). This device was compact, had pre-prepared disposables, three air detectors, the option of variable fluid infusion or discrete bolus infusion, a line pressure sensor with cutout, and a digital reading of total volume given, among other things. This machine was much safer and easier for us and our trainees to master.
At the initiation of the program, Dr. White would place all the lines, a CRNA would chart and hold the fort, and a junior resident (this was the era of two year anesthesia residencies) would just draw blood gases and coags. Later we rearranged things so that a senior resident placed the lines with the staff person and ran the case, and an anesthesia tech did the labs. This seemed to work quite well.
Initially, for pediatric cases, we migrated to C. S. Mott Children’s Hospital to anesthetize the young’uns, but as the caseload went up our pediatric anesthesiology colleagues took over. Infants and children do not usually require, or are too small, for venovenous (VVB) bypass or the RIS. For all adult patients and children over 30 kg our surgeons elected to use venovenous bypass, which had been used earlier by Starzl and perfected by Griffiths in 1983. This device circumvented the venous congestion and fall-in venous return (50%), and cardiac output caused by vena cava and hepatic vein cross clamping at hepatectomy, by routing venous blood from the portal vein and the left femoral vein through a centrifugal constrained vortex pump, and back into the left axillary vein. Renal, bowel, hepatic function, and operating conditions were much improved and bleeding was reduced. However, the surgeons had to place the necessary femoral and axillary shunts via cut downs and then close them at the end. This took time and kept them away from the task of donor liver anastomosis. Also, the patient suffered two additional incisions with their associated complications, which sometimes did not heal well. We thought if we could simplify and speed up this line placement we might reduce operating time and surgical complications.
We already needed large bore venous access to transfuse blood via the RIS, so we decided to try and combine the return flow from the VVB and the RIS infusion. Dr. Bruce Crider spoke to ECMO regarding large bore hoses, and at their suggestion we secured some 15 French gauge Bio-MedicusŪ cannulae. One cannula was placed percutaneously in the right internal jugular vein and the other in the left femoral vein. Later, due to occasional clotting in the femoral vein line, we decided to place a smaller, 16 s.w.g. access cannula in the left groin instead. The surgeons wired the big cannula over it when they were ready to start bypass during the anhepatic phase. When bypass had finished the cannula was promptly removed. This seemed to reduce clotting in the femoral vein. At the top end, the jugular cannula received a warmed blood/plasma/crystalloid infusion from the RIS to maintain fluid volume; later, a 1-4 liter blood flow return from the venovenous bypass pump was added via a Y connection. The 15 French cannula seemed to handle 5-liter per minute flows with equanimity. There were a few complications due to line placement but all in all the new system was well received by surgeon, perfusionist and anesthesiologist alike, with a reduction in operative time of 60-90 minutes, shrinking average total surgical time down to approximately five hours.
During some longer cases (12-15 hours) with 10-20 blood volume replacements, we found that the standard 20 s.w.g. radial arterial line tracings became irreversibly damped, or stopped working altogether. To circumvent this problem, after reviewing the available literature, some of us tried using a single 18 s.w.g. brachial arterial line as opposed to the older, standard 20 s.w.g. radial/16 s.w.g. femoral arterial line combination. The larger gauge brachial line gave a more aortic wave form and seemed to remain patent longer with few side effects. In general our residents seemed to enjoy placing these rather unusual lines.
As alcoholic cirrhotics were accepted as transplant candidates in the late 1980s, we experienced some very bloody cases. To help manage the various coagulation problems that arose, we combined laboratory measurement of PT, PTT, fibrinogen, and factor V and VIII levels with thromboelastography information, and later used the new bedside PT and PTT devices that would give us results within minutes. According to protocol, coagulopathies are treated with FFP, cryoprecipitate and platelets, and fibrinolysis with the antifibrinolytics epsilon-aminocaproic acid, tranexamic acid, or aprotinin.
Like most centers in the US, we do not use epidural anesthesia for transplants due to the usual concerns about coagulopathy and hematoma formation and infection in immunosuppressed recipients, but centers in Europe do place epidural catheters in appropriate patients, apparently with good results.
Unfortunately, although there are more than 4,000 liver transplants each year in the US (20% of all solid organ transplants), the death rate for suitable candidates on the waiting list is still over 20%. Various ways are being explored to expand the available donor organ pool. The limited supply of suitably-sized donor organs has led to the development of techniques to transplant part of a liver. Reduced size (split) liver allografts have enabled one donor liver to be used for multiple patients, however this method carries with it a higher complication rate so it is usually reserved for the desperately ill. In a variation on this theme, in 1989 surgeons in Chicago pioneered living-related (partial) liver donor transplantation and our team now performs this procedure as well. Usually, a healthy parent will donate part of his or her liver to their sick child, as there is a nearly 50% mortality of children waiting for a donor. The remaining donor liver regenerates remarkably quickly in most cases and the operative risk is relatively low. Researchers are also currently experimenting with xenograft transplants from animals such as baboons and pigs. Some surgeons have connected a heterotopic donor liver alongside an acutely failing organ until the ailing liver has recovered when the heterotopic organ is removed. Other centers are endeavoring to develop an artificial liver in attempt to support a patient in hepatic failure until a suitable donor becomes available.
The number of liver transplants performed at the U-M rose to its zenith of 94 in 1991, but has since fallen to between 60-70 per year as more potential donors have worn their crash helmets and seat belts and are driven by designated drivers. Overall survival figures countrywide show a one-year survival rate of around 80% and a five year survival rate of around 70%, with a re-transplant rate of approximately 15%.
In summary, orthotopic liver transplantation has evolved from a procedure of desperation, performed in moribund patients with end stage hepatic failure, to an almost routine treatment for patients often relatively early in the disease process, who are otherwise in moderately good physical condition. A large number of patients with liver failure who would have died twenty years ago now enjoy normal productive lives and some of the women have had successful pregnancies. Some recipients still have a functioning graft after nearly 30 years! In fact, the chance of meeting one of these lucky recipients in your OR for an elective surgical procedure is increasing as time goes by.