Liver transplantation for fulminant hepatic failure in a Jehovah's Witness
Clinical Transplantation 10:404-407, 1996

 
NOTES
CASE 
Veno-venous 
bypass 
 
 
 
 
 
CASE REPORT 
A 23-yr-old Asian man was admitted to an outside transplant center in fulminant hepatic failure. He was well until 2 wk prior to presentation when he developed symptoms of nausea. vomiting and weakness which progressed to jaundice, confusion and gastrointestinal bleeding. At the time of presentation to the transplant center he had stage II encephalopathy and his laboratory studies showed a bilirubin greater than 40 mg/dL, aspartate aminotransferase (AST) of 2800U/L, alanine aminotransferase (ALT)  of 2300 U/L and a protime international normalized ratio (INR) of 3.6. His viral serologies revealed positive hepatitis B surface antigen, negative hepatitis B IgM core antibody, positive hepatitis B e antibody, and negative hepatitis C antibody. He had no history of exposure or ingestion of potential hepatotoxins, and no risk factors for hepatitis B except for his Asian background. He deteriorated over the next 12 h and required intubation. It became known that the patient was a Jehovah's Witness and that he had expressed a strong convinction not to receive any blood or blood products, even in life threatening situations. This was supported by a previously signed statement, as well as by family members. Though liver transplantation was felt to be necessary, it was considered too hazardous and supportive measures were instituted. Bacause of continued deterioration our center was contacted and we accepted the patient as a liver transplant candidate since this was the only option in this young man. 
Upon arrival, the patient was in fulminant hepatic failure with stage IV coma. He had good renal funcion, a hematocrit of 34%, protime of 46 s, bilirubin of 32.2 mg/dL, and no evidence of contraindications to liver transplantation. The therapeutic options were discussed with patient's family, who reaffirmed their religious convincion that no blood or blood products, including albumin, be administered. They consented to a liver transplant with the understanding that the patient may exsanguinate without blood transfusions. They also consented to the use of veno-venous bypass and a continuous circuit cell saver during the operation. 
A suitable donor became available within 12h, and the patient underwent orthotopic liver tranplantation on 21 Jaunary 1995 using standard techniques including veno-venous bypass. Intraoperative monitors included radial and pulmonary arterial pressure catheters, as well as standard electrocardiogram, blood pressure and pulse oximetry. Anesthesia was maintained with isoflurane 0,2%, thiopental 1-3 mg/kg/h, and supplemented with fentanyl. Aprotinin was administered throughout the case (test dose, bolus of 2x106 U, then infusion of 50,000 U/h). Estimated blood loss was 400 cm3 and the total fluid replacement was 4300 cm3 of PlasmalyteR. The patient remained hemodynamically stable throughout the procedure, and immediate graft function was noted. Immunosuppression was with steroids and FK506. Hepatitis B immune globulin was administred according to the UCLA protocol. Post-operative blood draws were kept to a minimum, and pediatric phlebotomy tubes were used. The patient's mental status normalized, and he was extubated on postoperative day (POD) 5, and transferred out of the ICU on POD 7. He was started on erythropoietin, and oral iron supplementation was initiated when the patient as able to resume a diet. His immediate postoperative hematocrit was 29%; the nadir was 23,5% on POD 8, but increased steadily since then. He was discharged from the hospital on POD 18 with excellent hepatic funcion. He is doing well 6 months post-transplant, and his most recent hematocrit is 44%. 

DISCUSSION 
...Liver transplantation without using blood presents a formidable challenge. With the numerous advances in liver tranaplantation and increased experience, there has been a trend towards liberalization of recipient selection criteria. More difficult and challenging patients have been succcessfully transplanted. The transplantation of a Jehovah's Witness patient is an extreme example of this trend. Ramos et al.in 1994 reported 4 JW patients who underwent liver transplantation. These patients were selected on strict criteria that included a protime less 15 s, hematocrit greater than 35% and the absence of renal failure or other organ dynsfunction. They were prepared preoperatively by weeks of erythropoietin therapy, and the use of albumin was accepted by the patients. Three patients that met the criteria were successfully transplanted without transfusions. Our patient differed in that he met non of the above criteria. He was in fulminant hepatica failure with encefalopathy; his protime was 46 s, his hematocrit was 34%, and the use of albumin was not acceptable. given the advanced nature of our patient's hepatic failure, and continued deterioration despite medical management, his prognosis was dismal without transplantation. Owing to the emergent nature of the transplantation, preoperative preparation with erythropoietin was not an option.. We felt, however, that given the fact that liver replacement was the only optin for patient survival in this previously healthy patient, the risks were acceptable for an experienced team. 
Intraoperative measures in this patient included meticulous dissection, wich was done exclusively wit electrocautery, and use of  veno-venous bypass. Though use of veno-venous bypass requires two extra incisions and additional operative time, we chose to use it in this case for several reasons. It allows for hemodynamic stability without excessive fluid administration and safe extension of the anhepatic phase for precise vascular anastomoses and for achieving adequate hemostasis, expecially in retrohepatic space. Studies have suggested decreased blood requirements as well as better support of renal function with veno-venous bypass. Use of the cell saver in this patients required modification of the tubing circuit in order to accomodate the wishes of the family that withdrawn blood be kept in continuity with the patient at all times. It was, however, not a factor due to the low volume of blood loss. 
In addition to meticulous surgical techinque, antifibrinolytic agents have been shown to be beneficial in liver transplantation. We chose to use aprotinin for its potent antifibrinolytic effects and demonstrated benefits in decreasing the need for transfusion during liver transplantation. Aprtotinin's mechanism of action appears to be a reduction in tissue plasminogen activator activity and a reducion in alpha-2-antiplasmin degradation. The drug is usually well tolerated, though anaphylactic reactions and thrombotic complications may result from its use. The precise indications for aprotinin use in liver transplantation have yet to be determined; however, it is a powerful antifibrinolytic drug that can be an important adjunct to careful surgical technique. 
The precise crystalloid solution chosen to mantain normovolemia was carefully considered. Infusion of more than 15 cm3/kg/h of normal saline dilutes extracellular buffers and may cause hyperchloremic acidosis. For this reason crystalloid replacement was accomplished with Plasmalyte, a balanced salt solution. We were limited in the colloid solutions that could be used, since albumin was not permitted. Hetastarch is an option that may be useful in maintaining osmotic pressure in patients with liver disease and severe hypoalbuminemia. It was not used, however, due to its potential for worsening coagulopaty and dissemiated intravascular coagulation. 
Barbiturates were used as a maintenance anesthetic because of their known effects in decreasing cerebral oxygen consumption and possibly decreasing total body oxygen consumption. A majior factor in decreasing oxygen consumption is the treatment of hyperthermia. In this case, the patient was allowed to become mildly hypothermic, but severe hypothermia was avoided due to its deleterious effect on coagulation. 
During the postoperative period, we maximized erythropoiesis with early total parenteral nutrition, iron supplementation and erythropoietin. Erythropoietin has been shown to be effective in treating anemia in renal failure patients and has also bee used succesfully in surgical JW patients. Other measures that have been used in severely anemic JW patients are parenteral iron and perfluorochemical blood substitute, Fluosol, but these were not necessary in our patient. 
This case demonstrates that emergent liver transplantation is possible without the use of blood and blood products in the hands of ana experienced team, and that these patients should not be a priori excluded from this life-saving procedure.