Ischemic cholangiopathy following liver transplantation from donation after cardiac death donors.

The use of donation after cardiac death (DCD) donor hepatic allografts is becoming more widespread; however, there have been published reports of increased graft failure from specific complications associated with this type of allograft. The complication of ischemic cholangiopathy (IC) has been reported to occur more frequently after the use of DCD hepatic allografts. We report the results of 52 liver transplants from DCD donors and the factors that influenced the development of IC. We conducted a retrospective review of all DCD and donation after brain death (DBD) donor liver recipients from September 2003 through December 2006 at a single institution. Survival and complication rates were compared between the 2 groups. The Cox proportional hazards model was then used to identify recipient and donor factors that predict the development of IC in the DCD group. There was no difference in 1-year patient or graft survival rates between the 2 groups. There was no incidence of primary nonfunction from the DCD allografts. Hepatic artery complications and anastomotic bile duct complications were comparable in the 2 groups. There was, however, an increased risk for the development of IC in the DCD group (13.7% versus 1%, P = 0.001). Donor weight >100 kg and total ischemia times > or =9 hours, in donors older than 50 years of age, predicted the development of IC in the DCD group. In conclusion, there is a higher incidence of IC in recipients receiving DCD donor livers; however, patient and graft outcomes with DCD donors remain comparable to those with DBD donors. Careful donor selection may improve utilization of these grafts.

Hypercoagulable state associated with kidney-pancreas transplantation. Thromboelastogram-directed anti-coagulation and implications for future therapy.

BACKGROUND: The clinical consequences of type 1 diabetes mellitus (IDDM) include diabetic triopathy: retinopathy, nephropathy, and neuropathy, as well as microangiopathy, accelerated atherosclerotic disease, and hypercoagulability. The etiology of the hypercoagulability is multifactorial, involving various clotting factors or pathways (for example platelets, fibrinogen, individual components of the clotting system and/or fibrinolysis in different studies). The development of end-stage renal disease (ESRD), with the uremia-related platelet effect has the potential to protect from the existing hypercoagulable state. This has important implications for surgery, particularly simultaneous pancreas-kidney (SPK) transplantation, where the pancreas has historically been prone to thrombosis. This has led us to perform intra-operative thromboelastograms (TEG's) to evaluate the patient's current coagulation status. METHODS: A TEG was performed in 85 SPK recipients along with a control group of 54 non-diabetic kidney transplant (KT) recipients. RESULTS: For each of the 4 TEG coagulation parameters, the SPK recipients were significantly more hypercoagulable than the non-diabetic KT recipients. The use of intra-operative heparin is based on the degree of hypercoagulability by TEG and degree of operative hemostasis. There has been one PT lost to thrombosis (1%) in the first week following transplantation during this time. CONCLUSION: The use of TEG is a helpful adjunct to SPK surgery, demonstrating the patient's current coagulation status. Nearly all SPK recipients (type 1 IDDM with ESRD) have been demonstrated to be hypercoagulable. The TEG allows the judicious use of anti-coagulation at the time of surgery, and beyond.

The impact of donor chemical overdose on the outcome of liver transplantation.

BACKGROUND: To overcome the critical shortage of liver grafts, many centers have been widening the acceptance criteria for liver donation. Use of liver grafts from victims who have suffered chemical overdose (COD) may be one option that could help to expand the donor pool. However, this practice has been poorly documented. METHODS: Of 1,195 orthotopic liver transplantations performed at our institution between June 1994 and March 2001, 22 involved livers (1.8%) were retrieved from COD donors. Donor and recipient characteristics and posttransplantation outcomes were analyzed retrospectively. RESULTS: The main chemicals causing brain death of the donor were carbon monoxide (n=4), cocaine (n=4), tricyclic antidepressants (n=3), 3,4-methylenedioxy- methamphetamine (n=2), opiates (n=2), aspirin (n=1), gamma hydroxybutyrate (n=1), heroin (n=1), insulin (n=1), verapamil (n=1), barbiturate (n=1), and brompheniramine/phenylpropanolamine (n=1). Primary nonfunction developed in one patient who had received a liver from an 3,4-methylenedioxymethamphetamine-intoxicated donor. Another patient died of fungal meningitis 10 days after transplantation with a functioning graft. The remaining 20 patients experienced acceptable early graft function, as demonstrated by initial mean peak values of bilirubin (4.8 mg/dL), aspartate aminotransferase (624 U/L), and alanine aminotransferase (730 U/L). One-year graft survival rate estimated by the Kaplan-Meier method was 86%. CONCLUSIONS: Satisfactory outcomes of graft function were achieved in orthotopic liver transplantations from COD donors. The cautious use of liver grafts from selected COD donors may be a worthwhile method of increasing the availability of scarce donor organs.

Use of older controlled non-heart-beating donors for liver transplantation.

BACKGROUND: Use of liver grafts from non-heart-beating donors (NHBDs) warrants consideration so to expand the donor pool. Because the results of controlled NHBDs (CNHBDs) were acceptable, we have recently tried to expand the criteria to older CNHBDs. Here, we report our experience using liver grafts from older CNHBDs. METHODS: We retrospectively studied our donor records from June 1994 through December 2001. CNHBDs were divided into two groups by age: older donors (O) were more than or equal to 55 years old, and younger donors (Y) were less than 55 years old. We compared donor and recipient demographics and peak laboratory values during the first postoperative week. RESULTS: Twenty-five grafts from CNHBDs were transplanted in our center. Five livers were harvested from O (63+/-6 years) and 20 were from Y (32+/-15 years). No differences other than age in donor characteristics were noted between O and Y. Mean age of recipients was 50 years in both groups. Mean cold ischemic time (CIT) was 5.4 hours in O and 7.3 hours in Y (P<.05). Peak glutamic oxaloacetic transaminase (U/L), glutamic pyruvic transaminase (U/L), bilirubin (mg/dL), and prothrombin time (sec) during the first postoperative week were 611, 500, 3.9, and 16 in O and 846, 593, 5.9, and 17 in Y. There were no significant differences between the two groups. The graft survival at 1 year was 80% in O and 70% in Y. CONCLUSIONS: In our preliminary experience, recipients of liver grafts from older CNHBDs had an outcome equivalent to that of younger CNHBDs. With the strict evaluation of the donors and brief CIT, liver grafts from older CNHBDs may be used to expand the donor pool.

Simultaneous pancreas-kidney transplantation in Jehovah's Witness patients.

The safety and efficacy of renal and liver transplantation has been reported for Jehovah's Witness (JW) patients, with patient, and graft survival similar to that of non-JW patients. We report our experience in five JW recipients of simultaneous pancreas-kidney transplants. None of the patients received transfusion of blood or blood products, either before or after transplant. Like the other solid organ transplants, patient, and graft survival was similar to that of the non-JW group. Specific technical issues related to the operative procedure include the use of the cell saver until the donor duodenum is opened (enteric contamination). Post-operatively, care should be taken to minimize drawing of blood and optimize erythrocyte synthesis with erythropoetin, folic acid, vitamin B12, and iron. Finally, it is critical that the pre-operative evaluation demonstrates sufficient cardiac reserve to allow the JW patient to tolerate a possible temporary anemic state.

Daclizumab induction, tacrolimus, mycophenolate mofetil and steroids as an immunosuppression regimen for primary kidney transplant recipients.

BACKGROUND: Recent reports have demonstrated the efficacy of interleukin-2-receptor blockers in lowering the incidence of early acute rejection in cyclosporine-treated kidney recipients when compared to patients not induced with an antibody product. The addition of daclizumab to a tacrolimus-mycophenolate mofetil-based immunosuppressive protocol was tested to evaluate whether there might be an additional reduction of the risk of rejection after renal transplantation. METHODS: Since March 1998, we studied the effect of daclizumab in a nonrandomized, prospective study of 233 sequential recipients of first renal transplant. They were retrospective compared with a control group of 225 renal transplant recipients receiving a 10-day course of OKT3 induction, and tacrolimus, mycophenolate mofetil, and methylprednisolone maintenance. The study group received the same immunosuppressive regimen with the addition of daclizumab at 1 mg/kg for five doses over 10 weeks in the place of OKT3 therapy. There was at least 1HLA DR antigen compatibility match present between all donors and recipients. Patients were followed for 1 year after renal transplantation for the incidence of biopsy-proven acute rejection, patient and graft survival, and adverse events. RESULTS: At 12 months, patient and graft survival for the daclizumab was 98 and 96 vs. 96 and 94% for the OKT3 group, respectively, and were not statistically different. Acute rejection rates (<6 months) were lower in the daclizumab group as compared with the OKT3 group, i.e., 5 (2.1%) vs. 16 (7.1%) (P=0.011) respectively. The incidence of infection requiring hospitalization appeared to be lower with daclizumab (7.3 vs. 16%, P<0.0036) with a similar trend with cyclomegalovirus infection, i.e., 1.6 vs. 4%, respectively (P=0.14). CONCLUSIONS: The combination of daclizumab, tacrolimus, mycophenolate mofetil, and steroids is safe and effective for kidney transplant recipients in lowering the incidence of early acute rejection and without any increase in morbidity when compared to our previous protocol, which may have an eventual impact in long-term graft survival.