Clinical outcomes and costs associated with in-hospital biliary complications after liver transplantation: a cross-sectional analysis.

INTRODUCTION: In-hospital biliary complications (BCs) after liver transplantation (LT) are reported in up to 20 % of patients and contribute to poor outcomes and increased costs. Existing single-center outcome and cost analyses studies are limited in scope. METHODS: This is a cross-sectional analysis of national data involving 7,967 patients transplanted between 2011 and 2012 with the primary aim of determining the association between BCs and clinical outcomes and costs. Age, race, diagnosis, and severity of illness are associated with the development of BCs. RESULTS: BCs develop in 14.6 % of LT recipients and have substantial implications for perioperative outcomes, including length of hospital and ICU stay (27.9 vs 19.6 mean days, p < 0.001 and 12.0 vs 8.3 mean days, p < 0.001, respectively), in-hospital morbidity (39 vs 27 %, p < 0.001), 30-day readmissions (14.8 vs 11.2 %, p < 0.001), and in-hospital mortality (5.8 vs 4.0 %, p < 0.001). BCs contributed to a mean increase in in-hospital costs of $36,212 (p < 0.001), due to increases in accommodations ($9,539, p < 0.001), surgical services ($3,988, p < 0.001), and pharmacy services ($8,445, p < 0.001). DISCUSSION: BCs are a predominant etiology for in-hospital morbidity and mortality, while contributing significantly to the high cost of LT. Efforts should be focused on understanding salient and modifiable risk factors, while developing innovative strategies to reduce BCs.

Improving transplant patient safety through pharmacist discharge medication reconciliation.

Greater than 50% of medication errors are estimated to occur during transitions of care, and solid-organ transplant recipients are at an increased risk for errors due to significant changes in their medication regimen following transplantation. This prospective, observational study with a historical control group was conducted to evaluate the discharge process for transplant recipients and determine if transplant pharmacist involvement would improve safety. During the prospective period, a total of 191 errors were made on discharge medication reconciliations (n = 64, mean rate 3.0 per patient); however, pharmacists prevented 119 of these errors (1.9 errors per patient). In the retrospective period, none of the 430 errors identified were prevented at the time of discharge (n = 128, p < 0.0001). The 72 errors not prevented at the time of discharge in the prospective cohort were identified by the pharmacist at the patient's first clinic visit (1.1 errors per patient). In the historical cohort, all 430 errors made at discharge persisted until at least the time of the first clinic visit (3.4 errors per patient, p < 0.0001). This study demonstrates that transplant recipients are at a high risk for medication errors and that transplant pharmacist involvement leads to improved safety through the significant reduction of medication errors.

The impact of early corticosteroid withdrawal on graft survival in liver transplant recipients.

BACKGROUND: There has been increased interest in recent years in reducing or eliminating steroids from the immunosuppression regimen of transplant recipients to reduce adverse effects associated with their use. The purpose of this study was to compare clinical outcomes between early versus late steroid withdrawal after liver transplant to determine the optimal duration of steroid use in this population. METHODS: This large-scale, retrospective analysis of liver transplants occurred at our institution between 2000 and 2009. Patients were excluded if they were <18 years old, received a multiorgan transplant, or remained on steroids for >1 year. The early steroid withdrawal group had steroids eliminated by 3 months posttransplant; late steroid withdrawal patients had steroids withdrawn between 3 and 12 months posttransplant. RESULTS: A total of 586 liver transplants occurred during the study period; 330 patients were included in the analysis. Graft survival was significantly lower in the early steroid withdrawal group. There was no difference in patient survival or overall acute rejection. However, the late steroid withdrawal group had a significantly higher rate of early acute rejection episodes. There was no difference with regard to new-onset diabetes after transplant, hyperlipidemia, or cardiovascular events between groups. CONCLUSION: The results of this study suggest that late corticosteroid withdrawal is associated with better long-term graft survival without increasing the rates of diabetes, hyperlipidemia, or cardiovascular events in liver transplant recipients. A prospective study is warranted to confirm these findings.

Case report: gastrointestinal hemorrhage caused by a pancreas transplant arteriovenous fistula with large psuedoanuerysm 9 years after transplantation.

Reported cases of arteriovenous fistulae in transplant recipients are uncommon. We present a case of an arteriovenous fistula associated with a large pseudoaneurysm in the root of the small bowel mesentery of a pancreas transplant. Uniquely, in our case, the arteriovenous fistula presented with an episode of gastrointestinal (GI) hemorrhage 9 years postoperatively. Radiographic imaging including coronal computed tomography angiogram and conventional angiogram demonstrated an arteriovenous fistula in the patient's pancreas transplant between the distal superior mesenteric artery (SMA) and superior mesenteric vein (SMV) with 6 cm aneurysmal dilatation. The tremendous flow in the fistula in the root of the graft small intestine mesentery led to graft duodenal mucosal congestion and lower GI hemorrhage. After successful embolization of the SMA-SMV fistula and pseudoaneurysm using interventional radiographic techniques, the arteriovenous fistula remained thrombosed. The patient had no further episodes of GI bleeding and her endoscopic evaluation was otherwise negative. The presence of arteriovenous fistulae and pseudoaneurysms in pancreas transplant recipients is uncommon, but has been previously documented. This case is further distinguished from previous reports by the notable 9-year interval between transplantation and the onset of hemorrhage. Historically, symptomatic vascular malformations have been associated with significant patient morbidity and mortality. Successful patient management involves timely and accurate diagnosis and intervention.

A critical analysis of racial difference with mycophenolate mofetil (MMF) dosing, clinical outcomes and adverse effects in pediatric kidney transplant patients.

There is paucity in the data examining the differences in mycophenolate mofetil (MMF) dosing and outcomes among pediatric kidney transplant recipients (PKTX) between races. The aims of this study were as follows (i) to assess whether higher doses of MMF are being utilized in African American (AA) PKTX (ii) to determine whether there is a correlation between MMF dose and outcomes between races, and (iii) to assess the adverse effects of MMF between races. This study analyzed 109 PKTX who received MMF between 7/99 and 5/08. Demographics were similar between groups. Fewer AAs received kidneys from living donors (18% vs. 44%), spent more time on dialysis (1.0 vs. 0.5 yr), and had more human leukocyte antigen mismatches (4 vs. 3). MMF doses among AA patients were higher throughout the study, with statistical differences at week 4, month 3, and month 18. AA patients had significantly higher acute rejection rates and trended toward poorer graft survival; infections, adverse events from MMF and post-transplant lymphoproliferative disease tended to be lower in the AA patients. AA PKTX received higher MMF doses within the first three yr post-transplant compared to their non-AA counterparts, yet demonstrate significantly more acute rejection episodes. Importantly, MMF caused fewer adverse events in AA patients, despite these patients receiving higher doses.

Organ donation and utilization in the United States, 1999-2008.

Despite the Organ Donation Breakthrough Collaborative's work to engage the transplant community and the suggested positive impact from these efforts, availability of transplanted organs over the past 5 years has declined. Living kidney, liver and lung donations declined from 2004 to 2008. Living liver donors in 2008 dropped to less than 50% of the peak (524) in 2001. There were more living donors that were older and who were unrelated to the recipient. Percentages of living donors from racial minorities remained unchanged over the past 5 years, but percentages of Hispanic/Latino and Asian donors increased, and African American donors decreased. The OPTN/UNOS Living Donor Transplant Committee restructured to enfranchise organ donors and recipients, and to seek their perspectives on living donor transplantation. In 2008, for the first time in OPTN history, deceased donor organs decreased compared to the prior year. Except for lung donors, deceased organ donation fell from 2007 to 2008. Donation after cardiac death (DCD) has accounted for a nearly 10-fold increase in kidney donors from 1999 to 2008. Use of livers from DCD donors declined in 2008 to 2005 levels. Understanding health risks associated with the transplantation of organs from 'high-risk' donors has received increased scrutiny.

Potential differences in kidney allograft outcomes between ethnicities when converting to sirolimus base immunosuppression.

OBJECTIVE: The aim of this study was to determine whether ethnicity impacts graft outcomes in kidney transplant patients converted to sirolimus (SRL) and maintained on either calcineurin inhibitors (CI) or mycophenolate mofetil (MMF) with steroids. METHODS: This study analyzed kidney transplants converted to SRL and transplanted between July 1991 and April 2007. Patients were divided into 4 groups: group 1: African-Americans converted to SRL + CI; group 2: non-African-Americans converted to SRL + CI; group 3: African-Americans converted to SRL + MMF; group 4: non-African-Americans converted to SRL + MMF. RESULTS: A total of 242 patients was included. Demographics, baseline immunosuppression, and reason for SRL conversion were similar among groups. Patients converted to SRL + CI regimens had significantly higher rates of acute rejection before SRL conversion, but equal rates after conversion. Development of proteinuria was similar across groups. African-American patients converted to SRL + MMF tended to have poorer outcomes compared with African-American patients converted to SRL + CI. Non-African-American patients converted to SRL + MMF tended to have better graft outcomes compared with non-African-American patients converted to SRL + CI. CONCLUSIONS: African-Americans converted to SRL may benefit from continued CI, whereas non-African-Americans converted to SRL seem to have better outcomes with MMF. Further prospective studies are warranted to confirm these findings.

Long-term efficacy of induction therapy with anti-interleukin-2 receptor antibodies or thymoglobulin compared with no induction therapy in renal transplantation.

BACKGROUND: Although the utility of antibody induction therapy has been demonstrated in clinical trials, the ideal regimen to use based on patient risk factors has not been fully elucidated. The objectives of this study were to determine the impact of either anti-interleukin-2 receptor antibodies (IL-2RA) or thymoglobulin induction therapies versus no induction therapy on acute rejection rates and on 3-year graft survival rates. METHODS: This retrospective analysis compared 3 patient groups-those who did not receive induction, those who received IL-2RA induction, and those who received thymoglobulin induction. RESULTS: Three hundred eleven patients were included in this study. Patients were well matched for demographic and immunologic characteristics in the noninduced and IL-2RA induction therapy groups; the thymoglobulin induction group included significantly higher risk patients. The acute rejection rates were significantly lower in the IL-2RA and thymoglobulin groups when compared with the no induction therapy group (28% vs 15% vs 41%, respectively; P = .001), which was confirmed with multivariate analysis. The 3-year graft loss rates (no induction 21% vs IL2-RA induction 19% vs thymoglobulin induction 25%; P > .50) and creatinine concentrations (no induction 1.8 +/- 0.7, IL-2RA induction 2.0 +/- 1.0, and thymoglobulin induction 1.9 +/- 1.2; P = .47) were similar between all groups. CONCLUSION: The use of induction therapy significantly reduces the incidence of acute rejection. The use of thymoglobulin induction equalizes 3-year graft survival rates in high-risk patients to those seen in low-risk patients receiving either no induction or IL-2RA induction.

Can family attributes explain the racial disparity in living kidney donation?

BACKGROUND: Living donation is a safe, effective treatment for patients with end-stage renal disease (ESRD), yet rates of live kidney donation remain low. Potential transplant recipients may be more inclined to ask a family member for a living donation if they feel familial closeness. METHODS: The FACES II and the Living Organ Donor Survey were administered to patients attending pretransplant education to assess individual perceptions of family structure and willingness to request a living kidney donation from a family member. RESULTS: A total of 328 potential transplant recipients were included in the study: 200 (61%) African American and 128 (39%) Caucasian. Approximately half were willing to ask for a living donation. Individual's perception of family cohesion, adaptability, and type as measured by FACES II showed most families were mid-range with optimal cohesion and adaptability. Family cohesion and adaptability showed no association with being willing to request a live donation, but those single/never married were only half as likely to ask for donation (odds Ratio [OR] 0.51; 95% confidence interval [CI] 0.31-0.86, P = .01). Lower education (beta = -0.49) and unmarried status (beta = -0.31) predicted a lower cohesion score. CONCLUSION: Family type, cohesion, and adaptability showed no differences across race and was not related to the potential recipient's willingness to ask for a live donation. Although responses by race did not differ, an important finding showed that only half of ESRD patients are willing to ask for a live organ donation, and those patients that were single/never married were less likely to ask for a living donation. Research surrounding this reluctance is warranted.

Parenchymal transection of the kidney inflicted by endocatch bag entrapment during a laparoscopic donor nephrectomy.

We present a case of inadvertent decapsulation and grade IV renal parenchyma laceration during laparoscopic donor nephrectomy. The kidney was repaired, used and functioned immediately. There were no complications in the donor. To our knowledge, this type of injury has not been reported previously and the purpose of this report is to focus attention on the potential for this unusual injury, which can occur during delivery of the kidney using the endocatch bag.

Valganciclovir prophylaxis in patients at high risk for the development of cytomegalovirus disease.

BACKGROUND: Despite advances in antiviral therapies, cytomegalovirus (CMV) remains the leading opportunistic infection in the transplant population. Valganciclovir (VGC), the L-valyl ester prodrug of ganciclovir (GCV), provides an excellent oral alternative to GCV for the prevention of CMV in transplant recipients. We investigated the use of VGC for CMV prevention in high-risk renal and pancreas transplant recipients. METHODS: Patients at high risk for development of CMV disease were defined as either those who had donor positive, recipient-negative serostatus (D+/R-), or those who received antilymphocyte antibody (ALA) therapy for either rejection treatment or induction. A retrospective review was conducted of all kidney and pancreas transplants performed between August 2001 and December 2003. A total of 341 transplants were performed, of which 109 received VGC, and 88 were included in this analysis. RESULTS: The overall incidence of CMV disease was 5.7% (5/88). All of the CMV episodes were in patients who were D+/R- (17.2% [5/29] versus 0% [0/59], P<0.001). Of these patients, all the episodes of CMV were in patients who received VGC prophylaxis for<100 days post transplant (29% [5/17] versus 0% [0/12], P=0.06). The overall incidence of leukopenia was 11% and thrombocytopenia was 7%, with the incidence between the D+/R- group and the ALA group being similar. CONCLUSION: VGC is an effective agent in preventing CMV disease in kidney and pancreas transplant recipients who are at high risk for developing the disease. The optimal length of prophylaxis in D+/R- patients is still undefined, while 3 months of prophylaxis appears to be sufficient in patients who received ALA therapy.

Does treatment of cadaveric organ donors with desmopressin increase the likelihood of pancreas graft thrombosis? Results of a preliminary study.

Desmopressin (DDAVP) is commonly used in cadaveric organ donors to treat diabetes insipidus. The thrombogenic potential of DDAVP is well known. Recent animal data have demonstrated that DDAVP impairs pancreas graft (PG) microcirculation and perfusion. The aim of this study was too evaluate the effect of DDAVP on the incidence of PG thrombosis in clinical pancreas transplantation. A retrospective review of simultaneous kidney-pancreas transplant (SKPT) entered in the Scientific Registry of Transplant Recipients (SRTR) between 10/5/87 and 9/27/02 was performed. Patients were included for analysis if there was definitive documentation as to whether DDAVP was (DDAVP-Y) or was not (DDAVP-N) administered to the donor. Both dose and duration of DDAVP treatment were not recorded by SRTR. A total of 2804 SKPTs were available for analysis. Mean follow-up was 1.75 years (range, 1 month to 8.4 years). A total of 1287 SKPT patients (46%) received a PG from a DDAVP-Y donor. Graft ischemia times, donor and recipient ages, recipient gender distribution, surgical techniques, and immunosuppressive regimens were similar in both groups. The overall incidence of PG thrombosis was 4.3%. The incidence of PG thrombosis in recipients of grafts from DDAVP-Y donors was 5.1% compared to 3.5% in recipients of grafts from DDAVP-N donors (P =.04). Fifty-eight percent of thrombosed PG came from DDAVP-Y donors compared to 42% from DDAVP-N donors (P =.04). We conclude that there appears to be a relationship between donor treatment with DDAVP and PG thrombosis. A prospective study is needed to verify these findings and to determine their clinical significance.

Long-term outcome of sirolimus rescue in kidney-pancreas transplantation.

The aim of this study was to evaluate long-term outcome of sirolimus (SRL) rescue in kidney-pancreas transplantation (KPTx). We reviewed 112 KPTx performed at our institution from 12/3/95 to 6/27/02. All patients received antibody (Ab) induction, tacrolimus (TAC), mycophenolate mofetil (MMF), and steroids. Thirty-five patients (31%) had SRL substituted for MMF for the following indications: (1) acute rejection (AR) of kidney or pancreas despite adequate TAC levels; (2) intolerance of full-dose MMF; (3) rising creatinine; and (4) TAC-induced hyperglycemia. Target SRL and TAC levels were 10 ng/mL and 5 ng/mL, respectively. Mean follow-up was 3 +/- 2 years overall and 1.2 +/- 0.5 years after SRL rescue. No patients died. One- and 3-year actuarial kidney and pancreas graft survival was 97%, 97%, and 95%, 90%, respectively. Of 10 patients switched to SRL for AR, 1 kidney failed from Ab-resistant AR, 1 kidney developed borderline AR, and the other 8 remain AR-free. Seven other patients developed AR despite therapeutic SRL levels; of these, 6 (86%) had mean TAC levels of <4.5 in the month preceding AR. Mean creatinine overall and for the rising creatinine group remained stable. All patients switched to SRL for TAC-induced hyperglycemia or MMF intolerance demonstrated biochemical or clinical improvement. Sirolimus-related infection or other serious adverse events (SAE) were uncommon. In conclusion, KPTx recipients can be safely switched to SRL with long-term stabilization of renal function, excellent graft and patient survival, and no increase in SAE. A minimum TAC level of 4.5 ng/mL may be necessary to prevent late AR.

Use of autologous radial artery for revascularization of hepatic artery thrombosis after orthotopic liver transplantation: case report and review of indications and options for urgent hepatic artery reconstruction.

Hepatic artery thrombosis (HAT) is the most common vascular complication after orthotopic liver transplantation (OLT) and has traditionally been managed with re-OLT. However, several reports have shown that urgent revascularization is frequently an effective means of graft salvage. This most often involves hepatic artery (HA) thrombectomy and thrombolysis, with reestablishment of arterial inflow through a donor iliac artery conduit based on the supraceliac or infrarenal aorta. We report a 46-year-old man who developed HAT 13 days after OLT after angiographic splenic artery embolization to reduce splenic artery steal. A suitable donor iliac artery was not available for arterial reconstruction and could not be obtained from neighboring transplant centers. The patient underwent urgent HA thrombectomy, intrahepatic arterial thrombolysis, and revascularization using an autologous radial artery (RA) conduit based on the supraceliac aorta. The patient is alive more than 1 year after revascularization, with normal liver function and documented flow in the arterial conduit by Doppler ultrasound and arteriography. He has not developed late biliary complications or adverse sequelae of RA harvest. Autologous RA can be safely and successfully used as an aortic-based arterial conduit in urgent revascularization of HAT after OLT. RA should be considered for use in HA revascularization if an adequate donor iliac artery is not available and other potential conduits are not usable or desirable. The availability of autologous RA expands the armamentarium of vascular conduits that can be used in HA revascularization and may help minimize re-OLT for otherwise potentially salvageable liver allografts.

Further improvements in laparoscopic donor nephrectomy: decreased pain and accelerated recovery.

Fear of postoperative pain is a disincentive to living donor kidney transplantation. Laparoscopic donor nephrectomy (LDN) was developed in part to dispel this disincentive. The dramatic increase in the number of laparoscopic donor nephrectomies performed at our institution has been in part due to the reduction in postoperative pain as compared to traditional, open donor nephrectomy. We sought to further diminish the pain associated with this surgical technique. The purpose of this study was to compare the efficacy of three different postoperative pain management regimens after LDN. All living kidney donors performed laparoscopically (n=43) between September 1998 and April 2000 were included for analysis. Primary endpoints included postoperative narcotic requirements and length of stay. Narcotic usage was converted to morphine equivalents (ME) for comparison purposes. Patients received one of three pain control regimens (group 1: oral and intravenous narcotics; group II: oral and intravenous narcotics and the On-Q pump delivering a continuous infusion of subfascial bupivicaine 0.5%; and group III: oral and intravenous narcotics and subfascial bupivicaine 0.5% injection). Postoperative intravenous and oral narcotic use as measured in morphine equivalents was significantly less in group III versus groups I and II (group III: 28.7 ME versus group I: 40.2 ME, group II: 44.8 ME; P<0.05). Postoperative length of stay was also shorter for group III (1.8 days) versus group I (2.5 days) and group II (2.9 days). LDN has been shown to be a viable alternative to traditional open donor nephrectomy for living kidney donation. We observed that the use of combined oral and intravenous narcotics alone is associated with greater postoperative narcotic use and increased length of stay compared to either a combined oral and intravenous narcotics plus continuous or single injection subfascial administration of bupivicaine. The progressive modification of our analgesic regimen has resulted in decreased postoperative oral and intravenous narcotic use and a reduction in the length of stay. We recommend subfascial infiltration with bupivicaine to the three laparoscopic sites and the pfannenstiel incision at the conclusion of the procedure to reduce postoperative pain. We believe this improvement in postoperative pain management will continue to make LDN even more appealing to the potential living kidney donor.

Cyclosporine-induced hemolytic uremic syndrome and hemorrhagic colitis following renal transplantation.

Nephrotoxicity remains one of the most common side-effects of cyclosporine in the setting of transplantation. Acute reversible decreases in glomerular filtration rate and chronic irreversible renal damage are the most common manifestations, but hemolytic uremic syndrome and thrombotic thrombocytopenic purpura have been reported. Prognosis of cyclosporine-associated de novo hemolytic uremic syndrome (CyA-HUS) is poor, with nearly half of affected patients losing function in the transplanted kidney. Therapeutic options are limited, but good outcomes have been reported by switching patients from cyclosporine to tacrolimus. We report an unusual presentation of CyA-HUS associated with hemorrhagic colitis following renal transplantation. The patient was successfully managed by switching from cyclosporine to tacrolimus.