Immunosuppression in lung transplantation.

Lung transplantation can be a life-saving procedure for those with end-stage lung diseases. Unfortunately, long term graft and patient survival are limited by both acute and chronic allograft rejection, with a median survival of just over 6 years. Immunosuppressive regimens are employed to reduce the rate of rejection, and while protocols vary from center to center, conventional maintenance therapy consists of triple drug therapy with a calcineurin inhibitor (cyclosporine or tacrolimus), antiproliferative agents [azathioprine (AZA), mycophenolate, sirolimus (srl), everolimus (evl)], and corticosteroids (CS). Roughly 50% of lung transplant centers also utilize induction therapy, with polyclonal antibody preparations [equine or rabbit anti-thymocyte globulin (ATG)], interleukin 2 receptor antagonists (IL2RAs) (daclizumab or basiliximab), or alemtuzumab. This review summarizes these agents and the data surrounding their use in lung transplantation, as well as additional common and novel therapies in lung transplantation. Despite the progression of the management of lung transplant recipients, they continue to be at high risk of treatment-related complications, and poor graft and patient survival. Randomized clinical trials are needed to allow for the development of better agents, regimens and techniques to address above mentioned issues and reduce morbidity and mortality among lung transplant recipients.

Clinical outcomes associated with the early postoperative use of heparin in pancreas transplantation.

BACKGROUND: Graft thrombosis following pancreas transplantation is the leading non-immunologic cause of graft loss. Routine systemic anticoagulation is controversial because of an increased bleeding risk. METHODS: This was a retrospective, single-center analysis including all pancreas transplants performed over 9 years evaluating the use of low-dose heparin in the early postoperative period. Clinical outcomes were partial and complete graft thrombosis within 30 days, bleeding events, relaparotomy rates, and 30-day graft and patient survival. Multivariate regression analysis was performed to identify risk factors for early graft loss resulting from thrombosis. RESULTS: One hundred fifty-two patients were included, 52 in the heparin group. The overall complete thrombosis rate was 13.1%, 10% in those who received heparin, and 15% in those who did not. Partial thrombosis was higher in the heparin group (10% vs. 3%). Higher relaparotomy rates were seen in the heparin group (29% vs. 22%); however, bleeding events were similar between groups. Graft and patient survival at 30 days were similar between groups; however, there was a trend toward higher graft survival in the heparin group. Heparin showed a trend toward a protective benefit for early graft loss resulting from thrombosis in all multivariate regression models. CONCLUSION: These data suggest low-dose heparin early in the postoperative period may provide a protective benefit in the prevention of early graft loss resulting from thrombosis, without an increased risk of bleeding.

Timing of factor VIIa in liver transplantation impacts cost and clinical outcomes.

STUDY OBJECTIVE: To investigate the clinical and economic outcomes associated with the use of recombinant factor VIIa (rFVIIa) in perioperative liver transplantation (LT). DESIGN: Retrospective review. SETTING: Academic medical center. PATIENTS: A total of 63 adults who underwent LT between January 2000 and September 2008 and received rFVIIa prior to or during the procedure. Using a propensity-scoring method, these patients were matched in a 1:2 ratio with 120 controls. MEASUREMENTS AND MAIN RESULTS: Of the 473 patients who received any LT during the study period, 63 (13%) received rFVIIa and were matched with propensity score matched controls at a ratio of approximately 1:2. Of those who received rFVIIa, 27 (43%) received preemptive administration and 14 (22%) received intraoperative administration. (The remaining 22 patients received rFVIIa outside of a 12-hour window of time before or after surgery.) Clinical outcomes were similar between the preemptive and the control groups, although patients in the control group had a shorter length of stay in the intensive care unit (ICU) and incurred fewer expenses. Compared with both the preemptive and the control groups, patients who received rFVIIa intraoperatively required more blood products, longer stays in the ICU, and incurred higher costs. They also had poorer graft survival and decreased overall survival rates at 30 days and 1 year. CONCLUSION: Intraoperative administration of rFVIIa in LT was associated with higher blood product use, lower graft and patient survival rates, longer ICU stays, and higher overall costs compared with preemptive administration. The use of preemptive rFVIIa in select high-risk LT patients may prevent the development of poor clinical outcomes and may be more cost effective compared with intraoperative administration.