Acute antibody-mediated rejection following heart transplantation.

Acute antibody-mediated rejection (AMR) in heart transplantation is often associated with hemodynamic compromise, and is associated with increased mortality and development of accelerated transplant coronary artery disease (TCAD). The diagnosis of AMR has historically been controversial and outcomes with aggressive immunosuppressive therapy including plasmapheresis and cyclophosphamide are poor. Advances in diagnostic techniques like the demonstration of immunopathologic evidence for antibody-mediated rejection by deposition of the complement split product C4d in tissue and detection of anti-HLA antibodies by flow cytometry will assist in further characterizing AMR. Immunosuppression targeting B-lymphocytes and use of m-TOR inhibitors to alter the predilection to develop TCAD and improve survival in AMR remains to be proven.

CD3 monitoring and thymoglobulin therapy in cardiac transplantation: clinical outcomes and pharmacoeconomic implications.

INTRODUCTION: CD3 monitoring of antithymocyte globulin therapy in renal transplantation has been shown to be more cost-effective than standard regimens. The objective of this study was to evaluate CD3 monitoring with Thymoglobulin in cardiac transplantation. METHODS: Cardiac transplant patients who required antithymocyte globulin therapy were dose-adjusted to maintain absolute CD3 counts <25 cells/microL. Endomyocardial biopsies and hemodynamic parameters were used to assess efficacy. The incidences of hematological side effects, opportunistic infections, and malignancies were recorded; in addition we performed a cost comparison. RESULTS: Eight patients were treated with Thymoglobulin using CD3 monitoring to adjust the dosing. All patients responded with few side effects. Compared to standard dosing, CD3 monitoring allowed a 60% reduction in the average total dose and a 58% reduction in cost per patient. CONCLUSION: CD3 monitoring of Thymoglobulin therapy in cardiac transplant patients results in lower doses and reduced costs with equivalent efficacy and a low incidence of complications.

Esmolol for the management of pediatric hypertension after cardiac operations.

OBJECTIVE: Hypertension frequently occurs during the immediate postoperative period in children after repair of aortic coarctation but may also occur after repair of other congenital heart defects. Nitroprusside has often been used to control blood pressure in this setting. Because hypertension after coarctation repair is frequently associated with elevations in catecholamines, esmolol, a short-acting beta-blocking agent, may be an effective alternative. Therefore we undertook the first systematic investigation to determine the efficacy and disposition of esmolol in pediatric patients with acute hypertension after cardiac operations. METHODS: Twenty patients aged 1 month to 12 years (median 25.6 months) with acute hypertension after cardiac operations received esmolol in an opened-labeled trial. Esmolol was titrated to a blood pressure less than or equal to the 90th percentile for age. RESULTS: Ten patients had coarctation repair and the remaining patients underwent repair of other congenital heart defects. On final esmolol dose (mean +/- standard deviation dosage 700 +/- 232 microg/kg/min) there was a significant percent decrease in heart rate and systolic and diastolic blood pressures from postoperative values. Esmolol dose was significantly associated with percent reduction in systolic blood pressure. Final esmolol dose and total body clearance were significantly higher in patients after coarctation repair. There were significant associations between esmolol dose and esmolol blood concentrations at steady state. CONCLUSIONS: The dosage required to control hypertension in patients after repair of aortic coarctation was higher than patients who underwent repair of other congenital heart defects. Esmolol was effective in controlling blood pressure in 19 of 20 patients without adverse effects.

Amiodarone-cyclosporine interaction in a heart transplant patient.

We report the case of a heart transplant patient whose cyclosporine clearance decreased by more than 50% after the institution of amiodarone therapy. This interaction necessitated a significant dosage reduction to maintain cyclosporine concentrations within the therapeutic range. To investigate the mechanism of the interaction, a cyclosporine-lipoprotein-binding determination was performed. The results suggest that drug displacement from competitive lipoprotein-binding sites is not responsible for the alterations in cyclosporine pharmacokinetics. Clearance data suggests, however, that the primary mechanism for the interaction is the inhibition cyclosporine metabolism by the cytochrome P-450 system. This report emphasizes the importance of reevaluating therapeutic drug regimens when new agents are added to prevent complications caused by drug interactions. If amiodarone and cyclosporine must be used concomitantly, cyclosporine levels must be monitored frequently, in anticipation of this interaction.

In vivo inactivation of tobramycin by piperacillin.

In vivo inactivation of aminoglycosides by antipseudomonal penicillins in patients with renal failure can be a significant problem when these drugs are used together in certain gram-negative infections. Our article illustrates the possible magnitude of this interaction and the resultant effect on aminoglycoside pharmacokinetic parameters. Penicillin concentrations remain relatively unaffected by this interaction. This article stresses the need for close monitoring of aminoglycoside concentrations when combined with antipseudomonal penicillins in this patient population.