Prevention and treatment of severe hemodynamic compromise in pediatric heart transplant patients

Allograft rejection is a leading cause of severe hemodynamic compromise in pediatric heart transplant patients. A triple-drug immunosuppression regimen, which includes a calcineurin inhibitor, antiproliferative agent, and corticosteroid, suppresses the immune system at multiple different levels for optimal graft protection while minimizing the adverse effects of any one particular agent. Some pediatric centers also use induction therapy with anti-T cell antibodies immediately following transplantation as additional rejection prophylaxis. These antibodies augment immunosuppression by either depleting the T cell pool or blocking interleukin-2 receptors on activated T cells. Despite the aggressive preventive measures outlined above, some pediatric heart transplant patients will develop severe hemodynamic compromise, most commonly due to fulminant rejection. Such patients require attention to, and optimization of, the four determinants of cardiac output (heart rate, preload, contractility and afterload) to stabilize the circulation until the rejection can be reversed. Careful administration of volume, diuretics, inotropes, and afterload-reducing agents will meet this goal. Patients with allograft rejection require augmentation of immune suppression to facilitate myocardial recovery. Corticosteroids form the cornerstone of treatment for both cellular and vascular rejection. In patients with refractory cellular rejection, conversion to mycophenolate mofetil or tacrolimus may be appropriate if these agents are not already being used for maintenance immunosuppression. Critically ill patients may additionally benefit from muromonab-CD3 (OKT3) to augment lympholysis. Treatment employed specifically for humoral rejection is prescribed with the intention of suppressing new antibody formation, removing circulating antibody, and improving coronary blood flow. In addition to corticosteroids, cyclophosphamide and antithymocyte globulin or muromonab-CD3, along with plasmapheresis, may improve survival. Systemic heparinization should be considered to minimize coronary thrombosis in patients with humoral rejection. In the future, novel immunosuppressive agents may further assist in the prevention as well as treatment of severe hemodynamic compromise due to rejection in pediatric heart transplant recipients.