Info

Table 11.5. Immunosuppression

Preoperative

Azathioprine Intraoperative

Methylprednisolone Postoperative

Cyclosporine Azathioprine Methylprednisolone Prednisone

4 mg/kg IV 500 mg

125 mg every 8 hours x 3-4 doses 1 mg/kg/day tapering over 1 week to 0.5 mg/kg/day combination with allopurinol can cause significant bone marrow toxicity. Leukopenia and/or thrombocytopenia require dose reduction. Pancreatitis and hepatitis can occur.

Corticosteroids

Methylprednisolone is administered intraoperatively with reperfusion of the heart in a dose of 500 mg intravenously. This is repeated postoperatively in 125 mg/8hrs until the patient is able to take oral medications. Prednisone is then administered in a dose of 0.3-0.15 mg/kg/day as an initial dose for the first 3-6 months. Corticosteroids can cause pituitary adrenal suppression, glucose intolerance, hypercholesterolemia, peptic ulcer disease, osteoporosis, hypertension and behavioral changes. Prednisone may be tapered over time as determined by endomyocardial biopsies.

Induction of immunosuppression with antilymphocyte antibodies has also been used. They include antithymocuite globulin (ATGAM), rabbit antithymocyte globulin (RATG) and monoclonal antibody OKT3. These have been shown to prevent acute rejection and have primarily been used for treatment of acute and chronic rejection. Milder or moderate rejection is typically treated with a steroid pulse of methylprednisolone in a dose of 1 gm IV x 3 days. More severe rejection, or recurrent rejection, invokes the use of ATGAM or OKT3 for 7-14 days.

New immunosuppressor drugs include tacrolimus (FK506) and mycophenolite mofetil. FK506 restricts T-cell proliferation similar to the mechanism of action of cyclosporine and initially it was hoped that FK506 could replace cyclosporine. Clinical trials have not indicated a major advantage to FK506. It has been found to be an effective rescue therapy when regimens including cyclosporine were not effective at preventing rejection.

Mycophenolite mofetil is a lymphocyte-specific inhibitor of purine synthesis with impact proliferative effects on T and B lymphocytes. It possesses many of the properties of azathioprine. Early reports indicate it may be superior to azathio-prine in cardiac patients but long-term results are pending.

Other drugs such as rapamycin, deoxysperdualin and leflunomide are being evaluated. Additional treatments such as total lymphoid irradiation and photopheresis have also been tried with limited success.

0 0

Post a comment