Medication Summary
The goals of pharmacotherapy are to prevent complications, to reduce morbidity, and to reduce the chances for organ rejection.
Immunosuppressants
Class Summary
Immunosuppression is started soon after surgery. Transplant recipients are maintained on an immunosuppression regimen that includes 1-3 drugs. Generally, the drugs fall into 3 categories: steroids, antimetabolites, and other immunosuppressants.Several regimens can be used, including pretransplantation induction therapy and simple postoperative maintenance therapy; the choice of regimen depends on the training and experience of the transplantation center. [4, 5]
Cyclosporine (Neoral, Sandimmune, GENGRAF)
Cyclosporine is a cyclic polypeptide that suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions such as delayed hypersensitivity, allograft rejection, experimental allergic encephalomyelitis, and graft versus host disease for various organs.
For children and adults, base dosing on ideal body weight. Maintaining appropriate levels of the drug in the bloodstream is crucial to the maintenance of the allograft. Foods can alter the level of the drug and time of administration. Medication must be taken at the same time every day.
Neoral is the capsular form of cyclosporine, available in 25- and 100-mg capsules. Sandimmune is the liquid form. GENGRAF is the branded generic form, available in 25- and 100-mg capsules.
Prednisone
Prednisone is an immunosuppressant used for the treatment of autoimmune disorders. It may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear (PMN) leukocyte activity. It is an oral steroid with approximately 5 times the potency of endogenous steroids. Minimal to no oral prednisone should be given for the first 21 days after transplantation unless rejection occurs.
Methylprednisolone (Medrol, Solu-Medrol, A-Methapred)
Methylprednisolone is an immunosuppressant used to treat autoimmune disorders. It may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. It is the intravenous (IV) form of prednisone.
Tacrolimus (Prograf)
Tacrolimus suppresses humoral immunity (T-cell activity). It is a calcineurin inhibitor with 2-3 times the potency of cyclosporine. Tacrolimus can be used at lower doses than cyclosporine, but it has severe adverse effects, including renal dysfunction, diabetes, and pancreatitis. Levels are adjusted according to renal function, hepatic function, and adverse effects.
Mycophenolate mofetil (CellCept, Myfortic)
Mycophenolate mofetil inhibits inosine monophosphate dehydrogenase (IMPDH) and suppresses de novo purine synthesis by lymphocytes, thus inhibiting their proliferation. It inhibits antibody production.
Azathioprine (Imuran, Azasan)
Azathioprine antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. It may decrease proliferation of immune cells, which results in lower autoimmune activity. Antimetabolites are used to block the uptake of vital nutrients needed by the cells. As implied, these drugs affect not only the cells of the immune system but also other cells of the body. The potency of therapy is dose dependent. Azathioprine is not effective treatment for acute rejection episodes but remains an economical choice for long-term immunosuppression.
Sirolimus (Rapamune)
Sirolimus, also known as rapamycin, is a macrocyclic lactone produced by Streptomyces hygroscopicus. It is a potent immunosuppressant that inhibits T-cell activation and proliferation by a mechanism that is distinct from those of all other immunosuppressants. This inhibition suppresses cytokine-driven T-cell proliferation by inhibiting progression from the G1 phase to the S phase in the cell cycle.
Inotropic Agents
Class Summary
After the procedure, the patient is maintained on a combination of pressor agents while the donor heart regains energy stores. Once stabilized, the patient is rapidly weaned from the ventilator and the pressors. The chosen combination depends on the training and experience of the center.
Dopamine
Dopamine is a naturally occurring endogenous catecholamine that stimulates beta1-and alpha1-adrenergic and dopaminergic receptors in a dose-dependent fashion. It stimulates the release of norepinephrine.
In low doses (2-5 μg/kg/min), dopamine acts on dopaminergic receptors in renal and splanchnic vascular beds, causing vasodilatation in these beds. In midrange doses (5-15 μg/kg/min), it acts on beta-adrenergic receptors to increase heart rate and contractility. In high doses (15-20 μg/kg/min), it acts on alpha-adrenergic receptors to increase systemic vascular resistance and raise blood pressure.
Dobutamine
Dobutamine is a sympathomimetic amine with stronger beta than alpha effects. It increases the inotropic state. Vasopressors augment the coronary and cerebral blood flow during the low-flow state associated with severe hypotension.
Dopamine and dobutamine are the drugs of choice to improve cardiac contractility, with dopamine the preferred agent in hypotensive patients. Higher dosages may cause an increase in heart rate, exacerbating myocardial ischemia.
Epinephrine (Adrenalin)
Its alpha-agonist effects include increased peripheral vascular resistance, reversed peripheral vasodilatation, systemic hypotension, and vascular permeability. Its beta2-agonist effects include bronchodilation, chronotropic cardiac activity, and positive inotropic effects.
Norepinephrine (Levophed)
Norepinephrine stimulates beta1- and alpha-adrenergic receptors, increasing cardiac muscle contractility and heart rate, as well as vasoconstriction; this results in systemic blood pressure and coronary blood flow increases. After obtaining a response, the rate of flow should be adjusted and maintained at a low-normal blood pressure, such as 80-100 mm Hg systolic, sufficient to perfuse vital organs.
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View of the recipient's chest after the heart is removed, with the patient on cardiopulmonary bypass.
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Suturing of the donor heart. Note that the left atrial anastomosis is performed first.
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Completed operation. Note suture lines on now-implanted heart.
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Heterotopic transplantation.
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View after cardiectomy, showing cuffs for bicaval anastomosis.
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Completed bicaval transplantation technique.
Tables
Status |
Criteria |
1 |
Venoarterial extracorporeal membrane oxygenation (VA ECMO) Non-dischargeable, surgically implanted, non-endovascular biventricular support device Mechanical circulatory support device (MCSD) with life-threatening ventricular arrhythmias |
2 |
Non-dischargeable, surgically implanted, non-endovascular left ventricular assist device (LVAD) Intra-aortic balloon pump (IABP) Ventricular tachycardia/fibrillation, mechanical support not required MCSD with device malfunction/mechanical failure Total artificial heart, biventricular assist device, right ventricular assist device, or ventricular assist device for single-ventricle patients Percutaneous endovascular MCSD |
3 |
Dischargeable LVAD for discretionary 30 days Multiple inotropes or single high-dose inotrope with continuous hemodynamic monitoring VA ECMO after 7 days; percutaneous endovascular circulatory support device or IABP after 14 days Non-dischargeable, surgically implanted, non-endovascular LVAD after 14 days MCSD with one of the following: device infection, hemolysis, pump thrombosis, right heart failure, mucosal bleeding, aortic insufficiency |
4 |
Dischargeable LVAD without discretionary 30 days Inotropes without hemodynamic monitoring Retransplant Diagnosis of one of the following: congenital heart disease (CHD), ischemic heart disease with intractable angina, hypertrophic cardiomyopathy, restrictive cardiomyopathy, amyloidosis |
5 |
On the waitlist for at least one other organ at the same hospital |
6 |
All remaining active candidates |
