eMedicine Specialties > Transplantation > Surgery
Heart-Lung Transplantation: Treatment & Medication
Updated: Nov 5, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
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Treatment
Medical Care
During the waiting period for a potential candidate, carefully monitor for signs of clinical deterioration.
- Administer standard therapy for congestive heart failure and pulmonary hypertension.
- Maintain close contact with the transplant center, ensuring that the consultants are informed about the patient's ongoing medical and social issues.
- Patient deterioration
- In the event of deterioration, the transplant center may allow the patient to be admitted and may upgrade their status on the waiting list.
- Candidates may sometimes deteriorate to the point that transplantation is no longer an option.
- Thoroughly discuss these issues with the treating physician(s), patient, and family.
Surgical Care
The application of heart-lung transplantation is limited by the availability of suitable donors. All potential donors have succumbed to brain death secondary to some form of catastrophic event. The condition necessitates ventilator dependency in order to maintain organ viability. In this situation, the lungs become susceptible to injury because of neurogenic pulmonary edema, fat embolism, infectious processes, and atelectasis. These events, coupled with the donor's underlying pulmonary pathology, exclude the use of many organs. Direct major chest trauma also precludes donation. Because of the lung tissues' short preservation time (4-6 h), procurement distances are limited.
- Potential heart-lung donors must meet brain-death criteria and be free of cardiopulmonary pathology.
- Donors who smoked may be acceptable candidates provided their pulmonary function is preserved and no evidence of infection or malignancy exists.
- Current donor criteria include age younger than 50 years, clear lung fields on chest radiographs, and a PaO2 value greater than 100 mm Hg on 40% inspired oxygen. A 100% oxygen challenge must yield a PaO2 value greater than 300 mm Hg.
- No evidence of tracheobronchial infection on bronchoscopy should be evident, and peak inflation pressures should be low.
- Once donor criteria are met, the donor and potential recipients are matched according to ABO compatibility and organ size. Size matching has been accomplished by various methods, including chest circumference measurements, chest wall dimensions on chest radiographs, and estimation of height- and weight-adjusted lung volumes. Ideally, the donor organs for heart-lung transplantation should be slightly smaller than those of the recipient in order to avoid postoperative compression atelectasis.
- The final decision regarding the suitability of the donor heart-lung allograft can be made only by direct inspection.
- A median sternotomy incision is made for initial inspection of the heart and lungs.
- The heart and lungs are mobilized with minimal handling of the pulmonary tissue.
- The heart is flushed with cold cardioplegia solution, while the lungs are simultaneously flushed with cold, modified Collins solution after prostaglandins are administered into the pulmonary artery.
- The heart-lung block is then removed and placed into a sterile, cold electrolyte solution for transport. Care is taken to occlude the trachea during storage and transport.
- The recipient operative procedure is performed using cardiopulmonary bypass.
- The heart and lungs are removed while carefully preserving the phrenic nerves and addressing bronchial artery circulation in order to prevent postoperative bleeding complications.
- The donor heart and lungs are inserted; the tracheal anastomosis is performed first.
- The right atrial anastomosis is performed next, followed by the aortic anastomosis.
- Care is taken to keep the donor trachea as short as possible because of the limited vascularity of the area.
Consultations
- Pulmonologists are consulted to assist with determining the extent of pulmonary disease and the patient's suitability for transplantation. Pulmonologists also help manage patients during the waiting period.
- Cardiologists are consulted to help assess the extent of cardiac disease. Right heart failure may be reversible and convert a potential heart-lung candidate into a lung-transplant candidate. These consultants also play a key role in evaluating and managing the potential candidate.
- Psychiatrists are consulted to determine the psychosocial fitness of the patient to undergo the procedure and to provide rigorous posttransplant follow-up care. Psychiatric assistance is also invaluable in addressing issues of chronic terminal illness and patient compliance.
- Nephrologists are consulted to assist with renal management of patients in whom low cardiac output may have altered renal function.
- Infectious disease specialists are consulted to assist with evaluation and management in accordance with findings obtained during the evaluation period.
- Social services providers are consulted to assist with financial issues, medication availability, family stress, and patient adaptation.
- Dietitians are consulted to assist with dietary issues and patient compliance.
Diet
Because of the adverse effects of immunosuppressant drugs, patients are generally maintained on a low-sodium, low-cholesterol diet. Although the steroid regimen is tapered quickly, these patients tend to gain weight because of the therapy. Dietary discipline is therefore required.
Activity
Before transplantation, patients are encouraged to maintain as much normal activity as physically possible in order to maintain muscle tone. If tolerated, a cardiopulmonary rehabilitation program is implemented. After transplantation, the rehabilitation program is instituted early in order to assist the patient in regaining normal functional status and good general health.
Medication
The goals of pharmacotherapy are to prevent complications, to reduce morbidity, and to reduce the chances for organ rejection.
Immunosuppressants
Transplant recipients are maintained on an immunosuppression regimen that includes 1-3 drugs. The chosen combination depends on the training and experience of the center. Generally, the drugs fall into 3 categories: steroids, antimetabolites, and other immunosuppressants.
Cyclosporine (Neoral, Sandimmune, GENGRAF)
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 of cyclosporine.
GENGRAF is the branded generic form of cyclosporine, available in 25- and 100-mg capsules.
Adult
6-20 mg/kg/d PO to maintain whole blood trough levels between 500-700 ng/dL as measured by whole blood RIA
Pediatric
2.5-5 mg/kg/d PO to maintain whole blood levels between 500-700 ng/dL as measured by whole blood RIA
Carbamazepine, phenytoin, isoniazid, rifampin, and phenobarbital may decrease concentrations; azithromycin, itraconazole, nicardipine, ketoconazole, fluconazole, erythromycin, verapamil, grapefruit juice, diltiazem, aminoglycosides, acyclovir, amphotericin B, and clarithromycin may increase toxicity; acute renal failure, rhabdomyolysis, myositis, and myalgias increase when taken concurrently with lovastatin
Documented hypersensitivity; uncontrolled hypertension or malignancies; do not administer concomitantly with PUVA or UVB radiation in psoriasis because of increased risk of cancer
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Evaluate renal and liver functions often by measuring BUN, serum creatinine, serum bilirubin and liver enzymes; may increase risk of infection and lymphoma; reserve IV use for patients who cannot take PO
Prednisone (Deltasone, Orasone, Meticorten)
Immunosuppressant used for treatment of autoimmune disorders. May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Oral steroid with approximately 5 times the potency of endogenous steroids.
Minimal to no oral prednisone for the first 21 d after transplantation unless rejection occurs.
Adult
0.2 mg/kg/d PO after day 21
Pediatric
Administer as in adults
Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective-tissue infections; fungal or tubercular skin infections; GI disease
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use
Methylprednisolone (Medrol, Solu-Medrol)
Immunosuppressant used to treat autoimmune disorders. May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. IV form of prednisone.
Adult
1000 mg IV upon reperfusion of heart-lung block, then 125 mg IV q8h for 3 doses
Pediatric
Administer as in adults
Coadministration with digoxin may increase digitalis toxicity secondary to hypokalemia; estrogens may increase levels of methylprednisolone; phenobarbital, phenytoin, and rifampin may decrease levels (adjust dose); monitor patients for hypokalemia when taking medication concurrently with diuretics
Documented hypersensitivity; viral, fungal, or tubercular skin infections
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Hyperglycemia, edema, osteonecrosis, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, myopathy, and infections are possible complications of glucocorticoid use
Tacrolimus (Prograf)
Suppresses humoral immunity (T lymphocyte) activity. Calcineurin inhibitor with 2-3 times the potency of cyclosporine. Can be used at lower doses than cyclosporine but has severe adverse effects, including renal dysfunction, diabetes, and pancreatitis.
Levels are adjusted according to renal function, hepatic function, and adverse effects.
Adult
0.05 mg/kg/d PO (4-8 mg) in divided doses to maintain levels of 10-14 ng/dL as measured by whole blood RIA
Pediatric
Use per protocol
Levels may increase with diltiazem, nicardipine, clotrimazole, verapamil, erythromycin, ketoconazole, itraconazole, fluconazole, bromocriptine, grapefruit juice, metoclopramide, methylprednisolone, danazol, cyclosporine, cimetidine, clarithromycin; levels may decrease with rifabutin, rifampin, phenobarbital, phenytoin, and carbamazepine
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Do not administer simultaneously with cyclosporine; tonic-clonic seizures may occur; monitor levels to avoid overimmunosuppressing patient, precipitating end organ dysfunction, or causing unwanted adverse effects; caution in diabetes and pancreatitis
Mycophenolate mofetil (CellCept)
Inhibits inosine monophosphate dehydrogenase (IMPDH) and suppresses de novo purine synthesis by lymphocytes, thus inhibiting their proliferation. Inhibits antibody production.
Adult
250-1000 mg PO/IV bid to maintain WBC count >3000; average dose is 1000 mg bid
Pediatric
Use lower doses to maintain WBC count >3000
May elevate levels of acyclovir and ganciclovir; antacids and cholestyramine decreases absorption, reducing levels (do not administer together); probenecid may increase levels; salicylates may increase toxicity
Documented hypersensitivity; neutropenia; bone marrow suppression; hepatic dysfunction; pancreatitis
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Increases risk for infection; increases toxicity in renal impairment; caution in active peptic ulcer disease; monitor hepatic and pancreatic function
Azathioprine (Imuran)
Antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. 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. Potency of therapy is dose dependent. Not effective treatment for acute rejection episodes. Remains an economical chronic immunosuppressant choice.
Adult
2-2.5 mg/kg/d PO/IV to maintain WBC count >3000
Pediatric
0.5-1.5 mg/kg/d PO/IV to maintain WBC count >3000
Toxicity increases with allopurinol; concurrent use with ACE inhibitors may induce severe leukopenia; may increase levels of methotrexate metabolites and decrease effects of anticoagulants, neuromuscular blockers, and cyclosporine
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Increases risk of neoplasia; caution with liver disease and renal impairment; hematologic toxicities may occur; monitor WBC count for bone marrow suppression
Sirolimus (Rapamune)
Macrocyclic lactone produced by Streptomyces hygroscopicus. Also known as rapamycin, the drug is a potent immunosuppressant that inhibits T-lymphocyte activation and proliferation by a mechanism that is distinct from all other immunosuppressants. The inhibition suppresses cytokine-driven T-cell proliferation by inhibiting progression from the G1 phase to the S phase in the cell cycle.
Adult
1-5 mg PO qd; trough blood concentrations > 8 ng/mL correlated with immunosuppressive activity
Pediatric
Not established
Levels/toxicity may increase with diltiazem, nicardipine, clotrimazole, verapamil, erythromycin, ketoconazole, itraconazole, fluconazole, bromocriptine, grapefruit juice, metoclopramide, methylprednisolone, danazol, cyclosporine, cimetidine, and clarithromycin; levels may decrease with rifabutin, rifampin, phenobarbital, phenytoin, and carbamazepine
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May exacerbate hyperlipidemia and thrombocytopenia; caution with hepatic impairment (decrease maintenance dose by one third); monitor blood sirolimus blood levels in pediatric patients, patients with hepatic impairment, during coadministration of strong CYP450 3A4 inducers or inhibitors, or if cyclosporine dosing is markedly reduced or discontinued; not recommended for use in de novo liver or lung transplantation; coadministration with cyclosporine or tacrolimus in liver transplant patients increases hepatic artery thrombosis risk; bronchial anastomotic dehiscence, most fatal, has been reported in de novo lung transplantation when sirolimus has been part of the immunosuppressive regimen
More on Heart-Lung Transplantation |
| Overview: Heart-Lung Transplantation |
| Differential Diagnoses & Workup: Heart-Lung Transplantation |
 Treatment & Medication: Heart-Lung Transplantation |
| Follow-up: Heart-Lung Transplantation |
| Multimedia: Heart-Lung Transplantation |
| References |
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References
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Further Reading
Keywords
heart lung transplantation, heart lung transplant, heart-lung transplant, cardiopulmonary replacement, cardiopulmonary transplantation, cardiopulmonary allograft, heart-lung allograft, double-lung transplantation, end-stage cardiac disease, end-stage pulmonary disease, end-stage cardiopulmonary disease, Denton Cooley, cyclosporine A, immunosuppression, immunosuppressives, Eisenmenger syndrome, congenital heart defects, cystic fibrosis, end-stage bronchiectasis, allograft vascular disease, obliterative bronchiolitis, rejection
