4. Clinical Guidelines for Liver Transplantation (PDF) - British ...

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Guidebook for the Solid Organ Transplant Programme Chapter 4 4.3.2 EARLY COMPLICATIONS CONT. The fourth category is rejection: Acute rejection occurs in approximately 30 to 40% of the patients. This is usually suspected by an increase in liver enzymes. A liver biopsy is performed to confirm the diagnosis. Treatment is with Methylprednisolone (SoluMedrol ® ) 10mg/kg per day for three days. Patients with steroid resistant rejection may require antibody treatment (ATG) and/or alternate immunosuppressive regimens. Anti-rejection Protocols and Target Levels: Anti-rejection: medications for liver transplant recipients include: 1. Tacrolimus: Initial oral dose is 0.03 mg/kg/ dose given every 12 hours for the first few days post-transplant. Once liver function has been established increase dose to 0.12 to 0.15 mg/kg/day divided every 12 hours to achieve therapeutic concentrations (See Appendix D: Table - Target Cyclosporine/Tacrolimus Blood Concentrations) 2. Azathioprine: 1 mg/kg PO daily 3. Methylprednisolone: IV daily a. Day 0 – 500 mg b. Day 1 – 200 mg c. Day 2 – 160 mg d. Day 3 – 120 mg e. Day 4 – 80 mg f. Day 5 – 40 mg followed by 4. Prednisone: 20 mg (or 0.3 mg/kg) PO daily. Dose is tapered over 6 months so patient is steroid free by 6 months Guidelines for Use of Other Immunosuppressive Agents: 1. IL-2 Receptor Blockers: Basiliximab (Simulect ) The use of Basiliximab is restricted to patients who are heading into a liver transplant with renal impairment. For patients with renal impairment the use of a calcineurin inhibitor for induction may aggravate renal impairment and hinder post-transplant renal recovery. Under these circumstances, our program prefers to use an induction with an IL2 receptor antagonist, followed by either delayed low-dose Tacrolimus or, if renal recovery does not occur, continued avoidance of Tacrolimus with the use of Mycophenolate Mofetil plus/minus Sirolimus. Chapter 4 – Clinical Guidelines for Liver Transplantation – July, 2010 Page 13 See Page 1 for disclaimer
Guidebook for the Solid Organ Transplant Programme Chapter 4 4.3.2 EARLY COMPLICATIONS CONT. 2. Mycophenolate Mofetil (CellCept ) In the maintenance phase, Mycophenolate Mofetil (MMF) use is restricted to the following indications: a. Renal dysfunction: Under these circumstances, in order to allow the use of low-dose calcineurin inhibitors or, in some cases, no calcineurin inhibitor. Mycophenolate Mofetil is used. b. Graft rejection: In circumstances in which graft rejection occurs despite the use of Tacrolimus at therapeutic levels, Mycophenolate Mofetil will be used. Once graft function has stabilized, Mycophenolate Mofetil use may be discontinued after three to six months. c. Calcineurin neurotoxicity: In circumstances where neurotoxicity has occurred to a calcineurin inhibiting agent, Mycophenolate Mofetil use will be indicated on an indefinite basis. d. Mycophenolate Mofetil use as a steroid-sparing agent: There may be circumstances in which patient’s should be weaned off maintenance Prednisone, i.e. osteoporosis, osteopenia, diabetic mellitus, etc. and for which patients are either intolerant of Azathioprine or the continued use of Azathioprine is inadequate to maintain a rejection-free allograft. Under these circumstances, Mycophenolate Mofetil may have to be used on an indefinite basis. The goal is for all patients that are clinically stable and have reached one year on initial immunosuppression with Mycophenolate to switch to Azathioprine 1 mg/kg/day PO except patients with the following: Calcineurin inhibitor nephrotoxicity or neurotoxicity despite therapeutic calcineurin inhibitor concentrations Calcineurin inhibitor hypersensitivity reactions or microangiopathy Multiple rejection episodes (≥ 2 rejections within the first year post transplant), despite adequate maintenance immunosuppression, including the inability to discontinue steroids 3. Sirolimus (Rapamune ® ) The use of Sirolimus by the Liver Transplant Program is on a case by case individualized basis. Due to an increased risk of hepatic artery thrombosis (HAT) in de novo transplant recipients, Sirolimus should not be used within the first 3 months of transplantation. The risk/benefit ratio of Sirolimus use in any liver transplant recipients must be discussed with the liver transplant team and the patient. Sirolimus has a long half-life (around 72 hours) and takes about 7 to 10 days to reach therapeutic level. Therefore it should be used with another agent until therapeutic level is reached. (See Appendix E: Target Sirolimus Therapeutic Blood Concentrations) Chapter 4 – Clinical Guidelines for Liver Transplantation – July, 2010 Page 14 See Page 1 for disclaimer
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