i

Liver transplantation has become a standard therapy for adults and children with severe liver disease. The treatment is highly successful, with more than 80 percent of patients going on to live as long-term survivors. The quality of life of long-term survivors is excellent, with the majority returning to productive activities. Surgical improvements have decreased the chance of dying from surgical complications to less than 5 percent, while improvements in immunosuppression have decreased the risk of losing the graft due to rejection to less than 5 percent. These results are possible because of the development of specialized care teams and the application of rigorous patient-care protocols, both in the hospital and for the long term. Full integration of community physicians and gastroenterologists is essential for longterm success. Also crucial is the availability of a consistent array of patient data and an aggressive response to deviations from expected outcomes. This leads to early diagnosis and management of rejection and other complications.
The liver transplant service performs 100 to 120 transplants every year. 14-Moffitt and 6-
Long are the primary units for these patients. Living donor liver transplant donors are admitted to 14-Moffitt and are followed by the surgical service.
Pediatric patients are admitted to 6-Long surgery and are also followed by the liver transplant service. It is the responsibility of the liver transplant surgery resident to work collegially with the pediatric resident in caring for these patients.
Generally, the pediatric service is responsible for medical and fluid management, while the liver transplant service manages immunosuppression, although details of these arrangements may be worked out on an individual basis.
While hospitalized, patients in the liver transplant service are on the selfcare model and take their own medications. Their medications, along with their daily log sheets, are kept at the bedside. The service currently follows approximately 800 outpatients, with 60 pre-patient and post-patient clinic visits per week. ii

Table of Contents
Transplant Program Personnel ............................................................................................................................... v
Diseases Eligible for Liver Transplant .................................................................................................................. 1
Resident Responsibilities ....................................................................................................................................... 3
Rounds & Meetings .......................................................................................................................... 4
Computer Notes ................................................................................................................................ 5
Order Forms ...................................................................................................................................... 6
Pre-Transplant Recipient Admissions ............................................................................................... 7
Pre-Op Blood Work for All Transplant Recipients................................................................................................ 7
Inpatient Pretransplant Candidate Evaluation ........................................................................................................ 8
Phase I & II Evaluations ................................................................................................................. 10
Phase I & II Lab Work ................................................................................................................... 12
Management Suggestions for Pretransplant Patients ...................................................................... 13
Treatment of Pruritus ...................................................................................................................... 13
Large-Volume Paracentesis Protocol .............................................................................................. 14
Mucomyst Administration for Tylenol Overdose ........................................................................... 14
Living Donor Liver Transplantation .................................................................................................................... 16
Living Donor Evaluation ............................................................................................................... 16
Living Donor Liver Transplantation Donor Standing Orders ......................................................... 17
Liver Transplant Posttransplant Laboratory Routines .......................................................................................... 19
Routine Post-operative Course ........................................................................................................ 20
Discharge ........................................................................................................................................ 20
Discharge Prescriptions ................................................................................................................... 21
Common Post-Operative Problems ...................................................................................................................... 23
Fever Workup ................................................................................................................................. 23
Antibiotic Algorithm for Liver Transplant Patients ........................................................................ 23
Workup for Elevated LFTs ............................................................................................................. 25
Liver Biopsy .................................................................................................................................... 26
Pain Management after Liver Transplant ........................................................................................ 28
Prevention and Treatment of Opportunistic Infections ................................................................... 29
Hepatitis B Treatment Protocol ....................................................................................................... 31
Hepatitis C Treatment Protocol ....................................................................................................... 33
Post-transplant Treatment of Osteoporosis ..................................................................................... 34
Post-transplant Treatment of Hyperlipidemia ................................................................................. 36
Liver Transplantation for HIV Positive Patients .................................................................................................. 39
Adult Medications ................................................................................................................................................ 45
Routine Liver Allograft Immunosuppression Protocols.................................................................. 45
Additional Immunosuppression Protocols ...................................................................................... 47
Routine Post-operative Follow-up .................................................................................................. 48
Individual Immunosuppressive Medications ....................................................................................................... 49
Azathioprine (Imuran) ..................................................................................................................... 49
Cyclosporine (Neoral) ..................................................................................................................... 50
Tacrolimus (Prograf) ....................................................................................................................... 52
Mycophenolate Mofetil (Cellcept) .................................................................................................. 53
Sirolimus (Rapamune) .................................................................................................................... 54
Corticosteroids ................................................................................................................................ 55
Daclizumab (Zenapax) and Basiliximab (Simulect) ....................................................................... 55
OKT3 .............................................................................................................................................. 56
Antithymocyte Globulin (Thymoglobulin) ..................................................................................... 58
Commonly Used Antimicrobial Agents ............................................................................................................... 60
Trimethoprim/Sulfamethoxazole (Bactrim, Septra, Cotrim) ........................................................... 60
Acyclovir (Zovirax) ........................................................................................................................ 60 iii

Ganciclovir (DHPG) ....................................................................................................................... 61
Antifungal Agents ........................................................................................................................... 62
Fluconazole .............................................................................................................................. 62
Itraconazole .............................................................................................................................. 62
Voriconazole ............................................................................................................................ 63
Caspofungin ............................................................................................................................. 63
Nystatin .................................................................................................................................... 63
Clotrimazole Troches (Mycelex) ............................................................................................. 64
Amphotericin B (Fungizone) ................................................................................................... 64
Liposomal Amphotericin B (Ambizome) ................................................................................ 64
Diuretics .......................................................................................................................................... 65
Furosemide (Lasix) ......................................................................................................................... 65
Spironolactone (Aldactone) ............................................................................................................ 65
Acetazolamide (Diamox) ................................................................................................................ 66
Metolazone (Zaroxylin) .................................................................................................................. 66
Chlorothiazide (Diuril) .................................................................................................................... 66
Other Medications ................................................................................................................................................ 67
Pediatric Liver Transplant Protocols and Medications ........................................................................................ 70
Pediatric Pretransplant Evaluation Guidelines ................................................................................ 71
Minimum Volumes for Blood Tests ........................................................................................ 71
UCSF Pre-liver Transplant Worksheet .................................................................................... 72
Antibiotic Prophylaxis and Treatment of Pediatric Liver Transplant Recipients ............................ 74
Pediatric Immunosuppressive Therapy Protocols ........................................................................... 76
Immunosuppressants ................................................................................................................ 77
Prophylaxis Medications ................................................................................................................. 80
Diuretics .......................................................................................................................................... 83
Other Medications ........................................................................................................................... 84
Small Bowel/Liver Transplantation Protocols ................................................................................ 89
Pediatric Small Bowel/Liver Transplant Evaluation ................................................................ 89 iv

Main office, M-896, phone 353-1888; transplant clinic, phone 353-2323; followup clinic appts.:353-2318
Pediatrics, MU-4E, phone 476-5892; pediatric clinic, phone 353-2813
Transplant Surgeons
John P. Roberts, M.D…………………………………………. [b] 719-9552
Chief, Transplant Service
Nancy L. Ascher, M.D., Ph.D………………………………… [b] 719-9553
Chair, Dept. of Surgery
Peter G. Stock, M.D., Ph.D…………………………………… [b] 719-9362
Chris Freise, M.D……………………………………………... [b] 719-9684
Ryo Hirose, M.D……………………………………………… [b] 719-6456
Sang-Mo Kang, M.D………………………………………….. [b] 719-4240
Sandy Feng, M.D., Ph.D……………………………………… [b] 719-2085
Andrew M. Posselt, M.D., Ph.D………………………………. [b] 719-0682
Adult GI Faculty & Staff
Nathan (Tony) Bass, M.D., Ph.D…………………………….. [b] 719-9371
Medical Director, Liver Transplant
Norah Terrault, M.D………………………………………….. [b] 719-8640
Tim Davern, M.D…………………………………………….. [b] 719-7100
Monty Bissell, M.D…………………………………………... [b] 719-8983
Marion Peters, M.D…………………………………………... [b] 719-2549
Francis Yao, M.D…………………………………………….. [b] 719-6207
Associate Medical Director, Liver Transplant
Raphael (Ray) Merriman, M.D……………………………….. [b] 807-9179
Pediatric GI Faculty & Staff
Phil Rosenthal, M.D…………………………………………... [b] 719-4714
Pediatric Medical Director of Liver Transplant
Mel Heyman, M.D……………………………………………. [b] 719-1852
John Snyder, M.D…………………………………………….. [b] 719-9338
Transplant Coordinators
Pre-Transplant Coordinators
Barbara Moore, R.N. BSN……………..……………………... [b] 719-1933
Mike Dragovich, R.N., M.S…………………………………... [b] 719-7477
Cherie Bremer-Kamp, R.N…………………………………… [b] 719-6080
Post-Transplant Coordinators
Cynthia Galbraith, R.N., M.S., A.N.Pc……………………… [b] 719-9596
Ann Harris, R.N………………………………………………. [b] 719-2145
Pediatric Coordinators
Christine Mudge, R.N., M.S.,P.N.P…………………………... [b] 719-9515
Susan Stritzel, R.N., M.S.N., P.N.P.c………………………… [b] 719-2524
Case Manager/Clinical Nurse Specialist
Peggy Devney, R.N., M.S., CNS……………………………... [b] 719-2932
Other Liver Transplant Program Personnel
Sherry Laemmerman (Adult Social Worker)…………………. [b] 719-3955
Liz Manning (ICU/Adult living donor Social Worker)……… [b] 719-9742
Pauline Rogers (Adult Social Worker)……………………….. [b] 719-1655
Lee Jones/ John Chamberlain (In-patient psych evals)………. [b] 719-9538
Steve Tomlanovich, M.D. (Nephrology)……………………... [b] 719-9352 v

Gabe Gregoratos, M.D. (Cardiology)………………………… [b] 719-8806
Marian Devereaux, R.D, C.N.S.D. (Dietician)……………….. [b] 719-9445
John Feiner, M.D. (Anesthesiology)………………………….. [b] 719-2370
Bev Nikolai (Drug Study Coordinator)……………………….. [b] 719-3784
David Quan (Pharm. D.)……………………………………… [b] 719-3595
Patrick Sayerwin (Financial Counseling)……………………. 353-8776 vi

Cholestatic disorders: primary biliary cirrhosis biliary atresia
Alagille’s syndrome familial cholestasis secondary biliary cirrhosis primary sclerosing cholangitis
Parenchymal cirrhosis: cryptogenic cirrhosis chronic hepatitis B and C alcoholic cirrhosis congenital hepatic fibrosis autoimmmune hepatitis
Acute liver failure drug induced toxins hypersensitivity fulminant hepatitis/necrosis
Metabolic liver diseases
Metabolic defect in the liver resulting in end-stage liver disease: alpha 1 antitrypsin deficiency
Wilson’s disease hemochromatosis tyrosinemia protoporphyria cystic fibrosis
Metabolic defect in the liver, extrahepatic organs or systems primarily affected: urea-cycle defects familial hypercholesterolemia, type 2 glycogen-storage disease primary hyperoxaluria type 1
Crigler-Najjar syndrome type 1
Generalized metabolic disorders, e.g.: cystic fibrosis
Neimann-Pick disease familial amyloidosis
Malignancies:
Hepatocellular carcinoma: no extrahepatic disease
1

Hepatoblastoma: objective response to chemotherapy confined to the liver
Hemangioendothelioma (confined to the liver)
Noncarcinoid neuro-endocrine tumors (confined to the liver)
Vascular disease:
Budd Chiari syndrome portal-vein thrombosis giant hepatic hemangioma
Contraindications to Liver Transplantation
Malignancy:
Extrahepatic malignancy (unless patients meet standard oncologic criteria for cure
e.g.: stage-1 breast cancer greater than five years post-treatment)
Other primary hepatic malignancy (not noted above)
Sepsis unresponsive to treatment
Current substance abuse
Coma with evidence of irreversible brain injury
Addictions
Alcoholics in recovery and other prior substance abusers who have documented abstinence for a minimum of six months and who have undergone a thorough multidisciplinary assessment (including social and psychiatric evaluation) may be considered for liver transplantation if they possess appropriate psychosocial support systems so that they can comply with lifelong immunosuppressive therapy and be expected to maintain permanent abstinence from all addictive substances.
IV drug abusers must be drug free for 1 year prior to listing. All substance abusers must sign a contract and submit to periodic, random drug screening.
2

1. Liver transplant residents are responsible for overseeing the care of pre- and post-transplant patients admitted to the service as well as those patients admitted for other surgical procedures.
2. The resident on call or designee will work up patients admitted that day. a. For pediatric pre-transplant admissions, the surgical service will work them up in conjunction with the pediatric GI resident III. b. For pediatric post-transplant readmissions, the pediatric residents will work up the patient with consultation from the liver transplant service.
3. Residents are to oversee medical students.
4. Residents and/or fellows must co-sign all orders/notes by students.
5. Daily notes are to be written on every patient by the housestaff.
6. Residents in the operating room shall be covered by the other residents on the floor until they have returned to the floor. Residents who have clinic responsibilities will be covered by the other residents while they are in clinic.
7. A history and physical is required on every patient who is admitted.
8. All patients going to the OR require pre-oporders (see pre-transplant order form).
9. The operative consent is discussed with the patient by the attending in the transplant clinic before admission. The patient’s signature is obtained by the house staff at the time of transplant.
10. Requisition slips for lab tests, x-rays, cholangiograms, etc. must be completed by the resident, indicating the reason for the study.
11. Central line placement and removal may be performed by residents, overseen by the fellow or attending.
12. All central-line attempts must be followed by a stat chest x-ray.
13. Residents are expected to dictate all discharge summaries stat. The patients should take a copy home with them. Discharges will not be dalayed due to the discharge sumary not being available. Discharge summaries should be dictated the night prior to a potential discharge in order for the summary to be ready at the time of discharge.
14. The surgical attending dictates all operative notes unless specifically indicated by staff for resident dictation.
3

Rounds typically start in the ICU at 10 a.m. (if there are pediatric patients, start with pediatrics in 6ICU or 6L). Morning rounds are conducted by the surgical and medical attendings. Every member of the team is welcome on rounds. The liver transplant service is responsible for immunosuppression and surgical management of post-liver transplant pediatric patients. All potential patients ready for discharge should be reviewed prior to am rounds, labs discussed with the fellow or attending and orders written for discharge prior to the start of am rounds.
The resident lecture series is given by the hepatology staff before morning rounds and is outlined on the monthly schedule handouts.
MONDAY TUESDAY WEDNESDAY THURSDAY FRIDAY a.m. rounds:
10 a.m. a.m. rounds:
10 a.m. a.m. rounds:
10 a.m. a.m. rounds:
10 a.m.
M&M:
8 a.m. a.m. rounds:
10 a.m. selection conference:
1 p.m.
HS 322
In the evening, residents will sign out to the on-call resident and this process will be reversed in the morning. The patients will be presented by the resident who is assigned to that patient and the on-call resident will report on events of the previous night according to the following format:
1. Brief history
2. Review of past 24 hours
3. Pertinent physical exam of systems
4. Medication changes
5. Current problems
6. Plan
4

Daily lab sheets:
During the week this process is done by the secretaries in the main LTX office, M-
896 (ext. 8028).
It is the resident’s responsibility to pick up the labs before rounds at 10 a.m. It is advisable to call before picking up the labs.
On the weekend it is the responsibility of the residents to print the LTX lab flowsheet on every patient for rounds.
A. Steps to obtain the daily liver transplant lab flow sheet:
1. Pull up the main menu
2. Hit #21 Flow (make a flow sheet)
3. Hit return
4. Enter the patient’s unit number or “*Liverlist”
5. Hit return
6. The cursor will now be at “chart name.” Type in “LTX1”
7. Hit return
8. The cursor will now be at “output form.” Type in “C,” which indicates display flowsheet
9. Hit return
10. The flow sheet for this patient will appear on the screen. Print it.
11. Go on to option at the bottom of the screen. Select “P” to bring up the next patient on the list
12. Repeat
N.B. The software on some of the computers has macro capabilities to help with this iterative process.
B.
Updating the Liver Transplant Roster:
This needs to be done by the residents on a daily basis.
1.
Hit # 17 and access roster named “Liverlist”
2.
Add or delete patients as needed
3.
The roster must be updated daily by noon. This program will walk you through the process of adding or deleting patients based on admissions and discharges. Do not make a new Liverlist roster.
5

Please use these forms:
1. Please see examples of the routine liver transplant orders located on every nursing unit, including:
Form Number a. Pre-transplant work up adult pediatric
270-010 (1 page)
270-274 (2 pages) b. Admit pre-transplant orders 270-272 (2 pages) c. Immediate post-transplant adult pediatric
270-005A (4 pages)
270-005A (4 pages) d. Transfer orders adult, pediatric 270-276 (4 pages)
2. It is the housestaff’s responsibility to make certain that transplant orders are initiated.
3. Housestaff are responsible for ensuring all consents are signed.
4. Orders for immunosuppression are written in the morning in conjunction with the attending staff.
6

There is no advance planning for the admission of a liver transplant recipient.
When a liver becomes available, the recipient is identified and called in by the attending surgeon. It is the responsibility of the resident to notify the rest of the house-staff team and the resident on call for pediatric patients.
The surgical attending notifies the OR and the OR calls administration, transplant fellow, blood bank and ICU to inform them of the upcoming transplant. It is the responsibility of the liver transplant housestaff to make sure that the recipient has signed all the appropriate consent forms. All patients should sign a hospital operative consent form indicating hepatectomy and orthotopic liver transplant.
WBC with diff, CBC, lytes, BUN, creatinine, PT, PTT, LFTs, platelets, total and direct bili, GGT, fibrinogen, Mg, PO
4
, Ca, amylase, glucose, uric acid, total protein, and pregnancy test (women).
STAT TESTS
CBC w/ DIFF
PT, PTT, FIBRO
NA, K CL, CO
NONSTAT
2
, BUN, CR
1 lavender-top tube
1 blue-top tube
1 red-top tube serum separator
(red with gel on bottom)
LIV, CA ALB, ALKP, ALT,
AMY, BILD, BILT, GGT,
MG, PO
4
, TP, URIC
BLOOD BANK
20 u PACKED CELLS (8 U Children)
40 u FFP (8 u children)
4 u PLTS (4u children)
4 pink tubes
TO MICROBIOLOGY
UA with MICRO
Only if patient is febrile or has evidence of infection:
Urine for routine bacterial, fungal cultures
OTHER
Blood (2 sets of culture bottles) for routine bacterial, fungal cultures
CXR, EKG
7

Evaluation and selection of patients for transplantation is the result of a coordinated process which looks at the whole patient. A preliminary consultation can be obtained either at the center or in a regional liver clinic, but ultimately a comprehensive evaluation will require a visit to
UCSF. Patients with decompensated liver disease may undergo a complete inpatient transplant evaluation while being managed for complications of liver disease.
Evaluation is conducted in stages and is customized to efficiently address key issues that might preclude transplantation in a particular patient. After the evaluation is completed, patients are discussed in the multidisciplinary transplantation evaluation conference. A complete presentation is made and opinions welcomed from all participants in the program. Decisions about selection are made by consensus. Minutes are kept.
Evaluation goals
The comprehensive transplant evaluation seeks to determine the ability of the patient to benefit from transplantation and to enjoy a successful outcome with long-term good health.
Requirements for candidacy
1.
The patient has a progressive, potentially fatal liver disorder or suffers from a complication directly related to a liver disorder that substantially impairs the quality of life and daily function, and for which all alternative medical and surgical treatments short of liver transplantation have been exhausted or would be less effective.
2.
The patient’s liver disease is not expected to recur and cause disability within five years.
3.
The patient is not moribund and the OLT is likely to prolong life for at least five years (with a better-than-50-percent chance of five-year survival) and the OLT will restore the patient to a range of physical and social function suitable for the activities of daily living.
4.
The patient does not have involvement of a major system (e.g., cardiovascular or neurologic) that would preclude surgery or indicate a poor potential for rehabilitation.
5.
The patient’s psychological assessment, social arrangement and family support indicate reasonable expectation that the patient will adhere strictly to the difficult long-term medical regimen that will be required post-transplant
6.
The patient has no active alcohol or substance-abuse problems and has signed a contract, has completed at least six months of documented sobriety from alcohol and 1 year abstinence from unprescribed narcotics and illicit drugs, and has psychological clearance. For questions, please
8

see substance abuse protocol.
7.
The patient has a diagnosis meeting criteria for OLT, severity of illness meeting minimum listing criteria and does not have any absolute contraindication.
8.
The patient undergoes a comprehensive assessment, which is reviewed by the multidisciplinary transplantation committee.
UNOS Listing Criteria (as of 2/27/2002)
Status 1: The patient is in ICU with acute liver failure and a life expectancy of less than seven days, or the patient is less than18 years old with chronic liver failure.
MELD/PELD score (Model for End-Stage Liver Disease): This test characterizes patients on an objective scoring system to determine medical need for transplantation bases on current total bilirubin, INR and creatinine. Patients are given a score of 6 to 40 based on severity of illness. There is a STOR flowsheet (MELD) that can calculate the MELD score of the patients. A Palm-based system is available on this website: http://smi-web.stanford.edu/people/pcheng/medmath/
The pretransplant coordinators should be notified of any significant change in a patient’s MELD score, particularly if they begin dialysis.
The score a patients receives determines the timing of recertification.
Score
>25
24-19
Recertification every 7 days every 30 days
Lab Values
<48 hours old
<7 days old
18-11
<10 every 90 days every year
<14 days old
< 30 days old
MELD score exceptions: must be approved by the regional review board.
Child-Turcotte-Pugh (CTP) Scoring System to Assess Severity of Liver Disease
Points 1 2 3 encephalopathy ascites diuretics bilirubin (mg/dl) albumin (g/dl) prothrombin time
(seconds prolonged) or (INR) none absent
<2
>3.5
<4
<1.7
(or controlled by despite
1-2 slight
diuretics)
2-3
2.8-3.5
4-6
1.7-2.3
3-4
moderate
>3
<2.8
>6
>2.3
UNOS Minimal Listing Criteria for Transplantation: CTP score > 7
9

Evaluations are usually done on an outpatient basis. If patients are physically unable to tolerate an outpatient workup they may be admitted for an expedited workup. The transplant coordinator will arrange the admission and notify the attending or fellow on call. It is the attending’s or fellow’s responsibility to contact the resident. Pediatric patients will be evaluated by the liver transplant service and the pediatric GI team.
The resident is responsible for ordering the tests and lab work. The coordinator will contact the social worker and financial counselor.
For the admission of patients who have already undergone phase I and phase II evaluations as outpatients (or who are in the process of completing the phase II evaluation as outpatients) contact the pretransplant nurse coordinator in the main transplant office to review which tests have already been completed (tel. #’s:353-1014,-1015,-1166).
Avoid duplicate testing by checking with the nurse coordinator and reviewing records in STOR prior to ordering any phase I labs or phase II evaluation tests.
PHASE I REQ OPT TEST/PROCEDURE
A. Pathology
B. Cardiopulmonary
C. Radiology
D. Consults
X
X
X
X
X
X
X
X Review biopsy if available
Arterial blood gas or saturation on room air
Doppler-ultrasound to assess portal vein patency
Hepatologist
Surgeon (done by transplant fellow)
Social Service (coordinator will notify)
Financial counselor (coordinator will notify)
Transplant coordinator
X Addiction specialist
10

PHASE II
B. Consults
A. X-ray & Procedure
All men & women > 45 years; women < 45 years w/ CAD risk factors
X
X
X
X
REQ OPT
X
X
X
X
X
X
EKG
TEST/PROCEDURE
ECHO age >40 or at cardiologist request
Chest X-ray: PA & lateral
Upper endoscopy
Mesenteric angiography
Abdominal CT
Chest CT and bone scan for pts with HCC
X ERCP
Dobutamine echo/persantine thallium
X Coronary angiography
X
Gynecology: PAP all female recipients
Mammography: female recipients > 40
Cardiology for recipients >50
X Dental
X
X
Nutritional
Infectious Disease
Ophthamology, retinal examination for diabetics
11

 Laboratory ORDER PANEL: LTX1 AND LTX2 (CBC w/ diff, platelets, PT,PTT, AST,
ALT, alk phos, total/direct bili, albumin, total protein, Na, K, Cl, CO2, BUN, Cr, Mg, PO4, calcium, glucose, cholesterol, triglycerides, ferritin, iron, transferrin and saturation, TSH, uric acid), PSA (for men >50 yrs), AFP
 Serologies ABO with antibody screen, HBsAg, Anti-HBc, Anti-HBs, HCV, HAV-IgG,
HIV, RPR, CMV antibody, varicella titers,EBV (IgM and IgG),
 If HBsAg+ HBV DNA, HBeAg, HDV
 If HCV+ HCV RNA qualitative, HCV genotype
Urine
 UA with micro (pts with hematuria x 2 will need Urology consult to r/o bladder Ca)
 24-hour urine collection for cr/cl and protein for pts with renal insufficiency
Other tests
 HLA Typing if Pt is to receive combined liver-kidney transplant
 Abdominal ultrasound with Doppler measurement of portal vein
 Chest x-ray (PA and lateral)
 Arterial blood gas
 Hepatic angiogram or MRA (if MPV < 10 mm or to r/o PV thrombosis)
Cardiac
 EKG
 Echocardiogram (with PA pressure and EF), bubble study
 Persantine thallium scan (all men, women > 45 yrs, diabetics, and pts with CAD risk factors)
 Right heart cath for borderline/elevated PA pressures
 Left heart cath for ischemia on persantine thallium scan and high risk patients
Metastatic workup for pts with HCC
 Abdominal CT (with contrast)
 Chest CT (without contrast)
 Bone scan
Other consults 
 Chart note by hepatologist
 Surgeon
 Social worker evaluation
 Cardiology (PRN)
 Nephrology (PRN if pt may also need kidney transplant. KTU nephrologist on service)
 Urology (for pts with hematuria x 2)
Other documents
 Pre-transplant information--high-risk donor letter
 HHQ
 MELD information
 Substance-abuse specialist: Lee Jones, M.D., 719-8329 (PRN)
12

Many of the patients will be admitted from clinic for refractory ascites not amenable to diuretics. These patients will frequently need an abdominal ultrasound with Dopplers and measurement of portal vein diameter.
Many of the patients will be admitted for increasing encephalopathy.
These patients will need an increase in their lactulose, examination for sepsis and GI bleeding and an evaluation of mental status for causes other than hepatic encepholapathy.

Do NOT prescribe CNS depressants (opiates, benzodiazepines,
phenothiazines, etc) without attending approval. Patients with chronic
encephalopathy are especially sensitive to CNS depressants.
 Do NOT prescribe NSAIDS or aspirin in pre-liver transplant patient. Post transplant patients should also not receive NSAIDS; they may receive ECASA.

Tylenol is the safest analgesic, but is cumulatively hazardous. Limit to
2gm per day for no more than 3 days.
 No sodium containing IV solutions in patients with ascites.
 To treat hyponatremia, restrict free water.
 Do not correct INR with FFP unless 1:fulminant hepatitis pt
protocol(you will not be alone here) 2: active bleeding 3:invasive
procedure. INR should be <1.5 for invasive procedure.

Do not treat NH3 levels: treat clinical hepatic encephalopathy.

The most important single test on ascites fluid is a white cell count and differential.The diagnosis of SBP is made by a WBC count of
>500 and neutrophil count >250. Ascitic fluid for culture goes into blood culture bottles.

Do not over-transfuse patients with variceal hemorrhage. Aim for
hemodynamic stability and Hct about 28

Do NOT use aminoglycosides
Itching in patients with liver disease can be extremely uncomfortable. It occurs when bile salts are not excreted, accumulate in the skin, and act as irritants. The following measures are successful in decreasing pruritus either by stabilizing the skin cells or promoting the excretion of bile:

Decrease water temperature of shower or bath.

Use a moisturizing soap such as Dove and avoid deodorant soaps
 Do not dry off completely after shower or bath
 After shower/bath while skin is still damp apply eucerin cream to
all skin that is itching.
13


Wear fewer/lighter clothes

Sleep with fewer clothes and blankets
 Cholestyramine powder (Questran), a prescription medication, binds with bile salts in the intestine to decrease their absorption. It is taken one scoop/packet twice a day initially and may be increased to a total of 6 scoops/packets a day. Mix with water, tea, soda or juice.
All other medications should be taken one hour before and four hours after taking Questran.

Doxepin is a prescription medication. It is given at a very low dose for itching. Since this medication may cause drowsiness, it should be taken at bedtime. The medication can cause side effects: but at this low dose these are rare.
Cirrhotic patients with large quantities of ascites may benefit from large-volume paracentesis. The resident assisting with the procedure should order at least 4 bottles of 25-percent albumin to be administered during the procedure. The patient is given albumin according to the following guidelines:
Dose of Albumin Following Paracentesis of Cirrhotic Ascites in Adult Patients:
ParacentesisVolume
<4.0L
4.1-5.0 L
5.1-6.0 L
Albumin dose*
0
12.5 g
25.0 g
6.1-8.0 L 37.5 g
>8.1 L 50.0g
*Individualize albumin doses in patients with estimated or measuredCrCl <30 mL/min.
Mucomyst should be administered orally or via NGT for Tylenol overdoses. The patient needs a loading dose of 140 mg/kg, and if tolerated, should receive 17 doses q
4 hours at a dose of 70 mg/kg. Patients can be premedicated with intravenous Zofran.
If vomiting results, then intravenous administration of Mucomyst is recommended.
An attending physician should be consulted if intravenous Mucomyst is indicated. It has currently not been approved for intravenous administration by the FDA.
Other indications for IV dosing include:
*Intolerance to oral Mucomyst
*Co-ingestion with potential for morbidity and mortality necessitating ongoing gastrointestinal decontamination
*Gastrointestinal bleeding
14

*Gastrointestinal obstruction
*Medical conditions precluding oral administration
*Encephalopathy
*Neonatal Tylenol toxicity from maternal overdose
Procedure for IV administration of Mucomyst:
1.
Obtain informed consent
2.
Patient should be admitted to the ICU
3.
Intravenous Benadryl and Hydrocortisone must be at the bedside.
4.
Determine appropriate dose of Mucomyst ( see Appendix B)
5.
Oral Mucomyst should be diluted to a 3% or 5% solution in D5W
3% solution is the preferred dilution, but 5% can be used when fluid status is a concern. (Volume overload, renal failure)
6.
An in-line 0.22 Millipore filter should be used during intravenous infusion.
7.
Loading dose of 140 mg/kg should be infused intravenously over 60 minutes.
8.
Maintenance dose of 70 mg/kg should be initiated 4 hours after administration of loading dose and every four hours until a total of 17 maintenance doses is given
(this includes all oral and intravenous doses). Each maintenance dose should be infused over 60 minutes.
9.
Patients can be switched to oral administration at any time. If switched to oral administration the duration of therapy should be continued for 72 hours.
Management of Adverse Reactions to Intravenous Mucomyst
A Flushing
-continue Mucomyst if necessary
-consider decreasing infusion rate
-no other treatment warrented
B. Urticaria
-reassess need for Mucomyst
-continue meds if necessary
-administer benadryl 1 mg/kg IV (max50mg)
C. Angioedema
-discontinue infusion
-treat symptomatically
-Benadryl 50mg IV
-Reassess need for IV Mucomyst
For life-threatening reactions, consider:
decreasing infusion rate
Cimetidine 5mg/kg IV (maximum dose 300mg)
Ephedrine 0.5mg/kg orally (maximum dose 25mg)
-If no symptoms after 1 hour restart infusion
15

There is a severe organ shortage. Patients have to be critically ill before they are considered for a cadaveric liver transplant. For this reason we offer living donor liver transplant as a viable option for transplant.
A potential living donor liver transplant recipient must be deemed a candidate for a cadaveric liver transplant, meet our current listing requirements and be listed with UNOS. Patients who have fulminant hepatic failure or are critically ill have relative contraindications to live donor transplant.
Living Donor Evaluation
Donor criteria for living liver donation:
1) ABO-compatible donors who are between the ages of 18 and 55. Emancipated minors are considered on a case-by-case basis.
2) Absence of chronic illness.
3) Absence of liver disease.
4) Absence of severe psychological disorders.
5) No evidence of coercion or payment.
Evaluation of the living liver donor is done on an outpatient basis as outlined below:
1) Medical Evaluation: one of the transplant nephrologists evaluates the potential donor.
2) Social-work evaluation: to assess the donor’s social support, education level, relationship to recipient, financial status, health insurance and ability to understand the impact of donation.
3) Surgical consultation: to assess the donor’s surgical risk.
4) Laboratory evaluation: to assess ABO, CBC with differential, Pt/PTT, basic metabolic profile, hepatic function panel, hepatitis B surface antigen, hepatitis B core antibody, hepatitis B surface antibody, hepatitis C antibody, hepatitis A total and IGM, CMV IGG antibody, RPR, HIV antibody, cholesterol (total, LDL,HDL), triglycerides, TSH, iron, ferritin, TIBC, HCG, urinalysis
5) Chest x-ray
6) Electrocardiogram
7) CT angiogram: of the abdomen with intravenous contrast. It includes angiography of the celiac and mesenteric circulation and a three-phase image of the liver that includes pre-, early-, portal- and late-phase imaging. Images are to concentrate on portal- and hepatic-vein anatomy.
8) CT cholangiogram is performed with morphine injection.
9) Mammography (within one year): for females over 40 years old or with a strong family history of breast cancer.
10) Pap smear (within one year): for all females.
16

Optional tests:
1) Exercise stress thallium test: for all donors over 50 years old or with a pertinent history.
2) PFTs: for smokers and patients with a history of pulmonary disease.
3) Liver biopsy: as indicated.
Donor costs:
All donor medical fees are covered under the recipient’s insurance. Additional costs, such as visiting nurse services, outpatient pharmacy and parking, are considered on a case-by-case basis. Patients who donate their livers are not candidates for long-term disability.
Pre-op testing:
The donor and recipient return to the center for liver disease and transplantation prior to surgery and meet with the surgeon to discuss the risks and benefits of surgery.
Consents for surgery are signed. Patients interested in autologous blood donation should contact the blood donor center. They should donate two units prior to the surgery. Patients may require epogen and ferrous-sulfate supplementation prior to surgery. This is decided on a case-by-case basis.
Post-operative followup:
Patients are discharged to home on Norco (60) and Protonix for 90 days. Patients are seen in the transplant clinic one week after discharge and four weeks after that visit. Labs are sent until normal. Patients typically require six weeks of disability, however, sick time is determined on a case-by-case basis.
Preop
1) Admit to 14 Moffitt
2) Diagnosis:Living liver donor Treatment plan: Hepatectomy
3) Ambulate ad lib
4) Diet: Clear liquids after 2pm, NPO after midnight
5) Allergies:
6) Vitals: q shift
7) Labs:
CBC diff, PLTs, electrolytes, BUN, CR, PT, LFTs, UA ,
8) Medications: a) Benadryl - 25 mg po qhs prn insomnia, may repeat x 1 b) Kefzol 1 gram to accompany pt to OR c) Dulcolax suppository at 6 pm night prior to surgery d) IV Fluids: at 8 pm the night prior to surgery: D5LR at 125 cc/hr e) Type and Crossmatch: Donor has 2 autologous units to be used first.
17

Postop
1) Admit to 14M
2) Diagnosis: s/p hepatectomy
3) Ambulate tid
4) Diet: NPO except meds, and sips of water not to exceed 50 cc/hr
5) Allergies:
6) Vitals: BP,P,RR with O2 sats for first 12 hours then q 4; Temp q 4hr
7) Urine output q 2 hours for first 12 hrs, then q 8 hrs, I&O q 8 hrs.
8) Labs: QAM cbc,plts, electrolytes, BUN,Cr. PT/PTT, LFT’s Ca Mg, Phos in
PACU; Phos BID and replete as needed.
9) STAT CBC, AST, Phos at 6 hrs. after arrival to floor
10) Nursing:Foley to gravity, JP to bulb suction, compression stockings on at all times while in bed.
11) IVF: D5 NS + 15 mmol NaPhos/L at 150 cc/hr for 24 hrs, then D51/4NS +15
mmol NaPhos/liter at 100cc/hr
12) Meds: PCA (usually Dilaudid at 0.2 mg/dose, 10 min lock out, NO BASAL
13) See PCA order sheet
14) Protonix 40 mg PO QD
15) Colace 250 MG PO BID, Dulcolax supp prn
16)
Oxygen at 3 liters vis NC until PCA DC’D
17) Studies: CXR in PACU to check line placement
18

For patients on 14 Long/Moffitt: Write 14-L1, 14-L2 and daily CSA or Prograf levels.
Daily:
In the a.m.: CBC, platelets, BUN, creatinine, T-BILI, NA, K, ALT, AST, GLUC, CL,
CO
2
, alk. phos., P.T. (You may write 14-L1 on the adult floor and the lab will run these.)
1 red-top tube
1 purple-top tube
1 blue-top tube
1 purple top-tube for CSA or Prograf level
Note: Patient’s cyclosporine or Prograf levels must be drawn prior to the a.m. dose-they are 12-hour troughs. (Write 14-L1, 14-L2 and daily CSA or Prograf levels.)
M TH labs:
CA, PO
4
, Mg, DIFF. ( You may write 14-L2 and the lab will run these).
The lab will draw most of the patient’s blood work in the morning. It is the housestaff’s responsibility to review daily labs and micro prior to morning rounds.
19

The average length of stay is 13 days for children and 7-9 days for adults.
The average length of stay is 5-7 days for living-related donors.
Adult patients may shower on POD 3.
Staples are removed on POD 21-30 in recipients.
Immunosuppression: see section on immunosuppressive therapy .
1. It is the intern’s responsibility to dictate discharge summaries (PDP) stat!
Be sure that all meds are listed in exact doses. This is extremely important because these forms are used by the transplant coordinator to manage the patients when they go home.
2. The Adult/Peds Liver Transplant Clinic is held every Tuesday morning on the 6th floor of the ACC Building. The Pediatric Liver Transplant Clinic is also held every Thursday on the 2nd floor of the ACC Building. The CNS or housestaff are responsible for making post-transplant clinic appointments by calling 353-1012 (for adults) prior to the patient leaving the hospital.
3. Newly transplanted patients going home for the first time must be discharged with prescriptions for all their medications. Readmitted patients need prescriptions for any new medications started while in the hospital (i.e. antibiotics (See examples pg. a, b & c.) The pharmacists on service will write all the prescriptions, fax them to the patient’s pharmacy and give the patients their scripts.
4. In order to comply with the criteria mandated by UNOS, it is imperative that certain information be included in all liver-transplant recipient discharge summaries. The following information needs to be recorded in the patient’s discharge summary in order for this information to be passed on to UNOS: a. description of the patient b. primary liver disease c. all medications d. patient’s graft status
It is important for this information to be included in all discharge summaries for the patient, not only the transplant admission/discharge note.
All discharge summaries should be sent to the referring physician and the number and name included in the DC dictation.
5. For non-transplant patients, the house staff/CNS are resposible for making appointments for follow up. Call Raymond Cogen at 415-353-1016 to make the
20

appointments. The information needed to make the appointment is: the hepatologist who will be following the patient and the time frame for the next appointment.
6. For patients that are anticipated to be leaving, write for 4 am morning labs on the evening prior to discharge; any X-ray testing that is to be done on the day of discharge should be marked on the requisition as being done on a potentially dischargeable patient and sent down the night before discharge. All orders for discharge should be written by 8 am the morning of discharge after labs have been checked and discussed with the fellow or the attendings.
1. List full medication name.
2. Order the pharmacy-prepared dose. This is not the patient dose!
3. Write for a 30-day supply.
4. QD, BID, QID
5. List which organ was transplanted and the transplant date.
6. Write 11 refills. No refills on narcotics.
7. Must complete with MD’s CA license and DEA #.
8.
On the adult service, all prescriptions will be filled out by the PharmD or his/her
designee.
21

22

These are general guidelines for frequently seen problems; they should not exceed clinical judgment.
FEVER WORKUP:
1. Temp. > 38 C (100.4 F) and for fever spikes.
2. Pan culture for bacteria (lab will automatically screen cultures for fungi) a. urine not more often than once every 3 days b. blood x 2 c. stool (only if diarrhea is present; send for C. difficile) d. endotracheal aspirate and surgical drains as appropriate
3. CMV antigen: 2 green-top tubes, 1 tube for peds (must be in lab by 2 p.m.). a. once a week only b. lab will run them q day from 7 a.m. to 2 p.m. only c. specimen must be clocked in the lab by 2 p.m. or it will not run on that day d. only send blood, bronch washings or tissue for CMV cultures--the lab is unable to run CMV studies on urine, sputum, ascites or pleural fluid
4. CXR--if there is an infiltrate, consult with Pulmonary for a bronchoscopy. Right-sided pleural effusions are common in post-transplant patients. While they are usually exudative, they are generally sterile.
5. Tylenol q 4 hours, max dose 2 grams in 24 hours.
6. Change all lines, especially central lines, and culture catheter tips as indicated.
7. Doppler U/S if clinically indicated to look for a) patency of the hepatic vessels b) fluid collections
9.
Consider liver biopsy .
ANTIBIOTIC ALGORITHMS FOR LIVER TRANSPLANT PATIENTS:
Surgical Prophylaxis
1.) Ceftriaxone 1g IV intraop and 1g IV q24h postop x 1 dose
2.) Fluconazole 100mg PO/IV (depending on NPO status) pre-operative, followed by 100mg once weekly for fungal prophylaxis
23

Presumed Postoperative Infection, Infection Site Unknown
1.) Panculture as above
2.) Begin one of the following antimicrobials a.
Timentin 3.1gm IV Q6h (adjust for renal function)
OR
OR b.
Zosyn 4.5 gm IV Q8h (adjust for renal function) c.
Moxifloxacin 400mg PO QD

If patient is receiving a quinolone (i.e Ciprofloxacin, Levofloxacin) for SBP prophylaxis DO NOT use Moxifloxacin. Use either
Timentin or Zosyn
 If patient unable to tolerate PO, may give IV
 Separate PO Moxifloxacin from Mg2+, Ca2+, Fe2+, or Al2+ containing products/antacids/foods by at least 2 hours
PLUS/MINUS
Vancomycin 10-15mg/kg/dose IV Q12h (adjust for renal function, round to
nearest 250mg)

If no resistant gram-positive (e.g. MRSA, MRSE) infection is confirmed within 72h, DISCONTINUE Vancomycin
3.) If the patient is receiving SBP prophylaxis with a quinolone discontinue while on
Timentin/Zosyn.
4.) If cultures are POSITIVE : Refine antimicrobial therapy according to cultures to obtain the narrowest spectrum of activity
5.) If cultures are NEGATIVE and patient: a.
Clinically improves and no source of infection is identified, continue antimicrobials for 7-10 days. b.
Continues to be febrile and no source of infection is identified:
 Discontinue antimicrobials and reculture
OR

If patient is hemodynamically unstable and/or clinically worse:

Start Vancomycin (as above) plus Cefepime 1-2 gm IV Q12h
(adjust for renal function). If there is no clinical improvement after 48h, discontinue antimicrobials and revert to STEP 1
Septic Shock
1.) Culture blood (x 2 specimens, including one peripheral stick) and urine (plus urine analysis), as well as endotracheal aspirate and incision sites as appropriate
2.) Evaluate chest x-ray, line site(s), and surgical wound(s) as sources of infection
3.) Start Vancomycin plus either Meropenem OR Cefepime +/- Tobramycin until further results are available a.
Vancomycin 10-15mg/kg/dose IV Q12h (adjust for renal function, round to nearest 250mg)

If no resistant gram-positive (e.g. MRSA, MRSE) infection is confirmed
24

within 72h, DISCONTINUE Vancomycin
PLUS b.
Meropenem 1 gm IV Q8h (adjust for renal function)
OR c.
Cefepime 1-2 gm IV Q12h (adjust for renal function)
PLUS/MINUS d.
Tobramycin 5 mg/kg IV Q24h (adjust for renal function)
 Check baseline serum creatinine prior to initiating
4.) If cultures are POSITIVE : Refine antimicrobial therapy according to cultures to most narrow spectrum of activity
5.) If cultures are NEGATIVE and patient: c.
Clinically improves and no source of infection is identified, continue antimicrobials for 7-10 days. d.
Continues to be febrile and no source of infection is identified:
 Discontinue antimicrobials and reculture
OR
Discontinue Meropenem/Cefipime/Tobramycin after 72 hours and restart either Timentin or Zosyn or Moxifloxacin (if not on SBP prophylaxis with a quinolone)
Urine Cultures:
Urine cultures should be accompanied by a urinalysis with micro (UA with micro)
Urine cultures growing yeast should generally not be treated
Catheter Tip Cultures:
Catheter tip cultures generally should NOT be performed unless they are being used to confirm the source of a bacteremia
WORKUP FOR ELEVATED LFTs:
Common sources of elevated LFTs are rejection, hepatitis (CMV, HCV, HBV), vascular compromise and biliary tract problems.
1. Ultrasound to check for patency of hepatic vessels or for presence of fluid collections.
2. Liver biopsy (see routine liver-biopsy orders).
5. Institute fever-workup if fever is present.
25

LIVER BIOPSY:
1. Biopsy specimens must be in the lab by 9:45 a.m.
2. Biopsy slips must be labeled “rush permanent”.
3. Hepatologists, both adult and pediatric, use the Jamshidi 17-gauge (1.4-mm for peds) biopsy needle
4. If after review of the pathology report there is a question of CMV (or any other virus),
Microbiology must be called to culture the biopsy
5. Adult patient biopsies are done by the GI fellows or GI attending
6. Pediatric biopsies are done by the pediatric GI fellows in conjunction with the pediatric
GI attending. It is the on-call resident’s responsibility to make sure a 4-hour post-biopsy
Hct is obtained by the pediatric staff.
7. Pediatric liver biopsies are routinely performed under ultrasound.
Pre-biopsy orders (for adults--pediatrics writes its own pre- and post-biopsy orders):
1.
NPO except meds after midnight.
2.
Order a liver-biopsy tray and a 17-gauge Jamshidi soft-tissue biopsy needle.
3.
Check platelets. If the day before the biopsy the platelets are: a. > 75,000: it is not necessary to check them again in the a.m. b. < 75,000: they must be rechecked in the a.m. with results back by 6 a.m. c. < 50,000: give a 6-pack of pooled platelets ASAP just prior to and during biopsy
4. Check coag panel. If PT > 18 the biopsy should not be performed without FFP coverage. This generally requires a minimum of 2 units before and 1 unit during the biopsy procedure
5. Always consult with the attending staff the day before the biopsy to determine the potential need for platelets or FFP.
6. Ultrasound for localization is scheduled for all children by the Peds GI Service.
Post-biopsy:
1. Patients must lie on their side for 1 hour and remain on bedrest for 4 hours.
2. Obtain a 4-hour post-biopsy Hct (for pediatrics you will need to coordinate who will draw this level with the pediatric resident).
3. It is appropriate for patients to eat a late lunch if V/S are stable and Hct is unchanged.
Interpretation of Biopsy:
Rejection Activity Index (Banff Schema for Grading Liver Allograft Rejection, Hep 25:658, 1997)
Portal inflammation:
1. Mostly lymphocytic inflammation involving--but not noticeably expanding--a minority of the triads.
2. Expansion of most or all of the triads by a mixed infiltrate containing lymphocytes with occasional blasts (transformed lymphocytes), neutrophils and eosinophils.
26

3. Marked expansion of most or all of the triads by a mixed infiltrate containing blasts and eosinophils with inflammatory spillover into the periportal parenchyma.
Bile-duct inflammation or damage:
1. A minority of the ducts are cuffed and infiltrated by inflammatory cells and show only mild reactive changes such as increased N:C ratio of the epithelial cells.
2. Most or all of the ducts are infiltrated by inflammatory cells, more than an occasional duct shows degenerative changes such as nuclear pleomorphism, disordered polarity and cytoplasmic vacuolization of the epithelium.
3. As above for 2, with most or all of the ducts showing degenerative changes or focal luminal disruption.
Venous endothelial inflammation:
1. Subendothelial lymphocytic infiltration involving some--but not a majority of--the portal and/or hepatic venules.
2. Subendothelial lymphocytic infiltration involving most or all of the portal and/or hepatic venules.
3. As above for 2, with moderate or severe perivenular inflammation that extends into the perivenular parenchyma and is associated with perivenular hepatocyte necrosis.
Rejection activity index (sum of above scores):
Global assessment:
Indeterminate: portal inflammatory infiltrate that fails to meet the criteria for the diagnosis of acute rejection
Mild: rejection infiltrate in a minority of the triads that is generally mild and confined within the portal spaces
Moderate: rejection infiltrate expanding most or all of the triads
Severe: as above for moderate, with spillover into the periportal areas and moderate to severe perivenular inflammation that extends into the hepatic parenchyma and is associated with perivenular hepatocyte necrosis.
27

PAIN MANAGEMENT AFTER LIVER TRANSPLANT:
I. Initial management
24-48 hours post-op:
The patient will be on patient-controlled anesthesia (morphine/dilaudid).
Post-op (day 3-6): The drug of choice is:
Oxycodone 5-10 mg. PO q 4 to 6 hours PRN pain. Norco or Vicodin can be used as long as the cumulative tylenol dose is < 2grams every 24 hours.
If unable to take PO: Morphine 1-4 mg IV q 2-4 hours prn pain
Pain medication needs to be individually adjusted . To determine the dose and timing, please assess the following:
A. If there is no significant pain relief within the first 60 minutes of dose received, you may have to increase the amount.
B. If pain returns prior to the next dose, shorten the dosing interval.
C. If the patient is comfortable and pain free on standing doses of one of the above medications, switch to prn dose after post-op day 3. Prn medications should be offered q 4 to 6 hours.
Pain Medication Upon Discharge:
The patient should not take more than 2000mg per day of Tylenol. If still having significant pain: Percocet (5 mg. Oxycodone/325 mg. Tylenol) 1 to 2 tablets q 6 hours prn for 2 weeks. Alternate drugs: Tylenol #3, Norco, Vicodin.
If after one month the patient continues to need narcotics for pain relief, he/she will be switched to methadone.
II. Management of Side Effects Due to Narcotics
A.
Constipation: Colace 250 mg PO bid or Senokot 2 tabs or 10 cc po qhs.
B.
Nausea/vomiting: Anzemet 12.5mg iv prn 1 to 2 times a day or Compazine 10mg PO tid or Reglan 10mg PO tid
C.
Excessive sedation: please obtain Psychiatry consult. The patient may benefit from Ritalin 5 m. bid 8 a.m. and 1 p.m.
D.
Pruritus: change opioid.
E.
Confusion/delirium: lower narcotic dose. Change opioid. Call Psychiatry
F.
Anxiety: Ativan 0.5mg. tid. Call Psychiatry.
III. Conversion of Morphine to Methadone
Oral to parenteral morphine: 3:1.
Parenteral morphine dose is equivalent to oral methadone dose
28

PREVENTION AND TREATMENT OF OPPORTUNISTIC INFECTIONS:
1. CMV
Background: o Patients present with fever, malaise, GI symptoms, decreased WBC. o Theoretic role of CMV infection in inducing rejection, vasculitis. o Diagnosed using CMV antigen. Buffy coat or “shell vial assay” directed against an early CMV antigen are less sensitive. o Incidence peaks at 30 days post-transplant, then slowly decreases over several months
 Post-transplant patients’ risk for CMV can be stratified using the following criteria:

CMV Ab neg recipient/CMV Ab pos donor = high risk

CMV Ab pos recipient/CMV Ab pos donor = intermediate risk

CMV Ab pos recipient/CMV Ab neg donor = low-intermediate risk

CMV Ab neg recipient/CMV Ab neg donor = high risk
CMV Prophylaxis: a) Antibody Positive Recipient: Acyclovir 800 mg po qid is given from the time a patient can take po medication; it is renally dosed and continued for 3-months following transplant. b) Antibody Negative Recipient: Cytovene (oral ganciclovir) 1000 mg po tid is given from the time a patient can take po medication; it is renally dosed and continued for 3-months following transplant. c) Cytovene is also given during the treatment of rejection with Thymoglobulin and OKT3. Ganciclovir and Acyclovir are never given concomitantly .
Renal Dosing for Cytovene:
Creatinine<2: 1000mg PO TID
Creatinine 2.1 - 3: 500mg PO TID
Creatinine 3.1 - 4:
Creatinine >4:
500mg PO BID
500mg PO QD
CMV Treatment: a) If CMV Ag becomes positive begin preemptive treatment:
Valganciclovir 900mg PO BID x 14 days, then
Valganciclovir 900mg PO QD x 3 mos b) If the CMV Ag is positive and the patient has invasive CMV based on biopsy:
Administer IV Ganciclovir 5mg/kg IV BID (adjust for creatinine clearance, see below) for 14 days and recheck CMV Ag. If negative, begin
Valganciclovir 900mg po qd x 8 weeks
29

If positive, continue IV Ganciclovir for 7 more days and recheck CMV Ag. If negative, Valganciclovir 900mg po qd x 8 weeks.
Renal Dosing for Intravenous Ganciclovir:
Creatinine <2: 5.0mg/kg/dose BID
Creatinine 2.1 - 3:
Creatinine 3.1 - 4:
2.5mg/kg/dose BID
2.5mg/kg/dose QD
Creatinine >4:
Hemodialysis:
1.25mg/kg/dose OD
1.25mg/kg/dose post-dialysis only
Home Therapy:
Intravenous ganciclovir can be given to patients at home if there is no other reason for the patient to be in the hospital. Home ganciclovir is arranged through homecare agencies and is not dispensed by the in-patient pharmacy. Each homecare agency must arrange to provide the drug for the patient; if the agency is unable to provide the drug, another homecare agency should be contacted. This is arranged by the CNS on the service.
Ganciclovir side effects: neutropenia (30 percent of patients, reversible with discontinuation of drug) leukopenia (40 percent of patients) increased LFTs thrombocytopenia mental status changes phlebitis rash
GI symptoms azoospermia, mutagenesis and teratogenesis (reported in animals)
Acyclovir (Zovirax) :
Renal dosing of oral Acyclovir
Creatinine clearance > 25ml/min: 800mg PO QID
Creatinine clearance 10-25 ml/min: 800mg PO TID
Creatinine clearance < 10ml/min: 800mg PO OD
Hemodialysis: 800mg PO BID (give after dialysis)
Side effects:
Nephrotoxicity precipitation of Acyclovir crystals in renal tubules if concentration exceeds 2.5 mg/ml at 37C or if the drug is given by bolus injection.
Patients should be well hydrated, especially in the first 2 hours post-dose.
30

CNS toxicity mechanism of action:
Tremors, confusion, hallucination, lethargy and agitation have been reported.
Acyclovir triphosphate interferes with virus DNA polymerase and inhibits cellular alpha-DNA polymerase. When incorporated, the DNA chain is terminated. Acyclovir is much less toxic to normal noninfected cells because: 1) less is taken up 2) less is converted to the active form and 3) cellular alpha-DNA polymerase is less sensitive to the effects of the active form.
2. Mucocutaneous Candidiasis (Thrush)
Prophylaxis: (continue until prednisone dose is 10mg/day):
Fluconazole 100mg PO Qweek, or
Clotrimazole (Mycelex) troches 10mg PO QID, or
Nystatin oral suspension 10ml swish and swallow PO QID (pediatric patients)
3. Pneumocystis carinii Pneumonia (PCP)
Prophylaxis (continue for life):
Trimethoprim/sulfamethoxazole (Septra/Bactrim) single strength tablet PO
QMWF
If sulfa intolerant:
Dapsone 50mg PO QD (<70kg)
100mg PO QD (>70kg)
Adverse effects of dapsone: Hemolytic anemia (check for G6PD deficiency)
Methemoglobinemia
Dapsone is available in 25mg and 100mg tablets.
Inhaled pentamidine 300mg Qmonth
Adverse effects of inhaled pentamidine: Coughing, SOB, gagging
HEPATITIS B TREATMENT PROTOCOL:
Liver transplant for HBV has been controversial in the past because of early and aggressive post-operative recurrence. With the use of hepatitis B immunoglobulin (H-
BIg) and antiviral agents such as lamivudine and adefovir, liver transplantation for
HBV is now done routinely with excellent outcomes and minimal recurrence.
However, resistance to H-BIg, lamivudine and adefovir can develop, so ongoing surveillance for virological breakthrough is important.
Hepatitis B core antibody positive donor: All patients who receive a liver from a core-antibody positive donor should receive lamivudine 100 mg QD (adjust for renal insufficiency) for life.
31

Screening: At time of listing, all patients will be tested for HBsAg, anti-HBs and
HBV DNA (quant). If not done previously, anti-HDV should be ordered.
Pre-Transplant: HBV DNA levels should be monitored every 3 months in patients on antiviral therapy (lamivudine or adefovir) to monitor for virological breakthrough
(due to drug resistance) prior to transplant.
Additionally, a HBV DNA level will be sent immediately pre-op on all HBsAg patients regardless of pre-transplant HBV therapies.
Intra-op and First Year Post-Transplantation:
All patients are treated with combination H-BIg and antiviral therapy for the first 12 months post-transplantation. The patient will receive H-BIg infusions in the OR and post-operatively on days 1-6 according to the H-BIg protocol (see below).
Lamivudine (100mg, adjusted for renal insufficiency) or adefovir (10 mg, adjusted for renal insufficiency) will be given post-op on an indefinite basis regardless of DNA status pre-op.
Antiviral therapy: there are 3 drugs currently available for HBV in liver transplant patients: lamivudine (LAM), adefovir (ADV) and tenofovir. Which drug or drugs to use in what patient is detailed below – these recommendations are based upon current knowledge of cross-resistance patterns. i) No prior antiviral therapy, HIV negative: lamivudine or adefovir ii) LAM-resistant, HIV negative: adefovir (preferred) or tenofovir (and continue the
LAM) iii) LAM-resistant, HIV positive: tenofovir (preferred) or adefovir – but need to coordinate with HIV therapy. iv) ADV-resistant: lamivudine (and continue the ADV)
H-BIg will be infused monthly (at doses detailed below):
H-BIg protocol:

H-BIg 10,000 IU IV intraoperative and daily X 6 days (total 7 doses in first week).

H-BIg 10,000 IU IV monthly X 3 months, then reduce to 5000 IU monthly if anti-HBs titers are >250 IU/mL. If anti-HBs titers are <250 IU/mL, increase back to 10,000 IU monthly for remainder of first year.
Monitoring:

HBSAG and HBSAB will be checked monthly for first year

HBV DNA (quant) at 1 month, 3 months, 6 months and 12 months (first year) and then if AST/ALT increase or HBsAg becomes positive (to assess for treatment failure)

A liver biopsy will be performed if increase in liver enzymes (note: this should be done even if one if confident of HBV diagnosis – necessary to grade and stage disease).
32

HEPATITIS C TREATMENT PROTOCOL:
Recurrence of hepatitis C after liver transplantation is universal and has varied implications for patients, from mild elevation in transaminases to ESLD in a short time period. All patients with the preoperative diagnosis of HCV will follow the following postoperative management protocol.
Screening: All patients, regardless of liver function tests, will undergo yearly liver biopsy and hepatitis C PCR (quantitative) to guide therapy. In addition, any rise in transaminases precipitate a biopsy. (Empiric treatment of rejection should be avoided.
Immunosuppression Management: The goal of immunosuppression management in these patients is to keep immunosuppression to a minimum and avoid unnecessary pulse steroids. If patients have abnormal liver enzymes and a biopsy consistent with rejection, optimize immunosuppression. Only after 2 biopsies confirm rejection should patients receive IV Solumedrol.
Treatment: Only patients who have Stage 1 or greater fibrosis on biopsy will be considered for treatment. .
Dosing:
1) Pegasys (peginterferon 2a) i) Standard for all patients, no weight based dosing ii) 180 mcg = 1.0 mL (Starting Dose) iii) 135 mcg = 0.75 mL (First Step reduction) iv) 90 mcg = 0.5 mL (Second Step reduction)
2) Ribavirin: i) 100-1200mg QD— start with 800 mg QD (as divided dose) and increase to
1000-1200 mg QD aiming for final dose of ~13 mg/kg, if tolerated.
Dose Reductions:
ANC: i) > or equal to 1000: No dose reduction required. ii) 500-999: Reduce by one step. Repeat CBC with diff in one week. If
ANC still 500-999, reduce dose another step, consider Neupogen 300 ug
Qwk
iii) <500: Hold Pegasys and order Neupogen 300 ug q weekly. Repeat labs in one week and restart Pegasys with Neupogen.
Hemoglobin: i) >10.0: no dose reduction required
33

ii) 8-9.9: Reduce Ribavirin dose by half and start erythropoietin 40,000 IU weekly. Repeat CBC in one week. If Hgb>10, then increase dose (usually
1/2 way between initial and current dose). iii) <8.0: Hold Ribavirin. Consider transfusion if patient symptomatic. Repeat
CBC in one week. Start erythropoeitin 40,000 IU weekly. Once Hgb above
12.0 (males), 11.0 (females), restart ribavirin at half of starting dose.
Platelets: i) or equal to 50,000: No dose reduction required ii) 30-50,000: Reduce Pegasys by one step. Repeat platelets in one week. If platelets still 30-50, reduce dose another step. iii) <30: Hold Pegasys. Repeat labs in one week. If platelets over 50,000, consider restarting Pegasys at 1/2 dose.
Laboratory Testing:
-Weekly CBC for first 4-6 weeks, then resume monthly
-If the Pegasys or ribavirin doses have been reduced/adjusted, may need to continue
weekly CBC longer – should have stable blood counts for minimum of 2 weeks
before switching to monthly labs
-TSH every 3 months during treatment
-HCV RNA quantitation at 3 and 12 months
POST-TRANSPLANT TREATMENT OF OSTEOPOROSIS:
Background:

Osteoporosis is a known complication in cholestatic liver disease; however, its prevalence in all patients with cirrhosis is significant.

Risk factors include hypogonadism, malnutrition, abnormal vitamin D and K metabolism and exposure to drugs such as corticosteroids.

Over 50 percent of the patients referred to our center for liver transplant have some degree of osteopenia.

Use of corticosteroids in transplant patients is associated with rapid bone loss and fractures.

The literature reports a fracture incidence of 24-65% during the first year after liver transplantation.

Bisphosphonates such as Fosamax have been safely used in our patients.
Treatment:
Patients who have not had a bone-density within the previous year need a baseline bone-density within the first month post-op. Please note: patient should
34

be free of ascites, as it can interfere with the results of study. The patients are managed based on the results of their bone density. Using the WHO criteria:
BMD osteoporosis = T score > -0.25 osteopenia = 2.49< score> -0.10 normal = > -0.99
All patients post-liver transplant are prescribed:
*calcium and vitamin D supplements TID
(typically Citracal D or Oscal D are used)
*multivitamin OD
These medications should be continued for as long as the patient is on
Prednisone.
If osteopenia or osteoporosis is present, treat with bisphosphonates:
*Fosamax 70mg once weekly
(Alternate medications: Fosamax 10mg daily or Actonel 30mg once weekly)
*bone-density scans should be performed at 1 year post-transplant to assess for improvement.
* Bisphosphonate therapy can be discontinued in select patients:
Osteopenia: 1 year post-Prednisone discontinuation or if there is normalization of bone density. Only if male or pre-menopausal female without other risk factors for bone loss. If discontinued, recheck bone density at 6 months to assess for further bone loss. If none, no need to rescreen.
Osteoporosis : Indefinitely.
Instructions for patients:
When taking bisphosphonates, instruct patient to take with a full glass of water
30 minutes before first food and drink and other medications. Avoid lying down for 30 minutes.
Avoid antacids, as they can interfere with absorption of medication.
Side effects of Fosamax:
Caution should be used in patients with hypocalcemia, upper-GI disease and severe renal dysfunction. esophagitis dyspepsia gastritis abdominal pain myalgias arthtalgias back pain nausea constipation flatulence acid reflux headache vomiting dysphagia
POST-TRANSPLANT TREATMENT OF HYPERLIPIDEMIA
35

Background

Hyperlipidemia after liver transplant is observed in 20-60% of patients in longterm follow-up (Zachoval, 2001, Jindal 1997).

Transplant recipients have a triple risk for cardiovascular accidents: hyperlipidemia, HTN, and DM. Correction of these factors will lead to a decrease in morbidity and mortality.

Changes in lipids are typically observed during the first 3-6 months posttransplant.

Risk factors for coronary heart disease include pre-transplant lipid levels, obesity, immunosuppressive medications, hyperhomocysteinemia, diabetes
(fasting glucose of

126 mg/dL), HTN (BP

140/90mm Hg x 2 occasions),
HDL (

40 mg/dL), renal insufficiency, family history (father, brother, son with
CHD before age 55, and mother, sister, daughter with CHD before age 65), smoking (smoker or exposure every day) and age (men

45, women

55 or premature menopause without HRT).

Immunosuppressive agents can

BP, impair glucose metabolism and promote additional risk factors for atherosclerosis and therefore a more aggressive course of atherosclerosis when compared to the general population.
o Rapamycin > Cyclosporine > Prograf o Prednisone has significant effects on lipid levels
 promotes insulin resistance with secondary hyperinsulinemia
 increases hepatic secretion of VLDL
 can

HDL but withdrawl from steroids can cause a large

HDL and

triglycerides o Cyclosporine

TC and triglycerides
 75 percent remained hypercholesterolemic 1 year post-transplant
(Fellstrom, 2000) o FK506 increases oxidation of LDL leading to atherosclerosis

26 percent remained hypercholesterolemic 1 year post-transplant
(Fellstrom, 2000) o Cellcept and Imuran do not affect serum lipids or glucose levels o Rapamycin (Sirolimus) can markedly exacerbate hypercholesterolemia in renal transplant recipients and results in significantly higher TC and triglyceride levels than CSA based therapy (Fellstrom, 2000). However,
Rapamycin does not cause HTN, hyperglycemia or decreased renal function.
Lab Screening

The 2001 National Cholesterol Education Program (NCEP) recommends that after 20 years of age, cholesterol screening be done every 5 years in all adults. However, patients who are post-OLT need more stringent monitoring.

Pre-transplant: send 12-hour fasting total cholesterol, HDL, LDL and triglycerides as a baseline.
36


Post-transplant: check lipid profile at baseline, 3 months and 6months.
Follow algorithm.

Goal according to NCEP: o LDL

100 o HDL

40 o TC

200 o triglycerides

140 (Jindal, 1997)
Medication Options

Statins (HMG-CoA reductase inhibitors) are recommended for treating posttransplant patients with Pravastatin being the drug of choice due to its minimal side effects and no cases of rhabdomyolysis or hepatotoxicity in controlled studies (Zachoval, 2001). Also it doesn’t compete for the cytochrome P450 pathway, as other statins do.

Cholestyramine may interfere with absorption of FK506 and CSA.

Niacin may cause glucose intolerance and hyperuricemia and is poorly tolerated in post-transplant patients.

Lovastatin with CSA in heart-transplant recipients increases the incidence of rhabdomyolysis.

Gemfibrozil, a fibric-acid derivative, can cause biliary stones in liver transplant recipients.
37

Algorithm for Treating Hyperlipidemia in Liver Transplant Recipients
(Derived from NCEP 2001)
LDL

100 LDL 100-130 LDL

130
Recheck in 1 year
Initiate diet and drug therapy
Lifestyle modification, for 6 weeks, including decreaseing fat intake

7% of total calories, and limiting cholesterol intake to

200mg/day, smoking cessation, & diabetic control. Also consider weaning prednisone, and considering changing to
FK if on Neoral. Can also discontinue oc/s antidepressants, antiacne drugs, betablockers, thiazides and antiinfectives.
LDL>100 LDL

100
Check LFTs, CPK, HCG after 6 weeks of treatment, and every 3 months thereafter. Check lipid profile 4 weeks after any dosage adjustment, and every 6 months once stabilized
Check baseline CPK and HCG
Recheck every 6 mo on diet.
Initiate drug therapy with Pravastatin
(Pravachol) 20mg/d
PO Q HS with or without meals, (Preg
Cat. X)
Check LFTs, CPK, HCG after 6 weeks of treatment, and every 3 months thereafter.
Check lipid profile 4 weeks after dosage adjustments and every 6 months once stabilized. If CPK elevated stop drug.
38

Study objectives
The objectives of this phase I safety and efficacy study are to collect data in HIV positive liver transplant recipients and to address the following specific aims:
 To evaluate the impact of liver transplantation, and post-transplant immunosuppression on HIV disease progression and markers of immune function and activity.

To evaluate the impact of HIV infection on graft function and survival.

To describe the pharmacokinetic interactions between immunosuppressive agents and the hepatically metabolized antiretroviral (ARV) agents.
General Study Design
This is a prospective, open-label, non-randomized clinical trial evaluating the safety and efficacy of liver transplantation in HIV positive patients . All patients who are being considered for transplantation will be registered when placed on the waiting list. We anticipate approximately 75 liver transplants over 3 years with five years of follow-up. Following transplant and post-operative recovery, this will be an outpatient study with the exception of six (4 in the first year) or more inpatient 14-hour GCRC* visits at screening, Week 2, Week 28,
Week 52, Year 2 and Year 5. Patients are seen daily during the initial hospitalization, then weekly (x2), every other week (x5), monthly (x2), every 8 weeks (x4), every 12 weeks (beginning of Year 2 to the end of Year 3), then every
6 months for the final 2 years of follow-up.
Subject Selection
All individuals with end-stage liver disease and HIV infection who meet standard clinical criteria for transplantation and the study inclusion and exclusion criteria are eligible for registration in the study. When an organ becomes available, patient transplant eligibility will be determined based on the most recent CD4+ T-cell count and viral load result, not more than 10 weeks prior to transplant . Those criteria are as follows:
Inclusion Criteria
1. Documented HIV infection (by any licensed ELISA and confirmation by
Western Blot).
2. Current CD4+ T-cell count at or above 100/mL for the past 6 months.
3. HIV-1 RNA (individual sites to choose Option A or Option B):
Option A:
 Less than 50 copies/mL for three months (Amplicor Monitor
* If no GCRC is available, these studies can be done in a clinic setting per local site discretion.
39

Ultrasensitive PCR or bDNA Quantiplex version 3.0). (Intermittent elevations to 1000 copies/mL, if not persistent on more than two sequential measures and followed by undetectable levels, are permitted.)
OR

Detectable viral load in patients who are unable to tolerate antiretroviral therapy due to exacerbation of their underlying liver disease, only if the HIV clinician on the team is confident that they can predict HIV suppression post-transplant. This assessment should be made based on a thorough review of the patient's antiretroviral history, HIV-1 RNA levels while on medications, adherence and any resistance tests that are available. If there is any significant doubt about the ability to suppress viral replication post-transplant, the patient should not be enrolled under this criterion.
Option B:
 Less than 50 copies/mL for three months (Amplicor Monitor
Ultrasensitive PCR or bDNA Quantiplex version 3.0). (Intermittent elevations to 1000 copies/mL, if not persistent on more than two sequential measures and followed by undetectable levels, are permitted.)

Exceptions to this criterion may be allowed at the discretion of the local research team (e.g., an otherwise excellent transplant candidate in whom antiretroviral drugs cannot currently be tolerated because of liver disease) only if the HIV clinician on the team is confident that they can predict HIV suppression post-transplant. This assessment should be made based on a thorough review of the patient's antiretroviral history, HIV-1 RNA levels while on medications, adherence and any resistance tests that are available. If there is any significant doubt about the ability to suppress viral replication posttransplant, the patient should not be enrolled under this criterion.
4. Meet standard listing criteria for placement on transplant waiting list.
5. Able to provide informed consent. In the case of a minor, parental or legally responsible person will be asked to provide informed consent.
6. If currently using antiretrovirals, must be on a stable HAART regimen for at least 3 months prior to entry. Alternatively, must be able to maintain a persistently undetectable HIV-1 RNA level (<50 copies/mL) without the use of antiretroviral agents. See inclusion criterion #3 for exceptions.
7. Willing to use PCP prophylaxis, herpes virus and fungal prophylaxis as indicated.
8.
If the patient also has HBV or HCV infection, he/she must be willing to undergo frequent monitoring, including liver biopsies and treatment as
40

recommended by the study clinicians. Patients with bleeding disorders will require clotting factor replacement prior to any invasive procedure under the care of a hematologist familiar with bleeding disorders.
9.
The patient and his/her physician must be willing to submit laboratory studies within 7 days of draw and to notify the transplant team/study coordinator prior to any change in medication.
10.
Female subjects of child-bearing age must have a negative serum beta-
HCG pregnancy test within 14 days of screening. All subjects must practice barrier contraception.
11.
Karnofsky performance status > 70.
12.
Not suffering from significant wasting: o BMI > 18.5 kg/m 2 , calculated in conformance with the protocol contained in Appendix o Not more than 5-percent weight loss in the preceding 3 months, which can be based on self-reported weight history.
Exclusion Criteria
1.
Any history of any AIDS-defining opportunistic infection or neoplasm except drug-susceptible Candida esophagitis.
2.
History of disease caused by aspergillus or aspergillus colonization.
3.
History of pulmonary or extrapulmonary tuberculosis.
4.
History of pulmonary coccidiodiomycosis.
5.
History of resistant fungal infection (krusseii, glabrata, parapsilosis).
6.
History of documented influenza or RSV in the past 30 days.
7.
History of any neoplasm except in situ anogenital carcinoma, adequately treated basal or squamous cell carcinoma of the skin, solid tumors treated with curative therapy and disease free for more than 5 years.
8.
Inability or unwillingness to comply with immunosuppression protocol, ARV therapy and/or HBV and HCV monitoring and therapy if indicated.
9.
Substance use per local site policy.
10.
Advanced cardiac or pulmonary disease per local site policy.
11.
Documented anatomic abnormalities precluding transplantation.
12.
Pregnancy.
13.
Concomitant conditions that, in the judgment of the investigators, would preclude transplantation or immunosuppression.
14.
Use of IL-2 or GM-CSF in the prior six months.
41

Interventions
Immunosuppression Protocol
Immunosuppressant doses will be altered to obtain levels standard for liver transplants. The immunosuppressive regimens will be guided by transplant physicians and surgeons with expertise in the immunosuppressive protocols.
Modification of dosages and drugs will be made for toxicity as per usual protocols at each site. In the case of HIV disease progression, immunosuppressive doses may be reduced to prevent clinical decline. The transplant team/study coordinator must be notified of any change in immunosuppressive dosing because there may be interactions with antiretroviral drug dosing.
Rejection Treatment Protocol
A biopsy should be performed in all cases of suspected rejection, unless the managing physicians believe this is unsafe. However, therapy may be initiated prior to the results of the biopsy if clinically indicated. Treatment of rejection episodes will be according to local site practices and may include sirolimus. In all cases of suspected rejection, OKT3 should be avoided .
Prophylaxis (note overlap and differences in HIV and transplant-specific prophylaxis)
HIV-Related Prophylaxis:
Toxoplasmosis
Indicated for Toxo IgG-positive subjects with CD4+ T-cell count <
100.
Preferred: Bactrim DS 1 tab qd or Bactrim SS 1 tab qd.
Alternatives:
 Dapsone 100 mg daily + pyrimethamine 50 mg weekly + leucovorin 25 mg weekly, or

Atovaquone 1500 mg qd with or without pyrimethamine 25 mg qd + leucovorin 10 mg qd.
Mycobacterium Avium Complex
Indicated when CD4+ T-cell count < 50.
Azithromycin 1200 mg weekly is preferred. If unable to tolerate, consider Clarithromycin 500 mg bid, although drug interactions with immunosuppressive agents must be considered. If unable to tolerate a macrolide, consider Rifabutin 300 mg qd. Rifabutin can be administered at one-half the usual daily dose (i.e., reduce from 300 mg to 150 mg qd) with nelfinavir, indinavir and amprenavir.
Rifabutin should not be used with the protease inhibitor hard-gel saquinavir or the nonnucleoside reverse transcriptase inhibitor delavirdine. Information is lacking regarding co-administration of
42

rifabutin with soft-gel saquinavir or nevirapine.
Transplant-Related Prophylaxis:
Cytomegalovirus, Herpes Simplex Virus
Treatment will vary based on donor and recipient CMV antibody status.

If CMV negative recipient/negative donor, Acyclovir 400 mg bid x 1 year.
 If CMV negative or positive recipient/positive donor,
Gancyclovir 5 mg/kg IV qd while hospitalized then 1 gram
PO tid x 3 months. o If CD4+ > 100, change to Acyclovir 400 mg bid x
9 months. o If CD4+ < 100, continue Gancyclovir 1 gram PO tid.
 If CMV positive recipient/negative donor, Gancyclovir 5 mg/kg IV qd while hospitalized then change to Acyclovir
400 mg bid x 9 months. o If CD4+ < 100, change to Gancyclovir 1 gram PO tid.
Alternate option is no treatment while hospitalized and Acyclovir 400 mg bid x 1 year with close monitoring for CMV with PCR or antigenemia testing (per local site practices).
Epstein Barr Virus
Indicated for EBV negative recipient/positive donor.
Gancyclovir 5 mg/kg IV qd while hospitalized then change to
Gancyclovir 1 gram PO tid x 1 year.
HIV- and Transplant-Related Prophylaxis:
Pneumocystis Carinii Pneumonia
Indicated in all patients for life.
Preferred: Bactrim 1 double strength tablet (160 mg trimethoprim/800 mg sulfamethoxazole) daily or Bactrim 1 single strength tablet (80 mg trimethoprim/400 mg sulfamethoxazole) daily.
Alternatives: Bactrim DS 1 tab tiw or Dapsone 50 mg bid or
Dapsone 100 mg qd (Dapsone contraindicated if G6PD deficient).
43

If Bactrim and Dapsone allergic, consider Atovaquone 1500 mg daily or Aerosolized Pentamidine 300 mg via Respirgard II nebulizer monthly.
Strategies for managing mild reactions to Bactrim include discontinuation of the drug and resuming it at a lower dose or rechallenging with gradual dose escalation. Bactrim suspension for dose escalation (8 mg trimethoprim/40 mg sulfamethoxazole) 1 cc qd x 3d, 2cc qd x 3d, 5 cc qd x 3d, 1 single strength qd.
Vaccinations:
Vaccinations Prior To Transplant
Pneumovax, Hepatitis A & B (if not immune), Influenza.
Patients should NOT be vaccinated against varicella ; however patients exposed who are IgG(-) should receive varicella-zoster immune globulin
(VZIG) 5 vials (1.25 mL each) IM administered 96 hours after exposure, ideally within 48 hours .
PPD Testing and TB Prophylaxis
PPD testing will be performed by the primary care provider at screening and every 6 months.
Prophylaxis is indicated for TST reaction ≥ 5 mm or previous positive TST reaction without treatment or contact with a person with active tuberculosis.
Preferred:
 INH 300 mg qd + pyridoxine 50 mg qd x 9 months or

INH 900 mg + pyridoxine 100 mg biw x 9 months or

Rifampin 600 mg + pyrazinamide 20 mg/kg x 2 months
Alternatives:
 Rifabutin 300 mg qd + pyrazinamide 20 mg/kg x 2 months or
 Rifampin 600 mg qd x 4 months
Rifampin should not be administered with protease inhibitors or nonnucleoside reverse transcriptase inhibitors. Rifabutin can be administered at one-half the usual daily dose (i.e., reduce from 300 mg to 150 mg qd) with nelfinavir, indinavir and amprenavir. Rifabutin should not be used with the protease inhibitor hard-gel saquinavir or the nonnucleoside reverse transcriptase inhibitor delavirdine.
44

To avoid confusion, immunosuppressive medications should always be checked with the surgeon performing the surgery.
IA. Tacrolimus (Prograf, FK506)/Corticosteroids/Cellcept (1-1.5g PO bid)
0.1mg/kg NG/PO BID (based on renal function)
General tacrolimus starting dose: 1mg NG/PO BID
Intravenous tacrolimus is almost never used and must be approved by attending physician.
Maintenance dosage:

4 weeks:
4-12 weeks:
Trough levels
10-15 ng/ml

10 ng/ml
> 12 weeks: 5-10 ng/ml
Or:
IB. Cyclosporine (Neoral, CyA)/Corticosteroids/CellCept (1-1.5 gms PO bid)
5-10mg/kg NG/PO BID (based on renal function)
General cyclosporine starting dose: 1-2 mg/kg PO BID
Maintenance dosage: Trough levels
days 0-7: weeks 2-4: weeks 5-8:
weeks 9-52:
> 1 year:
300-400 ng/ml
250-350 ng/ml
200-300 ng/ml
150-250 ng/ml
100-200 ng/ml
II.
Steroids
Length of therapy varies depending on diagnosis. See tapers.
Solumedrol (IV),Prednisone (PO):
Steroids will be tapered according to charts below. The goal is to reduce prednisone as soon as possible so that patients will be off prednisone prior to 6 months. Patients with viral hepatitis will be discontinued sooner to reduce threat of recurrence of disease.
45

If the patient experiences an episode of rejection after 3 months, or more than 1 rejection in the first 3 months, the prednisone dose will not be tapered off, but will remain 5mg until it is determined that the risks of steroids outweigh the benefits.
Steroid-induced hyperglycemia is usually treated with an insulin sliding scale.
For patients with persistent problems with hyperglycemia, oral hypoglycemic agents (glyburide) or scheduled insulin doses are used. Be very careful: as steroids are tapered, patients will need less of their hypoglycemia agents.
Stress Coverage: Stress steroids are generally not required after liver transplant.
But they may be required in special cases.
Hydrocortisone 100mg IV q 8h until stress resolves, then:
50mg IV q 8h x 1 day
50mg IV q 12h x 1 day then return to normal steroid taper
Steroid taper after Liver Transplant
DAY
0 (INTRA-OP)
POD #1
POD #2
POD #3
POD #4
POD #5
POD #6 x one week
One week
One week
One week
One week
One week
STEROIDS (ADULTS)
1 gm intra-op
500mg 6 hours post-op
200 mg IV QD
160 mg IV QD
120 mg IV QD
80 mg IV QD
40 mg PO QD
20 mg PO QD
15 mg PO QD
12.5 mg PO QD
10 mg PO QD
7.5 mg PO QD
5 mg PO QD
Treatment of rejection with steroids
-Solumedrol 1g iv qd x 2 days then recycle prednisone taper. Start recycle on POD 2 on chart.
-If on Neoral, switch to prograf. If off cellcept, restart cellcept
-NOTE: patients with hepatitis C should not receive solumedrol bolus unless biopsy result of rejection has been confirmed and immunosuppression has been optimized
-If patient has resistant rejection, consider Thymoglobulin or OKT3 therapy
(see below)
46

III. Mycophenolate mofetil (Cellcept) (Note: patients need to be on a proton pump inhibitor.)
1. Pre-operative: none
2. Post-operative: 25mg/kg NG/PO q 12h (weight < 40 kg)
1.5g NG/PO q 12h (weight

40 kg)
3. 6 months: discontinue in viral hepatitis
4. 12 months: discontinue if not autoimmune
Note: Patients with a pre-transplant diagnosis of autoimmune hepatitis will remain on Cellcept 500mg PO BID indefinitely.
Additional Immunosuppression Protocols
I. Renal sparing protocol (excludes high-risk patients: patients with PSC, autoimmune disease, retransplants): MMF + steroids + delayed
Tacrolimus/Cyclosporine
Eligibility:
1. AHF patients in COMA III/IV
2. Selected patients with pre-operative renal dysfunction (serum creatinine

1.6 mg/dl +/- HD)
II. Steroid resistant rejection
First-line monoclonal antibody: OKT3 (5mg for adults, 2.5mg for children under 40kg) IVP. Maximum length of therapy is 14 days. Premedicate patient (see medication section).
First-line polyclonal antibody: Thymoglobulin 1.5mg/kg/day for 7-14 days. Infuse over 4-6 hours. Patient must be premedicated (see medication section).
III. Calcineurin inhibitor intolerance
Rapamune (Sirolimus) alone or with low dose calcineurin inhibitors for patients with renal insufficiency or those who do not tolerate calcineurin inhibitors. This drug cannot be prescribed without the attending’s permission.
IV. Cellcept intolerance
Patients unable to take Cellcept may be prescribed Imuran (Azathioprine) at
50mg to 150mg OD. Monitor amylase and lipase to rule out pancreatitis.
47

2 weeks
1 mo 6 weeks
2 mos 10 weeks
3 mos 4 mos
Meds
FK506
Level keep FK level between 10-15
Cyclo Level keep cyclo level between 250-350
Labs CMV antigen total cholesterol,
HDL,LDL.triglyceri
des
HepC-PCR, HCV genotype (if not done)
AFP
Tests
Consult bone-density thoracic & lumbar spine
Pred 10
DC
ASA
10
10
Pred
7.5
10 10
Pred 5
DC
Zovira x
5-10
Pred
2.5
5-10
250-
350
Cmv antigen
250-
350
Cmv antigen
200-
300
Cmv antigen
200-
300
150-
250
Cmv antigen
Cmv antigen total cholest erol,
LDL,
HDL, triglyce rides
150-
250
Social
Work
5 mos 6 mos
Pred
2.5
QOD
5-10
150-
250
Dc Pred
DC Nystatin
5-10
150-250 total cholesterol,
LDL,HDL, triglycerides
AFP (if
HCC) consider vaccination
9 mos 1 year
D/C Cellcept ( if not autoimmune)
5-10 5
150-250 100-200 total cholesterol,
LDL,HDL, triglycerides
AFP (if HCC)
Mammo PAP
Derm consult
PPD bone-density thoracic
& lumbar spine
48

Mechanism of action: Azathioprine is converted to 6-mercaptopurine and acts as an antimetabolite, blocking mRNA and DNA synthesis.
Dosing:
A. Begin at 1 mg/kg/day IV.
B. When patient can take PO meds, change to ~ 2 mg/kg/day as a single bedtime dose.
Dose should be rounded off to the nearest 25mg increment (azathioprine comes as a 50mg scored tablet. General guidelines for dosage adjustment:
WBC < 3: cut dose in half
WBC < 2.5: hold dose
C. Goal is to be at ~ 2 mg/kg/day in 1-2 months.
D. Most common side effect is leukopenia.
E. Allopurinol (Zyloprim) blocks the metabolism of AZA and increases its toxicity.
Therefore, do not use allopurinol in these patients.
SIDE EFFECTS: bone-marrow suppression (dose-related) leukopenia macrocytic anemia pancytopenia thrombocytopenia alopecia arthralgia retinopathy
Raynaud’s disease pulmonary edema cough dyspnea
N/V/A/D
Hepatotoxicity: within 6 months of transplant veno-occlusive disease: rare, occurs with chronic tx 1-2 years serum sickness hypotension hypersensitivity fever rigors arthralgias, myalgia generalized erythematous, maculopapular rash
49

All new transplant patients will be started on Neoral® brand of cyclosporine if this is to be the primary immunosuppressant identified at the time of transplant. The chart order must be written as “Neoral.” Patients who are readmitted to the hospital may be on
Neoral®, Sandimmune®, Gengraf® or another brand of cyclosporine, USP-modified. It will be important to find out from patients which cyclosporine preparation they are taking and write the orders accordingly. Do not just write cyclosporine, CSA or CYA for the order--this does not adequately specify which preparation the patient is taking.
Sandimmune® and Neoral and the modified or microemulsion form of cyclosporine are
not bioequivalent!
Mechanism of action:
Blocks IL-2, IL3, gamma-interferon production and lymphocyte proliferation
Dosing:
Neoral® doses should be started at 10-15 mg/kg po/ng bid when the patient is able to take oral medication. Based on toxicity, rejection status and cyclosporine levels, dosage adjustments are made in 25-100 mg increments. Neoral® is available as 25mg and
100mg capsules and 100 mg/ml solution.
Target cyclosporine trough levels during the first year post-liver transplant are 150-250 ng/ml. Greater than 1 year post-liver transplant the target range is 100-120 ng/ml.
Cyclosporine dosing and target trough levels are patient specific, so that patients with rejection problems may have their levels maintained higher than the usual target range, and patients with adverse reaction problems may have their levels maintained lower than the usual target range. Cyclosporine levels are measured using a whole-blood HPLC assay.
IV cyclosporine is rarely used in liver transplant patients. There is currently only one brand of IV cyclosporine (Sandimmune®), therefore it can be ordered simply as cyclosporine or CSA. If it is necessary to give IV cyclosporine to an adult patient based on instructions from the attending MD, it should be started at 1 mg/hour IV as a continuous infusion [alternative dosing: one-third the oral dosage as a continuous infusion over 24 hours.]
50

SIDE EFFECTS nephrotoxicity (increased SCr, BUN, K + ) hyperuricemia hypertension tremor (40 percent)
N/V/D/A nightmares hirsutism hyperlipidemia gynecomastia (3 percent)
CNS toxicity: occasional seizures
HA paraesthesia hyperaesthesia flushing confusion rare CNS toxicity anxiety flat affect depression hepatotoxicity (4 percent) first month, dose related bone-marrow suppression: rare leukopenia anemia thrombocytopenia
Cyclosporine-induced hypertension is usually treated with Amlodipine or
Nifedipine XL qd. For chronic hypertension treatments, scheduled calcium-channel blockers are usually the first step. Other antihypertensives used include beta blockers, hydralazine and clonidine. Ace inhibitors should be avoided due to hyperkalemia. Beta blockers should be avoided in patients with asthma or diabetes.
Cyclosporine-induced hypomagnesemia is treated with magnesium complex 300mg po tid to start and titrated to Mg ++ level and diarrhea.
Cyclosporine Drug Interactions
Drugs that decrease cyclosporine levels: phenobarbital rifampin phenytoin
Drugs that increase cyclosporine levels:
Azithromycin, erythromycin fluconazole, itraconazole, ketoconazole diltiazem, verapamil
51

Mechanism of action:
Blocks IL-2, IL3, gamma-interferon production and lymphocyte proliferation
Dosing:
Tacrolimus doses should be started at 0.075-0.15 mg/kg po/ng bid when the patient is able to take oral medications. Based on toxicity, rejection status and tacrolimus levels, dosage adjustments are made by 1mg increments. Tacrolimus is available as 1mg, 5mg, and 0.5mg capsules.
Target tacrolimus trough levels for liver transplant patients are 8-15 ng/ml.
Tacrolimus dosing and target trough levels are patient specific, such that patients with rejection problems may have their levels maintained higher than the usual target range, and patients with adverse-reaction problems may have their levels maintained lower than the usual target range. Tacrolimus levels are measured using a whole-blood IMX assay.
IV tacrolimus is rarely used in liver transplant patients. It should only be prescribed by the attending. If it is necessary to give IV tacrolimus based on instructions from the attending MD, it should be started at 0.05-0.06 mg/kg/day IV as continuous infusion.
SIDE EFFECTS: nephrotoxicity (increased Scr, BUN, K+) hyperuricemia hypertension tremor (40 percent)
N/V/D/A nightmares alopecia
CNS toxicity: occasional seizures hyperesthesia flushing confusion rash rare CNS toxicity anxiety flat affect depression bone marrow (rare) leukopenia anemia hyperlipidemia gynecomastia (rare) headache paraesthesia hypomagnesemia hyperglycemia
Stevens Johnson syndrome (rare) predisposition to infections pruritus predisposition to cancer
Tacrolimus-induced hypertension is usually treated with Amlodipine or Nifedipine.
Sometimes, nonsustained-release Nifedipine po or SL is tried first. For chronic treatment, switching to Nifedipine XL is appropriate. If additional antihypertensives are needed, using beta blockers, hydralazine or clonidine would be appropriate. Ace inhibitors should be avoided due to hyperkalemia in combination with tacrolimus. Beta blockers should be avoided in patients with asthma or diabetes.
Tacrolimus-induced hypomagnesemia is usually treated with magnesium complex
300mg po tid initially. Doses should be titrated based on Mg++ levels and toxicity
(diarrhea).
52

Tacrolimus Drug Interactions
Drugs that decrease tacrolimus levels: phenobarbital phenytoin rifampin
Drugs that increase tacrolimus levels: azithromycin fluconazole erythromycin diltiazem ketoconazole verapamil itraconazole
Mechanism of action:
Inhibits de novo purine synthesis thereby inhibiting the proliferation of lymphocytes
Dosing:
Adult dose: 1000-1500mg BID. Comes in 500mg and 250mg capsules. Oral solution can be prepared by pharmacy.
Pediatric dose: 20-25 mg/kg BID.
Mycophenolate mofetil can cause GI ulceration, therefore, peptic ulcer disease is a relative contraindication.
Due to the potential for GI ulceration, all adult patients on mycophenolate mofetil should be on Protonix 40mg po bid (or other proton pump inhibitor) for ulcer prophylaxis.
SIDE EFFECTS:
Gastrointestinal: nausea vomiting non-specific abdominal pain ulceration gastritis pancreatitis dizziness predisposition to cancer predisposition to infections
Bone Marrow: rash fever leukopenia pancytopenia weakness joint pain muscle cramps
53

Drug interactions:
Antacids (Maalox, Alternagel, Mylanta, etc.) decrease the absorption of mycophenolate mofetil and should not be used concomitantly.
Mechanism of action:
Macrolide antibiotic (structurally related to tacrolimus) that binds mTOR (mamalian target of rapamycin), resulting in inhibition of IL-2 driven lymphocyte proliferation. It is also believed to have antitumor effects.
Dosing:
Sirolimus has a long half-life (approximately 60 hours). To achieve therapeutic drug levels quickly, a loading dose can be given. The loading dose is usually 3x the maintenance dose. Maintenance doses are approximately 2-5mg/day. Typical loading doses are 5-10mg x 1, followed by the maintenance dose.
Cyclosporine can increase blood sirolimus levels when given together. It is recommended that sirolimus be given 4 hours after cyclosporine to minimize this interaction.
Sirolimus is available as a 1mg tablet, and a 1mg/ml oral solution.
SIDE EFFECTS:
Hypercholesterolemia, hypertriglyceridemia
Leukopenia, thrombocytopenia
Increased risk of hepatic artery thrombosis
Rash
Hypertension
Opportunistic infections
Oral ulceration
Monitoring:
Predisposition to cancer
Sirolimus levels can be monitored. Target blood levels are approximately 10ng/ml
(therapeutic range 3-15ng/ml). Sirolimus blood levels should be drawn as a trough level
(just before the dose). The blood levels are sent out to a reference laboratory, and it takes
3-5 days for the results to be reported in the lab system.
Drug Interactions:
Impaired wound healing
Anemia
Lymphocele formation
Headache
Interstitial pneumonitis
Sirolimus is metabolized in the gut and liver by cytochrome P450-3A4.
DRUGS THAT INCREASE SIROLIMUS LEVELS:
Azithromycin, clarithromycin, erythromycin
Fluconazole, ketoconazole, itraconazole, voriconazole
54

Diltiazem, verapamil
Nefazodone
Protease inhibitors: Indinavir, ritonavir
Grapefruits, grapefruit juice
Cyclosporine
DRUGS THAT DECREASE SIROLIMUS LEVELS:
Phenobarbital Carbamazepine
Rifampin
Phenytoin
Mechanism of action:
Inhibit IL-1 synthesis and have direct antiproliferative effects on lymphocytes
Dosing:
Methylprednisolone (solumedrol) is given IV, prednisone is given PO; they are essentially equivalent as far as dosing is concerned
Steroids are tapered according to the protocols outlined previously on page –
Manifestations of Adrenocortical Insufficiency and Excess:
Insufficiency: hyponatremia, hyperkalemia, dehydration, hypotension, muscle weakness, fatigue, skin pigmentation, loss of hair, low resistance to trauma/infection/stress, fevers, nausea/vomiting, hypoglycemia, depression, menstrual irregularity
Excess: Hypokalemia, edema, CHF, hypertension, muscle wasting, fatigue, hirsutism, acne, striae, skin atrophy, decrease in eos, masking of infection, decreased healing, gastritis, ulcers, impaired glucose tolerance, hyperglycemia, depression, euphoria, psychosis, impotence, amenorrhea, centripetal obesity, moon facies, buffalo hump, cataracts, osteoporosis.
Mechanisms of action:
Daclizumab and Basiliximab are humanized (90% human, 10% murine) IgG1 monoclonal antibodies that bind to and inhibit the IL-2 receptor.
Dosing:
Daclizumab: 1 mg/kg IV in 50ml NS over 15minutes. First dose is within 24 hours of the transplant procedure, then every 14 days for a total of 5 doses.
Basiliximab: 20mg IV at the time of transplant and 20mg IV on postoperative day 4
Adverse effects: Phlebitis
55


Use:
For treatment of acute hepatic, cardiac, renal, pancreas and bone-marrow transplant rejection episodes resistant to conventional treatment.
Mechanism of action:
OKT3 is a murine monoclonal antibody produced by inoculation of mice with hybridoma cells. The ascites is then collected from the mice and biochemically purified. The antibody reacts against 95 percent of peripheral T lymphocytes but does not react against
B lymphocytes, NK cells, granulocytes or monocytes. OKT3 acts by coating the circulating T lymphocytes, subjecting them to opsonization by the reticuloendothelial system. OKT3 modulates the T lymphocytes’ antigen-receptor CD3 complex, which results in the removal of all CD3 molecules from the cell surface so that the cell lacks the ability to function as a T lymphocyte.
Precautions/warnings:
1) Pulmonary edema: severe pulmonary edema has occurred in patients with fluid overload. Prior to initiation of OKT3, it is imperative that there be no clinical evidence of volume overload, uncontrolled hypertension or uncompensated heart failure. To minimize the risk of OKT3-induced pulmonary edema, the following must be observed:
*Chest X-ray must be obtained and cleared within 24 hours of first dose.
*Assessment of patient for signs and symptoms of volume overload.
2) First-dose effect: the first and/or second dose of OKT3 may be associated with flulike symptoms (fevers, rigors, headache). These symptoms may occur within 30 minutes to 6 hours and up to 24 hours after the first dose. To minimize symptoms, refer to the
“Pretreatment” guidelines.
3) Anaphylaxis:< 1 percent of patients may experience an anaphylactic reaction. Due to this risk, the following precautions must be adhered to:
*Children under the age of 5 must be admitted to the pediatric intensive care unit prior to the first and second dose.
*A physician or nurse practitioner must administer the first and second dose and observe the patient for at least 10 minutes after the injection.
4) The following medications must be at bedside: epinephrine (1:1000 dilution) hydrocortisone injection diphenhydramine injection
Note: the third and subsequent doses may be administered by a nurse if the patient has not had significant reactions to the first 2 doses and remains stable.
56

5) Infection: use of OKT3 may increase the patient’s susceptibility to infection. The following precautions should be carried out to minimize this risk:
*Cytovene (100 mg PO TID, adjust dose as necessary per renal function) should begin on day 1 of OKT3 and continue throughout OKT3 use.
*discontinue oral acyclovir
*dose reduction of concomitant immunosuppressant medications may be necessary. Dose adjustments will be determined by the liver transplant attending.
Adverse reactions:
> 10 percent: tachycardia, dizziness, trembling, shortness of breath nausea/vomiting
1 percent to 10 percent: headache, stiff neck, photophobia, pulmonary edema
1 percent: aseptic meningitis, seizures, chest pain/tightness, hyper-/hypotension, arthralgia, tremor, dyspnea, wheezing, anaphylactic reactions
Dosing:
Pediatric:
< 30kg: 2.5mg dose once daily for 7-14 days
> 30kg: 5mg dose once daily for 7-14 days
Adult:
5mg dose once daily for 7-14 days
Pre-treatment medications:
Pediatric:
*methylprednisolone (Solumedrol

): 5 mg/kg IVPB (infuse over 15 minutes), 4 to 6 hours prior to first and second dose and 1 hour prior to first and second dose
*diphenhydramine (Benadryl
*acetaminophen (Tylenol


): 2 mg/kg IV, 30 minutes prior to every dose
): 10 mg/kg PO, 30 minutes prior to every dose
Adult:
*methylprednisolone (Solumedrol

): 250 mg IVPB (infuse over 15 minutes), 1 hour prior to first and second dose
*diphenhydramine (Benadryl
*acetaminophen (Tylenol


): 50 mg IV, 30 minutes prior to every dose
): 650 mg PO, 30 minutes prior to every dose
Administration:
1) May be administered through any intravenous line (peripheral or CVP).
2) Administer IV push over 1 minute at a final concentration of 1 mg/mL
3) Filter each dose through a 0.22 micron filter (Millex GV) before administration. This may have already been done in the pharmacy when drawn into syringe from original ampul. Check with pharmacy.
Note: Patient’s temperature should not exceed 37.8C (100F) at time of administration
(notify physician).
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4) Preparation and infuson guidelines (when drawing up drug from original ampul).
*Prior to administration, parenteral drug products should be inspected visually for particulate matter and discoloration. Because Orthoclone OKT3 is a protein solution it may develop a few fine translucent particles which have been shown not to affect its potency.
*No bacteriostatic agent is present in this product--adherence to aseptic technique is advised.
*Prepare OKT-3 for injection by drawing solution into a syringe through a low proteinbinding 0.22 micron filter. Discard filter and attach a new needle for intravenous bolus injection.
* No data is available on compatibility of OKT-3 with other IV substances or additives.
Other medications should not be added or infused simultaneously through the same IV line. The IV line should be flushed with saline before and after infusion of OKT-3.
*Administer OKT-3 as intravenous bolus over 1 minute. Do not administer by intravenous infusion.
Monitoring:
Following administration, check vital signs every 30 minutes for 3 hours and then increasing to usual patient-care vital signs routine if patient remains stable. After the first and second dose, if the patient is tolerating the doses, vital signs may be checked every
30 minutes for 2 hours and then increasing to usual patient-care-unit vital-signs routine.
Uses:
Antithymocyte globulin is used for the treatment of acute rejection that is resistant to conventional (corticosteroids) treatment or to prevent acute rejection as part of an induction regimen in patients at high immunologic risk for rejection.
Mechanism of action:
Antithymocyte globulin is a polyclonal IgG antibody that is derived from rabbits
(Thymoglobulin) or horses (Atgam, rarely used in adults). The antibody binds to lymphocytes that express CD2, CD3, CD4, CD8, CD11a, CD18 and other markers, inactivates them and depletes them from the circulation.
Dosing and Administration:
Thymoglobulin is usually started at 1.5mg/kg/day (rounded off to nearest 25mg increment) for the first dose, then 1mg/kg/day thereafter. Preprinted orders are available
(see below) and should be written for on a daily basis. Check with the attending for the
Thymoglobulin dose, and the corticosteroid dose (premed).
Administration Orders:
May be administered either via central line or peripheral IV
58

Please check the box indicating central line or peripheral IV

Thymoglobulin ______mg IV via central line
Dilute in 250 cc of NS
Infuse over 4-6 hours
Premedicate:1/2 hour- 1 hour pre
Prednisone/ _______mg po/ solumedral ____mgIV
Aceteminophen 650 mg po
Diphenhydramine ______ mg po/IV

Thymoglobulin ______mg via peripheral infusion
Dilute in 500 cc of NS or 1/2NS
Add:
1000 units of heparin
20 mg of hydrocortisone
Infuse over 4-6 hours
Premedicate: ½-1 hour pre administration
Prednisone _______mg po//solumedral_______ mg IV
Aceteminophen 650 mg po
Diphenhydramine ____mg po/IV
Administer through a 22 micron filter
Assess IV site q 2 hours during infusion and q shift between infusions
Vital signs q ½ hour x 2 hours then q 4 hours

Diphenhydramine 25 mg po q 6 hours RTC x 48 hours
 Acetaminophen 650 mg po RTC q 6 hours x 48 hours

Cytovene _______mg po ____times a day See AOS
Adverse effects:
Flu-like symptoms: fever, chills, arthralgias, myalgias, headache, rigors
Bone marrow suppression: leukopenia, thrombocytopenia
Opportunistic infections
Predisposition for malignancies
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Used for prophylaxis against pneumocystis carinii.
Adult dose: 1 single-strength tablet 3 times a week (Mon., Wed., Fri.)
Pediatric dose: 2.5 mg/kg/dose TMP 3 times a week (Mon., Wed., Fri.)
SIDE EFFECTS
N/V agranulocytosis thrombocytopenia hemolytic anemia (esp. in G6PD deficiency) anemia (folate deficiency - only with large doses in patients already folate deficient) increased serum creatinine (TMP competes with creatinine for secretion) acute tubular necrosis (only in patients with preexisting renal damage) hypersensitivity reactions (can cause Stevens Johnson syndrome rarely)
Hemodialysis reduces TMP serum levels by approximately 40 percent in 8 hours and
SMX by 30 percent in 6 hours.
CSF penetration: concentrations of at least 50 percent of serum levels are obtained with
TMP and SMX.
Mechanism of action: TMP/SMX blocks the conversion of para-aminobenzoic acid to folate in bacterial, protozoal and, to a much lesser extent in mammalian enzyme systems.
Alternatives
Adults: Dapsone 100mg po qd
Pediatrics: Dapsone 1 mg/kg PO OD (available in 25mg and 100mg capsules). Inhaled
Pendamadine 4-8 mg/kg, 9 months if child is cooperative, otherwise use 4 mg/kg IV 9 2-
4 weeks.
Begin as soon as patient is taking oral medications.
Begin oral dosing as soon as patient taking po.
Adult dose: 800mg po QID. Continue for the first 3 months post-op.
Pediatric dose: 20 mg/kg/dose QID.
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Renal Dosing of Oral Acyclovir
Creatinine clearance > 25ml/min: 800mg PO QID
Creatinine clearance 10-25 ml/min: 800mg PO TID
Creatinine clearance < 10ml/min: 800mg PO OD
Hemodialysis: 800mg PO BID
EBV-mediated lymphoproliferative disorder or Herpes Zoster infection:
Doses should be adjusted based on creatinine clearance:
CrCl (ml/min) Dose (IV)
> 50
25-50
10-24
10 mg/kg q 8h
10 mg/kg q 12h or 6.7 mg/kg q 8h
10 mg/kg q 24h or 5 mg/kg q 12h
0-10 5 mg/kg q 24h
Hemodialysis reduces serum concentration by 50-60 percent, so daily dosage should be given after dialysis.
SIDE EFFECTS:
Nephrotoxicity: precipitation of acyclovir crystals in renal tubules if concentration exceeds 2.5 mg/ml at 37C or if the drug is given by bolus injection. Patients should be well hydrated, especially in the first 2 hours post dose.
CNS toxicity: tremors, confusion, hallucination, lethargy and agitation have been reported rarely.
Mechanism of action: acyclovir triphosphate interferes with virus DNA polymerase and inhibits cellular alpha-DNA polymerase. When incorporated, the DNA chain is terminated. Acyclovir is much less toxic to normal noninfected cells because: 1) less is taken up, 2) less is converted to the active form, and 3) cellular alpha-DNA polymerase is less sensitive to the effects of the active form.
Use only in CMV-negative adult patients or patients receiving OKT3 or
Thymoglobulin.
CMV Prophylaxis
Oral adult dose: Cytovene 1000mg PO TID (see page -- for renal function adjustments;
500mg capsules are commercially available)
Oral pediatrics dose: Cytovene 40 mg/kg/dose TID (capsules only)
CMV Treatment
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IV ganciclovir (DHPG) is used for the treatment of CMV infections. Full doses are given for the first 14 days. DHPG can be given to patients at home if there is no other reason for the patient to be in the hospital. Home DHPG is arranged through home care agencies, and is not dispensed by in-patient pharmacy.
Renal Dosing for Intravenous Ganciclovir :
Creatinine clearance > 70ml/min 5 mg/kg/dose BID
Creatinine clearance 50-69 ml/min: 2.5mg/kg/dose BID
Creatinine clearance 25-49 ml/min: 2.5 mg/kg/dose OD
Creatinine clearance < 25ml/min: 1.25mg/kg/dose OD
Hemodialysis: 1.25mg/kg/dose post-dialysis only
SIDE EFFECTS: neutropenia (30 percent of patients, reversible with discontinuation of drug) leukopenia (40 percent of patients) increased LFTs thrombocytopenia mental status changes phlebitis rash
GI symptoms azoospermia, mutagenesis and teratogenesis (reported in animals)
Fluconazole
Imidazole with activity against Candida albicans ; effective in preventing oral thrush, and for treating other infections caused by C. albicans.
NOT effective against other Candida species.
Prophylaxis dose: Fluconazole 100mg PO Qweek
Treatment dose: Fluconazole 100-400mg PO/IV QD (depending on infection)
Itraconazole
Imidazole with activity against Candida albicans and Aspergillus sp .
Available as an intravenous formulation, which should be reserved for patients who are
NPO and not in renal failure. Also available as capsules and liquid. The itraconazole liquid formulation is the preferred agent because it is better absorbed than the capsules.
Specify the liquid formulation when prescribing itraconazole.
Treatment doses: Itraconazole 200mg PO TID x3 days (loading doses), then
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Itraconazole 200mg PO BID
Voriconazole
Imidazole with activity against Candida sp.
and Aspergillus sp ., and is the preferred agent in the treatment of invasive Aspergillosis.
Well absorbed after oral administration.
Intravenous voriconazole should NOT be used in patients with renal dysfunction.
Voriconazole can cause transient visual disturbances.
Requires prior ID approval (ID Pharmacy pager 719-9421, ID fellow pager 719-9628).
Treatment doses: 6mg/kg IV Q12h x2 doses, then
4mg/kg IV Q12h or
200mg PO Q12h
Fluconazole, itraconazole and voriconazole are inhibitors of cytochrome P-4503A4, resulting in increased blood levels of cyclosporine, tacrolimus or sirolimus. The dose of these immunosuppressive drugs will need to be adjusted when antifungal therapy is initiated.
Caspofungin
New antifungal agent with activity against Aspergillus sp . and Candida sp.
Administered intravenously only.
Requires prior ID approval (ID Pharmacy pager 719-9421, ID fellow pager 719-9628).
Treatment doses: Caspofungin 70mg IV x1 (loading dose), then
50mg IV QD use 35mg IV QD in patients with liver dysfunction
Nystatin (Mycostatin)
Used for the prophylaxis against oral/esophageal candida (thrush). Patients are treated until prednisone dose is less than 10mg
Dose: 5cc swish and swallow q 4h
Infants: 1cc to each side of mouth QID
When the patient is able or desires, switch to clotrimazole troches. (Do not use in pediactrics.)
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Clotrimazole Troches (Mycelex Troches)
Used for the prophylaxis against and treatment of oral/esophageal candida (thrush)
Dose: Dissolve 10mg po qid
Not to be given to children < 3 years old
Amphotericin B (Fungizone)
Systemic fungal infections: Amphotericin is not the first line therapy for serious candidal or other fungal infections. It should be used only in cases of failure of other agents.
Adult dosing: 0.3-1 mg/kg IV qd or qod over 4-6 hours.
Pediatric dosing: 0.3-1 mg/kg IV qd or qod over 4-6 hours.
Test dose: 1 mg IV over 2 hours followed by 4 mg IV over 2-4 hours (total 5 mg test dose made up by pharmacy).
Pre-medications: acetaminophen 650 mg po/pr diphenhydramine 50 mg PO/IV hydrocortisone 25 mg IV
Demerol 12.5-25mg IV for rigors
Side-effects: chills, fevers, rigors renal dysfunction anaphylaxis hypotension hypokalemia, hypomagnesemia
Bladder irrigation: amphotericin B 50 mg/L sterile water/day administered via continuous bladder irrigation.
Liposomal Amphotericin B (Ambisome)
Antimicrobial spectrum same as fungizone. Liposomal formulation has less nephrotoxicity
Adult dosing: 3-5mg/kg IV qd over 1-2 hours (use same premeds as above)
64

Dose: Furosemide may either be given as intermittent bolus doses or by continuous infusion 1-10 mg/hour.
Adults: 5-10 mg/hour
Pediatrics: 1 mg/kg dose IV
2mg/kg dose PO
Commercially available solution: 10mg/ml
SIDE EFFECTS: hypovolemia hyponatremia hypokalemia hypocalcemia hypochloremia hypomagnesemia dizziness
fatigue confusion muscle cramps
A/N/V increased LFTs ototoxicity metabolic alkalosis
Most commonly used in pre-transplant patients for treatment of ascites. Often may be given concomitantly with furosemide in the treatment of severe ascites. Doses range from
50mg to 200mg daily. It is not necessary to dose more frequently than qd or bid because of the drug’s long half-life. DO NOT GIVE TO POST-TRANSPLANT PATIENTS
UNLESS INDICATED BY ATTENDING MD. It frequently interacts with the
Prograf or Neoral to cause significant hyperkalemia.
SIDE EFFECTS hyperkalemia hyperchloremic metabolic acidosis dehydration hyponatremia
A/N/V/D ulceration, abdominal cramps headache drowsiness lethargy ataxia mental confusion fever rash, urticaria (rare) gynecomastia decreased libido
Although acetazolamide has some diuretic effect, its primary use is as a treatment for mild metabolic alkalosis
65

Mechanism of action: Interferes with carbonic anhydrase and reduces the rate of renal bicarbonate regeneration.
Dose:
Adults: 250mg IV bid-qid
Pediactrics: 5mg/kg IV bid-qid
SIDE EFFECTS: metabolic acidosis paresthesia (often transient) anorexia, weight loss drowsiness malaise depression metallic taste hypokalemia renal calculi formation loss of libido dermatitis, myopia, agranulocytosis and aplastic anemia (rare)
Adult dose: 5mg-20mg daily
Pediatric dose: 0.1mg/kg/dose PO q 12h
Liquid preparation not commercially available.
Chlorothiazide (Diuril)
Intravenous thiazide type diuretic that is typically given with furosemide to increase diuresis.
Pediatric dose: 2mg/kg/dose intravenously (up to 4mg/kg/day)
Adult dose: 250-500mg intravenouly (up to 1000mg/day)
Fresh Frozen Plasma (FFP)
50-100 cc/hour, depending on prothrombin time. Rapid correction of INR requires 10-15
66

cc/kg.
Human Serum Albumin
25 percent albumin given for large-volume paracentesis 50 cc/L ascites removed.
Dopamine
2-5 mcg/kg/min used to increase renal blood flow.
10-15 mcg/kg/min used to maintain blood pressure.
Recombinant factor VIIa (Novo-7)
1) Fulminant hepatic failure a.
With renal insufficiency i.
NOT on CVVHD ii.
IF on CVVHD: With FFP therapy, INR still too high to perform procedures, e.g. ICP monitor b.
In patients with active bleeding whose coagulopathy is not adequately corrected with FFP c.
Single dose to expedite normalization of INR after commencing FFP in patients with INR >4.0 pre-procedure or to achieve hemostasis d.
Pre procedure – e.g. central venous catheters, intracranial pressure monitors if FFP is contraindicated or the patient does not respond to FFP e.
Single dose (1200mcg) given 15-30 min before planned procedure and
INR is checked 10 min after administration .
2) Chronic liver disease a.
With active bleeding and coagulopathy (INR>2.5) and need for rapid correction (time to thaw FFP prohibitive) b.
In anticipation of procedure (paracentesis, TIPS, central line) in setting of: i.
Significant coagulopathy (INR >2.5) unresponsive to FFP ii.
Renal insufficiency/acute renal failure iii.
Volume overload/pulmonary edema c.
Single dose (1200mcg) given to achieve hemostasis or 15-30 min before planned procedure, and check INR 10 min after administration
IV IG
Rarely IV IG 0.5 G/kg/day x 3 days is used for treatment of DHPG nonresponsive CMV infections.
DDAVP (desmopressin acetate)
Dosing:
0.3 mcg/kg IV over 15-30 minutes, administer 30 minutes prior to procedure.
67

Lamivudine (Epivir)
Nucleoside analogue (reverse transcriptase inhibitor) used in combination with HBIg in the treatment of hepatitis B after liver transplantation, or alone in recipients of hepatitis B core antibody positive organs (see hepatitis B treatment protocol)
Dose:
Adults: 100mg po qd (adjust for renal dysfunction)
Children: 4mg/kg daily; max 150mg daily (adjust for renal dysfunction)
Available in 150mg tablets or 10mg/ml liquid
Ribavirin (Capegus)
Used in the treatment of hepatitis C in combination with interferon alpha (see hepatitis C treatment protocol)
Mechanism of action unknown
Adult dose:
200-600mg PO bid
Contraindicated in renal insufficiency (causes severe hemolytic anemia)
Peginterferon alpha 2a (Pegasys)
Used in the treatment of hepatitis C alone or in combination with ribavirin (see hepatitis
C treatment protocol)
Inhibits viral replication and has a variety of immunomodulatory effects
Adult dose:
180micrograms SQ qwk
Side effects: depression, headache, fatigue, fevers, myalgias, neutropenia, thrombocytopenia, retinal hemorrhage/thrombosis, ? precipitation of graft rejection.
68

69

70

There is only one phase to the pediatric liver evaluation and it is generally completed in one clinic visit or during one admission. Most pediatric patients are evaluated on an outpatient basis. If patients are admitted for an evaluation, they are housed on 6L; those in fulminant failure go directly to 6 PICU.
Blood work to be drawn is listed below. Please check with the pediatrics GI/LTx attending if any optional blood work should be included. If the child is less than 10 kg, the blood work should be done over two days. If you are drawing the blood yourself, please use the Minimum Volumes for Peds Blood Tests, based on weight
(table below)
Hematology
Chemistries
Other
Serologies
CBC with differential and platelet count, PT, PTT, fibrinogen electrolytes (NA, K, Cl, Co2, MG, PO4), BUN, creatinine, glucose, albumin, total protein, AST, ALT, T. bili, D. bili, alk phos, LDH, GGTP, ferritin, iron
(transferrin & saturation), ammonia, AFP, cholesterol (LDL, HDL), triglycerides, TSH, uric acid, T4 free index (including total T4 and uptake)
ABO with antibody screen, arterial blood gas, HCG (pregnancy for ageappropriate girls, U/A with micro hepatitis B surface antigen (HbsAg) hepatitis B core antibody (anti-HBc) hepatitis B surface antibody (anti-HBs) hepatitis B E antigen (HbeAg) if HbsAg+ hepatitis B E antibody (anti-Hbe) if HbsAg+ hepatitis C antibody (anti-HCV)
RPR, routine, varicella titer
Epstein-Barr (IgG & IgM)
CMV antibody status
HIV antibody status
Based on 6 cc ACD yellow-top tubes and 3 cc red-top tube without preservative.
Tissue typing:
Children weighing <10 kg: . . . . . . . . . . . . . . . . . . . . . . . . . . 1 yellow-top tube, completely full
1 red-top tube = 3 cc
Children weighing 10-30 kg. . . . . . . . . . . . . . . . . . . . . . . . . .5 yellow-top tubes, completely full
1 red-top tube = 3 cc
Children weighing 30-50 kg. . . . . . . . . . . . . . . . . . . . . . . . . .7 yellow-top tubes, completely full
1 red top-tube = 3 cc
*1 yellow-top tube holds 10 cc
CBC with diff
Platelets. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .if done together: 1 cc purple-top tube
Retic
ESR. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 purple-top tubes
CBC w/ESR. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2 purple-top tubes
SMA 6. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 microtainer (MT)
SMA 12. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 cc red/black tube
SMA 6 & 12. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .7 cc red/black tube
Ca. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1 MT + .6 cc
71

Mg. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 MT if done together
PO4. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 MT
Bili T/D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 MT
Glucose. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.5-1 cc gray-top tube or 1 MT
SMA 6 with glucose. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1 MT
PT/PTT. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 cc pedi blue-top tube
Blood C & S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 cc in bottle (use sterile needle)
(may use discard from central line)
T & C (<6 months) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1 cc green/orange
(>6 months) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 cc green/orange
Fungal C & S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1 cc yellow-top tube
ABG. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .0.3 cc heparinized syringe
NH3. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1 cc green
Liver panel. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .0.3 cc heparinized
Albumin. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .0.6 cc MT
ALT (GPT) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.6 cc MT
CSA. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 cc green
Name_______________________________________ Unit #_________________
Weight ________ ( ____%) DOB_______________ Height ______ ( ____%)
 Required Labs
ABO, Rh, RBC Ab screen
CBC with diff, platelets
BUN, creatinine
Na, K, Cl, CO2, Ca, Mg, PO4
PT, PTT, fibrinogen albumin, total protein, uric acid, iron glucose, LDL, HDL, choles, triglycerides
Alk phos
AST
ALT
GGT total & direct bili ammonia pregnancy for age-appropriate girls alphafetoprotein
U/A with micro and lytes
Procedures & Consults
Doppler US of hepatic vessels
CXR, PA, lateral surgeon hepatologist anesthesiologist
72
 Required Labs
HAV Ab
HCV Ab
HBsAg
HBsAb
HBcAb
CMV Ab titer
EBV Ab titer
HSV I & II
Varicella Ab titer toxoplasmosis
RPR
IgG, IgM, IgA
HIV Ab ceruloplasmin alpha 1 antitrypsin
Comments

social worker nurse coordinator nutritionist financial counselor
Child Life Services
<12 months echocardiogram per anesthesia other
Admitting
Visit the Medical Center
6LS, 14 L, PICU & playroom waiting room 6 & 14 Long living-related evaluation in progress
Notes:
_____________________________________________________________________________________________________________________
73

S URGICAL P ROPHYLAXIS
1.)Ceftriaxone 50-75mg/kg IV pre-operative and 24h post-operative
2.) Nystatin 5cc swish and swallow pre-operative, followed by Q4h or 5 times daily for fungal prophylaxis
P RESUMED P OSTOPERATIVE I NFECTION I NFECTION S ITE U NKNOWN
1.)Culture blood (x 2 specimens, including one peripheral stick) and urine (plus urine analysis), as well as endotracheal aspirate and surgical wound sites as appropriate
2.)Evaluate chest x-ray, line site(s), and surgical wound(s) as sources of infection
3.)Begin one of the following antimicrobials a.Timentin (Ticarcillin/Clavulanate) IV 200-300mg Ticarcillin/kg/day divided Q4-6H (adjust for renal function)
OR b.Zosyn (Pipercillin/Tazobactam) IV 200-300mg Pipercillin/kg/day divided
Q6-8H (adjust for renal function)
PLUS/MINUS c.Vancomycin IV 40 mg/kg/day divided Q6h (adjust for renal function

If no gram-positive infection is confirmed within 72h,
DISCONTINUE Vancomycin
4.)If the patient is receiving cholangitis prophylaxis with TMP/SMX (Septra
®
) discontinue while on Timentin/Zosyn.
5.)If cultures are POSITIVE : Refine antimicrobial therapy according to cultures to most narrow spectrum of activity
6.) If cultures are NEGATIVE and patient: a.
Clinically improves and no source of infection is identified, continue antimicrobials for 7-10 days. b.
Continues to be febrile and no source of infection is identified:
 Discontinue antimicrobials and reculture
OR

If patient is hemodynamically unstable and/or clinically worse:

Start Vancomycin (as above) plus Cefepime 100mg/kg/day divided Q12h (adjust for renal function). If there is no clinical improvement after 48h, discontinue antimicrobials and revert to
STEP 1
S EPTIC S HOCK
1.) Culture blood (x 2 specimens, including one peripheral stick) and urine (plus urine
analysis), as well as endotracheal aspirate and incision sites as appropriate
2.) Evaluate chest x-ray, line site(s), and surgical wound(s) as sources of infection
3.) Start Vancomycin plus either Meropenem OR Cefepime +/- Tobramycin until further results are available a.
Vancomycin IV 40mg/kg/day divided Q6-8h (adjust for renal function)
74


If there is clinical improvement within in 72h, but no gram-positive infection is confirmed, DISCONTINUE Vancomycin
PLUS b.
Meropenem IV 60 mg/kg/day divided Q8h (adjust for renal function)
OR c.
Cefepime IV 100 mg/kg/day divided 12h (adjust for renal function)
PLUS/MINUS d.
Tobramycin IV 7.5 mg/kg/day divided Q8h (adjust for renal function)
 Check baseline serum creatinine prior to initiating
4.) If cultures are POSITIVE : Refine antimicrobial therapy according to cultures to most narrow spectrum of activity
7.) If cultures are NEGATIVE and patient: a.
Clinically improves and no source of infection is identified, continue antimicrobials for 7-10 days. b.
Continues to be febrile and no source of infection is identified:
 Discontinue antimicrobials and reculture
OR
 Discontinue Meropenem/Cefepime/Tobramycin after 72h, and restart Ceftriaxone IV 50-75mg/kg/day divided Q12-24h or Timentin or
Zosyn
U RINE C ULTURES
1.) A urine analysis (UA) should be performed with each urine culture (UCX)
2.) Urine cultures POSITIVE for yeast generally should not be treated. Treatment
should be based on patient symptoms.
C ATHETER T IP C ULTURES
1.) Catheter tip cultures generally should NOT be performed unless they are being used to confirm the source of a bacteremia
75

EDIATRIC
MMUNOSUPPRESSIVE
HERAPY
ROTOCOLS
NDUCTION
HERAPY
STANDARD THERAPY
All pediatric liver transplant recipients:
Living-related liver transplant recipients:
First rejection therapy:
Second rejection steroid failure:
Long-term management:
Neoral 57 mg/kg bid with daily trough levels
(preparation: 100 mg/cc)
CellCept 20-25 mg/kg bid/(preparation: 250mg capsule) (preparation: 200 mg/ml suspension).
Maximum dose of CellCept: 1000mg BID.
Ranitidine 0.8 mg/kg IV q 8 hrs 3 mg/kg/day IV continuous infusion. All children on CellCept will receive ranitidine until they are talking POs, at which time they will be switched to Prevacid (20mg capsules available): <5 years 7.5mg PO qd; >5 years 15mg PO qd (suspension 15mg/5ml compounded by pharmacy).
Prednisone 2 mg/kg in divided doses with the every-3-day taper (see taper).
In addition to the above medications, all living donor liver transplant recipients require:Neoral 5 mg/kg bid 2 days before transplant, CellCept 20-25 mg/kg bid 1 day before transplant, Omeprazole 1 day before transplant (dose is based on weight: > 40 kg: 20 mg bid, 20-40 kg: 20 mg qd, <20 kg: 10 mg qd)
Mild rejection: Solumedrol 20 mg/kg IV for 3 consecutive days, followed with a prednisone taper starting at 2 mg/kg in divided doses PO. Moderate rejection: As above and may change to Prograf
(tacrolimus)
Mild rejection: May Change to Prograf (tacrolimus); if the child is on Prograf increase the dose. In addition:
Children experiencing rejection occurring within 1 month of their last rejection episode and treated with steroids may also be treated with 7-10 days of OKT3.
Children experiencing rejection occurring more than 1 month after their last rejection episode should be treated with steroids as above.
Moderate rejection: Change to Prograf; if on
Prograf, increase the dose.
If the child has not had a rejection episode, slowly
76

taper and discontinue Prednisone at 6 months. If the child has had rejection, do not attempt to taper
Prednisone until 1 year, and after they have been rejection free for at least 6 months. Chronic-rejection patients are usually managed with Prograf. Some patients may require long-term Cellcept or Cytoxan.
Prevacid will be continued for a year for all children on
CellCept. For children unable to take Prevacid, ranitidine will be started at 2 mg/kg bid PO.
Prednisone 2 mg/ml in divided doses with a rapid taper.
Post-Transplant Steroid Taper: a. Begin at 2 mg/kg/day in 4 divided doses
(use total dry body weight) b. Goal is 0.1 mg/kg/day at 2-3 months post transplant. If the child has had no rejections Prednisone is tapered and discontinued at 6 months. If the child had rejection
Prednisone is continued at low dose and discontinued if the child has no rejection for 6 months prior. c. Patients should be sent home with prescriptions for 1 mg and
5 mg prednisone tablets - if on liquid Prednisone 5mg/5cc.
Pediatric Patients 25-50 kg
Prednisone po/ prednisolone iv
Body Weight Dose Frequency Duration
(kg)
50
40
30
25
(mg)
25
20
15
12.5
10
10
12.5
10
17.5
15
12.5 qid qid qid qid qid tid bid bid qd qd qd
(days)
3
3
3
3
3
3
3
7
7
7
7
77

10
7.5
5 qd qd qd
7
7
Start the taper at 2 mg/kg/day and taper dose from there according to the above taper. For patients with body weights less than 50 kg, continue taper below 5 mg by decreasing dose by
1 mg weekly until 0.1 mg/kg/day.
Pediatric Patients 5-20 kg
Prednisone po/ prednisolone iv
Body Weight
(kg)
20
18
15
Dose
(mg)
10
9
7.5
12
10
8
5
6
5
4
2.5
2
3
Frequency qid qid qid qid qid qid bid bid qd
Duration
(days)
3
3
3
3
3
3
7
7
7
2.5
2 qd qd
Start the taper at 2 mg/kg/day and taper dose from there
7 according to the above taper. For weights less than 20 kg, continue taper below 2 mg by decreasing dose by 0.5 mg weekly until 0.1 mg/kg/day.
Pediatric nurse practitioners or the pharmacist typically write the pediatric tapers.
Stress Coverage hydrocortisone
1.5 mg/kg iv q8h stress resolves, then
1 mg/kg iv q8h x 1 day, then
1 mg/kg iv q 12h x 1 day then return to normal steroid taper
78

Tacrolimus (Prograf) a) Prograf dose will be adjusted for toxicity and/or rejection. In general, the 12-hour whole-blood trough level goal is between 4 and 6 ng/mL.(pt dependent) b) Prograf is available in 1mg and 5mg tablets or a suspension of 0.5 mg/cc.
Mycophenolate Mofetil (CellCept) a) For patients not able to swallow capsule or taking medication in a G tube:
1) Carefully hand twist and pull apart the capsules shells directly into 1-2 teaspoons of Hershey’s strawberry, chocolate syrup or water. Do not mix with anything else.
2) Mix completely. Draw up contents and administer orally immediately. Rinse syringe and mixing container with a small amount of additional syrup and administer orally to patient. Do not administer capsules dissolved in Hershey’s syrup NG. b) For NG or G tube administration: mix with water c) Suspension of 200 mg/cc is available at UCSF and pharmacies. Concentrations at outside pharmacies can vary.
OKT-3 (Muromonab, mouse monoclonal antibody)
All children receiving OKT-3 are admitted to the PICU before the first dose. a) < 10 kg 2.5 mg IV push qd x 7-10 days
> 10 kg 5 mg IV push qd x 7-10 days b) Increase dose depending on biopsy results and CD3 counts. c) Monitor daily WBC, differential and CD3 levels (OKT-3 and leu 4). The goal is to have the absolute CD3 positive lymphocytes less than 100. This value is calculated by multiplying the absolute lymphocyte count by the percent which are CD3 positive. CD3 levels must be drawn in a purple-top tube. d) Prior to retreatment which OKT-3, baseline anti-murine antibody levels should be checked prior to starting therapy. Anti-murine antibody levels must be drawn in a red-top tube.
79

titer
<1:100
1:100
>1:1000 dose full dose double dose no point in treating with OKT-3 e) Premedications: acetaminophen 10-15 mg/kg po or pr diphenhydramine 1 mg/kg IV or po methylprednisolone 15 mg/kg IV--1st dose only f) Pediatric patients are moved to the PICU for the first 1-2 OKT-3 doses.
Treatment of OKT-3 Side Effects:
Fever: acetaminophen 10-15 mg/kg po/pr
NTE 30 mg/kg/day
Rigors:
SOB:
meperidine 0.5-1 mg/kg/dose furosemide methylprednisolone inhaled bronchodilator may have to intubate patient hypotension: volume expansion anaphylaxis: epinephrine 0.01 mg/kg sc may repeat in 15 minutes max: 0.5 mg/dose
PROPHYLAXIS MEDICATIONS:
Trimethoprim/Sulfamethoxazole (Bactrim, Septra, Cotrim)
2.5 mg/kg/po qd M +Th
Commercially available suspension concentration:
(40 mg TMP + 200 mg SMX) /5 mL
80

Dapsone
1mg/kg po qd
10mg/cc available as 25 mg and 100 mg tablets
Inhaled pentamidine
4-8 mg/kg inhaled q month only if child is cooperative, otherwise 4 mg/kg iv q 2-4 weeks.
Ganciclovir (DHPG) (Cytovene - po formulation)/Acyclovir CMV prophylaxis
Ganciclovir is given for prophylaxis against CMV and during the treatment of rejection with ATG or OKTstarted on Ganciclovir and continue on it for 3-4 months. All other children will receive
Acyclovir. Ganciclovir and Acyclovir should never be given concomitantly. Ganciclovir is also used for treatment of CMV with the same dose as is used for prophylaxis. Full dose is given for the first 7 days followed by half dose for the next 7 days.
Ganciclovir dosing:
Dose
(mg/kg)
Frequency
(hours)
CrCl
(mL/min/1.73m²)
>70
50-69
25-49
<10-24
5
2.5
2.5
1.25
12
12
24
24 post-dialysis dialysis 1.25
CrCl = usual Scr for pts. age x 120 mL/min
(mL/min/1.73m²) actual Scr
Age
(years)
Usual Scr
(mg/dL)
0-1
2-4
5-9
10-15
16-18
0.3
0.4
0.5
0.6
0.7
81

*These guidelines are meant to be initial estimates for dosing, and are by no means actual patient creatinine clearances.
Acyclovir
Pediatric patients with normal renal function should receive Acyclovir 2000 mg/m²/day po divided qid NTE 800 mg po qid.
Varicella exposure: Varicella immune globulin 96 hr. of exposure. 12.5 u/kg IM (max
625 units) start Acyclovir and continue for 21 days.
EBV-mediated lymphoproliferative disease or Herpes Zoster:
Dose should be adjusted based on creatinine clearance:
CrCl
(mL/min/1.73 m²)
Dose (IV)
>50
25-50
10-24
10 mg/kg q 8h
10 mg/kg q 12h or 6.7 mg/kg q 8h
10 mg/kg q 24h or 5 mg/kg q 12h
0-9 5 mg/kg q 24h
Hemodialysis reduces serum concentrations by 50-60% daily dosage should be given after dialysis.
Herpes Simplex virus
Dose should be adjusted based on creatinine clearance:
CrCl
(mL/min/1.73 m²)
>50
Dose (IV)
5 mg/kg q 8h
25-50
10-24
0-9
5 mg/kg q 12h
5 mg/kg q 24h
2.5 mg/kg q 24h
Hemodialysis reduces serum concentration by 50-60% daily dosage should be given after dialysis.
Commercially available suspension concentration:
Acyclovir 200 mg/5mL
Nystatin (Mycostatin)
Children: 5cc swish and swallow q 4h or 5 X daily
Infants: 1cc to each side of mouth qid
82

Commercially available suspension concentration: nystatin 100,000 U/mL
When patient is able or desires, switch to clotrimazole troches. All children 0-12 months are prescribed oral nystatin while on prednisone to minimize the risk of thrush – even if they are taking other antifungal agents.
Clotrimazole Troches (Mycelex)
Dissolve orally 10 mg qid
** Not to be given to children <3 years old**
Liquid formulation not commercially available.
DIURETICS:
Furosemide (Lasix)
May be given as intermittent bolus, continuous infusion or orally.
Infusion: start at 2 mg/kg/day and titrate to response
IV Bolus: start at 1 mg/kg/dose and titrate to response
PO: repeat q 6-12 hours, max 6 mg/kg/dose start at 2 mg/kg/dose and titrate to response, repeat q 6-24 hours, max 6 mg/kg/dose
Commercially available solution concentration: furosemide 10 mg/mL
Metolazone (Zaroxolyn)
0.1 mg/kg/dose po/ng q 12h
Liquid formulation not commercially available
Spironolactone (Aldactone)
Most commonly used in the pre-transplant patients for treatment of ascites.
83

1-3.3 mg/kgk/24h divided bid-qid
Liquid formulation not commercially available
Acetazolamide (Diamox)
5 mg/kg iv bid-qid
OTHER MEDICATIONS:
Fresh Frozen Plasma (FFP)
1-2 cc/kg/hour depending on prothrombin time
Human Serum Albumin
25-percent albumin given for large-volume paracentesis 50 cc/L ascites removed. 25percent albumin is also used to increase oncotic pressure in hypovolemic patients with edema or ascites.
Dopamine
2-5 mcg/kg/min used to increase renal blood flow
10-15 mcg/kg/min used to maintain blood pressure
HCl drip (There is a protocol available in the PICU)
**Must be given through a central line
For the treatment of severe metabolic alkalosis
Hcl 0.1 N iv 1cc/kg/h
Volume restricted patients:
Hcl 0.2 N iv 0.5 cc/kg/h
IV IGG (Immune Globulin)
84

Rarely used for treatment of DHPG non-responsive CMV infections
0.5 G/kg/day x 3 days
Amphotericin B
Test dose:
Infants:
Children:
0.1 mg/kg/dose
0.5 mg/dose followed by the remainder of the first daily dose, if tolerated.
Treatment dose: 0.3-1 mg/kg iv qd or qod over 4-6 hours
Pre-Medications: acetaminophen 10-15 mg/kg po or pr diphenhydramine 1 mg/kg po or iv hydrocortisone 0.5 mg/kg iv
Bladder Irrigation: 50 mg/L sterile water
Desmopressing Acetate (DDAVP)
For prolonged bleeding in uremic patients
0.3 mcg/kg iv over 15-30 minutes, administer 30 minutes prior to procedure.
Vasopressin (Pitressin)
0.1 -0.3 U/min and titrate to response
0.004 U/kg/min NTE 0.008 U/kg/min
Lactulose (Cephulac)
Infants: 2.5-10 mL/24h divided tid-qid
Children: 40-90 mL/24h divided tid-qid
Titrate to 2-3 soft stools/day and improvement in mental status.
85

Commercially available solution concentration: lactulose syrup 10 grams/15 mL
Lactulose enema: lactulose 200 grams (300 mL) diluted with 700 mL of sterile water or
0.9 percent normal saline. Administer rectally via rectal balloon catheter and retain for
30-60 minutes every 4-6 hours.
Vitamin A (Aquasol A)
Vitamin A deficiency:
Infants and children <1 year old:
10,000 IU/kg/24h x 5 days, then 7500-15000 IU/24h x 10 days
Children 1-8 years old:
10,000 IU/kg/24h x 5 days, then 17,000-35,000 IU/24h x 10 days
Children >8 years old and adults:
10,000 IU/24h x 3 days, then 50,000 IU/24h x 14 days
Maintenance with cholestatic disease
10,000-15,000 IU/24h qd
Commercially available solution concentration:
Vitamin A 5000 U/0.1 mL
Vitamin D
Maintenance: ergocalciferol 400 IU/24h (Calciferol)
Commercially available solution concentration: ergocalciferol 8000 U/mL (200 U/drop)
Hepatic osteodystrophy
Infants: 25-hydroxycholecalciferol 5-7 mcg/kg/24h qd
Children and adults: 25-hydroxycholecalciferol 25-100 mcg/24h qd or qod
25-hydroxycholecalciferool is non-formulary
86

Vitamin E (Aquasol E)
Patients with persistent cholestasis: 50-400 IU/24h
Commercially available solution concentration: vitamin E 50 U/mL
Vitamin K phytonadione 1-2 mg/dose IV or 2-5 mg/24h PO
Liquid formulation not commercially available available as 5 mg or 10 mg tablets
Ursodiol (Actigall)
8-10 mg/kg/day divided bid
Liquid formulation not commercially available
Ranitidine (Zantac) children 2-18 years old
IV: 0.1-0.8 mg/kg/dose q 6-8 hours
PO: 1.25-2 mg/kg/dose q 12 hours
Commercially available solution concentration: ranitidine syrup 15 mg/mL
Nifedipine start at 0.15 mg/kg/dose po/sl tid prn and titrate to response
Liquid formulation not commercially available
If the contents of the 10 mg capsule are removed: 5mg = 0.18 mL
10mg=0.36 mL
Clonidine
5-25 mcg/kg/24 h po divided q 6h
87

Liquid formulation not commercially available
Clonidine patch available as 0.1 mg/day, 0.2 mg/day or 0.3 mg/day
*safety and efficacy of clonidine patches in children < 12 years have not been established* a) patch should be changed every 7 days b) can take 2-3 days to see hypotensive effect of patch - other measures should be used in the interim period. c)dose adjustments should be made on a weekly basis d) for dosages less than 0.1 mg/day, do not cut patch - contact Pharmacy for instructions e) effects may last for several days after removal of system
Hydralazine
0.73-3 mg/kg/24 h po divided q 6-12 h
Liquid formulation not commercially available
Magnesium Sulfate
30 mg/kg/day po divided qid and titrate to Mg++ level and diarrhea compounded solutions may vary in concentration, at UCSF, concentrations available are
1 mEq/mL or 4 mEq/mL
(125 mg = 1 mEq)
Aspirin
40 mg qd <20 kg 81 mg qd >20 kg
Liquid formulation not commercially available available as 81 mg chewable tablet and 325 mg regular tablet
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MALL
OWEL
IVER
RANSPLANTATION
ROTOCOLS
Indications (include all of the following):
1. End-stage liver disease associated with short-bowel syndrome
2. No age limitation
3. Size limitation, determined by technical consideration
4. Functional stomach and esophagus
Contraindications:
1. Irreversible disease in other organ systems
2. Malignancy
3. Uncontrolled infection
4. Inability to comply with medical regime
5. Inadequate stomach and/or esophagus (relative consideration)
6.HIV+ or HBsAG+
7.
Advanced cardiopulmonary disease
Name ___________________________________________________________________ DOB_________ _________
Unit # ________________________________ _________Height_____________( ____%) Weight__________(______%)

(check if study completed)
Required Labs
ABO, Rh, RBC Ab screen
CBC with diff, platelets
PT, PTT, fibrinogen
Na, K, Cl, CO2
AST, ALT, GGT, alk phos, T/D bili ammonia albumin, TP, uric acid
BUN, creatinine, Ca, Mg, PO4 cholesterol total, LDL, HDL, triglycerides, glucose toxoplasmosis
HAV, HBsAg, HBcAb, HBsAb, HCV viral antibody titers: CMV, EBV, HSV I
HIV antibody
RPR
Pregnancy for age appropriate girls
Required
Doppler US of hepatic vessels
CXR, PA & lateral
CT: abdominal & pelvic ERCP
Optional Labs
T-cell crossmatch for LRLTx reticulocyte count free T4 index, TSH ferritin, iron, TIBC ceruloplasmin copper alpha fetoprotein alpha-1 antitrypsin bleeding time vitamin B12, A, D, E folate fungal & bacterial throat, blood and rectal cultures
ASMA, AMA varicella titer measles titer
U/A with micro urine lytes
Optional
89

angiography with PV anatomy endoscopy tissue sample of small bowel
Required Consults surgeon pediatric GI social worker financial counselor
Anesthesia transplant nurse nutritionist
Visit the Medical Center: Admitting, 6LS (ped. surg)
PICU, playroom, waiting room, 6th floor liver Bx
ABGs
EKG
PFTs on room air
Optional Consults dental
Infectious Disease
Ophthamology
Cardiology
Pulmonary endocrine orthopedic play therapy
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