liver transplantation for urea cycle disorder - a case study

Liver Transplantation for Urea Cycle Disorder - A Case Study

Sep. 26, 2003 Presented and Edited by Ri 吳智君 , 楊翔惟

Directed by Vs 詹光政 , CR 郭書麟

Anesthesiology Conference

Case Presentation (Liver transplantation)

Ri 楊翔惟

Brief history

A 2y/o+ boy Poor activity, poor appetite, short of breath,

unconsciousness and one episode of seizure with fever noted in Aug. 2002./08/20.

Initial ammonia=629, (<33 µmol./l) After enzyme study (discussed later), UCD

(urea cycle disorder) was impressed. Receive liver transplantation on Sep. 8, 2003.

Laboratory studies

9/5 9/8 9/14 Alb. 2.1 4.6 PT 11.6 18.7 15.7 PTT 27.3 45.4 30.4 BUN 2.1 3.7 10.9 Ammonia 53.8 53.8 30.8 T-bil. 8.1 1.1 1.1 ALT 41 405 210

Orthotopic Liver Transplantation

Preanhepatic phase

Hemodynamic instability hypovolemia, hemorrhage from venous

collaterals, citrate-induced hypocalcemia, hyperkalemia (rapid transfusion), hemolysis, diminished venous return (abd. retraction)

Aminocaproic acid (Amicar) help control hemorrhage secondary to fibrinolysis

Relation to UCD: May induce CNS infarction, Seizure attack,

worse the situation of hepatic encephalopathy.

Preanhepatic phase

Anhepatic phase Ischemic injury:

Oliguria: dopamine (2 to 5 mug/kg/min) Metabolic acidosis: sodium bicarbonate Hypercoagulation: heparin

Retraction near the right hemidiaphragm: Respiratory distress: PEEP

Relation to UCD: Coagulopathy may occur in UCS

(J. of Pediatrics No.138 Vol.1) Hyperammonemia triggers respiration

Anhepatic phase

Neohepatic phase

Elevate O2 consumption and CO2 elimination: Oxygen debt from graft tissue and GI systems

Hypotention, Arrhythmia, Thromboembolism

From ischemic metabolites (reperfusion injury), air embolism of reperfusion tissue

Avoid cardiovascular depressant anesthetics

Neohepatic phase

Discussion

Ri 吳智君

Enzymes: (1) carbamylphosphate synthetase (CPS) (2) ornithine transcarbamylase (OCT) (3) argininosucccinic acid synthetase (4) argininosuccinic acid lyase (5) arginase (6) ornithine 5-aminotransferase (7) N-acetylglutamate synthetase

Urea Cycle Disorder

Urea Cycle Disorder Enzyme deficiency→ hyperammonemia Clinical presentation:

(1)Nearly identical clinical presentations: despite the course with the exception of arginase, the last enzyme of the cycle

(2)Neonatal period: refusal to eat, vomiting, tachypnea, lethergy, quickly progress to a deep coma

(3)Infants and older children: vomiting and nurologic abnormalities: ataxia, mental confusion, agitation, irritability, combativeness

Urea Cycle Disorder

In Our Patient

Plasma: High glutamine, mild elevation of alanine

(secondary to hyperammonemia) Borderline low citrulline.

Tendam mass: low arginine level Urine GC-mass:

No orotic peak High hippuric acid.

Benzoate

hippuric acid

The Natural History of CPS (Carbamylphosphate synthetase) deficiency A wide variation in severity of symptoms and

the age presentation Most commonly symptoms occur during the

first few days: early-onset lethargy and seizures often are the first sign of abnormality

Coma and death may occur during these hyperammonic episodes

Current strategies for the management of neonatal urea cycle disorders Early supportive treatment Bulk ammonia removal—dialysis Pharmacologic management go to --Phenylacetate --Benzoate --Arginine supplement Long term correction --orthotopic liver transplantation --gene therapy Indications ~The journal of pediatrics vol138,no1,s30~38

Indications for Liver Transplantation for urea cycle disorder Who cannot follow the necessary dietary

restrictions Who has recurrent episodes of

hyperammonemia despite optimal medical management

Patients with CPS and OTC deficiency need early transplantation due to more difficult control of the natural history

Rigid dietary and pharmacotherapy regimen vs immunosuppression regimen

Contraindications to Liver Transplantation

Positive immunodeficiency virus culture

Severe irreversible neurologic injury

Indications for liver transplantation Urea cycle disorder, r/o CPS deficiency,

r/o N-acetylglutamate synthetase deficiencydifficult control of the natural course

Delayed growth of motor function, but no irreversible neurologic injury

Donor options

Donor allograft size reduction Living-donor liver transplantation Split-liver transplantation The mortality of potential recipients<20kg

await for OLT have reduced from 25%~50% to 2~5%

Outcome of Liver Transplantation

The overall patient survival rate

The goal of liver transplantation:(1) Preservation of neurologic function,(2) Rehabilitation,(3) A relatively normal quality of life

Outcome of Liver Transplantation

resulted in correction of hyperammonaemia in all patients.

The neurological outcome after transplantation correlated closely with the condition prior to transplantation.

relatively few problems in the long term related to the liver transplant itself.

The quality of life seems to be much improved~Journal of Inherited Metabolic Disease. 21 Suppl 1:112-8, 1998.

,Acta Gastroenterologica Belgica. 62(3):300-5, 1999 Jul-Sep.,

Comparison of outcome after pediatric liver transplantation for metabolic diseases and biliary atresia. Pediatric OLT: cholestatic liver disorders

ranking first, followed by hepatic based metabolic disorders

The mean infection, complication, intervention, and retransplantation rate was equal in both groups.

Mortality and morbidity are not different despite the better starting point for children with MD. ~European Journal of Pediatric Surgery. 11(1):28-35, 2001 Feb.

Donation from a donor with ornithine

transcarbamylase deficiency. The donor's OTC deficiency was diagnosed

retrospectively since the liver graft recipient developed cerebral edema postoperatively due to extremely hyperammonemia(3793 micromol/l), but was not accompanied by general liver dysfunction

In contrast to the fatal course of the liver graft recipient, the kidney, lung, and heart transplantations were successful.

~. Transplant International. 14(3):196-201, 2001 Jun.

Thank you~