liver transplantation for urea cycle disorder - a case study
DESCRIPTION
Anesthesiology Conference. 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. Case Presentation (Liver transplantation). Ri 楊翔惟. Brief history. A 2y/o+ boy - PowerPoint PPT PresentationTRANSCRIPT
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~