Living Related Donor Liver Transplantation In A Patient With Alagille's Syndrome With Severe Pulmonary Stenosis
- *Corresponding Author:
- Pelin Karaaslan
Department of Anaesthesiology, Medipol University Hospital Istanbul, Turkey
E-mail: [email protected]
Received date: August 07, 2016; Accepted date: September 23, 2016; Published date: September 23, 2016
Alagille's syndrome (AGS) is a multisystem disorder affecting liver, heart, face and skeletal system. Approximately 25% of AGS patients may need liver transplantation (LT) in childhood. Unfortunately AGS patients have multisystem pathologies and they should be carefully evaluated before LT. Especially congenital heart defects in AGS patients may cause hemodynamic effects perioperatively in transplantation surgery. In this case report we aimed to discuss successful anesthetic management for living related donor liver transplantation (LRDLT) in a patient with Alagille's syndrome and severe pulmonary stenosis. Successful anesthetic management of a growth retarded 11-months old, 5110 grams infant for LT is a challenge especially with coexisting cardiac pathologies. Complete preoperative evaluation and careful perioperative monitoring of the patient resulted in stable circulation.
Alagille's syndrome (AGS) has characteristics including chronic cholestasis; typical peculiar facies; posterior embryotoxon; butterfly-like vertebral-arch defects; and cardiovascular malformations (Lee, 2015., Vajro, 2015). Approximately 21% to 31% of AGS patients develop end-stage liver disease leading to the need for transplantation (Cheng, 2004., Emerick, 1999., Hoffenberg, 1995., Kamath, 2010., Tzakis, 1993). End-stage liver disease causes low systemic vascular resistance and liver transplantation may cause cardiovascular instability and huge haemorrhage (Adachi, 1999). This may lead to perioperative problems especially in coexisting cardiovascular pathology patients. Cardiac abnormalities, most commonly pulmonary stenosis, are found in 85% to 100% of AGS patients (Cheng, 2004., Alagille, 1987). Congenital heart defects in AGS patients may cause hemodynamic effects perioperatively in transplantation surgery (Kamath, 2010). In this case report we aimed to discuss successful anaesthetic management for living related donor liver transplantation (LRDLT) in a patient with Alagille’s syndrome and pulmonary stenosis.
The patient was a 54 cm female infant of 11 months weighing 5100 grams with AGS, end-stage liver disease and severe pulmonary stenosis (PS). She was diagnosed with severe bilateral pulmonary stenosis by echocardiography soon after birth. Her echocardiography record also showed supravalvular mild aortic stenosis (maximum gradient was 30 mmHg), mild hypoplasia of descending aorta and atrial septal defect. The electrocardiogram (ECG) showed sinus tachycardia with right ventricular hypertrophy (RVH). She also had a cleft lip and palate. Although paediatric cardiology department reported high risk potential for transplantation, in order to correct cardiac pathologies first step of strategical approach was liver transplantation. Her mother was chosen as the donor. The patient had severe jaundice (total bilirubin=19.484 mg/dL), pruritis, coagulopathy (aPTT=34.8 sec) and hypercholesterolemia (total cholesterol=437.8 mg/dL) (Table 1). After ECG and pulse oximetry monitoring, anaesthesia was induced with ketamine 3 mg/kg, fentanyl 3 mcg/kg and maintained with sevoflurane 2% in a mixture of 50% O2 + air. Neuromuscular block was achieved with vecuronium. Central venous catheter via right internal jugular vein, arterial monitoring via left radial artery and pulse contour cardiac output (PICCO) monitoring via the right femoral artery were performed. Urine output and nasopharyngeal temperature were monitored. In order to prevent right to left shunt due to hypercapnia, ventilation and oxygenation were followed by end-tidal CO2 and arterial blood gas analysis. Dopamine was infused continuously with a dosage strategy depending on PICCO monitoring guidance. During operation, systolic arterial pressure was 80 mmHg to 140 mmHg, CVP was 7 mmHg to 10 mmHg and CI was 2.61 litter/min/m2 to 2.89 litter/min/m2.
|Preoperative||Anhepatic phase||Postoperative 5th day|
|Bilirubin, total (mg/dL)||19.484||10.63||2.9|
|Bilirubin, direct (mg/dL)||16.447||8.9||2.2|
|Cholesterol, total (mg/dL)||437.8||169.6|
|BUN: Blood urea nitrogen; AST: Aspartate aminotransferase; ALT:Alanine aminotransferase|
Table 1: Perioperative data of the patient
The inferior vena cava was partially clamped during liver transection and hepatic vein reconstruction. The lateral segment of her mother's liver was transplanted. At the time of reperfusion of portal vein, the systemic arterial pressure was protected in normal range by dosing dopamine infusion and volume loading with crystalloid fluids. No additional catecholamine infusion was needed. Total operation time was 6 hours 35 minutes, total anaesthetic duration was 7 hours 55 minutes, total infused volume was 250 mL, total albumin volume was 60 mL, total blood transfusion was approximately 150 mL (Htc: 22% to 31%) and fresh frozen plasma was 150 mL. Urıne output during anaesthesia was 440 mL. The postoperative course was uneventful. She was extubated 15 hours after surgery. Total bilirubin decreased to 10.63 mg/dL on the first day after operation. She was discharged from hospital on day 12 (Table 2).
|SVRI (dyne s/cm5)||1524||1731||2073|
|CI: Cardiac index; GEDI: Global end diastolic index; ELWI: Extravascular lung water
index; SVRI: Systemic vascular resistance index
Table 2: Haemodynamic variables during surgery
Alagille's syndrome is a multisystem disorder affecting liver, heart, face and skeletal system (Kamath, 2010). Approximately 25% of AGS patients may need liver transplantation (LT) in childhood (Emerick, 1999., Hoffenberg, 1995., Kamath, 2010). Most AGS cases that needed LT compromised the complications of cholestasis, severe hypercholesterolemia and osteodystrophy. Published series describe 1-year survival after LT ranging between 71% to 100%. Success rate of LT absolutely depends on the severity of the cardiac anomaly. Pre-transplantation cardiac evaluation should be performed perfectly. Besides possible intraoperative problems, it should be kept in mind that long-term use of anti-rejection therapy drugs may lead to nephrotoxicity, bone changes and atherosclerosis. There are studies reporting experiences in which PS and RVH did not cause intraoperative problems during LT (Ovaert, 2001., Ozçay, 2006). Inferior vena cava clamping may increase the fluid requirements resulting in acute heart failure (Kamath, 2010). Cardiovascular instability is usually observed both during caval clamping and reperfusion phases. We used partial clamping during both liver transection and hepatic vein reconstruction. Thus, there was no need to overload fluids or blood products. Another major problem for end-stage chronic liver disease patients is peripheral vasodilatation which may worsen after reperfusion phase (Kamath, 2010). After reperfusion, pulmonary vascular resistance may increase leading to poor graft reperfusion and graft dysfunction. In order to avoid this condition, throughout all the operation, we monitored the cardiac index, systemic vascular resistance and global end diastolic index.
Maintaining stable and normal body temperature is very important in transplantation patients because it is well known that hypothermia results in coagulopathy and thromboembolic complications (Cheng, 2004). Even though normal levels of clotting factors and normal clotting test results are provided, hypothermia may present with decreased platelet activity and inhibited enzymatic reactions of coagulation cascade. In our patient we provided normothermia throughout the operation by warming the transfused fluids and using blankets.
Unfortunately, AGS patients have multisystem pathologies and they should be carefully evaluated before LT. Unremitting cholestasis, resistant pruritis, extensive xanthomatosis, bone fractures and growth retardation are major indications for LT (Frongillo, 2015., Kasahara, 2003). In this patient LT was indicated due to jaundice with pruritis and growth retardation. Success rate of LT depends on a strict preoperative multidisciplinary planning and perioperative management. The paediatric cardiology team indicated that no preoperative treatment or correction was needed for this patient before LT. Intraoperative CVP around 10 mmHg and stable hemodynamic parameters were maintained via proper fluid resuscitation and vasopressor infusion. The patient was discharged from hospital on day 12 but long-term prognosis is uncertain due to effects of immunosupressive treatment on renal and vascular disease.
In conclusion, successful anaesthetic management of a growth retarded 11-months old, 5110 grams infant for LT is a challenge especially with coexisting cardiac pathologies. Complete preoperative evaluation and careful perioperative monitoring of the patient resulted in stable circulation.
Adachi, T., Murakawa, M., Uetsuki, N., Segawa, H. (1999). Living related donor liver transplantation in a patient with severe aortic stenosis. BJA 83, 488-490.
Alagille, D., Estrada, A., Hadchouel, M., Gautier, M., Odievre, M., Dommergues, J.P. (1987). Syndromic paucity of interlobular bile ducts (Alagille syndrome or arteriohepatic dysplasia): review of 80 cases. J Pediatr 110, 195-200.
Cheng, K.W., Huangm, J.J., Wang, C.H., Chen, C.L., Jawan, B. (2004). Anesthetic management of a patient with Alagille’s syndrome undergoing living donor liver transplantation without blood transfusion. Chang Gung Med J 27, 449-452.
Emerick, K.M., Rand, E.B., Goldmuntz, E., Krantz, I.D., Spinner, N.B., Piccoli, D.A. (1999). Features of Alagille syndrome in 92 patients: frequency and relation to prognosis. Hepatology 29, 822-829.
Frongillo, F., Bianco, G., Silvestrini, N., Lirosi, M.C., Sanchez, A.M., Nure, E., … Agnes, S. (2015). Acute liver failure in an adult, a rare complication of Alagille syndrome: case report and brief review. Transplant Proc 47, 2179-2181.
Hoffenberg, E.J., Narkewicz, M.R., Sondheimer, J.M., Smith, D.J., Silverman, A., Sokol, R.J. (1995). Outcome of syndromic paucity of interlobular bile ducts (Alagille syndrome) with onset of cholestasis in infancy. J Pediatr 127, 220-224.
Kamath, B.M., Schwarz, K.B., Hadzic, N. (2010). Alagille syndrome and liver transplantation. J Pediatr Gastroenterol Nutr 50, 11-15.
Kasahara, M., Kiuchi, T., Inomata, Y., Uryuhara, K., Sakamoto, S., Fujimoto, Y., … Tanaka, K. (2003). Living-related liver transplantation for Alagille syndrome. Transplantation 75, 2147-2150.
Lee, H.P., Kang, B., Choi, S.Y., Lee, S., Lee, S., Choe, Y.H. (2015). Outcome of Alagille syndrome patients who had previously received Kasai operation during infancy: a single center study. Pediatr Gastroenterol Hepatol Nutr 18, 175-179.
Ovaert, C., Germeau, C., Barrea, C., Moniotte, S., Obbergh, L.V., Sokal, E., Reding, R., … Sluysmans, T. (2001). Elevated right ventricular pressures are not a contraindication tol iver transplantation in Alagille syndrome. Transplantation 72, 345-347.
Ozçay, F., Varan, B., Tokel, K., Cetin, I., Dalgiç, A., Haberal, M. (2006) Severe peripheral pulmonary stenosis is not a contraindication to liver transplantation in Alagille syndrome. Pediatr Transplant 10, 108-111.
Tzakis, A.G., Reyes, J., Tepetes, K., Tzoracoleftherakis, V., Todo, S., Starzl, T.E. (1993). Liver transplantation for Alagille’s syndrome. Arch Surg 128, 337-339.
Vajro, P., Ferrante, L., Paolella, G. (2012). Alagille syndrome: an overview. Clin Res Hepatol Gastroenterol 36, 275-277.