Ann Thorac Surg 2006;81:697-700
© 2006 The Society of Thoracic Surgeons
Original article: Cardiovascular
Cardiac Surgery in Children With End-Stage Liver Disease Awaiting Liver Transplantation
Jonah N.K. Odim, MD, PhD
a
,
b
,
*
,
Jeffrey Wu, BS
a
,
b
,
Hillel Laks, MD
a
,
b
,
Anamika Banerji, MS
a
,
b
,
Stacey Drant, MD
a
,
b
a Division of Cardiothoracic Surgery, David Geffen School of Medicine at the University of California-Los Angeles (UCLA), Los Angeles, California
b Division of Pediatric Cardiology, David Geffen School of Medicine at the University of California-Los Angeles (UCLA), Los Angeles, California
Accepted for publication July 19, 2005.
* Address correspondence to Dr Odim, Division of Cardiothoracic Surgery, David Geffen School of Medicine at UCLA, Room 62-266B CHS, Box 951741, 10833 Le Conte Avenue, Los Angeles, CA 90095-1741 (Email: jodim{at}mednet.ucla.edu).
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Abstract
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BACKGROUND: Cardiac repair for congenital heart disease in children awaiting liver transplantation presents unique therapeutic challenges and dilemmas. We tested the hypothesis that operations in these children requiring cardiopulmonary bypass (CPB) were not associated with prohibitive morbidity and mortality.
METHODS: Over the last 10 years (1994–2004), five infants were identified in our database with end-stage liver disease and awaiting liver transplantation that required cardiac surgery. Primary end point for the study was mortality. Secondary end points included morbidity and time to liver transplantation. The new pediatric end-stage liver disease (PELD) model was used to score liver disease severity.
RESULTS: Three boys and two girls with mean age of 8.6 months (range, 1.5–21 months) and mean PELD of 18.0 (range, 10–29) required CPB for repair. The only early mortality in the series occurred after cardiac arrest during creation of a central shunt. The child expired two days later despite extracorporeal membrane oxygenation support. The patient had important myocardial hypertrophy. All other patients survived and underwent successful liver transplantation.
CONCLUSIONS: Children with significant congenital heart disease awaiting liver transplantation can undergo safe cardiac repair with judicious perioperative support thereby reducing the risks of subsequent liver transplantation.
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Introduction
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Liver disease and cardiac disease coexist in a number of childhood disorders. These associations include Alagille syndrome (AGS), wherein audible cardiac murmurs and structural intracardiac disease are present in 97% and 24% of patients, respectively [1], and biliary atresia, which is associated with heart defects in 15% of cases [2]. Pediatric patients with important congenital heart and end-stage liver disease (ESLD) pose a difficult therapeutic dilemma. While orthotopic liver transplantation is an option in AGS patients with comorbid cardiopulmonary impairment, the procedure is associated with higher mortality in patients with more severe cardiac disease [3–5]. Alternatively, little research has examined the safety of cardiopulmonary bypass (CPB) in pediatric patients with end-stage liver disease. To test the hypothesis that cardiac operations requiring CPB in children with ESLD were not associated with prohibitive morbidity and mortality, this retrospective study was conducted.
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Patients and Methods
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We searched the cardiac surgery database at UCLA for patients with significant liver dysfunction and congenital heart disease requiring cardiac surgery. Between 1994 and 2004, five infants were identified with ESLD awaiting liver transplantation that underwent cardiac repair with CPB. Their charts were reviewed and key preoperative, intraoperative, and postoperative variables noted. Liver disease severity was assessed by the pediatric end-stage liver disease (PELD) score calculated on the United Network Organ Sharing (UNOS) website [6] from the following formula [7]:
PELD score = 10 [0.480 loge total bilirubin mg/dL + 1.857 loge INR – 0.687 loge albumin g/dL + 0.436 (if patient <1) + 0.667 (if patient has growth failure <-2 standard deviation)] rounded to the nearest integer.
Pediatric end-stage liver disease is used by UNOS for liver organ allocation and takes into account the following five factors: patient's age at listing, serum albumin, international normalization ratio, total bilirubin, and growth failure. Higher PELD scores predict greater risk for mortality in children awaiting liver transplantation [7–9]. The widely known Child-Turcotte-Pugh classification for liver disease severity was not used because it was designed for adult patients with liver cirrhosis and portal hypertension and thus not applicable for pediatric populations [8, 9]. Our standard operative protocol and technique was followed including systemic heparinization prior to establishment of hypothermic CPB with ascending aortic and bicaval cannulation and maintenance of activated clotting time (ACT) at a level greater than 600 seconds. Blood was cooled to temperatures between 18°C and 30°C during the operation and hematocrit was maintained between 21% and 34%. Myocardial protection included cold blood cardioplegia followed by warm blood cardioplegia and warm blood reperfusion. Modified ultrafiltration was performed in 4 of 5 cases at the conclusion of cardiopulmonary bypass. Aprotonin was used in 3 of 5 cases. Heparin was reversed with protamine after repair and before decannulation. Hemostasis was supported with blood component infusions dictated by laboratory derangements.
The primary end point of the study was mortality. Mortality was defined as death during hospitalization after surgery (early) or within 30 days of hospital discharge (late). Secondary end points included morbidity within 30 days after surgery, postoperative transfusion requirements, time to liver transplantation, and status at last clinic visit.
This study was approved by the Institutional Review Board of the UCLA medical center on May 11, 2004. Individual consent was waived by the board.
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Results
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Three patients were male and two were female, with a mean age of 8.6 months (range, 1.5–21 months). Liver disease diagnoses included congenital hepatitis (n = 1), biliary atresia (n = 2), and Alagille syndrome (n = 2), all of which were confirmed by liver biopsy. The patients had a mean PELD score of 18 (range, 10–29). Diagnosis, preoperative characteristics, and liver function are summarized in Table 1.
A variety of cardiac operations were performed (Table 2). Four patients underwent CPB for repair of intracardiac congenital defects. The remaining palliative procedure was an initial off-pump creation of an aortopulmonary central shunt, which was later completed on CPB due to patient instability. Median CPB and aortic cross-clamp time was 122 minutes (range, 80–188 minutes) and 61 minutes (range, 0–94 minutes), respectively. Two patients underwent reinstitution of CPB after initial repair. In one patient, a residual subaortic ventricular septal defect (VSD) leak was detected upon separation from CPB requiring rerepair. Another child required creation of an adjustable atrial septal defect (ASD) after important branch pulmonary artery stenosis and high right ventricular pressure were unveiled after biventricular repair.
All four children placed on CPB for their intended biventricular repair survived the on-pump cardiac operations. Their mean preoperative PELD score was 17.3 (range, 10–29). Patients were extubated between 1 and 5 days after the operation. Chest tube drainage was not prodigious, as shown in Table 2.
The sole mortality in this series occurred in a child with VSD, PA, and multiple aorta-to-pulmonary collateral arteries that developed bradycardia and cardiac decompensation during an initial off-pump aortopulmonary shunt procedure. The patient had severe biventricular hypertrophy and a preoperative PELD score of 21. Despite perioperative extracorporeal membrane oxygenation support, aggressive transfusion of blood products, and postoperative surgical evacuation of mediastinal hematoma, the patient died of intracranial hemorrhage and cardiac arrest two days after the palliative shunt operation.
The mean PELD score of the four survivors immediately after cardiac operation was 16.8 (range, 13–21). Postoperative transfusion needs and support are recorded in Table 3. There were a few important morbidities. One patient suffered temporary atrioventricular block requiring temporary pacing. Another child had a residual subaortic VSD leak requiring reinitiation of CPB for elimination. This patient's postoperative course was complicated by a seizure disorder attributed to midazolam toxicity and benzyl alcohol. The seizures ceased after termination of the drug and administration of phenobarbital. One patient had important pulmonary hypertension secondary to peripheral pulmonary stenosis requiring reinitiation of CPB for creation of an adjustable ASD. This infant's postoperative course was complicated by a Staphylococcus aureus sternal wound infection, which required sternal debridement. All surviving children subsequently underwent uneventful orthotopic liver transplantation at mean time to liver transplantation of 4.1 months (range, 1–10 months) and are doing well at their last clinic visit.
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Comment
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The current literature scarcely focuses on pediatric patients with end-stage liver and congenital heart disease undergoing cardiac surgery. Only one other study, by Bacha and colleagues [10], describes the clinical outcomes of open-heart surgery in this population. These authors conclude, based on a similarly small series, that performing cardiac surgery with CPB on children with ESLD is safe despite findings of higher mortality and morbidity. Other reports of CPB in adult populations with advanced liver disease, note high postoperative morbidity and mortality [11, 12]. The experience suggests cardiac interventions using CPB are contraindicated in patients with cirrhotic liver disease [13, 14] or should be done on the beating heart, whenever possible, in patients with chronic liver disease [11]. This present study describes our experience with pediatric patients and demonstrates that CPB was employed safely to repair cardiac defects in children with ESLD. Our results further support the experience by Bacha and colleagues [10].
The lone mortality in this series occurred in a cyanotic infant with Alagille syndrome and ventricular septal defect, pulmonary atresia, and major aortopulmonary collateral arteries. This 8-month-old child had severe myocardial hypertrophy and death followed a postoperative intracranial hemorrhage; a well-recognized complication in pediatric patients with Alagille syndrome. Children with Alagille syndrome have an increased risk of bleeding from factors beyond simply ESLD-related coagulopathy and therefore need special consideration before undergoing CPB [1, 15]. Other factors, which may have contributed to postoperative death, include emergent conversion to cardiopulmonary bypass for palliative aortopulmonary shunting and perioperative extracorporeal membrane oxygenation support.
The remaining children experienced some complications and all successfully underwent timely orthotopic liver transplantation after biventricular repair. It is notable that three of these patients had relatively normal preoperative coagulative function despite end-stage liver disease. One child had significant ESLD-related coagulopathy (patient 1) and was given aprotonin perioperatively to help combat potential bleeding issues. Careful management and support of hemostatic derangements and the coagulation system in all infants with ESLD undergoing CPB cannot be overemphasized and certainly contributed to the good outcomes in this report. The use of aprotonin in select patients peri-operatively may be useful in this regard.
We conclude that CPB and biventricular repair of congenital heart defects may be used without prohibitive morbidity and mortality in children with concurrent end-stage liver disease. Liver transplantation prior to cardiac surgery is associated with high postoperative mortality and morbidity in patients with severe cardiac disease 5]. Significant pressure and/or volume overload from congenital heart disease may confer important hemodynamic perturbations during and after transplantation that impact survival and optimal liver function, particularly with pulmonary hypertension or right heart failure. This sequentially staged approach, cardiac repair before liver transplantation, may be preferable to the reverse order or combined cardiopulmonary and liver transplantation. Our study is limited by the small sample size, which may reflect both the rarity of coexistent heart and liver disease and a potential selection bias in referral for pediatric cardiac surgery.
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References
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Abstract
Introduction
