Effect of treatment with prostaglandin E1 and N-acetylcysteine on pediatric liver transplant recipients: a single-center study.

Prostaglandin E1 (PGE1) and N-acetylcysteine (NAC) have been used as single agents to decrease reperfusion injury and improve outcome after solid-organ transplantation (Tx). We hypothesized that combined treatment with NAC and PGE1 would be safe and reduce reperfusion injury. We therefore carried out a pilot study to assess the safety of this drug combination and gain information regarding the efficacy of treating pediatric liver transplant recipients with NAC and PGE1. The pilot study took the form of an open-label study incorporating 25 pediatric liver transplant recipients (12 children in the treatment group and 13 children as controls). NAC (70 mg/kg) was given intravenously over 1 h following reperfusion and then every 12 h for 6 days. PGE1 (0.4 mg/kg/h) was given as a continuous intravenous infusion for 6 days, starting after the first NAC dose. The primary outcome was the safety of combined treatment with NAC and PGE1. Patient survival, graft survival, allograft rejection within the first 90 days after Tx, peak post-transplant serum alanine aminotransferase (ALT) concentration, post-transplant length of hospitalization, and post-operative complications were secondary outcomes. Post-operative complications occurred at similar rates in both control and treated groups. No complications or adverse events occurred in the treated group as a result of study drugs. The 3-month patient survival rate was 100% for both groups. For the group treated with NAC and PGE1, peak serum ALT was lower and median length of stay was shorter but the differences did not reach statistical significance. The proportion of patients with allograft rejection was not significantly different between the two groups. However, rejection was more severe in the control group than in the treated group. In summary, infusions of NAC and PGE1 were safely administered to pediatric liver transplant recipients. However, a randomized controlled study is needed to determine the efficacy of treatment with NAC and PGE1.

Long-term outcome after partial external biliary diversion for intractable pruritus in patients with intrahepatic cholestasis.

BACKGROUND: Chronic intrahepatic cholestasis is associated with severe pruritus that is often refractory to maximal medical management and leads to significantly impaired quality of life. The hypothesis in this study was that partial external biliary diversion (PEBD) can substantially improve intractable pruritus secondary to intrahepatic cholestasis with subsequent improvement of functional quality of life. METHODS: Parents' and/or patients' clinical rating of pruritus, growth percentiles, biochemical parameters, and liver biopsies performed before and after surgery were compared in a retrospective medical record review. RESULTS: Eight children underwent PEBD from 1990 through 1997. Complete follow-up data were available for seven patients. Before surgery, all patients had intense pruritus, which was not responsive to maximal medical therapy. Specimens obtained in preoperative liver biopsies showed moderate (n = 1), minimal (n = 6), or no (n = 1) portal fibrosis. After PEBD, all patients received ursodeoxycholic acid (10-15 mg/kg/dose two to three times daily) until resolution of pruritus. Of the seven patients with complete follow-up data, six had complete resolution of pruritus and sustained resolution up to 8 years after surgery. The patient with mild to moderate residual pruritus was the youngest to undergo PEBD. Growth improved from below the 5th percentile before surgery to the 5th through the 25th percentiles for five of six patients with more than 6 years' follow-up. All families reported improved quality of life, defined by school attendance and ability to resume normal activity with peers. There has been no clinical evidence of progression of liver disease. CONCLUSION: Partial external biliary diversion is effective in the long-term treatment of pruritus refractory to medical therapy and provides a favorable outcome in a select group of patients with chronic intrahepatic cholestasis without cirrhosis.

Long-term survival after liver transplantation.

BACKGROUND: Liver transplantation (LT) remains a high-risk operation, especially during the first months after LT when technical complications and preexisting illness exert their influence on survival. However, there are late deaths. The authors have reviewed their experience to identify factors impacting on long-term survival. METHODS: A total of 150 patients who had undergone liver transplantation over an 11-year period were reviewed. Thirty-three patients died after LT (22%). Of these, 18 of 33 (55%) died in the first 3 postoperative months. One hundred thirty-two patients survived beyond 3 months, and 15 patients (11%) suffered late deaths. This review concentrates on the latter group. RESULTS: The primary cause of death was sepsis in 11 of 15 (73%). In two, sepsis complicated retransplantation in chronically debilitated patients. Two additional patients had late-presenting postoperative complications (bile leak or abscess, intestinal obstruction with perforation). In two cases, pneumocystis carinii pneumonia occurred; noncompliance or unplanned discontinuation of prophylaxis was directly responsible. Multiple organ system failure from presumed immunoincompetence developed in four patients; one had undergone bone marrow transplantation for aplastic anemia (AA) after fulminant hepatic failure (FHF). Lymphoproliferative disease (LPD) was the cause of death in 3 of 15 cases (20%). In only three cases was the cause of death related to the patient's primary disease (chronic hepatitis, Alper's syndrome or seizures, and AA with FHF). Pretransplant diagnosis, and UNOS status at the time of LT did not influence the long-term survival. CONCLUSIONS: Long-term survival in patients who have undergone LT was compromised by immunosuppressive complications and sepsis. Early mortality factors, such as UNOS status, age at LT, primary diagnosis, and technical complications do not predict late deaths. In children who adhere to their medical regimen and have good initial allograft function, late postoperative infection, especially with Ebstein-Barr virus, accounts for most of the late mortality. Improved and decreased immunosuppression may further improve these long-term results.

Biliary atresia--surgical management and treatment options as they relate to outcome.

Results show that the use of sequential surgical treatment, employing Kasai portoenterostomy in infancy, followed by selective liver transplantation for children with progressive hepatic deterioration yields improved overall survival. All children with successful Kasai portoenterostomy procedures who do not require OLT are survivors. Using newer transplant techniques, the 5-year survival rate for children who receive transplants with a primary diagnosis of biliary atresia was 82%. This yields an overall survival rate of 86% in this entire study population. Limited donor availability and increased complications after liver transplantation in infants less than 1 year of age mitigate against the use of primary liver transplantation without prior portoenterostomy for infants with biliary atresia. At present, these two operative procedures should be used as sequential and complementary modes of treatment rather than as competitive procedures. When biliary atresia is not recognized in infancy and established cirrhosis has resulted, primary transplantation should be offered as the initial surgical treatment.

Liver transplantation in Ohio.

BACKGROUND: Since its inception in 1984, the Ohio Solid Organ Transplantation Consortium has tracked liver transplantation outcomes for its five member institutions. Presented herein is a 12-year summary of this data analyzed to determine whether, with increasing experience, outcomes have improved in a cost-effective manner. METHODS: Between July 1984 and June 1996, 1,063 liver transplants were performed in Ohio in 943 patients (772 adults and 171 children), of which 943 were primary and 120 were retransplants (13%). Outcome comparisons were made for three eras: 1984-1988, 1988-1992, and 1992-1996. RESULTS: The percentage of urgent (United Network for Organ Sharing status 1 and 2) transplants has decreased (62% to 41%), whereas that of homebound patients has increased (38% to 59%). Average time on the waiting list has increased from 39 to 165 days, and the average length of stay has decreased from 44 to 27 days. Patient survival at 1-year increased in each era (64%, 80%, and 82%, respectively). Although actual hospital charges have remained relatively constant, they have decreased substantially when compared in 1985 dollars as corrected for inflation. CONCLUSIONS: Patients undergoing liver transplantation in Ohio are now listed earlier in the course of their disease and wait longer for their transplant, but enjoy a better chance of survival, have a shorter hospital stay, and a relatively less expensive operation. These data indicate that with increased experience, the Ohio Solid Organ Transplantation Consortium liver transplantation teams perform liver transplantation in a more cost-effective manner.

The use of extracorporeal life support in pediatric burn patients with respiratory failure.

Respiratory failure is the most common cause of death after thermal injury and may be caused by inhalation injury, acute respiratory distress syndrome (ARDS) or pneumonia. ARDS is usually associated with sepsis; however, it may also occur during burn shock, especially in patients that have a delayed or inadequate fluid resuscitation. During the past 24 months, five pediatric burn patients underwent extracorporeal life support (ECLS) for respiratory failure unresponsive to optimal medical management. The mean age of the patients was 26 months (range, 8.5 to 48 months), with a mean burn size of 46% TBSA (> 95% third degree). The etiology of the respiratory failure included severe bronchospasm in a 22-month-old former premature infant with bronchopulmonary dysplasia; three patients with ARDS; and one patient with a severe inhalation injury. All five patients required greater than 56 cm H2O peak pressures and 100% FIO2 at the time of beginning ECLS. The oxygenation index (OI) ranged from 45 to 180. Three (60%) of the patients survived. In the three patients who ultimately survived, significant improvements in pulmonary and hemodynamic parameters occurred within 96 hours of ECLS. The two patients who died showed no improvement and were removed from ECLS at 10 and 11 days; both expired within hours. The patients who expired developed significant hemodynamic instability, coagulopathy, and hemorrhage from their burn wounds. The extent and degree of burn injury did not seem to alter the outcome. Indications for considering ECLS in the pediatric burn patient are unmanageable, life threatening pulmonary insufficiency in patients that undergo a relative short course of pre-ECLS ventilator support.(ABSTRACT TRUNCATED AT 250 WORDS)

Catheter-induced urinary bladder rupture presenting with pneumoperitoneum.

Neonatal bladder injury is rare and usually associated with umbilical artery catherization. Patients may present with apparent renal failure, abdominal distension, and respiratory distress. Treatment involves operative closure of the perforation and bladder drainage. A case of Foley catheter-induced bladder rupture in a premature infant, not previously reported in the literature, is detailed.

Traumatic delivery: a risk factor for bleeding during ECMO?

Traumatic delivery is associated with orthopedic, nervous, and soft tissue injuries. Anticoagulation for extracorporeal membrane oxygenation (ECMO) support may predispose to hemorrhage from these birth injuries. A case of delayed hemoperitoneum secondary to hepatic laceration after delivery and ECMO, not previously reported, is detailed herein.

Myocardial calcification: a predictor of poor outcome for myocarditis treated with extracorporeal life support.

Myocarditis is an inflammatory disease of the myocardium with a variety of causes. It is potentially reversible, and has been treated successfully with extracorporeal life support (ECLS). With increasing severity, myocarditis results in significant damage to myocardial cells. Dystrophic calcification of the myocardium may occur, serving as a marker of severe damage. At the authors' institution, from July 1990 to January 1992, five patients (four neonates, one 5 year old) with severe myocarditis refractory to medical management were treated with venoarterial ECLS. Three survived (60%) and two died. All patients were female, and their age range was 2 weeks to 5 years. Nonsurvivors had significant myocardial calcification, which was detected by a chest roentgenogram as well as a two-dimensional echocardiogram; the three survivors had no evidence of calcification. The nonsurvivors had minimal recovery of myocardial function and subsequently had their ECLS discontinued at 83 and 169 hours, respectively. The authors conclude that the development of progressive myocardial calcification in conjunction with a lack of recovery of cardiac function is a sign of severe myocardial damage and poor prognosis. Continuation of ECLS in this setting may not be warranted.

Antenatal diagnosis of choledochal cyst.

We report five infants in whom antenatal diagnosis of choledochal cyst was established by ultrasonography, and we review the seven previously reported cases. All but one infant had cystic dilatation of the common bile duct (type 1 cysts), and all infants were diagnosed during the second or third trimester. Eight of 12 infants (67%) developed jaundice in the first few days of life, but only 25% had a palpable abdominal mass. Seven of nine infants (78%) demonstrated complete obstruction of the distal common bile duct on intraoperative cholangiography. Liver histology was available for six patients. Five of six had cirrhosis or fibrosis with bile duct proliferation. All of the infants with fibrosis or cirrhosis had distal common bile duct obstruction. Despite liver biopsy findings of extensive fibrosis plus ascites with failure to thrive in one of our patients, all five patients demonstrated clinical and biochemical improvement following surgical excision and porto- or choledochoenterostomy. All were free of symptoms by 6 months of age. Congenital choledochal cyst should be considered in the differential diagnosis of any sonolucent abdominal mass of the fetus. Neonates with distal common bile duct obstruction and fibrosis in association with presumed choledochal cyst should have prompt surgical exploration, intraoperative cholangiography, and close postoperative follow-up. The long-term outcome with prompt surgical correction is excellent.

The spectrum of bile duct complications in pediatric liver transplantation.

It has been noted that reduced-size liver transplants are associated with increased rates of biliary complications, and it has been suggested that some of these complications can be handled nonoperatively. In a 6-year period, 91 orthotopic liver transplants were performed in 77 children. The medical records were reviewed to analyze the effect of reduced-size grafts on the incidence of bile duct complications and to investigate the utility of interventional radiology techniques for treatment. Forty-two children received 47 whole-organ transplants, and 35 children received 44 reduced-size transplants. The median age and weight were greater for children receiving whole-organ transplants (age, 4.25 years; weight, 16 kg) than for those receiving reduced-size grafts (age, 1.0 year; weight, 8 kg). The overall incidence of bile duct complications was 19.5% (n = 15). The incidence was not different between the whole organ group (17%) and the reduced-size group (16%). Four of the children with bile duct complications had associated hepatic artery thrombosis, two of whom had another transplant. Complications included anastomotic stricture (n = 6), anastomotic leak (n = 5), intraparenchymal biloma (n = 3), and multiple strictures (n = 1). Twelve of 15 children presented within 3 months of transplantation. Six children had initial percutaneous drainage or placement of transanastomotic stents (external). Operative repair was eventually required for all 15 children, three of whom received a second transplant. There was a 40% incidence of cytomegalovirus infection involving the liver or extrahepatic bile ducts near the time of presentation.(ABSTRACT TRUNCATED AT 250 WORDS)

Extracorporeal membrane oxygenation in the management of cardiac failure secondary to myocarditis.

While most patients with viral myocarditis have a relatively uncomplicated clinical course, a small number of patients will present with cardiogenic shock unresponsive to standard medical therapy. We describe the clinical course of three patients who developed profound cardiac failure secondary to a documented viral myocarditis. Each patient was managed using venoarterial (VA) extracorporeal membrane oxygenation (ECMO) support using the right common carotid artery/internal jugular vein for cannulation. While undergoing ECMO support, each patient developed elevated left-sided cardiac chamber pressures with resultant pulmonary edema. This was managed by balloon atrial septostomy in two cases and combined blade/balloon atrial septostomy in one case. Excellent decompression of the left heart was achieved in each patient. Two patients were successfully weaned from ECMO and are currently alive, with one demonstrating residual cardiac dysfunction. One patient developed global myocardial necrosis and ultimately died. This small series demonstrates a role for ECMO in the management of cardiac failure due to acute viral myocarditis unresponsive to medical therapy. Our experience also suggests that balloon atrial septostomy may be useful to decompress the left atrium and ventricle of patients with acute myocarditis while on ECMO.

Liver transplantation in children.

Children with end-stage liver disease now have a greater chance of survival through treatment with hepatic transplantation. This article reviews the pediatric liver transplantation process, including selection and evaluation of candidates, operative procedures, postoperative complications, and long-term survival.

The predictive value of head ultrasound in the ECMO candidate.

Cranial ultrasound (US) examination is the screening technique of choice for assessing preexisting neurological damage in potential neonatal extracorporeal membrane oxygenation (ECMO) candidates. Currently, US evidence of intracranial hemorrhage greater than grade I in severity is a contraindication to ECMO at this ECMO center. In the current study, radiological findings were reviewed in 129 consecutive neonatal ECMO cases in an attempt to identify which pre-ECMO US findings were associated with the development of subsequent intracranial complications while on ECMO. Pre-ECMO head US, post-ECMO head US, and head computed tomography (CT) scans were reviewed retrospectively by one radiology team. Ventricular, parenchymal, and extraaxial fluid abnormalities were recorded for each case. Pre-ECMO US findings were then correlated with the subsequent development of significant intracranial radiological abnormalities noted on post-ECMO studies as well as with clinical data regarding ECMO course and outcome. Results showed that infants with evidence of severe edema or periventricular leukomalacia on pre-ECMO imaging had a 63% incidence of subsequent major intracranial complications. This represents a significantly higher risk than in candidates with a normal examination or evidence of grade I intracranial hemorrhage, subependymal cysts, or mild edema. These results suggest that infants with sonographic evidence of ischemic or anoxic damage on pre-ECMO US are at high risk for the development of significant intracranial complications if ECMO therapy is instituted.

Segmental orthotopic hepatic transplantation as a means to improve patient survival and diminish waiting-list mortality.

Pediatric liver transplantation continues to be limited by the availability of suitable liver donors, a factor that restricts programmatic development and ultimately contributes to death on the recipient waiting list. We report the application of segmental liver transplantation as a technique to address both these problems as well as improving the outcome of the child undergoing the transplant procedure. Since 1986, 37 children have undergone orthotopic liver transplantation. Twenty-three children have received whole-organ grafts; 81% survived. Of those receiving whole-organ grafts, 15% had arterial thrombotic complications and 23% required retransplantation. More importantly, 29% of those children listed for transplantation died while waiting for a donor organ to become available, with a mean interval of 1.7 months (range, 2 days to 4.5 months). Since July 1988, segmental liver transplantation has been a component of our therapeutic armamentarium, and of the past 20 liver recipients, 16 have received a left lobe segmental graft. The results of the segmental transplant series have shown striking improvements. First, no child has died while awaiting donor organ availability. Second, segmental liver recipient survival is equivalent to that of whole-organ graft recipients (81%). Third, hepatic arterial thrombosis, especially a problem in high-risk infant transplants, was reduced by this technique (5%). Retransplantation due to graft complications has not increased (21%). These data suggest a vital role for segmental liver transplantation not only as a remedial salvage procedure for the critically ill child, but also as a primary transplant option.

Cardiac arrest in the ECMO candidate.

Extracorporeal membrane oxygenation (ECMO) improves survival in appropriately selected full-term neonates with severe respiratory failure. The clinical course and outcome of infants placed on ECMO after sustaining a cardiac arrest is not known. This study reviews the characteristics and outcome of 10 neonates, identified by retrospective review, placed on ECMO at Children's Hospital Medical Center (CHMC), Cincinnati, OH, after sustaining a cardiac arrest. Long-term survival in this group was 60%, significantly less than the 87% overall ECMO survival in infants at CHMC (P less than .01). Survivors and nonsurvivors in the cardiac arrest group were similar with regard to gestational age, birth weight, Apgar scores, and arterial PO2 prior to cannulation. Nonsurvivors had an ECMO course complicated by progressive multisystem organ failure. Head computed tomography obtained at the time of discharge demonstrated right-sided brain lesions in three of six survivors. Despite these radiographic findings, early clinical follow-up suggests adequate growth and development with no individuals demonstrating a severe neurological deficit. Thus, ECMO can play a role in the resuscitation of neonatal ECMO candidates sustaining cardiac arrest prior to or at the time of cannulation. Early clinical follow-up suggests adequate preservation of neurological function in this extremely high-risk group.

Continuous hemodiafiltration in children.

Continuous arteriovenous hemofiltration is a form of renal replacement therapy whereby small molecular weight solutes and water are removed from the blood via convection, alleviating fluid overload and, to a degree, azotemia. It has been used in many adults and several children. However, in patients with multisystem organ dysfunction and acute renal failure, continuous arteriovenous hemofiltration alone may not be sufficient for control of azotemia; intermittent hemodialysis or peritoneal dialysis may be undesirable in such unstable patients. Recently, the technique of continuous arteriovenous hemodiafiltration has been used in many severely ill adults. We have used continuous arteriovenous hemodiafiltration in four patients at Children's Hospital Medical Center. Patient 1 suffered perinatal asphyxia and oliguria while on extracorporeal membrane oxygenation. Patients 2 and 4 both had Burkitt lymphoma and tumor lysis syndrome. Patient 3 had septic shock several months after a bone marrow transplant. All had acute renal failure and contraindications to hemodialysis or peritoneal dialysis. A blood pump was used in three of the four patients, while spontaneous arterial flow was adequate in one. Continuous arteriovenous hemodiafiltration was performed for varying lengths of time, from 11 hours to 7 days. No patient had worsening of cardiovascular status or required increased pressor support during continuous arteriovenous hemodiafiltration. The two survivors (patients 2 and 4) eventually recovered normal renal function. Continuous arteriovenous hemodiafiltration is a safe and effective means of renal replacement therapy in the critically ill child. It may be ideal for control of the metabolic and electrolyte abnormalities of the tumor lysis syndrome.

Multiple endocrine neoplasia type II B with symptoms suggesting Hirschsprung's disease: a case report.

A 3-year-old child was referred with a tentative diagnosis of Hirschsprung's disease because of life-long constipation and "megacolon" demonstrated radiographically. Our rectal biopsy revealed hyperganglionosis suggestive of multiple endocrine neoplasia (MEN) type II B. This, in addition to an elevated serum calcitonin level, prompted surgical removal of her thyroid, which appeared grossly normal but on sectioning, contained a medullary carcinoma in each lobe. She remains disease-free 5 years later. Gastrointestinal symptoms are a significant component of the MEN type II B syndrome, and often antedate the full phenotypic expression of the syndrome and the development of potentially lethal endocrine neoplasms. On the basis of this experience, it is recommended that MEN II B be included in the differential diagnosis of chronic constipation.