Use of airway pressure release ventilation in a child with refractory hepatopulmonary syndrome after liver transplantation

HPS is a life‐threatening condition in patients with end‐stage liver disease, in which intrapulmonary vascular dilatations result in intrapulmonary shunts and hypoxemia. The only successful treatment is liver transplantation. Hypoxemia may be severe prior to transplantation; however, it can worsen or become refractory after liver transplantation and result in increased post‐operative mortality. Here, we present the case of a 10‐month‐old female infant with progressive end‐stage liver disease and severe HPS, who developed refractory hypoxemia after a successful liver transplantation. After 19 days of unsuccessful attempts to reverse the hypoxemia using conventional mechanical ventilation and HFOV, the patient responded dramatically to APRV, with rapid improvement in her PaO₂ and sharp decline in her OI. She was able to begin weaning from APRV two days later and was extubated within seven days. APRV was successful in treating refractory hypoxemia in this patient with severe HPS after liver transplantation, possibly by modifying distribution of pulmonary blood flow. Although we cannot rule out coincidental natural resolution of the HPS, APRV could be a useful rescue therapy in patients with HPS and refractory hypoxemia.     

Successful venoarterial extracorporeal membrane oxygenation for prolonged hepatopulmonary syndrome following pediatric liver transplantation: A case report and review of the literature

HPS is a major complicating feature of end‐stage liver disease. Diagnosis is clinical, and LT is the only definitive treatment. While the general impression is that HPS improves quickly after transplantation, it may not always be the case. We describe the smallest reported child with HPS prior to LT and requiring prolonged venoarterial extracorporeal membrane oxygenation after LT; especially as it is a rare occurrence, physician managing such cases should be aware of the circumstances under which HPS may require specific treatment.     

Therapeutic coil embolization of dominant shunt in hepatopulmonary syndrome enhances post‐liver transplant respiratory recovery

Coil embolization of the atypical enlarged pulmonary artery/arteriole with visible shunting may improve hypoxemia in patients with hepatopulmonary syndrome (HPS). When used selectively in cases with large shunts, either pre‐ or post‐liver transplantation (LT), it can aid an early recovery and reduce morbidity. We present a case where a large intrapulmonary shunt was embolized preoperatively to improve hypoxemia associated with HPS and enhance post‐operative recovery.     

Brain abscess in hepatopulmonary syndrome associated with biliary atresia

The first‐choice therapy for biliary atresia (BA) is Kasai hepatoportoenterostomy, which has been shown to greatly improve outcome. Various long‐term complications, however, such as portal hypertension and hepatopulmonary syndrome (HPS), can occur in patients with native liver. A rare case of brain abscess in an 11‐year‐old girl with HPS associated with BA is reported. The patient underwent hepatoportoenterostomy for BA at 53 days of age, with resolution of hyperbilirubinemia. At 10 years of age, she was diagnosed with severe HPS with right‐to‐left shunting, and preparations for liver transplantation proceeded. Three months after the diagnosis, she had a right parietal brain abscess. Given that the brain abscess enlarged in size, surgical drainage of the brain abscess was performed. The postoperative course was uneventful, but a slight left hemiplegia remained at discharge. The presumed mechanism of abscess formation in HPS may be right‐to‐left bacterial transit through intrapulmonary vascular dilatations and/or arteriovenous fistulae.     

Childhood cirrhosis, hepatopulmonary syndrome and liver transplantation

Abstract: Objectives: The hepatopulmonary syndrome (HPS) is characterized as a triad: liver disease, intrapulmonary vascular dilatatiton, and arterial hypoxemia. The aim of this study is to analyze outcome of children with HPS in liver transplant era. Methods: Between September 1996 and November 2006, 172 cirrhotic patients (median age 5 years; range 0.2–22 years, M/F; 97/75) were followed at Ege University Pediatric Gastroenterology, Hepatology and Nutrition Unit. All patients were evaluated by chest radiography, arterial blood gas analysis, and alveolar‐arterial oxygen tension difference, contrast echocardiography (CEE) after and before the liver transplantation. Results: HPS was diagnosed in 33 patients (19%) by CEE. None of them had pulmonary hypertension. HPS was not found related to etiology of the liver disease. Portal hypertension was found related to the development of HPS (75.7% in patients with HPS and 54.6% in others, p = 0.02). 17 of 33 patients with HPS underwent liver transplantation. Preoperative and postoperative period of these patients was uneventful. Patients were extubated in the operating room except for two. Median follow up of transplanted children was 1.9 year (range; 0.75–10 years). Arterial blood gas analysis and CEE positivity regressed in all of them by postoperative 6th month. Conclusions: HPS is a serious and important complication of cirrhotic children that leads to tissue hypoxia and central cyanosis. HPS seems reversible after liver transplantation in all patients.     

Hepatopulmonary syndrome associated with nodular regenerative hyperplasia after liver transplantation in a child

HPS is a significant complication of portal hypertension in children with chronic liver disease and is an established indication for LT. It is characterized clinically by the triad of pulmonary vascular dilatation causing hypoxemia in the setting of advanced liver disease. NRH, a cause of non‐cirrhotic portal hypertension, is characterized by diffuse benign transformation of the hepatic parenchyma into small regenerative nodules with minimal or no fibrosis. Development of NRH and HPS in pediatric LT recipients has not been reported, although occasional cases have been reported in adult LT recipients. In this report, we discuss a case of a three‐yr‐old male who developed HPS, two yr after LT. Pulmonary and cardiac causes for hypoxemia were ruled out by appropriate investigations including a chest X ray, echocardiogram, cardiac catheterization, and a CT angiographic study. The diagnosis of HPS was confirmed via bubble echocardiogram that demonstrated intrapulmonary shunting. Open liver biopsy revealed marked NRH. The patient underwent liver retransplantation that resulted in complete reversal of his pulmonary symptoms and normal oxygen saturations within three months after LT.     

Autoimmune hepatitis in a child presenting with hepatopulmonary syndrome (HPS)

HPS has been described in 9–20% of children with end‐stage liver disease. We present a case of a previously, asymptomatic nine‐yr‐old incidentally found to have low oxygen saturation. Physical exam was remarkable for digital clubbing, splenomegaly and orthodeoxia. Laboratory evaluation revealed a low platelet count, hyperammonemia, and prolonged coagulation studies. Sonography showed evidence of splenomegaly and portal venous hypertension. High resolution CT thorax and CTA were normal. HPS was confirmed by agitated saline contrast enhanced echocardiography and Tc‐99m MAA scan with evidence of intrapulmonary vascular dilatations. Liver biopsy was performed and consistent with autoimmune hepatitis. A high clinical index of suspicion should be maintained for HPS in pediatric patients who have unexplained hypoxemia as typical signs and symptoms of severe liver disease are often absent. In this report, we discuss a case of HPS complicated AIH in a pediatric patient and review the relevant literature.     

Late complications of biliary atresia: hepatopulmonary syndrome and portopulmonary hypertension

Children with biliary atresia (BA) following Kasai portoenterostomy have a high risk for portal hypertension, however, while variceal and hemorrhagic complications have been more commonly studied, less frequent but no less possibly devastating complications of hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PPH) remain less well understood. HPS and PPH both occur in a setting of portal hypertension, however, paradoxically patients with HPS develop pulmonic vasculature dilation leading to shunting and hypoxia, while those with PPH develop an opposite progression of pulmonary vasoconstriction eventually leading to cor pulmonale and decompensation. Given the near diametric evolution of diseases, HPS and PPH differ widely in therapy, though liver transplantation can have a role for treatment in either disease state. We reviewed our series of 320 pediatric patients with biliary atresia treated at our institution over 44 years, highlighting two cases that developed HPS and PPH, respectively, using these cases in further discussion of hepatopulmonary syndrome and portopulmonary hypertension regarding disease etiology, diagnosis, management, and prognosis. The complicated nature of these processes demand a careful multidisciplinary approach to optimize patient outcomes, including mindful evaluation for when transplantation may offer benefit.     

Nitric oxide for post‐liver‐transplantation hypoxemia in pediatric hepatopulmonary syndrome: Case report and review

Schiller O, Avitzur Y, Kadmon G, Nahum E, Steinberg RM, Nachmias V, Schonfeld T. Nitric oxide for post‐liver‐transplantation hypoxemia in pediatric hepatopulmonary syndrome: Case report and review.
Pediatr Transplantation 2011: 15: E130–E134. © 2010 John Wiley & Sons A/S. Abstract: HPS is rare in the pediatric population. Liver transplantation is the ultimate treatment for severe HPS. There are only a few case reports and one series of children in whom HPS was the main indication for liver transplantation. Outcome was good in most of them, with full regression of the pulmonary process. However, hypoxemia in the early post‐operative course can have severe consequences, and effective treatment modalities are needed. There are rare instances of the use of iNO for the treatment of post‐operative hypoxemia. We describe a 10.5‐yr‐old boy with severe HPS owing to chronic liver disease after bone marrow transplantation. Liver transplantation from a living related donor (the same sister who donated the bone marrow) was complicated by severe hypoxemia on POD 2. iNO was administered via the ventilator circuit and, after extubation, through nasal prongs. It was slowly tapered down and stopped on POD 10. The child had an otherwise uneventful course and was discharged home on POD 21 with normal oxygen saturation. Liver transplantation should be offered to children with severe HPS. iNO can reverse the hypoxemia that may occur after the operation.     

Long‐term outcome and management of hepatopulmonary syndrome in children

Al‐Hussaini A, Taylor RM, Samyn M, Bansal S, Heaton N, Rela M, Mieli‐Vergani G, Dhawan A. Long‐term outcome and management of hepatopulmonary syndrome in children.
Pediatr Transplantation 2010:14:276–282. © 2009 John Wiley & Sons A/S. Abstract: We aim to report a single center experience of the management and long term outcome of HPS in pediatric liver transplant recipients. A retrospective review of children with HPS from 1990 to 2004. Inclusion criteria: liver disease or portal hypertension, hypoxemia (PaO₂ < 70 mmHg or SaO₂ < 95%) and intrapulmonary shunting documented by macroaggregated albumin scan ratio of >4% (classified mild group [<20%], moderate group [20–40%] and severe group [>40%]). Resolution of HPS post‐liver transplant was defined as PaO₂ > 70 mmHg or SaO₂ > 95%. Eighteen children (six male [34%], median age at diagnosis of HPS 8.6 [1–15.5] yr) had HPS: biliary atresia (n = 8), idiopathic biliary cirrhosis (n = 4), progressive intrahepatic cholestasis (n = 2), miscellaneous (n = 4). The majority had mild shunting (n = 8). Fourteen underwent transplantation with resolution of HPS in 13. Six developed complications: hepatic artery thrombosis (n = 4), biliary (n = 2). Four children died (28%), two pretransplant. There was a tendency towards shunt fraction worsening to a slower degree over time. One‐yr survival rate post‐transplant was 93%. Median PaO₂ was significantly lower in non‐survivors compared to survivors (43 vs. 55.2 mmHg, p = 0.03). There was correlation between oxygen parameters pretransplant and time to HPS resolution post‐transplant. HPS is reversible after transplant, but is associated with increasing mortality and morbidity.     

Pediatric living donor liver transplantation for biliary atresia with hepatopulmonary syndrome: the gift of a second wind

Purpose

Hepatopulmonary syndrome (HPS) is a progressive, deteriorating complication of end-stage liver disease (ESLD) that occurs in 13?C47% of liver transplant candidates. Although LT is the only therapeutic option for HPS, it has a high morbidity and mortality, especially in patients with severe hypoxemia before transplantation, but the course of HPS after living donor liver transplantation (LDLT), especially for biliary atresia (BA) patients is not well established.

Patients and methods

The present study evaluated 122 patients who received an LDLT for BA and of these, 3 patients had HPS at the time of LDLT in a single-center series.

Results

Two patients of the HPS patients them had biliary and/or vascular complications, but they recovered uneventfully with interventional treatment. None of the patients required supplemental oxygen and had no residual cardiopulmonary abnormalities at a follow-up of more than 24?months.

Conclusion

Although a series of three patients is too small for definitive conclusion and further investigations must be conducted, pediatric LDLT can be a favorable therapeutic option for HPS.     

儿童噬血细胞综合征54例临床及预后因素分析

目的分析儿童噬血细胞综合征(HPS)的临床特征及影响预后的危险因素,以提高本病的早期诊断率,减少误诊。方法回顾性分析54例儿童HPS的病因、临床特征、实验室检查结果及转归。结果 54例患儿均以发热为首发症状(100%),其余临床表现按发生率多少依次为脾脏肿大、肝脏肿大、淋巴结肿大、黄疸、多浆膜腔积液、水肿、呼吸系统症状、消化道出血、皮疹、泌尿系出血、中枢神经系统症状。实验室检查以肝功能异常最为突出(100%),以酶学(ALT、LDH、AST)改变为主(100%),其后依次为骨髓见噬血细胞、外周血至少两系细胞减少、高甘油三酯血症、血清铁蛋白升高、低纤维蛋白原血症、NK细胞活性降低、肾功能异常。病因分析显示,感染相关性(IAHS)占72%,以EB病毒相关性噬血细胞综合征(EBV-AHS)最多,占IAHS的82%。54例HPS患儿中,自动出院19例(随访中16例死亡),接受治疗35例,9例(26%)死亡,21例治愈或有效(60%),5例正在治疗中。死亡25例中,IAHS19例(EBV感染17例,败血症2例),恶性肿瘤2例,原因不明者4例。单因素分析显示发病年龄、EBV感染、血小板计数降低、LDH和ALT水平升高与患儿死亡有关。将以上因素进行Logistic多因素分析,显示EBV感染、血小板降低、ALT升高是噬血细胞综合征患儿死亡的独立危险因素。结论 HPS由多种病因所致,临床表现多样,预后凶险。病因分析,EBV-AHS占首位。EBV感染、PLT计数、ALT水平是影响HPS预后的独立危险因素,采用HLH-04方案治疗有助于提高HPS患儿的生存率。     

儿童噬血细胞综合征68例临床研究

目的探讨儿童噬血细胞综合征(HPS)的临床特点、诊断、治疗及预后。方法回顾分析2002年1月至2007年6月广东省9所医院诊治的68例儿童HPS的临床特点、治疗及预后。结果68例病例中放弃治疗16例(23.5%),死亡9例(13.2%)。2005年前治疗者共4例,1例完全缓解后失访,余3例死亡。2005年后(釆用HLH-04方案)治疗痊愈20例(20/42,47.6%),完全缓解继续治疗中4例(9.5%),完全缓解后失访6例(14.3%),复发治疗中5例(11.9%)。结论广东地区儿童HPS的发病有逐年增多的趋势;其原发病最常见为EBV感染;采用HLH-04方案治疗后疗效有所提高。     

Anesthetic management of a pediatric patient with pulmonary arteriovenous fistula undergoing liver transplantation – a case report

For patients with HPS who require anesthesia for a procedure, HPV should be maintained to prevent worsening hypoxemia. Here, the case of a 9‐yr‐old girl who was scheduled for a living donor liver transplantation is presented. The patient suffered from end‐stage liver disease with HPS due to biliary atresia, which contributed to the development of a diffuse pulmonary AVF. Consequently, anesthetic management of this patient involved two different types of pulmonary shunt. It is important to maintain HPV, not only to prevent worsening of the hypoxia caused by HPS but also to inhibit an increase in PVR that could cause an increase of shunt flow through the pathological fistula. A TIVA technique was performed, and a nitrous oxide inhaler was prepared in case of a possible increase in PVR during the reperfusion period. There were no adverse events during the operation. Thus, anesthesiologists should be aware of the pathophysiological status of HPS and its potential to progress to a pulmonary AVF in order to meticulously determine an anesthesia plan that accounts for the hypoxia and PVR that are associated with HPS.     

Poor response to desmopressin acetate (DDAVP) in children with Hermansky-Pudlak syndrome

BACKGROUND: Hermansky-Pudlak syndrome (HPS) is a common genetic disorder in Puerto Rico. In children with HPS, bleeding is the most disturbing and incapacitating problem. Desmopressin (1-deamino-8-D-arginine vasopressin, (DDAVP)) has been recommended in the management of bleeding disorders characterized by platelet dysfunction, such as HPS. METHODS: Nineteen pediatric Puerto Rican patients with HPS and prolonged bleeding time (BT) were tested for response to administration of DDAVP. RESULTS: Baseline BT was abnormal in 18 (95%) of the patients. The BT following DDAVP administration improved in two cases (11%): one from 7.2 to 5.6 min and the other from 8 to 6 min (Tables II and III). BT measurements remained very prolonged (>15 min) in 17 (89%) of the patients. Patients with the HPS 1 gene mutation had a statistically significant correlation with the poor response following DDAVP (P = 0.03). CONCLUSIONS: DDAVP seldom improves the BT of Puerto Rican children with HPS. Response to DDAVP should be determined individually and platelet transfusion should remain the treatment of choice for a major bleeding episode or surgical procedure.     

Rubella-associated hemophagocytic syndrome in an infant

Hemophagocytic syndrome (HPS) is a fulminant disorder characterized pathologically by multiple-organ infiltration of hemophagocytic histiocytes in the lymphoreticular tissues. The characteristic pathologic feature is reactive histiocytic hyperplasia with leukoerythrophagocytosis in a variety of organs. This disorder occurs most often in patients in whom the immune system is compromised and has been associated with a variety of infectious agents, including viruses, bacteria, mycobacteria, spirochetes, fungi, and parasites. The authors describe a 2.5-month-old girl with rubella-associated HPS, demonstrated by postmortem liver necropsy.     

Hemophagocytic syndrome after Kawasaki disease

Hemophagocytic syndrome (HPS) is a rare and life-threatening disease in which a generalized histiocytic proliferation results in hemophagocytosis and up-regulation of inflammatory cytokines. This syndrome has been associated with infections, malignancy, drugs and immunologic triggers such as Kawasaki disease (KD). We describe the clinical and laboratory features of two children with HPS after KD and review the three previously reported pediatric cases of recrudescence of HD leading to HPS.     

Rapid correction of metabolic alkalosis in hypertrophic pyloric stenosis with intravenous cimetidine: preliminary results

Purpose  Pyloromyotomy has been the treatment of choice for hypertrophic pyloric stenosis (HPS) for the past century. In most HPS cases, there is mild metabolic alkalosis, which requires intravenous fluid resuscitation with 5% dextrose/normal saline for 1–2 days. However, in some cases, due to a delay in diagnosis, alkalosis becomes severe and a much longer resuscitation period (5–10 days) is required to normalize serum pH. Metabolic alkalosis of HPS results from excessive vomiting of hydrochloric acid; and therefore if its production is reduced, serum pH can be normalized faster. In this study, the use of intravenous cimetidine (CM) in a small number of infants with HPS is presented. Methods  Over a 28-month period, 32 HPS cases, including a sub-group of 17 infants (aged 7–9 weeks) with arterial pH >7.60, were admitted to a tertiary referral unit. Four infants in this sub-group were treated with standard resuscitation fluids for 4 days prior to intravenous CM, while 12 infants received CM immediately. Intravenous CM (10 mg/kg) was given at twice daily until arterial pH was less than 7.50. In one case, intravenous omeprazole at 0.1 mg/kg was given instead of CM. Results  In all 17 cases, CM treatment or omeprazole therapy (for 12–48 h) reduced pH to less than 7.50, thus allowing for Ramstedt pyloromyotomy the same day. These patients were allowed oral feeding on the following day and were discharged at 1–3 post-operative days. No complications due to CM (or omperazole) treatment were observed. Conclusion  Intravenous CM administration can rapidly normalize severe metabolic alkalosis in HPS patients. As a result, pyloromyotomy can be performed sooner reducing both hospital stay and costs.     

Acute vulvar ulceration as the main presenting manifestation of hemophagocytic syndrome

A 14-year-old female exhibited an acute vulvar ulcer during the course of hemophagocytic syndrome (HPS). The patient presented persistent high fever and a deep painful vulvar ulcer lasting for more than 2 weeks. Neither infection with sexually transmitted agents nor autoimmune disorder were found to be positive. The presence of hemophagocytosis in the bone marrow and elevation of urinary β-2-microglobulin ( β-2M) prompted the diagnosis of HPS. Acute vulvar ulcer is rare, but it should be recognized as a mucous manifestation of HPS. During the clinical course, urinary β-2M was the most sensitive marker for the evaluation of the disease activity of HPS.     

Pediatric split liver transplantation after Fontan procedure in left isomerism combined with biliary atresia: A case report

LI is a subset of the heterotaxy syndrome and a rare birth defect that involves the heart and other organs. It can be combined with extracardiac abnormalities, especially BA. CHD can be associated with LI in up to 15% of cases, although it is rare in BA. Pediatric LT for a child with ESLD due to BA combined with LI and CHD is a challenging issue for a transplant surgeon. Herein, we report a successful split LT on a three‐yr‐old boy with LI who survived after a Fontan procedure due to single ventricle, but who suffered from HPS associated with BA.