Severe Hepatopulmonary Syndrome Research Articles

Hepatopulmonary syndrome

Hepatopulmonary syndrome

Liver Transplantation: Perioperative Care and Update on Intraoperative Management

We will present some relevant concepts on the preoperative evaluation of patients with end-stage liver disease and describe some new intraoperative management strategies for liver transplantation. This review is limited to three topics: cardiac issues, pulmonary issues, and coagulation issues. While dobutamine stress echocardiography and myocardial perfusion scintigraphy are the most common screening methods for coronary artery disease, computed tomography techniques are gaining popularity although their value is still unclear. Positive screening tests should be followed by coronary angiography and revascularization. Severe valvular heart disease has to be corrected before transplantation is attempted; percutaneous techniques virtually eliminate the risk of acute hepatic failure frequently associated with cardiopulmonary bypass in patients with severe liver disease. Extracorporeal membrane oxygenation is a viable treatment option when severe pulmonary and cardiac complications develop. Patients with severe hepatopulmonary syndrome can undergo successful liver transplantation, but portopulmonary hypertension remains challenging. Perioperative coagulation management will likely evolve with the availability of prothrombin complex concentrate and fibrinogen concentrate. Rather than trying to provide a complete discussion, we emphasize new and interesting findings with significant clinical significance.

Impact of Bacterial Translocation on Hepatopulmonary Syndrome: A Prospective Observational Study.

Hepatopulmonary syndrome (HPS) is characterized by a defect in oxygenation induced by pulmonary vascular dilatation in cirrhosis. While severe HPS is responsible for a high rate of mortality, the prevalence and pathophysiology of HPS are not fully elucidated. We evaluated the prevalence and pathophysiology of HPS in patients with cirrhosis. A total of 142 patients with cirrhosis who underwent saline-agitated contrast echocardiography were enrolled in this prospective observational study. HPS was defined by positive findings on contrast echocardiography, cirrhosis, and the presence of an oxygenation defect (alveolar-arterial oxygen gradient>15mmHg). HPS grades from 0 to 3 were assigned based on the density and spatial distribution of microbubbles in the left ventricle. The primary endpoint was the prevalence of HPS. The secondary endpoints included clinical characteristics and levels of lipopolysaccharide (LPS), LPS-binding protein (LBP), nitric oxide, and endothelin-1 in HPS. Fifty-nine patients (41.5%) were diagnosed with HPS (grade 1: 24, grade 2: 23, and grade 3: 12 patients). The mean levels of LPS (0.36±0.02, 1.02±0.18, 2.86±0.77, and 6.56±1.46 EU/mL, p<0.001) and LBP (7026±3336, 11,445±1247, 11,947±1164, and 13,791±2032ng/mL, p=0.045) were found to be increased according to HPS grade (negative, grade 1-3). Endothelin-1 levels were significantly elevated according to HPS grade (1.83±0.17, 2.62±0.22, 3.69±0.28, and 4.29±0.34pg/mL, p<0.001), demonstrating a significant difference between each grade (p<0.05). HPS is a common complication with a prevalence of 41.5% in patients with cirrhosis. Bacterial translocation and portal pulmonary vascular dilatation are key mechanism involved in the progression of HPS.

Extracorporeal membrane oxygenation for post-transplant hypoxaemia following very severe hepatopulmonary syndrome

Hepatopulmonary syndrome (HPS) associated with end-stage liver disease has a high morbidity when room air PaO2 is less than 50 mm Hg. Safe levels of oxygenation to facilitate transplantation have...

Prolonged Unexplained Hypoxemia as Initial Presentation of Cirrhosis: A Case Report

Patient: Male, 43Final Diagnosis: Hepatopulmonary syndromeSymptoms: DyspneaMedication: —Clinical Procedure: —Specialty: Gastroenterology and HepatologyObjective:Unusual clinical courseBackground:Hepatopulmonary syndrome (HPS) is a pulmonary complication of advanced liver disease with dyspnea as the predominant presenting symptom. The diagnosis of HPS can often be missed due to its nonspecific presentation and the presence of other comorbidities.Case Report:We present an interesting case of an obese 43-year-old man who presented with progressive, unexplained hypoxemia and shortness of breath in the absence of any symptoms or signs of chronic liver disease. After extensive cardiopulmonary investigations, he was diagnosed with severe HPS as a result of non-alcoholic steatohepatitis (NASH) leading to cirrhosis. He subsequently underwent successful hepatic transplantation and continues to improve at 12-month follow-up.Conclusions:HPS needs to be considered in the differential diagnosis of unexplained hypoxemia. Given its poor prognosis, early diagnosis is warranted and treatment with liver transplantation is the preferred choice.

Hepatopulmonary syndrome and liver transplantation: the review and a case report

Hepatopulmonary syndrome is a liver disease complication characterized by the clinical triad of an advanced chronic liver disease, a pulmonary vascular dilatation, and a reduced arterial oxygenation (hypoxemia: PaO2 less than 70 mm Hg at rest) in the absence of intrinsic cardiopulmonary disease. Precapillary vasodilatation, intrapulmonary angiogenesis and hyperdynamic circulation lead to arteriovenous shunting and reduced gas diffusion. In case of detecting macroscopic shunts, the pulmonary artery branch embolization could be performed. However, the hepatopulmonary syndrome can be cured nowadays by means of liver transplantation only. A 5-year survival in these patients is about 70%. The observed mortality is the highest during the surgery or early after, especially in patients with PaO2 lower than 50 mm Hg. It ranges from 8.5 to 29%. A prolonged oxygenation support is often required after liver transplantation using invasive or non-invasive ventilation, or even extracorporeal membrane oxygenation. In this review, we have focused on the recent advances in this field as described in available literature and have presented a case report of successful liver transplantation in a patient with a severe hepatopulmonary syndrome.

Liver Transplantation After Bone Marrow Transplantation for End Stage Liver Disease with Severe Hepatopulmonary Syndrome in Dyskeratosis Congenita: A Literature First

Dyskeratosis congenita is a multisystem genetic disorder. Although hepatic involvement is reported in about 7% of patients with dyskeratosis congenita, it is not well characterized and often attributed to hemochromatosis from frequent blood transfusions. A few case reports describe cirrhosis and hepatic cell necrosis in affected individuals in autosomal dominant pedigrees. Bone marrow failure and malignancies are the principal causes of death in dyskeratosis congenita. We describe the first case of living donor liver transplantation, in dyskeratosis congenita for decompensated cirrhosis with portal hypertension. The patient also had associated severe hepatopulmonary syndrome, interstitial lung disease, bilateral hip replacement for avascular necrosis of the head of femur, and a past history of bone marrow transplantation for bone marrow failure.

Dyskeratosis congenita induced cirrhosis for liver transplantation-perioperative management.

Dyskeratosis congenita (DC) is an inherited disorder with progressive multisystem involvement. End stage liver disease (ESLD) in patients with DC is rare. We describe the perioperative management of a patient with DC induced ESLD and severe hepatopulmonary syndrome for living donor liver transplantation.

Pulmonary complications in liver diseases

Pulmonary-hepatic vascular disorders are frequent complications in patients with portal hypertension and cirrhosis. Hepatopulmonary syndrome (HPS), portopulmonary hypertension (POPH), and hepatic hydrothorax are relevant disease entities in these patients. HPS occurs in up to 30 % of patients with cirrhosis and is associated with a more than 2-fold increased mortality. The diagnosis of HPS should be established early by arterial blood gas analysis and contrast-enhanced echocardiography, whereas POPH is diagnosed by the presence of pulmonary arterial hypertension evaluated via right heart catheterization and the presence of portal hypertension. Therapeutic options include initiation of long-term oxygen therapy and liver transplantation in patients with severe HPS. Patients with POPH should receive targeted medical therapies with endothelin receptor antagonists, phosphodiesterase-5 inhibitors and/or prostanoids. In contrast, β-blockers should be avoided. This review summarizes current knowledge regarding pulmonary-hepatic vascular disorders, with a focus on HPS.

The successful use of inhaled nitric oxide in the management of severe hepatopulmonary syndrome after orthotopic liver transplantation.

Hepatopulmonary syndrome (HPS) is characterized by pulmonary vasodilation and subsequent hypoxemia in the setting of hepatic dysfunction. There is currently no pharmacologic intervention that has been shown to significantly affect outcomes and liver transplantation remains the mainstay of therapy. Unfortunately, patients undergoing liver transplantation are at high risk of significant hypoxemia and mortality in the early postoperative period. In the following case series, we present two cases of patients with severe HPS who underwent liver transplantation and experienced marked hypoxemia in the early postoperative period. In both cases, we successfully treated the patients with inhaled nitric oxide for their severe refractory life-threatening hypoxemia which led to immediate and dramatic improvements in their oxygenation. Although the use of inhaled nitric oxide in patients with HPS has been sporadically reported in pediatric literature and in animal studies, to our knowledge, our cases are the first recorded in adult patients.

The Frequency and Significance of Portopulmonary Venous Anastomosis (PPVA): A Case Report and Literature Review

A Portopulmonary Venous Anastomosis (PPVA) is a direct vascular connection between the portal venous system and the pulmonary veins, close to the left atrium. We describe a patient with advanced cirrhosis and moderately severe Hepatopulmonary Syndrome (HPS) in whom (PPVA) was demonstrated by a high resolution computed tomographic scan. In order to reduce the symptoms of hypoxia in our patient, we sequentially performed Transjugular Intrahepatic Portosystemic Shunt (TIPS) followed by a catheter based obliteration of the PPVA. The case raised three questions which were addressed through an extensive literature review. Among patients with advanced cirrhosis, what is the frequency of PPVA? Our literature review suggests that the frequency of finding a PPVA in patients with portal hypertension depends on the imaging technique used. Transhepatic or transvenous portal venography may demonstrate PPVA in about 20% of patients with cirrhosis and varices. Limited published experience with contrast enhanced (bubble) echocardiography suggests that PPVA may be present in about 30% of such patients. An increasing number of case reports of PPVA have been published in recent years. This observation indicates that routine use of High Resolution Computed Tomography (HRCT) and magnetic resonance imaging is able to identify PPVA in cirrhotic patients. The visualization of PPVA with HRCT depends on the timing of the contrast injection and the expertise of the viewer. Among cirrhotic patients with PPVA, what is the clinical significance of the PPVA? There are multiple causes of clinically significant hypoxia in patients with cirrhosis. A PPVA is a right to left shunt that, theoretically, could be associated with clinically significant systemic arterial hypoxemia or emboli. There is not definitive evidence in the published literature that PPVA alone causes clinically significant hypoxia in cirrhotic patients. PPVA is, however, a documented important risk factor for systemic emboli when needle or catheter techniques are used to treat or prevent bleeding from gastroesophageal varices. What is the evidence that the obliteration of a documented PPVA will improve oxygenation in a cirrhotic patient with hypoxemia? Modern imaging methods may demonstrate a PPVA when patients with cirrhosis are investigated because of hypoxia. Previous authors have argued that the right to left shunting of blood in a PPVA does not have enough flow to significantly lower arterial oxygen concentration. Our report documents that the obliteration of a PPVA can be accomplished. However, our patient's oxygenation did not improve with obliteration of the PPVA. We do not believe that PPVA causes hypoxia. But knowledge of the frequency and clinical significance of PPVA is important for the care of patients with cirrhosis.

The Use of Transtracheal Oxygen Therapy in the Management of Severe Hepatopulmonary Syndrome After Liver Transplantation

Hepatopulmonary syndrome (HPS) is a unique form of hypoxemia found in patients who have chronic liver disease. The definitive treatment for HPS is liver transplantation (LT), with resolution of hypoxemia occurring weeks to months after LT. Because there has been an increase in the use of LT to treat severe HPS (PaO2 ≤ 50 mm Hg), alternatives to oxygen administration via nasal cannula (NC) or face mask must be examined to facilitate early postoperative mobilization and to minimize postoperative pulmonary complications. Transtracheal oxygen (TTO) therapy is a practical alternative that has been shown to improve oxygen requirements, facilitate patient mobility, and improve exercise tolerance in advanced lung disease. In this case series, we describe the use of TTO in the management of hypoxemia associated with severe HPS after LT. A transition from NC to TTO resulted in a significant reduction in oxygen requirements, early postoperative mobilization and discharge from the hospital, and a subsequent expedited liberation from supplemental oxygen. This case series emphasizes the potential utility of TTO therapy as an alternative to conventional oxygen delivery modalities in the management of severe HPS after LT.

Excellent outcome of living donor liver transplantation in patients with hepatopulmonary syndrome: a single centre experience

Hepatopulmonary syndrome (HPS) worsens the prognosis of cirrhosis and liver transplantation is only definitive treatment. There is paucity of data about role of living donor liver transplantation (LDLT) in HPS. Fourteen patients with HPS and cirrhosis who underwent LDLT were prospectively included. HPS was defined as PaO2 < 80 mmHg in presence of demonstrable macro-aggregated albumin (MAA) scan shunt fraction >6%. The study group composed of 11 male and three female patients, mean age 50.3 ± 8.6 yr. Most common presentations were dyspnea (92.8%), cyanosis (78.5%) and clubbing (64.2%). Mean model for end-stage liver disease (MELD) score was 18.2 ± 4.7, mean MAA shunt fraction was 23.0 ± 13.2%, mean PaO2 was 58.7 ± 8.4 mmHg. Two patients had very severe HPS (PaO2 <50 mmHg), five had severe HPS (PaO2 >50 <60 mmHg) and seven had moderate HPS (PaO2 >60 <80 mmHg). All patients underwent right lobe LDLT. The overall time to extubation was 2 (1-32 days) and for hospital stay was 20 (17-46 days). The main complications in post-LT course were infection in 57% (cytomegalovirus or bacterial). All the patients are alive and off oxygen at a mean follow up of 29 ± 25 months. We report one of the largest series of LDLT in HPS which has shown excellent results.

Methylene Blue “Avatar” Brain

Methylene blue is a safe and effective therapeutic agent used in a variety of different clinical settings, including as treatment for methemoglobinemia, reversing ifosfamide-induced encephalopathy, severe hepatopulmonary syndrome, and as a pressor during catecholamine-refractory septic shock (1). Of more relevance to neuropathologists, it has recently been experimentally tested as a dye in multimodal confocal imaging of brain tumors for intraoperative detection of brain tumors (2), for ischemic/reperfusion injury (3), and, because it seems to prevent aggregation of tau and β-amyloid, as a potential therapeutic agent for neurodegenerative disorders such as Alzheimer disease (4) and Huntington disease (5, 6). As such, neuropathologists may encounter patients at autopsy treated with methylene blue. Methylene blue generates a clinically innocuous, self-limiting, but striking blue-green discoloration to the urine, skin, and mucosa of treated individuals as a by-product of its use (1, 7, 8). This systemic tissue discoloration is more well known than is discoloration of brain tissues, which, to our knowledge, has only been reported once previously (9). The tissues were reported to transform into a bright blue-green color when the colorless leukomethylene blue molecule undergoes oxidation to methylene blue on exposure to air (9). We share our recent experience with brain tissue discoloration and methylene blue use, capturing the transition from colorless to colorful during a very short time interval at the time of autopsy. A 20-year-old woman with asthma and surgically repaired coarctation …

Transition from Hepatopulmonary Syndrome to Portopulmonary Hypertension: A Case Series of 3 Patients

Hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PPHTN) are the two major pulmonary vascular complications of liver disease. While HPS is characterized by low pulmonary vascular resistance, PPHTN is defined by the presence of elevated pulmonary vascular resistance. Given these seemingly opposing pathophysiologic mechanisms, these conditions were traditionally felt to be mutually exclusive. In this series, we present three patients with severe hepatopulmonary syndrome who had spontaneous resolution of their HPS with the subsequent development of PPHTN. To our knowledge, this is the largest case series presented of this phenomenon in nontransplanted patients. One proposed mechanism for the occurrence of this phenomenon involves dysregulation of the same vascular signaling pathway, which may lead to both pulmonary vascular dilatations and pulmonary arterial remodeling in the same patient. Another theory involves the possible differential binding of endothelin-1, a vasoactive signaling peptide that induces vasoconstriction when bound to receptor A and vasodilation when bound to receptor B. Although the mechanisms for this phenomenon remain unclear, it is important to be vigilant of this phenomenon as it may change the patient's overall treatment plan, especially in regard to appropriateness and timing of liver transplant.

Hypertrophic Osteoarthropathy Associated to Liver Cirrhosis

The patient, a 45-year-old male, was referred to the rheumatology clinic due to diffuse joint pain on the wrists and knees. The patient was diagnosed with liver cirrhosis and severe hepatopulmonary syndrome. Physical examination showed swelling of the knees and wrists (arthritis) and clubbing. The X-rays requested showed periosteal thickening observed continuously, in a diaphysometaphysiary location of the radius and ulna in both forearms, and predominantly in distal femurs and both knees, compatible with nonaggressive periosteal reaction. Fig. 1 shows periosteal thickening affecting both femurs on the concave bone edge and respecting the epiphysis, and equal involvement of the radius and ulna on the right wrist, in Fig. 2.

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Case Reports: Hepatopulmonary syndrome (HPS) is defined as a clinical triad of chronic liver disease, abnormal pulmonary gas exchange resulting in arterial hypoxemia, and evidence of intrapulmonary vascular dilations producing a right to left intrapulmonary shunt. The only definitive treatment option is liver transplantation, with an anticipated improvement and subsequent resolution of hypoxemia weeks to months following transplantation. In light of an increasing trend to transplant patients with severe HPS characterized by profound hypoxemia, practical alternatives to high flow nasal cannula (HFNC) need to be considered in order to facilitate post-transplant patient mobilization and early discharge from the hospital while treating severe hypoxemia. To this end, we describe our experience with the application of transtracheal oxygen therapy in the management of post-operative hypoxemia following OLT for severe HPS in three patients. Persistent arterial hypoxemia in the immediate post-operative period required the use of high-flow nasal cannula (HFNC) oxygen. Although allograft function steadily improved, the patients’ hypoxemia did not improve in the immediate post-operative period, and they subsequently underwent placement of a transtracheal oxygen (TTO) catheter to facilitate mobilization and weaning from HFNC. Therapy with oxygen via the TTO catheter led to early patient mobilization and discharge, and rapid weaning and eventual liberation from supplemental oxygen. To our knowledge, this is the first report of such a management technique for this unique group of patients. Our observations highlight the utility of transtracheal oxygen therapy in the management of severe HPS after liver transplantation.

Review article: liver transplantation for the pulmonary disorders of portal hypertension

Liver transplantation is potentially a life-saving therapeutic intervention for patients with portopulmonary hypertension and hepatopulmonary syndrome. However, due to limited data, listing criteria for patients with these conditions have not been clearly established. Indeed, this has led some to speculate that transplantation may not be appropriate in cases of moderate-to-severe portopulmonary hypertension and severe hepatopulmonary syndrome. To critically discuss the utility of LT for the treatment of hepatopulmonary syndrome and portopulmonary hypertension. A literature search was conducted in 2012 on PubMed, Ovid Embase, Ovid Medline and Scopus using the following search terms: hepatopulmonary syndrome, portopulmonary hypertension, pulmonary arterial hypertension, liver transplantation. Relevant manuscripts were included in the review. Liver transplantation has established itself as an effective treatment for selected patients with hepatopulmonary syndrome and portopulmonary hypertension. A multidisciplinary team approach incorporating focused strategies (both pre- and post-operatively) aimed at improving oxygenation in patients with hepatopulmonary syndrome has led to a dramatic improvement in patient outcomes. Additionally, careful patient selection and the use of targeted pulmonary vascular therapies are successfully being used to treat portopulmonary hypertension and 'bridge' patients to successful liver transplantation. Liver transplantation is an effective therapy for patients with hepatopulmonary syndrome and portopulmonary hypertension. However, rigorous screening and early identification of these conditions allied with aggressive pre-operative optimisation of physiology and diligent post-operative care are imperative to ensuring a good outcome.

Reversal of severe hepatopulmonary syndrome in chronic hepatic cirrhosis by living donor liver transplantation: Report of two cases

Severe hepatopulmonary syndrome (HPS) is a rare complication of decompensated liver cirrhosis and a relative contraindication for liver transplantation. This report describes the treatment of two cases with severe HPS resulting from chronic liver failure by living donor liver transplantation (LDLT). The clinical data of the two cases were reviewed. The parameters included the intrapulmonary shunt ratio as measured by (99m)Tc pulmonary scintigraphy, perioperative treatment and examination results, and the duration of post-transplant hypoxemia. Liver dysfunction was reversed in both patients 2-3 weeks after LDLT. Both patients experienced slightly increased intrapulmonary shunt ratios in the first postoperative month, followed by substantial decreases at postoperative days 90 and 361. These findings suggest severe HPS can be resolved by LDLT. Pulmonary infection requires proper treatment and may be anticipated during the early postoperative course. The differences in the intrapulmonary shunt ratio between these patients may contribute to the differences in the time required for rehabilitation.

Living donor liver transplantation for end-stage liver disease with severe hepatopulmonary syndrome: Report of a case

Hepatopulmonary syndrome (HPS) is a serious complication of terminal liver disease, which manifests as severe hypoxia without any pulmonary anatomic or functional causes. The precise indications for liver transplantation in patients with severe HPS also remain unclear. A 49-year old woman was referred to our department for investigation and management of liver cirrhosis with severe hypoxia (PaO(2), 38 mmHg). A pulmonary perfusion scintigram showed an intrapulmonary shunt ratio of 40%, confirming a diagnosis of severe HPS. She underwent living donor liver transplantation using a right lobe graft donated by her 27-year-old daughter. Her post-transplant graft function was excellent, and her oxygenation recovered slowly but steadily. She was discharged from hospital on posttransplant day 39 with an SpO(2) of 94% under 3 l/min of O(2), delivered nasally. Despite the severity of the HPS, her postoperative recovery was smooth after the liver transplant.