Hepatopulmonary syndrome.

The hepatopulmonary syndrome (HPS) is a rare complication of liver cirrhosis and is characterised by the typical triad of liver cirrhosis, arterial hypoxemia, and intrapulmonary vascular dilatation. Except for pleural effusions associated with liver cirrhosis no other disease of the lungs or the heart is detectable. The structural hallmark of HPS is dilatation of pulmonary precapillary vessels which impairs diffusion-perfusion and causes unequal ventilation-perfusion. The diagnosis of HPS is based on PaO2 measurements when breathing room air and 100% oxygen. The increased intrapulmonary vascular diameter allows microbubbles to traverse the lung capillaries when agitated saline is administered intravenously. Only on rare occasions is a patient limited by his pulmonary impairment, the leading morbidity is that of liver disease and its classical complications. Drug therapy is of no proven benefit, oxygen supplementation might improve dyspnea. Vascular embolisation of discrete arteriovenous shunts, if present, or liver transplantation may dramatically improve pulmonary function in selected patients.     

对比增强超声心动图对拟肝移植患者肺内分流的评估价值

背景：晚期肝病患者的肺内血管异常可以导致肺内右向左分流及严重低氧血症，目前国内对筛查肺内血管扩张尚缺乏一种简便、敏感、有效的方法。 目的：评估对比增强超声心动图对晚期肝病肺内分流的临床诊断价值。 设计、时间及地点：前瞻性病例对比观察，于2004-02／2006-02在解放军第四五八医院肝病中心完成。 对象：解放军第四五八医院肝病中心收治的男性拟行肝移植的晚期肝病患者24例。 方法：在无任何血管扩张药治疗情况下例行常规检查。采用对比增强超声心动图筛查晚期肝病患者肺内右向左分流的发生率，并根据左心室微泡的显示程度半定量分析记录为1^＋～3^＋。将患者分为经超声心动图证实有肺内分流组和无肺内分流组。 主要观察指标：拟行肝移植的晚期肝病患者肺内右向左分流的发生率及临床特点。结果：①24例患者中10例（41．7％）经对比增强超声心动图证实肺内右向左分流，左心室显影异常程度1^＋～2^＋，其中6例1^＋，4例2^＋，出现在右心室显影后6～10余个心动周期。②两组患者的年龄、性别、动脉血气分析指标、肝功能指标差异无显著性意义（P〉0．05）。③经超声心动图证实肺内分流组患者的上消化道出血发生率、门脉高压指征脾脏厚度及右心功能参数肺动脉收缩压、Tei指数均高于无肺内分流组（P〈0．05～0．01）。 结论：晚期肝病合并肺内分流而无低氧血症时肺血管扩张比较常见，对比增强超声心动图为诊断肺内血管扩张提供了一种敏感、非创伤的早期检查手段。门脉高压症是发生肺内血管扩张的主要因素，右心室Tei指数可作为评估肺内血管扩张患者右心功能的重要参数。     

Pulmonary aspects of chronic liver disease and liver transplantation

A vast spectrum of pulmonary pathologic conditions occurs in association with chronic liver diseases, and clinically important manifestations, such as arterial hypoxemia, can result. Both pulmonary vascular and parenchymal abnormalities can contribute to the dysfunction, as evidenced by results of pulmonary function tests and gas exchange studies. The clinical implications of identifying such pulmonary problems range from alleviation of symptoms, especially dyspnea, to comprehensive assessment of patients before and after liver transplantation. Physicians should be aware of these potential pulmonary disorders that can complicate liver disease and liver transplantation so that management of affected patients can be improved.     

Rehabilitating patients with hepatopulmonary syndrome using living-related orthotopic liver transplant: a case report

The objective of this study was to rehabilitate a patient with hepatopulmonary syndrome (HPS) who underwent living-related orthotopic liver transplantation (LT). HPS is rare; it presents severe complication in patients with liver disease. A 17-year-old woman with HPS developed portal hypertension after undergoing Kasai's surgery for congenital biliary atresia and underwent a living-related orthotopic LT. After LT, her allograft functioned well, but she continued to have hypoxemia and orthodeoxia. She was referred for rehabilitation for disuse atrophy, contracture of hip and shoulder joints, left common peroneal nerve palsy, and rehabilitation for respiratory dysfunction. By day 106 after LT, her orthodeoxia and disuse atrophy had improved because of daily exercise training and active joint range of motion exercises. Patients with HPS have orthodeoxia and poor responsiveness to oxygen therapy, and correction of hypoxemia after LT may be delayed. Therefore, rehabilitation approaches for patients with HPS should be based on the pathophysiology and characteristics of HPS.     

The effect of severe closed chest trauma on gas exchange

Ventilation and gas exchange lung functions were studied in 110 patients with severe closed chest trauma. In chest trauma that was not accompanied by intrapulmonary traumatic changes the main pathogenetic mechanism of gas exchange damage was marked pain syndrome. Such patients did not suffer from severe arterial hypoxemia and their intrapulmonary shunting did not exceed 15%. Analgesia and, if necessary, lung decompression improved considerably respiratory parameters and prevented the onset of severe pulmonary failure. Patients with intrapulmonary traumatic changes (lung contusion, intrapulmonary hematomas) were characterized by progressing arterial hypoxemia due to a considerable increase in intrapulmonary shunting. These patients are managed mainly by preventive therapy of pulmonary hyperhydration, thorough tracheobronchial cleansing, cough stimulation, prevention of pneumonia.     

肝肺综合征研究进展

肝肺综合征(hepato-pulmonary syndrome,HPS)是在慢性肝病和(或)门脉高压的基础上出现肺内血管异常扩张、气体交换障碍、动脉血氧合作用异常,导致低氧血症及一系列的病理生理变化和临床表现,是终末期肝脏病的严重肺部并发症。动物实验表明肺微血管扩张、血管新生和血管内单核巨噬细胞聚集是导致气体交换异常的主要原因,但具体机制仍不明确。目前HPS尚缺乏有效的治疗药物,肝移植仍是最有效的治疗方法。本研究将重点讨论HPS的发病机制和临床诊治相关的新进展。     

Respiratory dysfunction and pulmonary disease in cirrhosis and other hepatic disorders

End-stage liver disease and its complications are a leading cause of death among adults in the United States, and thousands of patients await liver transplantation. The liver plays a central role in health and homeostasis and thus the diseased liver leads to many deleterious effects on multiple organ systems, including the pulmonary system. We review the general effects of cirrhosis on the respiratory system, including mild hypoxemia, atelectasis, and hepatic hydrothorax. Cirrhosis is associated with 2 unique entities that affect the pulmonary vasculature: hepatopulmonary syndrome and portopulmonary hypertension. Hepatopulmonary syndrome, which is found in approximately 20% of patients awaiting liver transplantation, refers to the triad of hepatic dysfunction, hypoxemia, and intrapulmonary vascular dilations, and responds well to liver transplantation. In portopulmonary hypertension, cirrhosis and portal hypertension lead to pulmonary arterial hypertension, and portopulmonary hypertension has been considered a contraindication for transplantation. Currently, patients must have mild to moderate pulmonary hypertension to be considered for transplantation, and may still require long-term therapy with vasodilators to prevent right-ventricular failure and, consequently, failure of the newly transplanted liver allograft.     

Hepatopulmonary syndrome-attributed extreme hypoxemia and polycythemia revealing liver cirrhosis

We report an unusual case of severe hepatopulmonary syndrome with previously unrecognized cirrhosis, presenting with acute on chronic dyspnoea, extreme hypoxemia, secondary polycythemia as well as direct identification of arteriovenous communications on computed tomography angiography. Hepatopulmonary syndrome, defined as the combination of hepatopathy, arterial deoxygenation and pulmonary vascular dilatation, is increasingly recognized as a life-threatening complication in advanced liver disease and transplant candidacy. It is usually diagnosed in chronic liver disease patients following pre-transplant evaluation or mild dyspnea investigation. Diagnosis relies on the indirect evidence of pulmonary arteriovenous communications suggested by echocardiography with a bubble study. Clinicians need to be aware of this rare but potential acute presentation at the emergency room.     

Severe exercise-induced hypoxemia

Exercise training is an essential component of pulmonary rehabilitation and is associated with improved function and other important outcomes in persons with chronic lung disease. A subset of pulmonary rehabilitation patients experience hypoxemia that may occur or worsen with exercise. For the purpose of this review, severe exercise-induced hypoxemia is defined as an S(pO(2)) of < 89% during exercise, despite use of supplemental oxygen delivered at up to 6 L/min. There is a paucity of evidence and clinical guidelines that address assessment and management of this important manifestation of chronic lung disease. This review presents background of this topic and suggests strategies for assessment, management, and safety measures for patients with severe exercise-induced hypoxemia.     

Mechanisms of gas exchange abnormality in patients with chronic obliterative pulmonary vascular disease.

We have examined the mechanisms of abnormal gas exchange in seven patients with chronic obliteration of the pulmonary vascular bed secondary to recurrent pulmonary emboli or idiopathic pulmonary hypertension. All of the patients had a widened alveolar-arterial oxygen gradient and four were significantly hypoxemic with arterial partial presssures of oxygen less than 80 torr. Using the technique of multiple inert gas elimination, we found that ventilation-perfusion (VA/Q) relationships were only minimally abnormal with a mean of 10% (range, 2--19%) of cardiac output perfusing abnormal units. These units consisted of shunt and units with VA/Q ratios less than 0.1. In addition, the dead space was found to be normal in each patient. There was no evidence for diffusion impairment, and the widened alveolar-arterial oxygen gradient was completely explained by VA/ inequality. Significant hypoxemia occurred only when VA/Q inequality was combined with a low mixed venous oxygen content.     

Diagnosis and treatment of pulmonary hypertension

Primary pulmonary hypertension is a rare disease of unknown etiology, whereas secondary pulmonary hypertension is a complication of many pulmonary, cardiac and extrathoracic conditions. Chronic obstructive pulmonary disease, left ventricular dysfunction and disorders associated with hypoxemia frequently result in pulmonary hypertension. Regardless of the etiology, unrelieved pulmonary hypertension can lead to right-sided heart failure. Signs and symptoms of pulmonary hypertension are often subtle and nonspecific. The diagnosis should be suspected in patients with increasing dyspnea on exertion and a known cause of pulmonary hypertension. Two-dimensional echocardiography with Doppler flow studies is the most useful imaging modality in patients with suspected pulmonary hypertension. If pulmonary hypertension is present, further evaluation may include assessment of oxygenation, pulmonary function testing, high-resolution computed tomography of the chest, ventilation-perfusion lung scanning and cardiac catheterization. Treatment with a continuous intravenous infusion of prostacyclin improves exercise capacity, quality of life, hemodynamics and long-term survival in patients with primary pulmonary hypertension. Management of secondary pulmonary hypertension includes correction of the underlying cause and reversal of hypoxemia. Lung transplantation remains an option for selected patients with pulmonary hypertension that does not respond to medical management.     

The history of long-term oxygen therapy.

Early investigators of oxygen therapy reported an overall clinical improvement in persons with chronic lung disease who received oxygen. Later American and British studies showed that oxygen therapy could decrease pulmonary vascular pressures and red cell mass in some patients with pulmonary hypertension and polycythemia secondary to severe hypoxemia. The British Research Council Study showed that survival rates were significantly higher in patients receiving 15 hours of oxygen than in those receiving no oxygen. The Nocturnal Oxygen Therapy Trial showed that survival rates for persons receiving continuous oxygen therapy has also been shown to improve exercise tolerance and neuropsychiatric function. Further advances in the administration of long-term oxygen therapy and studies in the criteria for its use are needed.     

Continuous positive airway pressure and high-frequency independent lung ventilation in patients with chronic obstructive lung diseases

The original hypoxemia, hypercapnia, high pulmonary hypertension, high resistance of microcirculation vessels, right volumetric ventricular overload, persistent sub-edema of pulmonary intersticium as well as disparity of ventilation and perfusion between both lungs are the main problems in patients with chronic obstructive disease of the lungs (CODL). Such patients are, as a rule, intolerant to the independent lung collaboration or artificial single-stage ventilation (ASV). Patients with respiratory insufficiency, stages 2 and 3, and with a pronounced impaired type of ventilation have originally a deranged blood gas composition, like hypoxemia or hypercapnia. The application of volume-controllable bi-pulmonary ASV in such patients maintains an adequate gas exchange hemodynamics. However, ASV is accompanied by a significantly reduced gas-exchange function of the single ventilated lung and by essentially worsened intrapulmonary hemodynamics. Therefore, what is needed is to use alternative methods of independent lung ventilation in order to eliminate the gas-exchange impairments and to enable surgical interventions at thoracic organs in such patients (who are intolerant to ASV). A choice of a method and means of oxygen supply to the independent lung is of great importance. The possibility to avoid a high pressure in the airways, while maintaining, simultaneously, an adequate gas exchange, makes the method related with maintaining a constant positive pressure in the airways (CPPA) a priority one in case of CODL patients. The use of constant high-frequency ventilation in the independent lung in patients with obstructive pulmonary lesions does not improve the gas exchange or hemodynamics. Simultaneously, a growing total pulmonary resistance and an increasing pressure in the pulmonary artery are observed. Consequently, the discussed method must not be used for the ventilation support of the independent lung in patients with the obstructive type of the impaired external breathing function.     

Pulmonary function studies in acute pulmonary histoplasmosis.

We performed follow-up pulmonary function studies on three patients with acute pulmonary histoplasmosis over a period of several months, and found that the disease is benign and usually responds well to treatment or is self-limiting. There are four major changes in lung function, namely a restrictive defect, an impairment of diffusing capacity, stiff lung, and obstruction in small airways. These changes usually lead to disturbance of ventilation-perfusion ratios and impaired gas transport across alveolar capillary membranes, resulting in arterial hypoxemia. There is also hypocapnia from alveolar hyperventilation commonly found in restrictive and stiff lung syndrome.     

Sports fitness in pulmonary hypertension

In patients with pulmonary hypertension caused by a large ventricular septal defect, the cardiopulmonary performance capacity (CPC) depends on the relation of pulmonary to systemic vascular resistances. Changes in this relation occurring on exercise are mainly due to an exercise - induced fall of the systemic vascular resistance. If the ratio of pulmonary to systemic resistance is below 1 at maximal exercise, the CPC is reduced as a result of the left to right shunt. In case of a pulmonary to systemic resistance ratio of higher than 1 at maximal exercise hypoxemia will be a limiting factor. Only in cases of a moderate degree of pulmonary vascular changes, resulting in a relation of resistances at maximal exercise in the range of 1, will the CPC be normal. Patients with primary pulmonary hypertension always present with reduced CPC as a main symptom. Cardiac output cannot be adequately increased during exercise. Only by excessive peripheral oxygen desaturation can a certain adaptation to the oxygen demand of the exercising organism be possible to a certain degree, though only at low work rates. Uneven perfusion and the corresponding ventilation-perfusion inequality are only moderate. However, due to the widened arterial-venous oxygen difference, ventilation-perfusion inequality with its distinct alveolar-arterial oxygen pressure difference can result in a considerable degree of venous admixture. In adolescents, pulmonary hypertension caused by obstructive lung disease is seen almost only in patients with advanced stages of cystic fibrosis. It is then combined with increased venous admixture, and often with CO2-retention.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chronic active Epstein–Barr virus infection with intrapulmonary shunting: A case report

Chronic active Epstein–Barr virus (EBV) infection (CAEBV) is a high-mortality form of EBV infection. However, chronic hypoxemia is rare in these patients. We herein reported a case of severe hypoxemia due to intrapulmonary shunting in CAEBV. A 17-year-old girl presented with fever, dyspnea, cyanosis, and hepatosplenomegaly. Laboratory tests showed mild liver dysfunction and high copy numbers of EBV-DNA in the peripheral blood. A left supratrochlear lymph node biopsy showed infiltration of highly proliferative T lymphocytes with positive EBV encoded small RNA by in situ hybridization. Technetium-99m-labeled macroaggregated albumin and contrast-enhanced echocardiography confirmed the existence of intrapulmonary shunting, which was probably related to hepatopulmonary syndrome. The final diagnosis was CAEBV with intrapulmonary shunting. The patient was treated with cyclosporine A, etoposide, and dexamethasone. Finally, the patient died of respiratory failure. Intrapulmonary shunting is a rare complication of CAEBV. Early recognition and exploring the cause of hypoxemia should be highlighted in patients with CAEBV.     

肝肺综合征与气体信号分子

肝肺综合征是在慢性肝病、门静脉高压症的基础上,由多种因素共同参与、相互作用而导致低氧血症,肺血管扩张的一种疾病。肝肺综合征的发病机制较复杂且不完全明确,但气体信号分子参与了肺血管张力调节,并导致肺血管扩张。肝肺综合征预后差,严重威胁患者身体健康,积极有效地研究和防治肝肺综合征具有重要意义。本文就气体信号分子在肝肺综合征发病机制中的作用作一综述。     

Right ventricular response to high-dose almitrine infusion in patients with severe hypoxemia related to acute respiratory distress syndrome

OBJECTIVE: To evaluate the effects of high-dose almitrine infusion on gas exchange and right ventricular function in patients with severe hypoxemia related to acute respiratory distress syndrome (ARDS). DESIGN: Prospective study. SETTING: Medicosurgical intensive care department (ten beds). PATIENTS: Nine patients with ARDS and severe hypoxemia (PaO2/FIO2 ratio, <150 torr [20 kPa]). INTERVENTION: High-dose almitrine infusion (16 microg/kg/min for 30 mins). MEASUREMENTS AND MAIN RESULTS: Gas exchange and hemodynamic parameters were recorded before and after almitrine infusion. Right ventricular function was evaluated by using a fast response thermistor pulmonary artery catheter that allowed measurement of right ventricular ejection fraction and calculation of right ventricular end-diastolic and end-systolic volumes. Almitrine did not significantly alter arterial oxygenation and intrapulmonary shunt. Almitrine increased mean pulmonary arterial pressure (MPAP) from 31 +/- 4 to 33 +/- 4 mm Hg (p < .05), pulmonary vascular resistance index from 353 +/- 63 to 397 +/- 100 dyne x sec/ cm5 x m2 (p < .05), and right ventricular end-systolic volume index from 71 +/- 22 to 77 +/- 21 mL/m2 (p < .05); almitrine decreased right ventricular ejection fraction from 36% +/- 7% to 34% +/- 8% (p < .05). Stroke volume index and cardiac index did not change. The almitrine-induced changes in right ventricular ejection fraction were closely correlated with the baseline MPAP (r2 = .71, p < .01). CONCLUSION: In patients with severe hypoxemia related to ARDS, high-dose almitrine infusion did not improve arterial oxygenation and impaired the loading conditions of the right ventricle. The decrease in right ventricular ejection fraction induced by almitrine was correlated with the baseline MPAP. Thus, high-dose almitrine infusion may be harmful in ARDS patients with severe hypoxemia and pulmonary hypertension.     

慢性阻塞性肺疾病患者血气分析与血浆纤维蛋白原的相关性研究

目的：探讨慢性阻塞性肺疾病患者血浆纤维蛋白原（FIB）水平及与血气分析相关性。方法：对30例慢性阻塞性肺疾病患者治疗前后血气分析、血浆纤维蛋白原及30例对照组的血浆纤维蛋白原分别进行测定。结果：血浆纤维蛋白原水平在慢性阻塞性肺疾病加重期患者明显升高，与对照组相比有显著性差异；治疗后血浆纤维蛋白原明显下降，与对照组相比无显著性差异；血浆纤维蛋白原与动脉血氧分压（PaO2）呈负相关。血浆纤维蛋白原与动脉血二氧化碳分压（PaCO2）呈正相关。结论：慢性阻塞性肺疾病患者血浆纤维蛋白原增高，可导致血液高凝状态，并易导致肺小动脉血栓形成、低氧血症和高碳酸血症。临床应改善缺氧、通气及适当的抗凝治疗对控制病情有益。     

Chronic obstructive pulmonary disease: diagnostic considerations

Chronic obstructive pulmonary disease is characterized by the gradual progression of irreversible airflow obstruction and increased inflammation in the airways and lung parenchyma that is generally distinguishable from the inflammation caused by asthma. Most chronic obstructive pulmonary disease is associated with smoking, but occupational exposure to irritants and air pollution also are important risk factors. Patients with chronic obstructive pulmonary disease typically present with coughing, sputum production, and dyspnea on exertion. However, none of these findings alone is diagnostic. The Global Initiative for Chronic Obstructive Lung Disease diagnostic criterion for chronic obstructive pulmonary disease is a forced expiratory volume in one second/forced vital capacity ratio of less than 70 percent of the predicted value. Severity is further stratified based on forced expiratory volume in one second and symptoms. Chest radiography may rule out alternative diagnoses and comorbid conditions. Selected patients should be tested for alpha1-antitrypsin deficiency. Arterial blood gas testing is recommended for patients presenting with signs of severe disease, right-sided heart failure, or significant hypoxemia. Chronic obstructive pulmonary disease also is a systemic disorder with weight loss and dysfunction of respiratory and skeletal muscles.