肝性脑病的药物治疗

肝性脑病常可发生于失代偿肝硬化或各种重型肝炎,指导患者合理饮食、避免诱发因素固然重要,但对已发生的肝性脑病,在去除诱因的基础上采取包括药物治疗在内的综合治疗更为迫切,其中,药物治疗是最重要的治疗方法之一。本文主要介绍一些常用的药物。降血氨治疗动物实验和临床患者监测表明,血氨与肝性脑病的症状和脑电图异常程度相关,所以,氨中毒仍然被认为是肝性脑病的重要机制。而且,降血氨治疗对于缓解肝性脑病的症状有效,所以,降血氨是肝性脑病药物治疗的主要部分。减少氨的产生与吸收1. 乳果糖　乳果糖是人工合成的双糖(6 半乳糖5葡萄…     

Lactulose for Minimal Hepatic Encephalopathy in Patients with Extrahepatic Portal Vein Obstruction

Background/Aims:

Minimal hepatic encephalopathy (MHE) is common in patients with extrahepatic portal vein obstruction (EHPVO). There is no study on the treatment of MHE using lactulose in patients with EHPVO.

Patients and Methods:

Consecutive EHPVO patients were assessed by psychometric (number connection test (NCT-A and B), digit symbol test (DST), serial dot test (SDT), line tracing test (LTT)), and critical flicker frequency (CFF) at inclusion. Patients diagnosed as MHE were treated with lactulose and psychometric tests, CFF, and were reassessed after 3 months.

Results:

Of the 70 patients screened, the prevalence of abnormal psychometric test was as follows: NCT-A (41%), NCT-B (53%), DST (38%), SDT (40%), and LTT (44%). Thirty patients (43%) had two or more than two abnormal (>2 SD) psychometry tests. Lactulose improved MHE in 16/30 (53%) of patients after 3 months of treatment. Arterial ammonia decreased after lactulose treatment compared to baseline (83.7±19.1 vs. 65.1±19.3 μmol/l, P=0.001). A total of 9 (75%) of 12 patients with large spontaneous shunt and 7 (39%) of 18 patients without spontaneous shunt improved with lactulose (P=0.07). CFF in patients with MHE (n=30) was significantly lower than those without MHE (n=40) (38.1±2.4 vs. 41.5±3.1 Hz, P=0.01). CFF was less than 38 Hz in 21 (70%) of 30 patients before treatment and in 10 (33%) patients after lactulose therapy in MHE patients. All patients could tolerate lactulose without any significant side effects. Four patients (13%) developed transient diarrhea in whom dose needed reduction, 3 (10%) did not like its taste but have continued, and 2 (6%) developed abdominal bloating sensation.

Conclusions:

Lactulose is effective in the treatment of MHE in patients with EHPVO.     

Hepatic Encephalopathy Associated with Extensive Portal Hepatic Venous Shunts: A Case Report

Extensive intrahepatic portal-hepatic venous anastomosis is very rare. This report describes a 47-year-old man with cirrhosis who presented with mental confusion and flapping tremor, and in whom percutaneous transhepatic portography and superior mesenteric angiography demonstrated shunting between the portal vein branches and the right hepatic vein. Measurements of pressure, ammonia, and immunoreactive insulin in blood of the portal and right hepatic veins clearly indicated that a large amount of portal vein blood was being shunted into the right hepatic vein. These findings suggest that hepatic encephalopathy in this patient is accounted for at least in part by an intrahepatic portal-hepatic venous shunting.     

Systemic Corticosteroid Therapy for Acute Asthma Exacerbations

Acute exacerbations of asthma may represent reactions to airway irritants or failures of chronic treatment. The costs to both the patient and society are high. Exacerbations often are frightening episodes that can cause significant morbidity and sometimes death. The emergency department (ED) visits and hospitalizations often required lead to significant health care expenses. Thus, preventing and optimizing management of acute exacerbations is critical. Corticosteroids are a cornerstone of asthma therapy. They have been shown to lower admission rates and reduce risk of relapse. This article provides an overview of the role of corticosteroids (including betamethasone, dexamethasone, methylprednisolone, and prednisolone) in the management of acute asthma exacerbations, with an aim toward effective decision making about the choice of therapy.     

Systemic Corticosteroid Therapy for Acute Asthma Exacerbations

Acute exacerbations of asthma may represent reactions to airway irritants or failures of chronic treatment. The costs to both the patient and society are high. Exacerbations often are frightening episodes that can cause significant morbidity and sometimes death. The emergency department (ED) visits and hospitalizations often required lead to significant health care expenses. Thus, preventing and optimizing management of acute exacerbations is critical. Corticosteroids are a cornerstone of asthma therapy. They have been shown to lower admission rates and reduce risk of relapse. This article provides an overview of the role of corticosteroids (including betamethasone, dexamethasone, methylprednisolone, and prednisolone) in the management of acute asthma exacerbations, with an aim toward effective decision making about the choice of therapy.     

Idiopathic Portal Hypertension Associated with Progressive Systemic Sclerosis

Herein we describe the clinical course of a case of idiopathic portal hypertension accompanied by splenomegaly, portal hypertension, and pancytopenia in addition to progressive systemic sclerosis. Immunological studies revealed positive antinuclear antibodies, hypergammaglobulinemia with increases in IgG and IgA, a decrease in peripheral T lymphocytes, and a decrease in the rate of lymphocyte blast transformation induced with phytohemagglutinin. The spleen weighed 1070 g, and the portal pressure was 270 mm H₂O. Esophageal varices were also noted. These findings suggest the possibility of association of some immunological abnormalities with the etiology of idiopathic portal hypertension.     

纳洛酮治疗肺性脑病的研究

目的　研究纳洛酮治疗肺性脑病的效应 ,并探讨其作用机理。方法　选择 48例 COPD并肺脑患者为治疗组。随机另选46例同期住院 COPD并肺脑患者为对照组。在综合治疗措施相同 ,治疗组加用盐酸纳洛酮。结果　治疗组应用纳洛酮 2 4h后 ,与对照组比较。 SBP[(12 0 .3± 8.78) mm Hg比 (95 .2 5± 7.8mm Hg],SPO2 [(96 .6 8± 2 .39) %比 (92± 3.18) % ],Pa O2 [(89.6 1± 10 .2 5 )mm Hg比 (75 .6 8± 12 .78) mm Hg]显著升高 ,P<0 .0 1。 HP[(81.18± 7.98)次 /分比 (91.0 2± 8.6 2 )次 /分 ]R[(2 1.12± 3.0 8)次 /分比(2 5 .32± 8.6 6 )次 /分 ],显著降低 ,P<0 .0 1.结论　纳洛酮治疗肺性脑病 ,能使昏迷和呼吸抑制的病人快速逆转意识障碍 ,解除呼吸抑制     

Transjugular Intrahepatic Portal Systemic Shunt for the Management of Symptomatic Cirrhotic Hydrothorax

Objective: To investigate the safety and effectiveness of performing transjugular intrahepatic portal systemic shunt (TIPS) for the management of symptomatic cirrhotic hydrothorax in patients with advanced cirrhosis. Methods: TIPS was performed by standard technique after portal vein patency had been established by ultrasound. Portal-hepatic vein pressure gradient was determined before and after placement of the shunt. A portal-hepatic vein gradient of less than 12 mm Hg was the treatment goal. Results: Five patients underwent TIPS placement over an 11-month period. Despite use of diuretics, the patients had required a median of seven thoracenteses (range 2–11) for control of symptoms preceding placement of the shunt. A TIPS was placed without serious complications in all live patients. In two patients, insertion of the shunt was associated with no further need for thoracentesis. The other three patients had recurrent need for thoracentesis. These three patients were found to have occluded shunts which were rendered patent by angiopiasty and/or urokinase. Subsequently, two required no further thoracentesis, whereas, in the other patient, the need for thoracentesis was decreased dramatically. Conclusions: TIPS appears to be a safe and useful technique for the management of patients with symptomatic cirrhotic hydrothorax that is refractory to medical therapy. Recurrence of the pleural effusion after placement of TIPS may be an indication of shunt occlusion.     

New Developments in Hypertensive Encephalopathy

Purpose of Review

This review summarizes the latest science on hypertensive encephalopathy and posterior reversible encephalopathy syndrome (PRES). We review the epidemiology and pathophysiology of these overlapping syndromes and discuss best practices for diagnosis and management.

Recent Findings

Diagnosis of hypertensive encephalopathy largely relies on exclusion of other neurological emergencies. We review the extensive causes of PRES and its imaging characteristics. Management strategies have not changed substantially in the past decade, though newer calcium channel blockers simplify the approach to blood pressure reduction. While this alone may be sufficient for treatment of hypertensive encephalopathy in most cases, management of PRES also depends on modification of other precipitating factors.

Summary

Hypertensive encephalopathy and PRES are overlapping disorders for which intensive blood pressure lowering is critical. Further research is indicated to both in diagnosis and additional management strategies for these critical conditions.

     

Portal Hypertension Is Associated With Congestive Encephalopathy and Delirium After Cardiac Surgery

BackgroundVenous congestion might lead to congestive encephalopathy after cardiac surgery. However, objective signs of congestion have yet to be associated with delirium. Portal vein flow pulsatility is a congestion marker that may identify a subgroup of patients at risk.MethodsWe performed a retrospective study and a prospective study in patients undergoing cardiac surgery. Adult patients who underwent portal vein Doppler imaging by the attending physician during usual care in the intensive care unit were included in the retrospective cohort. For the prospective cohort, patients had a cognitive and echocardiographic evaluation the day before surgery and daily for 3 days after surgery. Delirium was independently assessed by the nursing staff in the prospective cohort.ResultsA total of 237 patients in the retrospective cohort and 145 patients in the prospective cohort were included, for whom 1074 portal Doppler evaluations were performed. An association was found between delirium and portal vein pulsatility in the retrospective cohort (odds ratio [OR], 2.69; confidence interval [CI], 1.47-4.90; P = 0.001). In the prospective cohort, significant associations were found between the presence of portal vein pulsatility and the development of cognitive dysfunction and asterixis assessed by the investigators (OR, 2.10; CI, 1.25-3.53; P = 0.005 and OR, 2.23; CI, 1.13; 4.41; P = 0.02, and delirium detected by the nursing staff (hazard ratio, 2.63; CI, 1.13-6.11; P = 0.025). Higher N-terminal pro-beta natriuretic peptide measurements (OR, 4.03; CI, 1.78-9.15; P = 0.001) and cerebral desaturations (OR, 2.54; CI, 1.12-5.76; P = 0.03) were associated with cognitive dysfunction.ConclusionThese data present an association among hepatic congestion, delirium, and encephalopathy in patients undergoing cardiac surgery. Further studies should explore whether those neurological complications may have a congestive origin in some patients.     

Cardiac Toxicity From Systemic Cancer Therapy: A Comprehensive Review

Cardiovascular toxicity is a potential short- or long-term complication of anticancer therapy. Exposure to chemotherapy medications, primarily the anthracycline class, can lead to potentially irreversible clinically significant cardiac dysfunction. The advent of novel biologic agents, including monoclonal antibodies and tyrosine kinase inhibitors, has revolutionized the treatment of several types of malignancies. Although targeted therapies are considered less toxic and better tolerated by patients compared with classic chemotherapy agents, rare serious complications have been observed; and longer-term follow-up is needed to determine the exact profile of related cardiac adverse effects. Cardiac toxicity associated with cancer therapies can range from asymptomatic subclinical abnormalities, including electrocardiographic changes and temporary left ventricular ejection fraction decline, to life-threatening events such as congestive heart failure or acute coronary syndromes. Assessment of the prevalence, type, and severity of cardiac toxicity caused by various cancer treatments is a critical topic for patient management and specifically for new drug development. Guidelines for monitoring cardiac adverse effects have been formulated; however, appropriate supportive evidence remains limited. Given the rate of new drug development designed to fulfill unmet oncologic needs, efforts are needed to promote strategies for cardiac risk detection and management and to avoid unintended consequences potentially impeding development of, regulatory approval for, and patient access to novel therapies. These advances require ongoing research to assess and manage the cardiovascular safety of patients treated with anticancer agents, as well as a well-organized collaboration between oncologists and cardiologists. The aim of this review is to summarize potential cardiovascular toxicities for a range of cancer chemotherapeutics and to review general mechanisms of cardiovascular toxicity for each agent.     

Pathophysiology of Hepatic Encephalopathy: A New Look at Ammonia

Results of neuropathologic, spectroscopic, and neurochemical studies continue to confirm a major role for ammonia in the pathogenesis of the central nervous system complications of both acute and chronic liver failure. Damage to astrocytes characterized by cell swelling (acute liver failure) or Alzheimer Type II astrocytosis (chronic liver failure) can be readily reproduced by acute or chronic exposure of these cells in vitro to pathophysiologically relevant concentrations of ammonia. Furthermore, exposure of the brain or cultured astrocytes to ammonia results in similar alterations in expression of genes coding for key astrocytic proteins. Such proteins include the structural glial fibrillary acidic protein, glutamate transporters, and peripheral-type (mitochondrial) benzodiazepine receptors. Brain–blood ammonia concentration ratios (normally of the order of 2) are increased up to fourfold in liver failure and arterial blood ammonia concentrations are good predictors of cerebral herniation in patients with acute liver failure. Studies using ¹H magnetic resonance spectroscopy in patients with chronic liver failure reveal a positive correlation between the severity of neuropsychiatric symptoms and brain concentrations of the brain ammonia-detoxification product glutamine. Increased intracellular glutamine may be a contributory cause of brain edema in hyperammonemia. Positron emission tomography studies using ¹³HN₃ provide evidence of increased blood–brain ammonia transfer and brain ammonia utilization rates in patients with chronic liver failure. In addition to the use of nonabsorbable disaccharides and antibiotics to reduce gut ammonia production, new approaches to the treatment of hepatic encephalopathy by lowering of brain ammonia include the use of L-ornithine–L-aspartate and mild hypothermia.     

Estrogen Therapy in Systemic Lupus Erythematosus

Given the female preponderance of systemic lupus erythematosus (SLE) in humans, the adverse effects of female gender and sex hormones in murine lupus, and numerous reports (retrospective, often anecdotal and uncontrolled) that describe a temporal association between estrogen exposure and development or exacerbation of SLE, it is tempting to accept that estrogens and SLE simply do not mix. While there are valid concerns regarding the use of exogenous estrogens in women with SLE, there are also potential health benefits to be considered. Oral contraceptives (OCs) offer effective birth control and may be bone protective in corticosteroid-treated patients. Recent studies, albeit retrospective, suggest that OCs are well tolerated in patients with SLE. Several salutary effects of postmenopausal estrogens assume particular importance in SLE where the risks of osteoporosis, exaggerated by menopause (natural or cyclophosphamide-induced) and corticosteroids, are substantial. However, the results of the Women's Health Initiative trial significantly limit the use of hormone replacement therapy in the general population, and raise particular concern for SLE patients. Other exogenous hormones (clomifene, gonadotropins, gonadotropin-releasing hormones) may be used to elevate levels of endogenous estrogen and to stimulate ovulation in patients with diminished fertility. Patients with inactive or stable/moderate disease and at low risk for thrombosis may benefit from OCs and other hormonal therapies without a change in lupus activity. Large prospective, double-blind, placebo-controlled studies inclusive of all ethnic groups should provide the basis for more definitive recommendations.     

Interrelationship between Type of Spontaneous Portal Systemic Shunt and Portal Vein Pressure in Patients with Liver Disease

The interrelationship between the type and degree of spontaneous portal systemic shunting, and portal vein pressure was studied in 155 patients with liver disease by catheterizing the portal vein. The degree of portal vein shunting was measured in 100 patients and that of splenic vein shunting in 50 and that of total portal systemic shunting in 52, using macroaggregated radioalbumin. Increasing portal vein pressures were associated with progressively higher indices of portal vein shunt, splenic vein shunt, and total portal systemic shunt up to a certain level. Beyond this level, portal vein pressure did not increase further, and rather it decreased with further increasing degrees of splenic vein shunt and total portal systemic shunt. These results indicate that spontaneous portal systemic shunt keeps the portal vein pressure within certain limits or decreases it.     

Chronic Systemic Endotoxin Exposure: An Animal Model in Experimental Hepatic Encephalopathy

Plasma levels of gut-derived endotoxins (lipopolysaccharides, LPS) are often elevated in cirrhotics and are thought to contribute to hepatic encephalopathy. Circulating LPS activates macrophages to produce tumor necrosis factor ά (TNF-ά) and other potentially cytotoxic proinflammatory mediators. A pathogenic role forendotoxins is supported by studies showing that treatment with Lactobacillusor antibiotics, both of which reduce LPS-producingintestinal Gram-negative bacteria, alleviates experimental liver damage. To mimic the “leaky gut” syndrome with endotoxin translocation into the circulation in cirrhotics, a new animal model was developed. Rats were chronically exposed to ethanol and for the four last weeks also infused with endotoxin into the jugular vein from subcutaneously implanted osmotic minipumps. Animals receiving endotoxin had elevated hepatic expression of both pro- and anti-inflammatory cytokines, but compared to ethanol treatment alone hepatic steatosis and inflammatory changes were only marginally increased. This demonstrates marked endotoxin tolerance, probably as a consequence of a counteracting anti-inflammatory cytokine response. The role of gut-derived endotoxin in hepatic encephalopathy has recently received considerable attention. To further delineate the role and actions of endotoxin and its extrahepatic effects, studies applying both acute challenge and chronic infusion seem warranted. The chronic endotoxin model, mimicking the “leaky gut,” may best be combined with more robust ways to impair liver function, such as carbon tetrachloride treatment, bile duct ligation, or galactosamine administration.     

A New Look at Precipitants of Overt Hepatic Encephalopathy in Cirrhosis

Digestive Diseases and Sciences - Overt hepatic encephalopathy (HE) is a major cause of significant morbidity and mortality in patients with liver cirrhosis. We examined the frequency and profile...