Branched-chain amino acids in sepsis and hepatic failure.

The pathophysiologic mechanisms for the metabolism of hepatic failure and severe sepsis are complex, and in many ways similar. The similarities concern abnormalities in peripheral and hepatic protein metabolism. The ability of enteral and parenteral solutions containing increased amounts of branched-chain amino acids to ameliorate many of the derangements observed in these disease states relates to this shared pathophysiology.

Septic encephalopathy. Evidence for altered phenylalanine metabolism and comparison with hepatic encephalopathy.

We elected to test the hypothesis that the metabolic encephalopathy associated with systemic sepsis may have a pathogenesis that is similar to hepatic encepathology, ie, as the consequence of hepatic dysfunction that induces alterations in synthesis of catecholic and noncatecholic neurotransmitters. Eleven patients with septic encephalopathy were compared with nine patients with septic encephalopathy and nine normal controls with respect to blood and cerebrospinal fluid (CSF) amino acid profile, phenylethylamine and its metabolite phenylacetic acid, and blood ammonia. Blood and CSF levels of phenylacetic acid increased markedly in septic and hepatic encephalopathy while CSF phenylethylamine levels were not increased in either condition, presumably due to rapid turnover. The CSF concentrations of all the aromatic amino acids were increased in hepatic encephalopathy, whereas in the patients with sepsis, only phenylalanine levels were increased. Evidence of stimulated neutral amino acid transport into brain was demonstrated in hepatic not septic encephalopathy and appeared to correlate with the CSF glutamine concentration. Blood ammonia levels were increased in hepatic but not in septic encephalopathy. Our data support the hypothesis that metabolites of phenylethylamine contribute to encephalopathy in systemic sepsis and hepatic failure; however, the entities differ in other respects.

Alterations in carbohydrate metabolism during stress: a review of the literature.

Patients with sepsis, burn, or trauma commonly enter a hypermetabolic stress state that is associated with a number of alterations in carbohydrate metabolism. These alterations include enhanced peripheral glucose uptake and utilization, hyperlactatemia, increased glucose production, depressed glycogenesis, glucose intolerance, and insulin resistance. The hypermetabolic state is induced by the area of infection or injury as well as by organs involved in the immunologic response to stress; it generates a glycemic milieu that is directed toward satisfying an obligatory requirement for glucose as an energy substrate. This article reviews experimental and clinical data that indicate potential mechanisms for these alterations and emphasizes aspects that have relevance for the clinician.

Alterations in fuel metabolism in critical illness: hyperglycaemia.

Hyperglycaemia is common during critical illness and may be viewed teleologically as a means of ensuring an adequate supply of glucose for the brain and phagocytic cells. Under normal conditions, euglycaemia is maintained by neural, hormonal and hepatic autoregulatory mechanisms. Critical illness promotes hyperglycaemia through an activation of the hypothalamic-pituitary-adrenal axis, which in turn increases hepatic glucose production and inhibits insulin-mediated glucose uptake to skeletal muscle. Sustained hyperglycaemia is associated with adverse consequences that demand its control. Appropriate management includes discontinuing causative drugs, correcting hypokalaemia, treating infection and administering insulin. Insulin therapy also appears to be useful for promoting an anabolic response in skeletal muscle.

Confirmation of spurious hypoxemia using continuous blood gas analysis in a patient with chronic myelogenous leukemia.

Patients with extreme leukocytosis or thrombocytosis who have hypoxemia on arterial blood gas analysis may demonstrate normal oxygen saturation using pulse oximetry. The most commonly invoked explanation for this phenomenon is oxygen consumption in the blood gas sample prior to analysis. However, others have challenged the premise that the hypoxemia is spurious. We describe a patient with extreme leukocytosis and hypoxemia in whom normoxia was confirmed by continuous blood gas analysis.

Nutritional support in hepatic encephalopathy.

Hepatic encephalopathy (HE) is a syndrome of global cerebral dysfunction resulting from underlying liver disease or portal-systemic shunting. HE can present as one of four syndromes, depending on the rapidity of onset of hepatic failure and the presence or absence of preexisting liver disease. The precise pathogenesis is unknown but likely involves impaired hepatic detoxification of ammonia as well as alterations in brain transport and metabolism of amino acids and amines. The etiology of malnutrition in hepatic failure is multifactorial. Nutritional deficits may be clinically manifest as marasmus or kwashiorkor, or both. Nutritional support in HE is directed toward reducing morbidity related to underlying malnutrition and concurrent disease. However, reaching nutritional goals is often complicated by protein and carbohydrate intolerance. The use of protein restriction in HE is controversial. Modified formulas that are supplemented in branched chain amino acids may be of value in patients who exhibit protein intolerance with standard feeding solutions or in patients who present with advanced degrees of encephalopathy.

Metabolic derangements in sepsis and septic shock.

This article examines the spectrum of metabolic alterations in sepsis and septic shock. The clinical manifestations, neuroendocrine control, and bioenergetics of the "ebb" and "flow" phases of sepsis are reviewed. Characteristic alterations in carbohydrate, fat, and protein metabolism induced by sepsis are outlined. Finally, the implications of these metabolic alterations for the nutritional support of patients with sepsis are discussed.

Left ventricular outflow tract pulmonary artery fistula in endocarditis.

Patients with infective endocarditis are at risk for the development of a fistulous communication between chambers or great vessels of the heart. The presence of a continuous murmur may suggest the diagnosis. The first case of aortic valve endocarditis complicated by the development of a fistulous communication between the left ventricular outflow tract and the pulmonary artery is reported. Transesophageal Doppler echocardiography did not detect the defect preoperatively. However, pulmonary artery catheterization revealed very high mixed venous oxygen saturation which supported the presence of a left-to-right shunt.

Lactic acidosis.

An understanding of the pathophysiology of lactic acidosis is crucial in facilitating the optimal care of critically ill patients. The relevant biochemistry of lactic acidosis is reviewed, and the more controversial aspects relating to the genesis of the acidosis are highlighted. The current system of classification of lactic acidosis divides etiologies on the basis of the presence or absence of clinical signs of tissue hypoperfusion. Several types of lactic acidosis in which clinical evidence of tissue hypoperfusion is lacking demonstrate hemodynamic evidence of occult hypoperfusion. The diagnostic and therapeutic implications of this observation are discussed. Current diagnostic criteria for lactic acidosis include a pH less than 7.35 and blood lactate concentration greater than 5 to 6 mM/L. An important issue relates to the implications of lactate values that are greater than normal but below this diagnostic range. The use of the oxygen flux test may be valuable in the diagnosis of occult tissue hypoperfusion in patients with low-grade elevations in lactate levels. The current therapy for lactic acidosis involves addressing the primary cause and supportive management. The use of bicarbonate in the therapy for lactic acidosis is controversial due to potential adverse effects on cardiac function. The specifics of this controversy are outlined, and newer therapeutic alternatives are reviewed. The use of blood lactate concentration as a prognostic index may be more useful in patients with shock than without shock.

Nutritional support of the hospitalized patient.

Comprehensive care of patients in hospitals includes assessment of nutritional status and provision of appropriate support. This approach is facilitated by knowledge of the essential differences in metabolism between starved and stressed states. Nutritional assessment and care of patients in a hospital are based on answers to the following questions: Who gets it? When do they get it? How much do they get? What route is used to administer it? What kind do they get? What are common complications of enteral and parenteral support? What nutritional aspects are pertinent to common diseases?

Controversies in lactic acidosis. Implications in critically ill patients.

Lactic acidosis is common in critically ill patients and is usually caused by tissue perfusion that is inadequate to meet metabolic demand. However, it has also been noted in conditions in which tissue perfusion is apparently adequate. Hyperlactatemia can occur in the absence of acidosis, usually in the setting of hypermetabolic disease. Numerous areas of controversy exist regarding the pathogenesis of lactic acidosis, as well as certain of its diagnostic, therapeutic, and prognostic features. Knowledge of these areas of controversy should facilitate the clinician's approach to diagnosis and management.

Lactic acidosis in critical illness.

PURPOSE: This article reviews the current body of knowledge regarding lactic acidosis in critically ill patients. The classification of disordered lactate metabolism and its pathogenesis are examined. The utility of lactate as a metabolic monitor of shock is examined and current therapeutic strategies in the treatment of patients suffering from lactic acidosis are extensively reviewed. The paper is designed to integrate basic concepts with a current approach to lactate in critical illness that the clinician can use at the bedside. DATA SOURCES: Comprehensive review of the available, basic science, medical, surgical, and critical care literature. CONCLUSIONS: The severity of lactic acidosis in critically ill patients correlates with overall oxygen debt and survival. Lactate determinations may be useful as an ongoing monitor of perfusion as resuscitation proceeds. Therapy of critically ill patients with lactic acidosis is designed to maximize oxygen delivery in order to reduce tissue hypoxia by increasing cardiac index, while maintaining hemoglobin concentration. Buffering agents have not been shown to materially affect outcome from lactic acidosis caused by shock. The benefits of other specific therapies designed to reduce the severity of lactic acidosis remain unproven.

Computed tomographic brain scan of thrombotic thrombocytopenic purpura.

Computed tomographic (CT) brain scan findings in a patient with severe thrombotic thrombocytopenic purpura (TTP) are described. Multiple scattered lucencies were noted which correlated with thrombotic occlusions found at autopsy. In this patient, the neurologic manifestations of TTP preceded the haemolytic anaemia. In the correct clinical setting, multiple areas of lucency should suggest multiple infarcts secondary to thrombotic vessel occlusions as a diagnostic possibility.

Reactive hemophagocytic syndrome: a new presentation of disseminated histoplasmosis in patients with AIDS.

We report the cases of six patients with AIDS in whom reactive hemophagocytic syndrome (RHPS) secondary to disseminated histoplasmosis was diagnosed. RHPS was diagnosed by established criteria, including fever (duration of > or = 7 days, with peak temperatures of > 38.5 degrees C), unexplained thrombocytopenia with anemia and/or neutropenia, and bone marrow biopsy findings of hemophagocytic histiocytosis. Disseminated Histoplasma capsulatum infection was diagnosed on the basis of the results of cultures of the bone marrow sample. The serum lactate dehydrogenase (LDH) level was elevated (> 1,000 IU/L) in all patients, and five of six patients had hyperferritinemia (range of ferritin level, 15,848-425,984 ng/mL). Five patients had features resembling severe sepsis with multiorgan dysfunction. Three patients recovered, and the findings of RHPS resolved following therapy with amphotericin B. In patients with AIDS, the combination of fever, cytopenia, elevated serum LDH level (> 1,000 IU/L), and/or hyperferritinemia (ferritin level of > 10,000 ng/mL) is a clue to the diagnosis of RHPS and disseminated histoplasmosis; bone marrow biopsy is valuable in establishing the diagnosis.