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      Effects of Polymyxin B-Immobilized Fiber Hemoperfusion on Amino Acid Imbalance in Septic Encephalopathy

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          Background: Septic encephalopathy is a common term denoting the signs of progressing central nervous system dysfunction in septic patients. Metabolic alterations including amino acid imbalance are involved in the pathogenesis of septic encephalopathy. The aim of the present study was to determine whether the ratio of branched-chain amino acids to aromatic amino acids is altered in patients with septic encephalopathy and whether polymyxin B-immobilized fiber (PMX-F) hemoperfusion affects this balance. Methods: 16 septic patients with encephalopathy, 10 septic patients without encephalopathy, and 20 healthy controls were included in this study. Sepsis was diagnosed according to the ACCP/SCCM Consensus Conference criteria. Plasma endotoxin levels, interleukin-6 (IL-6) levels, and amino acid ratios were measured before and after PMX-F treatment. Results: Within 12 h of the onset of septic encephalopathy, plasma endotoxin and IL-6 levels were increased significantly in septic patients with encephalopathy in comparison to those in septic patients without encephalopathy (endotoxin, p < 0.05; IL-6, p < 0.01) and those in healthy controls (endotoxin; p < 0.001; IL-6, p < 0.001). The ratio of branched-chain amino acids to aromatic amino acids in septic patients with encephalopathy was decreased in comparison to the ratio in septic patients without encephalopathy (p < 0.05) and that in healthy controls (p < 0.01). PMX-F treatment reduced plasma endotoxin (p < 0.01) and IL-6 levels (p < 0.01) and increased the ratio of branched-chain amino acids to aromatic amino acids (p < 0.01). Conclusion: The amino acid imbalance in patients with septic encephalopathy may be a marker for the severity of the septic syndrome, and PMX-F hemoperfusion is effective in ameliorating the increased plasma endotoxin and IL-6 levels and the amino acid imbalance in these patients.

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          Most cited references 9

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          Pathophysiology of septic encephalopathy: a review.

          Encephalopathy is a common complication of sepsis. This review describes the different pathologic mechanisms that may be involved in its etiology. The studies described here were derived from the database PubMed (http:¿¿ and from references identified in the bibliographies of pertinent articles and books. The citations are largely confined to English language articles between 1966 and 1998. Older publications were used if they were of historical significance. All investigations in which any aspect of septic encephalopathy was reported were included. This selection encompasses clinical, animal, and in vitro cell culture work. The literature cited was published in peer-reviewed clinical or basic science journals or in books. Contradictions between the results of published studies are discussed. The most immediate and serious complication of septic encephalopathy is impaired consciousness, for which the patient may require ventilation. The etiology of septic encephalopathy involves reduced cerebral blood flow and oxygen extraction by the brain, cerebral edema, and disruption of the blood-brain barrier that may arise from the action of inflammatory mediators on the cerebrovascular endothelium, abnormal neurotransmitter composition of the reticular activating system, impaired astrocyte function, and neuronal degeneration. Currently, there is no treatment.
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            Treatment of sepsis by extracorporeal elimination of endotoxin using polymyxin B-immobilized fiber.

             T Tani,  H. Aoki,  M Kodama (1994)
            Despite the use of potent antibiotics and intensive supportive care, mortality remains high among septic shock patients, especially those with endotoxemia. To remove endotoxin directly from the blood, a material consisting of polymyxin B that is immobilized on fibers (PMX-F) and that can selectively detoxify endotoxin was developed. In a preliminary clinical study, 16 patients with septic multiple organ failure were treated with direct hemoperfusion using a PMX-F column. This therapy significantly decreased the endotoxin level from 76 pg/mL to 21 pg/mL after 2 hours of direct hemoperfusion. The hyperdynamic state of the cardiac index, which is a characteristic of endotoxic shock, returned to normal levels after treatment. In septic shock patients with a systolic pressure of less than 100 mm Hg, the systolic arterial pressure increased significantly from the pretreatment level. The alleviation of fever caused by this therapy continued until the day after treatment. Of the 16 patients who underwent this therapy, 9 were alive 2 weeks after this therapy and 7 patients were discharged from the hospital alive. Hemoperfusion with PMX may be an effective treatment for sepsis and septic shock.
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              Amino acid imbalance early in septic encephalopathy.

              To evaluate plasma amino acid concentrations and markers of inflammation in the early stage and the course of septic encephalopathy. Prospective, case series of patients with well-defined septic encephalopathy. Surgical department and intensive care unit of a university hospital. Seventeen patients with sepsis according to the ACCP/SCCM consensus conference criteria and encephalopathy based on neuropsychological tests, compared to a control group undergoing uncomplicated thoracic surgery. None. SOFA score, blood samples for plasma amino acids, procalcitonin and interleukin-6. Sepsis was determined to be the cause of encephalopathy in 14 of the 17 patients. Six patients developed septic shock, four died within the study period of 28 days. Within 12 h of the onset of septic encephalopathy, mean values of PCT and IL-6 were elevated ( p<0.001) and the amino acids unbalanced (the ratio of branched-chain to aromatic amino acids was decreased, p<0.001). During the course of sepsis the decreased amino acid ratio was significantly, but moderately, correlated with elevated PCT and IL-6 levels. On study days when PCT was higher than 2 ng/ml, the amino acid ratio was significantly lower. In no patient was severe liver dysfunction seen. Metabolic disturbances with changes in amino acid levels can occur early in septic patients, without serious liver abnormalities. The present data suggest a possible role of amino acids in the pathogenesis of septic encephalopathy.

                Author and article information

                Blood Purif
                Blood Purification
                S. Karger AG
                29 August 2003
                : 21
                : 4-5
                : 282-286
                aDepartment of Medicine, Shinmatsudo Central General Hospital, Chiba, bRenal Unit, Misato Junshin Hospital, Saitama, and cDepartment of Medicine, Koto Hospital, Tokyo, Japan
                72546 Blood Purif 2003;21:282–286
                © 2003 S. Karger AG, Basel

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                Figures: 2, Tables: 1, References: 17, Pages: 5
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