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

Mizock, Barry A.; Sabelli, Hector; Dubin, Alvin; Javaid, Javaid I.; Poulos, Ann; Rackow, Eric C.

doi:10.1001/archinte.150.2.443

Cited by 37 publications

(31 citation statements)

References 43 publications

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“…The loss of metabolic regulation of brain perfusion and local cerebral ischemia also contribute to the etiology of septic encephalopathy [2]. Some investigators reported that an amino acid imbalance exists in patients with septic encephalopathy who were already in septic shock [10,11]. Basler et al [3] recently reported that the imbalance between the BCAAs and AAAs is observed early in septic encephalopathy.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2003

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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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Section: Discussionmentioning

confidence: 99%

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

et al. 2003

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“…In brain-injured rats, sustained systemic inflammation significantly impairs cerebral vascular and metabolic response [206] and aggravates TBI-induced local inflammation [207]. Under these conditions, norepinephrine is of importance as the increased cerebral oxygen consumption and cerebral perfusion are mediated by b-adrenergic activation [208], cerebral norepinephrine uptake and synthesis is impaired [209,210], and central (brain) as well as peripheral (thrombocytes) a 2 -adrenergic transmission is disturbed [211]. While norepinephrine infusion does not adversely affect cerebral perfusion in endotoxemic sheep [212], similar investigations have not yet been performed following TBI with severe inflammation.…”

Section: Inflammation-and Sepsis-mediated Encephalopathymentioning

confidence: 99%

Controversial Issues Concerning Norepinephrine and Intensive Care Following Severe Traumatic Brain Injury

Stover¹,

Steiger²,

Stocker

2006

Eur J Trauma

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“…Die Erhöhung der Aminosäure LTryptophan konnte ebenfalls bei septischen Ratten im Gehirn gefunden werden [16], während beim septischen Patienten im Liquor nur eine Erhöhung der aromatischen Aminosäure Phenylalanin gezeigt wurde [32]. Im Unterschied dazu war bei Patienten mit hepatischer Enzephalopathie eine Erhöhung aller aromatischen Aminosäuren im Liquor nachgewiesen worden [32].…”

Section: Neurotransmitterunclassified

“…Im Unterschied dazu war bei Patienten mit hepatischer Enzephalopathie eine Erhöhung aller aromatischen Aminosäuren im Liquor nachgewiesen worden [32]. Im Plasma von Patienten mit septischer Enzephalopathie war jedoch eine Erhöhung sowohl von Phenylalanin als auch von Tryptophan festzustellen [44].…”

Section: Neurotransmitterunclassified

Septische Enzephalopathie

et al. 2003

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23% of all septic patients develop septic encephalopathy which is associated with an increased mortality rate. Symptoms such as agitation, confusion and disorientation ranging from stupor to coma often develop in early sepsis. Severe hypotension is significantly associated with the development of septic encephalopathy. Several other factors which may play a role are also discussed: effects of inflammatory mediators on the brain, inadequate cerebral perfusion pressure, blood-brain barrier derangements, disturbances of the cerebral microcirculation, cerebral ischemia e.g. due to hypocapnia,metabolic changes, altered amino acid levels, transmitter imbalances, liver insufficiency, multiple organ failure and infections of the CNS, respectively. Compared to patients with an isolated infection,patients in septic shock have increased levels of aromatic amino acids such as phenylalanine and tryptophan in the plasma and brain as well as decreased levels of branched chain amino acids. Patients who died had higher levels of aromatic amino acids than the survivors. The correlation between aromatic amino acids and the APACHE II score was significant. The tryptophan metabolite quinolinic acid which can be synthesized in activated macrophages could act as an excitatory transmitter on the N-methyl-D-aspartate (NMDA) -receptor. Observations from experimental models indicate that activated NMDA receptors activate the neuronal isoform of the NO-synthase and other calcium dependent enzymes. This releases free radicals which may damage the DNA and activate the nuclear enzyme Poly-ADP-ribose-synthetase (PARS), resulting in energy depletion and cell death. Sepsis is the main cause of metabolic encephalopathies in critically ill patients. The differential diagnoses include hepatic, renal,hypoxic-ischemic or cardiovascular encephalopathies as well as encephalopathies,metabolic disorders and organ dysfunctions of other origin. Therapeutic interventions are numerous,however, so far only investigated in few controlled studies. The primary therapeutic goal is to maintain an adequate perfusion pressure and to prevent hypoxia and hypocapnia. Although the infusion of branched chain amino acids is controversial, experimental investigations demonstrated improvements improvements in an animal model with septic encephalopathy. Further investigations with respect to glutamate receptor antagonists, new radical scavengers, NO- and PARS-inhibitors may show whether these substances are suitable for the prophylaxis or early therapy of septic encephalopathy.

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

Cited by 37 publications

References 43 publications

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

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

Controversial Issues Concerning Norepinephrine and Intensive Care Following Severe Traumatic Brain Injury

Septische Enzephalopathie

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