Albumin dialysis: a new therapeutic strategy for intoxication from protein-bound drugs

Sen, Sambit; Ytrebø, Lars Marius; Rose, Christopher F.; Fuskevaag, Ole-Martin; Davies, Nathan; Nedredal, Geir I.; Williams, Roger; Revhaug, Arthur; Jalan, Rajiv

doi:10.1007/s00134-003-2141-0

Cited by 67 publications

(46 citation statements)

References 13 publications

(9 reference statements)

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“…While midazolam was removed against a concentration gradient (dialysate concentration Ͼ plasma concentration), plasma fentanyl levels remained higher than those in the dialysate, suggesting that fentanyl it was removed along the concentration gradient. 3 As also suggested by Evenepoel et al, these data support the hypothesis that only the free drug is actually being removed by the MARS membrane, with constant re-equilibration of the free and bound components in the plasma and without any actual "stripping" of the drug from its binding protein by the membrane.…”

Section: Factors Determining Transfer Of Albumin-bound Toxinssupporting

confidence: 81%

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Letter to the Editors

2005

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Section: Factors Determining Transfer Of Albumin-bound Toxinssupporting

confidence: 81%

“…This gradient is much more pronounced than observed in the in vitro experiments by Steiner et al. 1,3 Despite the preservation of this important gradient for the length of the albumin dialysis session (Fig. 1), the clearance of tB declines over time and becomes negligible and even negative after 6 hours.…”

Section: To the Editorsmentioning

confidence: 65%

Letter to the Editors

2005

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“…Several controlled clinical trials have shown that MARS therapy is an effective treatment for HE. [11][12][13][14][15][16] The mechanism by which MARS treatment results in improved HE is not clear, as results showing a reduction in blood ammonia with MARS have been inconsistent. In keeping with the results in humans, we recently showed attenuation in the rise in ICP (following a 4-hour MARS treatment) in a porcine model of ALF (induced by liver devascularization).…”

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Association of reduced extracellular brain ammonia, lactate, and intracranial pressure in pigs with acute liver failure

et al. 2007

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We previously demonstrated in pigs with acute liver failure (ALF) that albumin dialysis using the molecular adsorbents recirculating system (MARS) attenuated a rise in intracranial pressure (ICP). This was independent of changes in arterial ammonia, cerebral blood flow and inflammation, allowing alternative hypotheses to be tested. The aims of the present study were to determine whether changes in cerebral extracellular ammonia, lactate, glutamine, glutamate, and energy metabolites were associated with the beneficial effects of MARS on ICP. Three randomized groups [sham, ALF (induced by portacaval anastomosis and hepatic artery ligation), and ALF؉MARS] were studied over a 6-hour period with a 4-hour MARS treatment given beginning 2 hours after devascularization. Using cerebral microdialysis, the ALF-induced increase in extracellular brain ammonia, lactate, and glutamate was significantly attenuated in the ALF؉MARS group as well as the increases in extracellular lactate/pyruvate and lactate/glucose ratios. The percent change in extracellular brain ammonia correlated with the percent change in ICP (r 2 ‫؍‬ 0.511). Increases in brain lactate dehydrogenase activity and mitochondrial complex activity for complex IV were found in ALF compared with those in the sham, which was unaffected by MARS treatment. Brain oxygen consumption did not differ among the study groups. A cute liver failure (ALF) is defined by the occurrence of hepatic encephalopathy (HE), which is characterized by an increase in intracranial pressure (ICP) that may lead to cerebral herniation, an important cause of death. 1 Current hypotheses suggest that increased ICP in ALF is the result of multiple factors that involve the effects of hyperammonemia, increased cerebral blood flow, and inflammation. 2 Increased brain ammonia, arising from the onset of hyperammonemia, is detrimental to neurological function. 3 Arterial ammonia levels, ammonia brain delivery, and metabolic rate correlate with severity of intracranial hypertension and risk of cerebral herniation. 1,4,5 Alterations in brain energy metabolism have been hypothesized to be involved in the cerebral consequences of ALF because ammonia is known to inhibit the rate-limiting enzyme ␣-ketoglutarate dehydrogenase in the tricarboxylic acid cycle (TCA). 6 This is supported by experiments demonstrating an increase in de novo synthesis of lactate 7,8 from glucose (using nuclear magnetic resonance spectroscopy) in the brains of rats with ALF. As a result, this would lead to less adenosine triphosphate (ATP) production per molecule of glucose compared with that in aerobic metabolic pathways (through TCA cycle). Therefore, increased ammonia in the brain reduces generation of ATP. On the other hand, elevated ammonia

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“…In their recent experimental study, Sen et al (1) showed that Molecular Adsorbents Recirculating System (MARS ® ) could remove efficiently both albumin and protein-bound drugs from the plasma. The authors herein report the first case of successful blood detoxification using MARS ® therapy allowing full recovery in a patient presenting with a refractory shock secondary to acute diltiazem poisoning.…”

Section: To the Editormentioning

confidence: 99%

Letter to the Editor: Albumin Dialysis: A New Therapeutic Alternative for Severe Diltiazem Intoxication

Pichon

Dalmay

Clavel

et al. 2006

Clinical Toxicology

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Albumin dialysis: a new therapeutic strategy for intoxication from protein-bound drugs

Abstract: The results of the study show that MARS can remove both albumin and other protein-bound drugs efficiently from the plasma, and it may have a place for the treatment of patients suffering from intoxication with this class of compounds.

Cited by 67 publications

References 13 publications

Letter to the Editors

Letter to the Editors

Association of reduced extracellular brain ammonia, lactate, and intracranial pressure in pigs with acute liver failure

Letter to the Editor: Albumin Dialysis: A New Therapeutic Alternative for Severe Diltiazem Intoxication

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