Treatment of Phenytoin Toxicity by the Molecular Adsorbents Recirculating System (MARS)

• Published in: Epilepsia (Copenhagen) Vol. 44; no. 2; pp. 265 - 267
• Main Authors: Sen, Sambit, Ratnaraj, Neville, Davies, Nathan A., Mookerjee, Rajeshwar P., Cooper, Christopher E., Patsalos, Philip N., Williams, Roger, Jalan, Rajiv
• Format: Journal Article
• Language: English
• Published: Boston, MA, USA Blackwell Science Inc 01-02-2003; Blackwell
• Subjects: Albumin dialysis; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Anticonvulsants - administration & dosage; Anticonvulsants - adverse effects; Anticonvulsants - pharmacokinetics; Biological and medical sciences; Drug intoxications. Doping; Drug Overdose - blood; Drug Overdose - therapy; Emergency and intensive care: renal failure. Dialysis management; Equipment Design; Hemofiltration - instrumentation; Humans; Intensive care medicine; Kidney Failure, Chronic - blood; Kidney Failure, Chronic - complications; Liver, Artificial; Male; Medical sciences; Middle Aged; Oxidative stress; Pharmacology. Drug treatments; Phenytoin; Phenytoin - administration & dosage; Phenytoin - adverse effects; Phenytoin - pharmacokinetics; Protein Binding; Renal Dialysis - instrumentation; Serum Albumin - metabolism; Status Epilepticus - blood; Status Epilepticus - drug therapy; Treatment Outcome; Human; Oxidative stress; Nervous system diseases; Purification; Toxicity; Epilepsy; Drug intoxication; Overdosing; Albumin dialysis-Phenytoin-Oxidative stress; Male; Anticonvulsant; Blood; Cerebral disorder; Extrarenal dialysis; Chemotherapy; Treatment; Hemofiltration; Central nervous system disease; Adult; Dialysis; Adsorbent; Mechanism of action; Status epilepticus; Phenytoin
• ISSN: 0013-9580; 1528-1167
• DOI: 10.1046/j.1528-1157.2003.31402.x

Purpose: Toxicity is common in patients of epilepsy treated with phenytoin (PHT), requiring careful drug level monitoring and supportive care. Specific treatment options are limited, although charcoal haemofiltration has been used previously. We attempted to demonstrate that severe PHT toxicity can be treated successfully with the Molecular Adsorbents Recirculating System (MARS). The mechanism of drug removal by the system also was studied.
Methods: A 45‐year‐old patient of status epilepticus with acute renal failure and severe PHT toxicity, associated with cardiac arrhythmias, hepatotoxicity, and altered sensorium, was treated with the MARS, a blood‐purification system based on albumin dialysis, and including a charcoal filter, for 11.5 h. Serum PHT levels and blood levels of oxygen‐based free radicals (by electron paramagnetic resonance spectroscopy) were measured before and after treatment.
Results: Serum total and free PHT levels declined sharply (32 to 11 μM and 9.8 to 2.0 μM, respectively), with clinical improvement and a 65% reduction in measured oxidative stress. The mechanism of drug removal, deduced by measuring PHT in the dialysate collected from different segments of the MARS circuit, was by clearance from blood into the albumin dialysate, and ultimately removal by the charcoal filter.
Conclusions: The observed removal of PHT by MARS, along with the clinical improvement of the patient and reduction of the associated oxidative stress after treatment, indicates that MARS offers a promising option in PHT toxicity.