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

Objective: Although water-soluble drugs can be removed by haemofiltration/haemodialysis, morbidity and mortality from intoxication with protein-bound drugs remains high. The present study investigates whether albumin dialysis in the form of the Molecular Adsorbents Recirculating System (MARS) is effective in removal of protein-bound drugs. Design: Prospective animal study. Setting: Surgical research laboratory in a university hospital. Subjects: Seven female Norwegian Landrace pigs. Intervention: We studied whether midazolam (97% albumin-bound) and fentanyl (85% alpha-1-acid glycoprotein-bound), administered as anaesthetics to pigs with induced acute liver failure, could be removed by MARS dialysis lasting for 4 h. Measurements: After 4 h of dialysis, total and free anaesthetic concentrations were measured in the blood and dialysate from different segments of the MARS circuit. Main results: Midazolam: total plasma concentrations fell by 47.1+/-2.1% (in 4 h) across the MARS filter (p<0.01). The charcoal component of the system reduced the total dialysate drug concentration by 16.4 +/- 2.2% (p<0.05). Free midazolam removal followed a similar pattern. Fentanyl: total plasma concentrations fell by 56.1+/-2.4% (in 4 h) across the MARS filter (p<0.01). Clearance of fentanyl from the dialysate by the charcoal was 70 +/- 0.7% at 4 h (p<0.001). Conclusions: 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.