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Albumin dialysis: a new therapeutic strategy for intoxication from protein-bound drugs
Sambit Sen1, Lars M Ytrebø, Christopher Rose
1Liver Failure Group, Institute of Hepatology, 69-75 Chenies Mews, London WC1E 6HX, UK.
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.
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