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.


METHODS
Prospective animal study.


METHODS
Surgical research laboratory in a university hospital.


METHODS
Seven female Norwegian Landrace pigs.


METHODS
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.


METHODS
After 4 h of dialysis, total and free anaesthetic concentrations were measured in the blood and dialysate from different segments of the MARS circuit.


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.
Sen
Sambit
S
Liver Failure Group, Institute of Hepatology, 69-75 Chenies Mews, London WC1E 6HX, UK.
Ytrebø
Lars M
LM
Rose
Christopher
C
Fuskevaag
Ole-Martin
OM
Davies
Nathan A
NA
Nedredal
Geir I
GI
Williams
Roger
R
Revhaug
Arthur
A
Jalan
Rajiv
R
D018686:Anesthetics, Intravenous / Q000097:blood* / Q000737:chemistry; D000818:Animals; D005260:Female; D005283:Fentanyl / Q000097:blood* / Q000737:chemistry; D016014:Linear Models; D017114:Liver Failure, Acute / Q000628:therapy*; D008874:Midazolam / Q000097:blood* / Q000737:chemistry; D009961:Orosomucoid; D011485:Protein Binding; D012709:Serum Albumin; D016060:Sorption Detoxification / Q000379:methods*; D013552:Swine
D018686:Anesthetics, Intravenous; D009961:Orosomucoid; D012709:Serum Albumin; D008874:Midazolam; D005283:Fentanyl