Infusion of albumin attenuates changes in serum protein binding of drugs in surgical patients compared with volume replacement with HAES.
BACKGROUND
In vitro studies have indicated that stabilizers present in pharmaceutical-grade albumin influence albumin-binding capacity for highly protein bound drugs.


METHODS
A randomized study including 40 surgical patients, treated with either albumin or starch solutions, was performed. Volumes of colloids were given based on clinical indication. Blood samples were obtained. The serum samples were analyzed to determine the concentrations of albumin, tryptophan, N-acetyl-dl-tryptophan, caprylate and alpha-1-acid glycoprotein as well as in vitro drug binding of naproxen, warfarin and digitoxin.


RESULTS
During surgery, the albumin concentration declined in the Starch group from 26.8 to 15.3 g/l. It remained unchanged in the Albumin group (29.2 g/l). The two groups were analyzed with the pre-operative sample acting as the control. In the starch group, the percent free concentration of the drugs increased significantly (P<0.01): for naproxen from 0.2% to 0.6%, for warfarin from 1.2% to 1.8% and for digitoxin from 6.8% to 11.1%. In the Albumin group, the % free fraction of naproxen doubled from 0.1% to 0.2% (P<0.05), whereas the % free fraction of warfarin decreased from 1.1% to 1.0% (P<0.05). The free fraction of digitoxin remained unchanged.


CONCLUSIONS
Infusion of albumin during surgery resulted in maintained albumin values and almost maintained binding parameters for the study drugs, although some statistically significant changes were found. The use of starch solutions, however, led to in a reduction in albumin values and a significant reduction in binding parameters.
Reine
P A
PA
Department of Anaesthesia, Medical Faculty, University of Oslo, Norway.
Kongsgaard
U E
UE
Andersen
A
A
Thøgersen
A-K
AK
Olsen
H
H
D000328:Adult; D000368:Aged; D000418:Albumins / Q000008:administration & dosage / Q000378:metabolism*; D004074:Digitoxin / Q000378:metabolism*; D005260:Female; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000008:administration & dosage / Q000009:adverse effects; D007263:Infusions, Parenteral; D008297:Male; D008875:Middle Aged; D009288:Naproxen / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010952:Plasma Substitutes / Q000008:administration & dosage / Q000009:adverse effects; D011485:Protein Binding; D013514:Surgical Procedures, Operative; D014859:Warfarin / Q000378:metabolism*
D000418:Albumins; D006895:Hydroxyethyl Starch Derivatives; D004364:Pharmaceutical Preparations; D010952:Plasma Substitutes; D009288:Naproxen; D014859:Warfarin; D004074:Digitoxin