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The Journal of Thoracic and Cardiovascular Surgery, Vol 96, 634-641, Copyright © 1988 by The American Association for Thoracic Surgery and The Western Thoracic Surgical Association
RF Davies, LM Dube, N Mousseau, I McGilveray and DS Beanlands
This study examined the effect of changes in plasma concentrations of total
protein, albumin, alpha 1-acid glycoprotein, and free fatty acids occurring
after heart operations on the protein binding of chemically basic drugs.
Plasma protein and free fatty acid concentrations were measured
simultaneously with in vitro determinations of the protein binding of
lidocaine, quinidine, and propranolol: immediately before operation,
immediately on weaning from cardiopulmonary bypass, on arrival in the
recovery room, and 12, 24, 72, and 120 hours postoperatively. Initial
decreases in the concentrations of all proteins were followed by a rise in
alpha 1-acid glycoprotein to 254% of baseline at 72 to 120 hours. The free
fractions of drug were initially increased to 168% of baseline for
lidocaine, 206% for quinidine, and 200% for propranolol and fell
progressively with time, reaching sustained troughs of 65% for lidocaine,
50% for quinidine, and 57% for propranolol at 72 to 120 hours. Regression
analysis indicated a major influence of changing alpha 1-acid glycoprotein
concentrations on free fractions of all three drugs, with a smaller effect
of albumin that reached statistical significance only for lidocaine. There
were no significant perioperative changes in plasma concentrations of free
fatty acids when the in vitro effects of heparin were controlled. In
conclusion, sequential changes in plasma protein concentrations after
cardiac operations predictably alter the protein binding of lidocaine,
quinidine, and propranolol and should be considered when interpreting total
plasma drug concentrations.
ARTICLES
Perioperative variability of binding of lidocaine, quinidine, and propranolol after cardiac operations
University of Ottawa Heart Institute, Ontario, Canada.
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