Effects of imposed acid-base derangement on the cardiovascular effects and pharmacokinetics of bupivacaine and thiopental.
BACKGROUND
By changing physicochemical properties such as effective lipophilicity, changes in blood pH could alter the distribution, elimination, and effects of weakly ionizing drugs. The authors examined the outcome of imposed acid-base derangement on cardiovascular effects and myocardial and whole body pharmacokinetics of bupivacaine, a weak base, and thiopental, a weak acid.


METHODS
Intravenous infusions of rac-bupivacaine HCl (37.5 mg) or rac-thiopental sodium (250 mg, subanesthetic dose) were administered over 3 min to previously instrumented conscious ewes with normal blood pH, acidemia imposed by lactic acid infusion, or alkalemia imposed by bicarbonate infusion. Hemodynamic and electrocardiographic effects were recorded; arterial and coronary sinus drug blood concentrations were analyzed by chiral high-performance liquid chromatography.


RESULTS
Bupivacaine decreased myocardial contractility, coronary perfusion, heart rate, and cardiac output; however, cardiac output and stroke volume were not as affected by bupivacaine with acidemia. Thiopental decreased myocardial contractility and stroke volume and increased heart rate; acidemia enhanced the tachycardia and produced a greater decrease in stroke volume than with alkalemia. Taken as a whole, the cardiovascular changes were not systematically modified by acid-base derangement. Overall, the tissue distribution of bupivacaine was favored by alkalemia, but thiopental pharmacokinetics were essentially unaffected by acid-base derangement. Acid-base derangement did not influence the kinetics of either drug enantioselectively.


CONCLUSIONS
At the doses used, the hemodynamic and electrocardiographic effects of bupivacaine and thiopental were not systematically modified by acid-base derangement, nor were there changes in regional or whole body pharmacokinetics of either drug that were clearly related to acid-base status.
Mather
Laurence E
LE
Centre for Anesthesia and Pain Management Research, Department of Anesthesia and Pain Management, University of Sydney at Royal North Shore Hospital, St. Leonards, NSW, Australia. lmather@med.usyd.edu.au
Ladd
Leigh A
LA
Copeland
Susan E
SE
Chang
Dennis H-T
DH
D000137:Acid-Base Imbalance / Q000378:metabolism*; D000818:Animals; D002045:Bupivacaine / Q000493:pharmacokinetics* / Q000494:pharmacology; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects*; D005260:Female; D012756:Sheep; D013874:Thiopental / Q000493:pharmacokinetics* / Q000494:pharmacology
D013874:Thiopental; D002045:Bupivacaine