Cefazolin and netilmicin serum levels during and after cardiac surgery with cardiopulmonary bypass.
The kinetics of cefazolin and netilmicin were studied in 10 patients undergoing elective cardiac surgery with hemodilution and cardiopulmonary bypass (CPB). During surgery, but before CPB, cefazolin, 25 mg/kg, and netilmicin, 2 mg/kg, were administered intravenously over 30 minutes. For the 48-hour period following CPB, cefazolin, 25 mg/kg, and netilmicin, 1 mg/kg, were administered intravenously every 8 hours. Initiation of CPB was accompanied by a 28% to 30% decrease in hematocrit and serum antibiotic levels. At the conclusion of surgery, cefazolin and netilmicin serum levels were 41 +/- 12 micrograms/L and 2.5 +/- 0.6 micrograms/mL (mean +/- SD), respectively. During the postoperative period, cefazolin levels were consistently greater than the minimum inhibitory concentration (MIC) for sensitive bacteria (4 micrograms/mL); average netilmicin levels were greater than MIC of sensitive bacteria (2 micrograms/mL) for 2 hours after antibiotic infusion. The netilmicin trough levels were 0.6 +/- 0.5 micrograms/mL. Pharmacokinetic parameters were determined using a model-independent method, and gave the following results during surgery: cefazolin--elimination half-life, 231 minutes, total body clearance, 1.05 mL/kg/min, and steady-state volume of distribution, 243 mL/kg. The values for netilmicin were 249 minutes, 1.18 mL/kg/min, and 353 mL/kg, respectively. Postoperatively there were no significant changes in the disposition of cefazolin, but the elimination half-life of netilmicin was shorter (124 minutes, P less than 0.01) and the total body clearance greater (3.58 mL/kg/min, P less than 0.01) than during surgery.
Lehot
J J
JJ
Département d'Anesthésie Réanimation, Hôpital Cardiovasculaire Louis Pradel, Lyon, France.
Reverdy
M E
ME
Etienne
J
J
Corot
C
C
Nervi
C
C
Sear
J
J
Fleurette
J
J
Estanove
S
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D006348:Cardiac Surgical Procedures; D002315:Cardiopulmonary Bypass; D002437:Cefazolin / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D006207:Half-Life; D006400:Hematocrit; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D016343:Monitoring, Intraoperative; D009428:Netilmicin / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011182:Postoperative Care; D011292:Premedication; D013997:Time Factors
D009428:Netilmicin; D002437:Cefazolin