Effects of cardiopulmonary bypass on the disposition of cefazolin in patients undergoing cardiothoracic surgery.
The aim of the study was to evaluate the disposition of plasma unbound cefazolin in patients undergoing cardiothoracic surgery with cardiopulmonary bypass (CPB). Adult patients undergoing cardiothoracic surgery with CPB were enrolled in the study. Cefazolin sodium was given intravenously before skin incision (1 g) and at the beginning of CPB (2 g). Thereafter, an additional dose (1 g) was given every 4 hours. Seven to ten blood samples were collected before and during surgery. Plasma total and unbound (ultrafiltrated) cefazolin concentrations were analyzed using an HPLC-UV method. Plasma protein binding was analyzed with the Langmuir model. Twenty-seven patients (aged 70 ± 12 years, body weight 62 ± 12 kg, mean ± SD) with GFR >30 mL min-1 completed the study. There was a significant (P < 0.001) increase in median plasma unbound fraction of cefazolin from 21% before skin incision to 45% during CPB (P < 0.001), which was accompanied by a significant (P < 0.001) reduction in median plasma albumin concentration from 36 to 27 g L-1. Plasma concentrations of unbound cefazolin exceeded the assumed target thresholds of 2 μg mL-1 in all samples and of 8 μg mL-1 in all but one of 199 samples. The increased plasma unbound fraction of cefazolin would be attributable to dilutional reduction of serum albumin at the beginning of CPB and to saturable plasma protein binding of cefazolin. These data reveal CPB may alter the plasma protein binding and possibly distribution of cefazolin. Further studies are warranted to reappraise the protocol of antimicrobial prophylaxis with cefazolin in patients undergoing surgery with CPB.
['Asada|Mizuho|M|', 'Nagata|Masashi|M|0000-0003-3169-7210', 'Mizuno|Tomohiro|T|', 'Uchida|Tokujiro|T|', 'Kurashima|Naoki|N|', 'Takahashi|Hiromitsu|H|', 'Makita|Koshi|K|', 'Arai|Hirokuni|H|', 'Echizen|Hirotoshi|H|', 'Yasuhara|Masato|M|']
D000328:Adult D000368:Aged D000369:Aged, 80 and over D000900:Anti-Bacterial Agents D019072:Antibiotic Prophylaxis D002315:Cardiopulmonary Bypass D002437:Cefazolin D005260:Female D006801:Humans D008297:Male D008875:Middle Aged D011485:Protein Binding D000075462:Serum Albumin, Human D013530:Surgical Wound Infection
cardiopulmonary bypass cefazolin plasma protein binding unbound fraction surgical site infection