Cephalothin kinetics: Before, during, and after cardiopulmonary bypass surgery

The effects of cardiopulmonary bypass (CPB) with hypothermia and systemic heparinization on ceftriaxone disposition were evaluated in seven male patients. A bolus dose of drug (14 mg/kg of body weight) was given, and blood and urine specimens were collected before, during, and after CPB for 96 h. Creatinine, albumin, and total and free ceftriaxone concentrations in plasma were measured. The ceftriaxone free fraction (ff) in vitro was estimated by equilibrium dialysis, and the in vivo ff was obtained by the ratio of renal clearance due to filtration to creatinine clearance. Pharmacokinetic parameters were based on concentrations of total drug and free drug. Albumin decreased from 3.10 ± 0.29 g/dl presurgery to 1.42 ± 0.17 g/dl and recovered to 2.46 ± 0.26 g/dl on postoperative day 4. CPB markedly increased the in vitro ff, which was reversed by protamine post-CPB (if pre-CPB, 0.15 ± 0.01; during CPB, 0.53 ± 0.20; post-CPB, 0.16 ± 0.02). The in vitro ff exceeded the in vivo if (0.53 ± 0.20 versus 0.24 ± 0.07), probably due to continued free fatty acid release caused by heparin during dialysis. Clearances based on free drug decreased, and the renal clearance due to filtration increased (7.6 ± 2.8 versus 15.0 ± 4.5 ml/min) while the creatinine clearance decreased (114 ± 29 versus 72 + 28 ml/min) during CPB. Diminished binding owing to low albumin and free fatty acids explain this behavior.Lower binding also increased the volume of distribution (154 ± 41 ml/kg) and extended the half-life (15 ± 6 h). In summary, ceftriaxone disposition was significantly altered by CPB, resulting in marked increases in free drug concentrations, half-life, and volume of distribution and in decreased intrinsic clearance.

Section: Discussionmentioning

confidence: 84%

mentioning

confidence: 99%

Ceftriaxone disposition in open-heart surgery patients

Jungbluth

Pasko

Beam

et al. 1989

“…First, despite its relatively large size for a pharmacokinetic study during CPB, our study was not powered to determine efficacy and safety in terms of SSIs and other adverse effects. It is noteworthy that most investigations of antibiotic pharmacokinetics during CPB have 10 or fewer subjects (1,4,13,21,24,25,(30)(31)(32)(33)45), so our investigation was relatively robust. Second, all subjects came from a single study site and may not represent patients at other centers or their surgical standards of practice.…”

Section: Discussionmentioning

confidence: 99%

“…However, there are no data on its plasma concentrations during CABG surgery with CPB. Many physiologic changes occur during CPB that may result in the alteration of the pharmacokinetics of medications, including antibiotics (4,13,17,21,29,32,38,39). The pharmacokinetics of any antibiotic during CPB must be evaluated, since factors such as hemodilution, protein binding, and the sequestration of the drug by the CPB apparatus during CPB have been known to alter drug concentrations (17,24,29,39).…”

mentioning

confidence: 99%

Prospective, Open-Label Investigation of the Pharmacokinetics of Daptomycin during Cardiopulmonary Bypass Surgery

Nguyen

Eells

Tan

et al. 2011

As methicillin-resistant Staphylococcus aureus (MRSA) becomes more prevalent, vancomycin is becoming increasingly used as a prophylaxis against surgical-site infections for cardiothoracic surgeries. However, vancomycin administration can be challenging, and the pharmacokinetics of alternative antibiotics in this setting are poorly understood. The primary objective of this investigation was to describe the pharmacokinetics of daptomycin in patients undergoing coronary artery bypass graft surgery. We enrolled 15 patients undergoing coronary artery bypass surgery requiring cardiopulmonary bypass. Each subject was administered a single open-label dose of daptomycin (8 mg/kg of body weight) for surgical prophylaxis. Fourteen daptomycin plasma samples were collected. Safety outcomes between subjects who received daptomycin and 15 control subjects who received the standard-of-care antibiotic were compared. The mean maximal concentration of daptomycin (C max ) was 84.4 ؎ 27.1 g/ml; the mean daptomycin concentration during the cardiopulmonary bypass procedure was 33.2 ؎ 11.4 g/ml and was 30.9 ؎ 12.7 g/ml at sternum closure. Mean daptomycin concentrations at 12, 18, 24, and 48 h were 22.7 ؎ 9.7, 16.2 ؎ 8.2, 12.0 ؎ 4.7, and 3.5 ؎ 2.3 g/ml, respectively. Mean daptomycin concentrations were consistently above the MIC at which 90% of the tested isolates are inhibited (MIC 90 ) for S. aureus and S. epidermidis during the cardiopulmonary bypass procedure. Daptomycin was not associated with surgical-site infections or differences in adverse events compared to findings for control subjects. We found that a single dose of daptomycin at 8 mg/kg was well tolerated and achieved adequate plasma concentrations against common pathogens associated with surgical-site infections after cardiothoracic surgery. Daptomycin may be considered an alternative surgical prophylaxis antibiotic for patients undergoing cardiothoracic bypass surgery who are unable to receive vancomycin.

“…A notable variance from the PRE phase of the protocol was a modest decline in mean V., from 2.1 ± 0.7 to 1.7 ± 0.2 liters/kg ( Table 3). The most likely sources of this variance in V.. are changes in tissue perfusion and penetration and/or hemodilution (1,12,19). Ciprofloxacin distributes widely into tissues, including extensive penetration into bronchopulmonary and peripheral tissues.…”

Section: Discussionmentioning

confidence: 99%

Effects of cardiopulmonary bypass surgery on intravenous ciprofloxacin disposition

Pryka

Rodvold

Ting

et al. 1993

The pharmacokinetic parameters of intravenous ciprofloxacin were examined in five adult male patients on three separate occasions of open heart surgery: the 24 h before cardiopulmonary bypass (CPB) surgery, (PRE), during surgery (SURG), and 48 to 72 h after surgery (POST). Serial blood (n = 16), urine, and SURG tissue samples were collected after intravenous administration of a single 300-mg dose of ciprofloxacin during each study period. All samples were assayed for ciprofloxacin by a specific high-performance liquid chromatographic method. Serum ciprofloxacin concentrations remained constant or continued to decline during the course of CPB surgery. A significant (P < 0.05) decrease in total body clearance was observed during the SURG and POST phases (298 and 306 ml/min/1.73 m2, respectively) compared with that during the PRE phase (364 ml/min/1.73 m2). Renal clearances and elimination half-lives were similar during all three study phases. A nonsignificant decline occurred in the apparent volume of distribution, from mean values of 2.1 and 2.0 liters/kg during the PRE and POST phases, respectively, to 1.7 liters/kg during the SURG phase. The mediastinal fat tissue ciprofloxacin concentrations ranged from 0.45 to 2.89 ,ug/g. Overall, little significant difference was noted in the disposition of intravenous ciprofloxacin during CPB surgery compared with that before and after surgery.