AIMS: The aim of this pharmacokinetic study was to describe and quantify population pharmacokinetics of three antibiotics, cefazolin, ampicillin, and ciprofloxacin, used as antibacterial prophylaxis during cardiovascular surgery with the use of extracorporeal circulation (ECC). METHODS: Adult patients undergoing cardiac surgery with ECC were enrolled to this prospective, pharmacokinetic study. An intravenous bolus of 2 g of ampicillin, 2 g of cefazolin or 400 mg of ciprofloxacin was administered 60-30 min before surgery. Blood samples were collected at 15, 30, 45, 60, 120 and 180 min after the administration and at the end of the surgery. Plasma concentrations of the antibiotics were measured using HPLC methods. Serum concentration-time profiles were analyzed using nonlinear mixed-effects modeling approach. RESULTS: A total of 54 patients were enrolled into the study, 20 with ampicillin, 25 cefazolin and 9 ciprofloxacin. For all antibiotics, population pharmacokinetic models have been successfully developed. CONCLUSION: We identified estimated glomerular filtration rate (eGFR) as the main factor determining the achievement of the pharmacokinetic/pharmacodynamic (PK/PD) target in ampicillin or cefazolin and body weight in ciprofloxacin prophylaxis during cardiac surgery with ECC support.

• Klíčová slova
• ampicillin, cardiac surgery, cefazolin, ciprofloxacin, extracorporeal circulation, population pharmacokinetics,
• MeSH
• ampicilin MeSH
• antibakteriální látky terapeutické užití   MeSH
• antibiotická profylaxe metody   MeSH
• cefazolin * farmakokinetika   terapeutické užití   MeSH
• ciprofloxacin MeSH
• dospělí MeSH
• kardiochirurgické výkony * MeSH
• lidé MeSH
• mimotělní oběh MeSH
• prospektivní studie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ampicilin MeSH
• antibakteriální látky MeSH
• cefazolin * MeSH
• ciprofloxacin MeSH

The objectives of this study were to develop a population pharmacokinetic model of prophylactically administered cefazolin in patients undergoing cardiac surgery with and without the use of the cardiopulmonary bypass of both existing types-standard (ECC) and minimallyu invasive extracorporeal circulation (MiECC)-and to propose cefazoline dosing optimization based on this model. A total of 65 adult patients undergoing cardiac surgery were recruited to this clinical trial. A prophylactic cefazolin dose of 2 g was intravenously administered before surgery. Blood samples were collected using a rich sampling design and cefazolin serum concentrations were measured using the HPLC/UV method. The pharmacokinetic population model was calculated using a nonlinear mixed-effects modeling approach, and the Monte Carlo simulation was used to evaluate the PK/PD target attainment. The population cefazolin central volume of distribution (Vd) of 4.91 L increased by 0.51 L with each 1 m2 of BSA, peripheral Vd of 22.07 L was reduced by 0.77 L or 0.79 L when using ECC or MiECC support, respectively, while clearance started at 0.045 L/h and increased by 0.49 L/h with each 1 mL/min/1.73 m2 of eGFR. ECC/MiECC was shown to be covariate of cefazolin Vd, but without relevance to clinical practice, while eGFR was most influential for the PK/PD target attainment. The standard dose of 2 g was sufficient for PK/PD target attainment throughout surgery in patients with normal renal status or with renal impairment. In patients with augmented renal clearance, an additive cefazolin dose should be administered 215, 245, 288 and 318 min after the first dose at MIC of 4, 3, 2 and 1.5 mg/L, respectively.

• Klíčová slova
• antibiotic prophylaxis, cardiopulmonary bypass, cefazoline, glomerular filtration rate, nonlinear mixed-effects modeling,
• Publikační typ
• časopisecké články MeSH

Long-term mechanical circulatory support (LT-MCS) is an important treatment modality for patients with severe heart failure. Different devices are available, and many-sometimes contradictory-observations regarding patient selection, surgical techniques, perioperative management and follow-up have been published. With the growing expertise in this field, the European Association for Cardio-Thoracic Surgery (EACTS) recognized a need for a structured multidisciplinary consensus about the approach to patients with LT-MCS. However, the evidence published so far is insufficient to allow for generation of meaningful guidelines complying with EACTS requirements. Instead, the EACTS presents an expert opinion in the LT-MCS field. This expert opinion addresses patient evaluation and preoperative optimization as well as management of cardiac and non-cardiac comorbidities. Further, extensive operative implantation techniques are summarized and evaluated by leading experts, depending on both patient characteristics and device selection. The faculty recognized that postoperative management is multidisciplinary and includes aspects of intensive care unit stay, rehabilitation, ambulatory care, myocardial recovery and end-of-life care and mirrored this fact in this paper. Additionally, the opinions of experts on diagnosis and management of adverse events including bleeding, cerebrovascular accidents and device malfunction are presented. In this expert consensus, the evidence for the complete management from patient selection to end-of-life care is carefully reviewed with the aim of guiding clinicians in optimizing management of patients considered for or supported by an LT-MCS device.

• Klíčová slova
• Expert consensus, Heart failure, Left ventricular assist devices, Mechanical circulatory support,
• MeSH
• implantace protézy přístrojové vybavení   metody   MeSH
• kardiochirurgické výkony přístrojové vybavení   metody   MeSH
• lidé MeSH
• perioperační péče metody   MeSH
• podpůrné srdeční systémy * MeSH
• pooperační komplikace diagnóza   terapie   MeSH
• srdeční selhání komplikace   diagnóza   chirurgie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• konsensus - konference MeSH