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The scope of extracorporeal membrane oxygenation (ECMO) is expanding, nevertheless, pharmacokinetics in patients receiving cardiorespiratory support are fairly unknown leading to unpredictable drug concentrations. Currently, there are no clear guidelines for antibiotic dosing during ECMO. This study aims to evaluate the pharmacokinetics (PK) of cefazolin in patients undergoing ECMO treatment. Total and unbound plasma cefazolin concentration of critically ill patients on veno-arterial ECMO were determined. Observed PK was compared to dose recommendations calculated by an online available, free dosing software. Concentration of cefazolin varied broadly despite same dosage in all patients. The mean total and unbound plasma concentration were high showing significantly (p = 5.8913 E−09) greater unbound fraction compared to a standard patient. Cefazolin clearance was significantly (p = 0.009) higher in patients with preserved renal function compared with CRRT. Based upon the calculated clearance, the use of dosing software would have led to lower but still sufficient concentrations of cefazolin in general. Our study shows that a “one size fits all” dosing regimen leads to excessive unbound cefazolin concentration in these patients. They exhibit high PK variability and decreased cefazolin clearance on ECMO appears to compensate for ECMO- and critical illness-related increases in volume of distribution.
Background: The aim of this study was to evaluate the longer-term results of bicuspid aortic valve (BAV) repair with or without aortic root replacement. Methods: From 1999 to 2017, 142 patients with or without aortic root dilatation who underwent repair of a regurgitant BAV were included in the study. Ninety-four patients underwent isolated BAV repair (Group 1; median age 43 years) and 48 patients underwent valve-sparing aortic root replacement plus BAV repair (aortic valve reimplantation—Group 2; median age 48 years). Median clinical follow-up time was 5.9 years (range 0.5–15) in Group 1 and 3 years (range 0.5–16) in Group 2, respectively. Results: In-hospital mortality was 1% in Group 1, and 2% in Group 2 (p = .6). The 5- and 10-year survival was 93 ± 2.9% and 81 ± 5.8% in Group 1 and 96 ± 3.1% and 96 ± 3.1% in Group 2, respectively (p = .31). Eleven patients of Group 1 (1.7%/patient-year) and five patients of Group 2 (2.2%/patient-year) underwent reoperation of the aortic valve (p = .5). The 5- and 10-year freedom from reoperation were 93.0 ± 2.1% and 77.1 ± 7.1% in Group 1 and 93.0 ± 5.0% and 76.7 ± 9.6% in Group 2 (p = .83), respectively. At the latest follow-up, only two patients of Group 1 and 1 patient of Group 2 had AV regurgitation = 2° (p = .7). The cumulative linearized incidence of all valve-related complications (bleeding, stroke, endocarditis, and reoperation) was 2.9%/patient-year in Group 1% and 4%/patient-year in Group 2, respectively (p = .6). Conclusions: Isolated BAV repair and combined aortic valve reimplantation plus BAV repair provide good clinical longer-term outcomes with relatively low reoperation rate and durable valve function.