BackgroundSurgical site infections are common, so effective antibiotic concentrations at the sites of infection are required. Surgery can lead to physiological changes influencing the pharmacokinetics of antibiotics. The aim of the study is to evaluate contemporary peri-operative prophylactic dosing of cefazolin by determining plasma and subcutaneous interstitial fluid concentrations in patients undergoing elective of semi-elective abdominal aortic aneurysm (AAA) open repair surgery.Methods/DesignThis is an observational pharmacokinetic study of patients undergoing AAA open repair surgery at the Royal Brisbane and Women's Hospital. All patients will be administered 2-g cefazolin by intravenous injection within 30-minutes of the procedure. Participants will have samples from blood and urine, collected at different intervals. Patients will also have a microdialysis catheter inserted into subcutaneous tissue to measure interstitial fluid penetration by cefazolin. Participants will be administered indocyanine green and sodium bromide as well as have cardiac output monitoring performed and tetrapolar bioimpedance to determine physiological changes occurring during surgery. Analysis of samples will be performed using validated liquid chromatography tandem mass-spectrometry. Pharmacokinetic analysis will be performed using non-linear mixed effects modeling to determine individual and population pharmacokinetic parameters and the effect of peri-operative physiological changes on cefazolin disposition.DiscussionThe study will describe cefazolin levels in plasma and the interstitial fluid of tissues during AAA open repair surgery. The effect of physiological changes to the patient mediated by surgery will also be determined. The results of this study will guide clinicians and pharmacists to effectively dose cefazolin in order to maximize the concentration of antibiotics in the tissues which are the most common site of surgical site infections.
Cardiac output (CO) is a key determinant of major organ blood flow and solute delivery to drug eliminating organs. As such, CO assessment is a key covariate in understanding altered drug handling in the critically ill. Newer minimally-invasive devices are providing unique platforms for such an application, although comparison data are currently lacking. In this study we evaluated the Vigileo ® (Edwards Lifesciences, Irvine, CA, USA) and USCOM ® (USCOM Ltd, Sydney, NSW) devices in 62 critically ill patients requiring antibacterial therapy. The mean CO Vigileo and CO USCOM for the first paired measurements were 8.20±2.65 l/minute and 6.84±2.57 l/minute respectively (P <0.001). A significant correlation was evident in all patients (r=0.537, P <0.001), although the recorded bias was large (1.36±2.51 l/minute, limits of agreement-3.6 to +6.3 l/minute). The overall percentage error was 65%. There was an improved correlation in those admitted with sepsis (r=0.639, P <0.001) compared to trauma (r=0.373, P=0.066), although bias, precision and percentage error were similar in both subgroups. In 54 patients a second paired assessment was obtained at three hours. A weak, although significant correlation (r=0.377, P=0.005) was observed suggesting that gross trends over time were similar. In conclusion, our findings demonstrate poor agreement between these techniques suggesting that these devices are not simply interchangeable when assessing CO in a research or clinical setting.
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