The first step in the prevention of PONV is assessment and reduction of risk factors. Although nonpharmacologic therapies may play a role in the treatment of PONV, the mainstay of therapy for PONV is pharmacologic modalities. Patients at moderate to high risk for PONV need prophylactic antiemetic therapy. High-risk patients may require combination therapy with 2 or 3 agents from different antiemetic classes. Rescue antiemetic therapy is needed by patients who actually develop PONV. The agents of choice in such cases should be from antiemetic classes different from those used for prophylaxis of PONV.

Background:The increasing use of vancomycin to treat methicillinresistant Staphylococcus aureus (MRSA) has resulted in reduced susceptibility of MRSA to this drug. It is important to optimize vancomycin dosing in patients who are undergoing hemodialysis to attain a pre-hemodialysis serum concentration sufficient to eradicate MRSA, in accordance with recent guideline recommendations.Objectives: To establish the optimal strategy for vancomycin loading dose in patients undergoing hemodialysis and to explore the determinants of pre-hemodialysis serum concentration of vancomycin measured in these patients. Methods:A prospective observational cohort study was conducted between January and June 2010. Eligible participants were adults with established stage 5 chronic kidney disease who were undergoing inpatient hemodialysis. Data were collected on loading dose administered, body weight, serum concentration of vancomycin before the subsequent hemodialysis session (pre-hemodialysis concentration), and time between end of vancomycin infusion and measurement of pre-hemodialysis serum concentration. Multivariate stepwise linear regression was performed to examine independent associations between variables and measured pre-hemodialysis serum concentration of vancomycin.Results: Eighty-one patients were included in the study. Of 24 patients who achieved the recommended pre-hemodialysis serum concentration of vancomycin (15-20 mg/L), 14 had a loading dose between 15 and 20 mg/kg. Further analysis suggested that the pre-hemodialysis serum concentration of vancomycin was independently associated with weightbased loading dose (mg/kg) (ß = 0.293, p = 0.003), age (ß = -0.358, p < 0.001), and time between administration of the loading dose and initiation of hemodialysis (ß = -0.247, p = 0.011). Conclusions:The findings of this study indicate that a loading dose of 15-20 mg/kg (actual body weight) is likely to yield an optimal pre-hemodialysis serum concentration at a median elapsed time of 24 h. In addition to loading dose, patient age and time between administration of the loading dose and initiation of hemodialysis also influenced the pre-hemodialysis serum concentration of the drug.

Components of grapefruit juice have been shown to inhibit CYP3A4 activity, the enzyme involved in cyclosporine metabolism. Eleven medically stable patients (seven males, four females) receiving cyclosporine following kidney transplantation were instructed to take their usual dose of cyclosporine with water for 1 week (Phase 1), with grapefruit juice (8 ounces) for 1 week (Phase 2) and again with water for 1 week (Phase 3). Trough blood samples were obtained at the end of each phase for measurement of cyclosporine concentration using a specific monoclonal whole blood radioimmunoassay. Cyclosporine trough concentrations averaged 116.9 ± 51.6 ng ml-' in the first phase, 145.3 ± 44.7 ng ml-' with grapefruit juice (P < 0.05 compared with the first and third phases) and 111.2 ± 56.1 ng ml-' in the third phase. Cyclosporine concentrations increased in 8 of 11 patients when given with grapefruit juice (mean increase 32%; range -4 to 97%) and declined in 10 of 11 when subjects resumed taking cyclosporine with water (mean decrease 27%). These results suggest that grapefruit juice increases trough concentrations of cyclosporine in blood, possibly by inhibiting pre-hepatic gut wall metabolism, and could be useful in optimizing therapy with this drug.

A 26-year-old man with thrombotic thrombocytopenic purpura resulting in respiratory and renal failure was treated with plasmapheresis (PP). Coexisting pulmonary infiltrates were empirically treated as pneumonia with various antibiotics, including vancomycin and tobramycin. The half-life of tobramycin was 6.93 hours. During PP the half-life of tobramycin decreased to 4.47 hours as determined by three random levels. The fraction eliminated due to PP was 35.5% and the fraction cleared by PP was 10.9%. We conclude that PP contributed significantly to the total clearance of tobramycin. The need for supplemental doses must be evaluated in each patient based on post-PP serum concentrations.