Gentamicin pharmacokinetics and pharmacodynamics during short-daily hemodialysis.

BACKGROUND/AIMS: Gentamicin pharmacokinetics have not been described in patients undergoing short-daily hemodialysis (SDHD). The aim of this study is to describe gentamicin pharmacokinetics and dialytic clearance (Cl(dial)) in SDHD patients and simulate gentamicin exposure after six dosing regimens to help guide future dosing. METHODS: Six anuric patients undergoing SDHD were enrolled. Patients received intravenous infusion of 2 mg/kg gentamicin on day 1 after the first HD session followed by HD sessions on days 2, 3, and 4. Blood samples for determination of gentamicin concentrations were serially collected. Gentamicin pharmacokinetic parameters and Cl(dial) and interindividual variability terms (IIV) were estimated using NONMEM VII. Influence of patient weight on systemic clearance (Cl(s)) and central volume of distribution (V(c)) and influence of urea removal estimates on Cl(dial) were assessed. The model was used to simulate gentamicin concentrations after six dosing regimens including pre- and postdialysis as well as daily and every-other-day dosing. RESULTS: A two-compartment model with first-order elimination from central compartment described gentamicin pharmacokinetics. Population estimates for Cl(s) and Cl(dial) were 7.6 and 134 ml/min, respectively. Patient weight was statistically significantly associated with Cl(s) and V(c). Predialysis every-other-day regimens were as effective (C(max) ≥8 mg/l and AUC(48 h) ≥140 mg·h/l) and less toxic (C(min) <2 mg/l and AUC(48 h) <240 mg·h/l) than postdialysis regimens. CONCLUSIONS: Estimated gentamicin Cl(dial) is higher than previous estimates with thrice-weekly regimens. Predialysis every-other-day dosing may be recommended during SDHD.

Is it a safe practice to administer oxygen during uncomplicated delivery: a randomized controlled trial?

BACKGROUND: Newborns exposed to oxygen suffer from an oxidative stress with significant alterations in the concentrations of superoxide dismutase (SOD) and glutathione (GSSG). OBJECTIVE: To investigate the biological and clinical effects of oxygen administration to delivering mothers. METHODS: We conducted a randomized, double-blinded, controlled trial on a cohort of delivering women (n=56) with an uncomplicated term pregnancy. Women were randomly assigned to one of two groups: Oxygen group or Room Air group. The Oxygen group received 100% oxygen (2l/min) via nasal cannula for at least 30 min before delivery. Subjects in the Room Air group were connected to a nasal cannula while on room air. Concentrations of SOD (µg/g of Hb) and GSSG (µM/ml) were measured in maternal and umbilical cord blood. Bivariate and multivariate analyses were used to compare the two groups using the SAS system. RESULTS: Maternal SOD and GSSG did not differ between the two groups at baseline or after delivery. Concentrations of SOD and GSSG in umbilical cord blood did not differ between groups. More infants in Oxygen Group required delivery room resuscitation (20% vs. 0%, P=0.03). This difference could not be explained by mode of delivery, infant sex, or other confounders. CONCLUSIONS: Maternal exposure to oxygen during delivery is not associated with changes in umbilical cord SOD or GSSG. Further studies are needed to explore mechanisms responsible for the need of resuscitation in the oxygen group.