Population Pharmacokinetic Study of the Suitability of Standard Dosing Regimens of Amikacin in Critically Ill Patients with Open-Abdomen and Negative-Pressure Wound Therapy.

The aim was to assess the appropriateness of recommended regimens for empirical MIC coverage in critically ill patients with open-abdomen and negative-pressure therapy (OA/NPT). Over a 5-year period, every critically ill patient who received amikacin and who underwent therapeutic drug monitoring (TDM) while being treated by OA/NPT was retrospectively included. A population pharmacokinetic (PK) modeling was performed considering the effect of 10 covariates (age, sex, total body weight [TBW], adapted body weight [ABW], body surface area [BSA], modified sepsis-related organ failure assessment [SOFA] score, vasopressor use, creatinine clearance [CLCR], fluid balance, and amount of fluids collected by the NPT over the sampling day) in patients who underwent continuous renal replacement therapy (CRRT) or did not receive CRRT. Monte Carlo simulations were employed to determine the fractional target attainment (FTA) for the PK/pharmacodynamic [PD] targets (maximum concentration of drug [Cmax]/MIC ratio of ≥8 and a ratio of the area under the concentration-time curve from 0 to 24 h [AUC0-24]/MIC of ≥75). Seventy critically ill patients treated by OA/NPT (contributing 179 concentration values) were included. Amikacin PK concentrations were best described by a two-compartment model with linear elimination and proportional residual error, with CLCR and ABW as significant covariates for volume of distribution (V) and CLCR for CL. The reported V) in non-CRRT and CRRT patients was 35.8 and 40.2 liters, respectively. In Monte Carlo simulations, ABW-adjusted doses between 25 and 35 mg/kg were needed to reach an FTA of >85% for various renal functions. Despite an increased V and a wide interindividual variability, desirable PK/PD targets may be achieved using an ABW-based loading dose of 25 to 30 mg/kg. When less susceptible pathogens are targeted, higher dosing regimens are probably needed in patients with augmented renal clearance (ARC). Further studies are needed to assess the effect of OA/NPT on the PK parameters of antimicrobial agents.

The association between hemispheric specialization for language production and for spatial attention depends on left-hand preference strength.

Cerebral lateralization for language production and spatial attention and their relationships with manual preference strength (MPS) were assessed in a sample of 293 healthy volunteers, including 151 left-handers, using fMRI during covert sentence production (PROD) and line bisection judgment (LBJ) tasks, as compared to high- and low-level reference tasks. At the group level, we found the expected complementary hemispheric specialization (HS) with leftward asymmetries for PROD within frontal and temporal regions and rightward asymmetries for LBJ within frontal and posterior occipito-parieto-temporal regions. Individual hemispheric (HLI) and regional (frontal and occipital) lateralization indices (LI) were then calculated on the activation maps for PROD and LBJ. We found a correlation between the degree of rightward cerebral asymmetry and the leftward behavioral attentional bias recorded during LBJ task. This correlation was found when LBJ-LI was computed over the hemispheres, in the frontal lobes, but not in the occipital lobes. We then investigated whether language production and spatial attention cerebral lateralization relate to each other, and whether manual preference was a variable that impacted the complementary HS of these functions. No correlation was found between spatial and language LIs in the majority of our sample of participants, including right-handers with a strong right-hand preference (sRH, n=97) and mixed-handers (MH, n=97), indicating that these functions lateralized independently. By contrast, in the group of left-handers with a strong left-hand preference (sLH, n= 99), a negative correlation was found between language and spatial lateralization. This negative correlation was found when LBJ-LI and PROD-LI were computed over the hemispheres, in the frontal lobes and between the occipital lobes for LBJ and the frontal lobes for PROD. These findings underline the importance to include sLH in the study sample to reveal the underlying mechanisms of complementary HS.

How is norepinephrine used in intensive care? A field study.

OBJECTIVE: To assess how norepinephrine (NE), an emergency treatment of cardiovascular collapse, is used in intensive care. METHODS: Nurses and physicians of 14 intensive care units of the Bordeaux University Hospital were given questionnaires on the way they say they use NE and on actual NE treatment of patients. RESULTS: The clinical monitoring parameters cited were blood pressure, heart rate and hourly urine flow. Only 25% of the prescribers indicated the systematic use of hemodynamic monitoring. All the prescribers indicated they adapted the treatment to clinical objectives and blood pressure, and 77.5% to hourly urine flow. Initial NE concentrations ranged from 0.5 to 2 mg/ml, diluted in saline or dextrose. Initial prescribed dose ranged from 0.1 to 1 microg/kg/min. Large differences were observed between services and even within units. CONCLUSION: These data clearly show the need for recommendations regarding the use of norepinephrine.