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.

Nutrition risk assessment in the ICU.

PURPOSE OF REVIEW: Nutrition risk assessment is of great importance to identify patients who may benefit from nutritional intervention to prevent ICU starvation and avoid side-effects of nutrition care. The full spectrum of nutrition risk assessment in ICU has not been defined in guidelines. RECENT FINDINGS: Many patients are admitted to ICUs with nutritional deficits related to acute and chronic disease. The vast majority of patients who cannot resume sufficient oral feeding within a few days will lose body cell mass due to the severe and prolonged inflammatory process and insufficient nutrient intake. All patients staying longer than 1-2 days in the ICU need nutrition support, close monitoring and risk assessment. Risk assessment has to be constantly maintained throughout the ICU stay to manage properly risks associated with critical illness and nutrition care. Many patients are at risk to develop a refeeding syndrome, to experience serious motility disorders and finally dysphagia after extubation. The dramatic consequences of intra-abdominal hypertension may be decreased by early detection and treatment. There is a close interaction between evolution of critical illness, the associated inflammatory reaction, ICU treatments and nutrition care. SUMMARY: Safe and efficient nutrition care may only be obtained when gastrointestinal function and metabolic tolerance of nutrients are regularly assessed.