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.

Forced vital capacity assessment for risk stratification of blunt chest trauma patients in emergency settings: A preliminary study.

OBJECTIVE: The aim of this study was to assess the performance of Forced Vital Capacity (FVC) for prediction of secondary respiratory complications in blunt chest trauma patients. METHODS: During a 15-month period, all consecutive blunt chest trauma patients admitted in our emergency intensive care unit with more than 3 rib fractures were eligible, unless they required mechanical ventilation in the prehospital or emergency settings. FVC was measured at admission and at emergency discharge after therapeutic interventions. The main outcome was the occurrence of secondary respiratory complications defined by hospital-acquired pulmonary infection, secondary admission in the intensive care unit or mechanical ventilation for respiratory failure or death. The performance of FVC for prediction of secondary respiratory complications was assessed by receiver operating characteristic (ROC) curve and multivariate analysis after logistic regression. RESULTS: Sixty-two consecutive patients were included and 13 (21%) presented secondary respiratory complications. Only FVC measured at emergency discharge - not FCV at admission - was significantly lower in patients who developed secondary respiratory complications (44±15 vs. 61±20%, P=0.002). The area under the ROC curves for FCV in predicting secondary pulmonary complications was 0.79 [95% CI: 0.66-0.88], P=0.0001. An FVC at discharge≤50% was independently associated with the occurrence of secondary complications with an OR at 7.9 [1.9-42.1], P=0.004. CONCLUSION: The non-improvement of FVC≤50% at emergency discharge is associated with secondary respiratory complications and should prevent the under-triage of patients with no sign of respiratory failure at admission.