Monitoring plasma voriconazole levels following intravenous administration in critically ill patients: an observational study.

Data relating to the pharmacokinetics of voriconazole in critically ill patients are lacking. A prospective observational study was conducted on 18 non-consecutive critically ill patients aged 24-97 years, comprising 12 patients with normal renal function (NRF) [creatinine clearance (CL(Cr)) > or = 60 mL/min] and 6 patients with moderate renal impairment (MRI) (CL(Cr) 40-55 mL/min), administered voriconazole intravenously (6 mg/kg loading dose and 3-4 mg/kg twice daily thereafter) in order to determine the suitability of these doses in this patient population. Steady-state blood levels were monitored and liver and renal function were recorded throughout treatment. Large variability in patient plasma levels was observed, ranging from 37% at < or = 1 mg/L (minimum inhibitory concentration at which, for most fungal pathogens, 90% of isolates are susceptible) to 19% at >5.5mg/L. Moreover, maintaining trough concentrations above clinical breakpoints was not consistently achieved because 16/30 (53%) were < or = 1 mg/L. In a few MRI patients, average concentrations were found to be significantly different compared with those of NRF patients administered the same dose, however this difference was not noted in pharmacokinetic parameters following dose normalisation. None of the patients experienced deterioration in renal or liver function. Recommended voriconazole doses are inadequate to achieve drug concentrations >1 microg/mL over the entire dosing interval in some critically ill patients.

Urinary neutrophil gelatinase-associated lipocalin (NGAL) as an early marker of acute kidney injury in critically ill multiple trauma patients.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL), an iron-transporting protein rapidly accumulating in the kidney tubules and urine after nephrotoxic and ischemic insults, has been put forward as an early, sensitive, non-invasive biomarker for acute kidney injury (AKI). The aim of this study was to evaluate urinary NGAL levels as a predictor of early AKI (first 5 days after injury) in multi-trauma patients. METHODS: We studied multi-trauma adult patients admitted to the intensive care unit of a trauma hospital. Exclusion criteria were a) known cardiac or chronic kidney disease, and b) initial evaluation after more than 24 h had elapsed from injury. Urinary NGAL was measured using an ELISA technique upon admission and at 24 and 48 h. Presence of AKI was defined by the risk injury failure loss and end-stage kidney classification (RIFLE) criteria. Data are reported as median and interquartile range. RESULTS: A total of 31 patients (25 male, 6 female) were studied. NGAL levels at admission were significantly higher among patients who subsequently developed AKI [155.5 (50.5-205.9) ng/mL vs. 8.0 (5.7-17.7) ng/mL, p=0.0000] and these higher levels persisted over the following 2 days. On the basis of receiver-operating characteristic analysis both NGAL and serum creatinine baseline measurements could predict AKI [area under the curve (95% confidence interval) 0.977 (0.823-0.980) and 0.789 (0.556-0.906), respectively], but the area under the curve for NGAL was significantly larger (p=0.024). A cut-off point >25 ng/mL for NGAL had a sensitivity of 0.91 and specificity of 0.95 in predicting AKI. CONCLUSIONS: Urinary NGAL can be used from the 1st day of injury as a reliable predictor of early AKI in multi-trauma patients.