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BACKGROUND The safety and efficacy of hydroxyethyl starch (HES) for fluid resuscitation have not been fully evaluated, and adverse effects of HES on survival and renal function have been reported. METHODS We randomly assigned 7000 patients who had been admitted to an intensive care unit (ICU) in a 1:1 ratio to receive either 6% HES with a molecular weight(More)
OBJECTIVES To compare the plasma and subcutaneous tissue concentration-time profiles of meropenem administered by intermittent bolus dosing or continuous infusion to critically ill patients with sepsis and without renal dysfunction, and to use population pharmacokinetic modelling and Monte Carlo simulations to assess the cumulative fraction of response(More)
We randomized 18 critically ill patients to receive ceftazidime 6 g/day by continuous infusion or bolus dosing (2 g 8 hourly), each with a loading dose of 12 mg/kg ceftazidime. During the first 8 h, plasma ceftazidime concentration fell below 40 mg/L in only one patient (trough 38 mg/L) from the infusion group, compared with eight from the bolus group (2-33(More)
INTRODUCTION The assessment of adrenal function in critically ill patients is problematic, and there is evidence to suggest that measurement of tissue glucocorticoid activity may be more useful than estimation of plasma cortisol concentrations. Interstitial cortisol concentrations of cortisol represent the available pool of glucocorticoids able to enter the(More)
Rapid intracerebroventricular (icv) injections in the conscious mouse are described, using a small volume gas-tight syringe with repeating dispenser device (Hamilton Bonadoz, Switzerland). The device gives reproducibility within 2% of chosen volume, while facilitating rapid icv injections to groups of animals. The technique is used to demonstrate in the(More)
BACKGROUND Beta-lactam antibiotics are a commonly used treatment for severe sepsis, with intermittent bolus dosing standard therapy, despite a strong theoretical rationale for continuous administration. The aim of this trial was to determine the clinical and pharmacokinetic differences between continuous and intermittent dosing in patients with severe(More)
INTRODUCTION Increasingly, derived estimates of glomerular filtration, such as the modification of diet in renal disease (MDRD) equation and Cockcroft-Gault (CG) formula are being employed in the intensive care unit (ICU). To date, these estimates have not been rigorously validated in those with augmented clearances, resulting in potentially inaccurate drug(More)
OBJECTIVES To compare the clinical and bacteriological outcome of critically ill patients with sepsis treated by ceftriaxone administered as a once-a-day intermittent bolus dose or by 24 h continuous infusion. PATIENTS AND METHODS We conducted an open-label, randomized controlled pilot study in 57 patients clinically diagnosed with sepsis(More)
Controversy continues regarding whether the presence of meticillin resistance increases mortality risk in Staphylococcus aureus infections. In this study, we assessed the role of meticillin resistance in survival of patients with S. aureus infection included in the EPIC II point-prevalence study of infection in critically ill patients performed on 8 May(More)
The level of an endogenous opioid (peak B endorphin) was measured in chromatographically fractionated cerebrospinal fluid (CSF) sampled from two groups of chronic pain patients before and after intrathecal saline (placebo) injection. As assessed by a verbal rating scale, one group reported no change in their level of pain (non-responders, NR; n = 6) while(More)