French Ministry of Health and the Société Française d'Anesthésie Réanimation.

Cerebrospinal fluid (CSF) penetration and the pharmacokinetics of vancomycin were studied after continuous infusion (50 to 60 mg/kg of body weight/day after a loading dose of 15 mg/kg) in 13 mechanically ventilated patients hospitalized in an intensive care unit. Seven patients were treated for a sensitive bacterial meningitis and the other six patients, who had a severe concomitant neurologic disease with intracranial hypertension, were treated for various infections. Vancomycin CSF penetration was significantly higher (P < 0.05) in the meningitis group (serum/CSF ratio, 48%) than in the other group (serum/CSF ratio, 18%). Vancomycin pharmacokinetic parameters did not differ from those obtained with conventional dosing. No adverse effect was observed, in particular with regard to renal function.Vancomycin has a slow bactericidal activity with a low MIC and a time-dependent activity with a limited penetration in cerebrospinal fluid (CSF) when administered by intermittent infusion over a period of at least 90 min every 8 or 12 h (5). Continuous infusion of vancomycin makes it possible to achieve a constant bactericidal level in blood and may also result in better CSF penetration (4). The benefit of prescribing continuous infusion has been reported for children (1) with postneurosurgical meningitis (2) and staphylococcus-resistant bone infections (3). The pharmacokinetics of antibiotics are modified in intensive care unit (ICU) patients due to the large daily fluid balance, acute changes in body weight, hypoalbuminemia, edema, and low hematocrit values. These modifications lead to marked changes in elimination half-life, volume of distribution, and clearance (12,20,25).The aim of this study was to evaluate vancomycin penetration of CSF and its pharmacokinetics after administration by continuous infusion in ICU patients under mechanical ventilation in whom pharmacokinetic modifications could be expected.After institutional approval and informed consent from a close relative were obtained, 13 consecutive patients of either sex, 25 to 58 years of age, hospitalized in the ICU and infected by vancomycin-sensitive bacteria were enrolled in the study. These patients underwent mechanical ventilation for acute respiratory failure. Exclusionary criteria included an age of Ͻ18 years, renal dysfunction, and an expected hospital stay of Ͻ72 h. Seven patients were treated for sensitive bacterial meningitis. Primary pathologies were head trauma (five cases) and medical coma (two cases). The other six patients were treated for various infections, and an external CSF shunt was already in place for the treatment of a primary pathology (severe neurologic disease with intracranial hypertension). Primary pathologies were medical coma (three cases), subarachnoid hemorrhage (two cases), and stroke (one case). The bacteria involved in infections were Staphylococcus epidermidis (six cases), Staphylococcus aureus (three cases), Streptococcus pneumoniae (two cases), Enterococcus faecalis (one case), and Corynebacterium (one case). The cases...

The reference method to measure serum osmolality (Mosm) is the delta cryoscopic method. However, the technology may not be available. Clinicians therefore must calculate osmolality (Cosm) as the sum of concentrations of selected principal solutes such as sodium, potassium, urea, and glucose. To evaluate the validity of Cosm in patients in hyperosmolar state we compared Cosm to Mosm. Twenty-two ICU patients treated by infusion of hypertonic solutes for intracranial hypertension following head injury were prospectively studied. A control group of 10 patients with hypernatremia due to medical causes was also evaluated. Na+, blood urea nitrogen (BUN), and glucose were measured to calculate serum osmolality: Cosm = (2 x Na+) + BUN + glucose (in mOsm/kg). Measurement of serum osmolality was performed using the delta-cryoscopic method. The results of the two methods were compared by correlating the difference (Mosm-Cosm) between each pair of results with the mean of the pairs of results. Cosm underestimated Mosm (3.4 mOsm/kg, P < 0.02) in the control group whereas Cosm overestimated Mosm in patients who received hypertonic fluids (2.3 mOsm/kg, P < 0.03). Calculation of osmolality introduced a systematic bias, overestimating osmolality in the lower ranges and underestimating it in the higher ranges. In the range of hyperosmolality commonly used to manage intracranial hypertension following head trauma, serum osmolality, as determined by sum of principal serum solutes, compares poorly with direct measurement using standard osmometry.

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