Jens Schierbeck

The pharmacokinetic profile of plasma-derived mannan-binding lectin in healthy adult volunteers and patients with Staphylococcus aureus septicaemia

Mannan-binding lectin (MBL) is a member of the innate immune system, and MBL-deficiency affects 10–15% of Caucasians. With development of a plasma-derived MBL, substitution has become a therapeutic option in diseases associated with MBL insufficiency. The pharmacokinetics of injected MBL is weakly described, particularly in patients with infectious diseases. The pharmacokinetic profile of MBL following administration of 0.08 mg/kg to 20 healthy MBL-deficient volunteers and 0.2 mg/kg to 2 patients with Staphylococcus aureus septicaemia was established. In the volunteers, the maximal concentration was 2849 µg/l; the mean half-life (T1/2) was 69.6 h (14.6–114.9 h). The normalized clearance was 9×10−6 l/min×kg, and the mean residence time was 82 h. In the patients the serum-MBL versus time curves were similar to those in the volunteers, and T1/2 values were 36 and 40 h. In conclusion, MBL is distributed into a median volume of 3.4 l similar to the plasma volume, and the elimination in septicaemic patients was within the range of the controls. Due to the large individual variation in T1/2, we recommend that MBL therapy, with respect to dose and infusion intervals, is based on the chosen therapeutic target (≥1000 µg/l) and MBL serum determinations following the first infusion.

Mortality after discharge from the intensive care unit during the early weekend period: a population-based cohort study in Denmark.

Background:  As a result of a shortage of intensive care capacity, patients may be discharged prematurely early during weekends which may lead to an increased mortality and risk of readmission to intensive care units (ICU). We examined whether discharge from the ICU during the first part of the weekend was associated with an increased mortality and readmission to the ICU.

Patterns of cerebral tissue oxygen tension and cytoplasmic redox state in bacterial meningitis

Compromised cerebral energy metabolism is common in patients with bacterial meningitis. In this study, simultaneous measurements of cerebral oxygen tension and lactate/pyruvate ratio were compared to explore whether disturbed energy metabolism was usually caused by insufficient tissue oxygenation or compromised oxidative metabolism of pyruvate indicating mitochondrial dysfunction.