Crit Care 1999, 3 3 ( (s su up pp pl l 1 1) ):P1 I In nt tr ro od du uc ct ti io on n: : Critically ill patients requiring intensive care are at risk of iatrogenic ocular damage.Studies have reported an incidence of eye problems of up to 40% in critically ill ventilated patients.We conducted this study to assess the incidence of ocular complications in our intensive care unit where all patients are cared for according to an eye care standard.M Me et th ho od ds s: : All ventilated patients over a 2 month period were included.Ophthalmic assessment was performed on admission and repeated every other day during the period of ventilation.At each assessment the average Ramsey sedation score over the previous 24 h, the presence of tracheal secretions and the presence of ventilation associated pneumonia was noted.Eye care performed was recorded.R Re es su ul lt ts s: : Sixty patients were included.One patient developed corneal exposure keratopathy.No patient developed conjunctivitis or corneal ulceration.Further advice on appropriate measures of eye care was given in five cases (8%).Nine patients (15%) had large amounts of respiratory secretions with positive microbiological results.C Co on nc cl lu us si io on n: : This study confirms that the use of an eye care standard is associated with a low incidence of ocular surface complications.The incidence of ocular complications in this group of patients is far lower than previously described.

In France, the legal routes used to administer midazolam to a patient are intravenously and intramuscularly. For anaesthetists, these routes are not well adapted to paediatric use; they lead to pain at injection site and stress on children. The sublingual route should be a good compromise between stress and quick efficiency. We have developed a sublingual tablet of midazolam. The aim of the present investigation is to compare the pharmacokinetic parameters of midazolam tablets administered by the sublingual and intravenous routes in 6 rabbits to determine the bioequivalence between these routes. We have estimated the 1-hydroxy-midazolam serum level by difference between RRA and HPLC values. By the sublingual route, midazolam absorption is substantial and fast. The statistical analysis, on data obtained with HPLC dosage, shows no significant difference between pharmacokinetic parameter values calculated after intravenous and sublingual administration (0.5 mg). The absolute bioavailability was close to 100%. With RRA dosage, however, AUCs were greater than those obtained by HPLC dosage (174%). 1-hydroxy-midazolam seems to have a great importance in BZD activity. To estimate the bioequivalence between intravenous and sublingual midazolam administration, it is necessary to take into account the active metabolites.

A routine high-performance liquid chromatographic method for measuring midazolam in human serum has been developed. The sample preparation procedure consisted of simple liquid-liquid extraction with dichloromethane, followed by evaporation under nitrogen. The mobile phase used was a mixture of acetonitrile at 0.02 M and sodium acetate at pH 3.0 (80:20, v/v) and a flow-rate of 1.2 mL/min. The separation was performed on two cyanopropyl columns (150 x 4.6 mm). The detection was by UV absorption at 240 nm. A linear range from 10 to 1,000 ng/mL and a quantification limit of 7.4 ng/mL of serum was reached. The mean intra-assay and inter-assay reproducibility from serum sample spiked with 100 ng/mL were 4.1 and 4.7%, respectively. The recoveries from serum sample spiked with 50, 100, 500 ng/mL were 85.46, 85.38 and 85.57%, respectively. This method was developed to allow pharmacokinetics study of midazolam in young patients in short surgical interventions.

Clozapine is an antipsychotic drug with few extrapyramidal motor side-effects, used to treat schizophrenia which is resistant to classical neuroleptic therapy. This report shows that norclozapine but not clozapine-N-oxide has the same D2 receptor affinity as clozapine. Assay results suggest a bimodal distribution which may be explained by CYP1A2 polymorphism. Extensive metabolizers could produce other active metabolites, probably other hydroxy-clozapine derivatives.

An isocratic reversed-phase high performance liquid chromatographic method has been developed for th e determination of dobutamine in the plasma of dialysed patients. A solid phase extraction method with a Sep-Pak C18 cartridge was used to isolate the drug and isoxsuprine (internal standard) from plasma. The separation was carried out on an ODS-Hypersil column with 0.1 M phosphate buffer:acetonitrile:methanol (72:20:8 v/v/v) as the mobile phase. The recovery of dobutamine added to plasma by the extraction procedure was 87 +/- 2.3% (mean +/- SD). The accuracy and reproducibility of the method were within acceptable limits over the concentration range 0-1000 ng/mL. Quantification was by fluorescence detection at 275 nm excitation and 310 nm emission wavelengths with a detection limit of 5 ng/mL for dobutamine. This procedure was applied to ascertain the pharmacokinetics of dobutamine infusion in nine patients with cardiogenic shock and end-stage renal disease undergoing haemodialysis.

A radioreceptor assay (RRA) was developed to determine plasma levels of amisulpride. In in vitro binding conditions, the RRA technique was sensitive (11.6 nmol/l) and reliable, with a high degree of precision. The reproducibility of the method through statistical coefficients was < 7%. This method was applied to a pilot pharmacokinetic study in rabbits following single i.v. administration of amisulpride at 10 mg/kg. The results obtained were compared with those obtained by high performance liquid chromatography method (HPLC) in order to assess the validity of this new RRA technique.