: ICP/CPP-targeted intensive care results in prolonged mechanical ventilation and increased levels of therapy intensity, without evidence for improved outcome in patients who survive beyond 24 hrs following severe head injury.

Aims To investigate the pharmacokinetic and pharmacodynamic profile of midazolam administered as a concentrated intranasal spray, compared with intravenous midazolam, in healthy adult subjects. Methods Subjects were administered single doses of 5 mg midazolam intranasally and intravenously in a cross-over design with washout period of 1 week. The total plasma concentrations of midazolam and the metabolite 1-hydroxymidazolam after both intranasal and intravenous administration were described with a single pharmacokinetic model. b-band EEG activity was recorded and related to midazolam plasma concentrations using an exponential pharmacokinetic/pharmacodynamic model. Results Administration of the intranasal spray led to some degree of temporary irritation in all six subjects, who nevertheless found intranasal administration acceptable and not painful. The mean (ts.d.) peak plasma concentration of midazolam of 71 (t25 ng ml x1 ) was reached after 14 (t5 min). Mean bioavailability following intranasal administration was 0.83t0.19. After intravenous and intranasal administration, the pharmacokinetic estimates of midazolam were: mean volume of distribution at steady state 1.11t0.25 l kg x1 , mean systemic clearance 16.1t4.1 ml min x1 kg x1 and harmonic mean initial and terminal half lives 8.4t2.4and 79t30 min, respectively. Formation of the 1-hydroxymetabolite after intranasal administration did not exceed that after intravenous administration.Conclusions In this study in healthy volunteers a concentrated midazolam nasal spray was easily administered and well tolerated. No serious complications of the mode of administration or the drug itself were reported. Rapid uptake and high bioavailability were demonstrated. The potential of midazolam given via a nasal spray in the acute treatment of status epilepticus and other seizure disruptions should be evaluated.

Clinical, laboratory and electrodiagnostic studies are the mainstay in the diagnosis of polyneuropathy. An accurate etiological diagnosis is of paramount importance to provide the appropriate treatment, prognosis and genetic counselling. High resolution sonography of the peripheral nervous system allows nerves to be readily visualized and to assess their morphology. Ultrasonography has brought pathophysiological insights and substantially added to diagnostic accuracy and treatment decisions amongst mononeuropathies. In this study the literature on its clinical application in polyneuropathy is reviewed. Several polyneuropathies have been studied by means of ultrasound: Charcot-Marie-Tooth, hereditary neuropathy with liability to pressure palsies, chronic inflammatory demyelinating polyneuropathy, Guillain-Barré syndrome, multifocal motor neuropathy, paraneoplastic polyneuropathy, leprosy and diabetic neuropathy. The most prominent reported pathological changes were nerve enlargement, increased hypo-echogenicity and increased intraneural vascularization. Sonography revealed intriguingly different patterns of nerve enlargement between inflammatory neuropathies and axonal and inherited polyneuropathies. However, many studies concerned case reports or case series and showed methodological shortcomings. Further prospective studies with standardized protocols for nerve sonography and clinical and electrodiagnostic testing are needed to determine the role of nerve sonography in inherited and acquired polyneuropathies.

High-resolution sonography in addition to electrodiagnostic testing improves diagnostic reliability in CF neuropathy.

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