EFNS guideline on the management of status epilepticus in adults

The objective of the current article was to review the literature and discuss the degree of evidence for various treatment strategies for status epilepticus (SE) in adults. We searched MEDLINE and EMBASE for relevant literature from 1966 to January 2005 and in the current updated version all pertinent publications from January 2005 to January 2009. Furthermore, the Cochrane Central Register of Controlled Trials (CENTRAL) was sought. Recommendations are based on this literature and on our judgement of the relevance of the references to the subject. Recommendations were reached by informative consensus approach. Where there was a lack of evidence but consensus was clear, we have stated our opinion as good practice points. The preferred treatment pathway for generalised convulsive status epilepticus (GCSE) is intravenous (i.v.) administration of 4–8 mg lorazepam or 10 mg diazepam directly followed by 18 mg/kg phenytoin. If seizures continue more than 10 min after first injection, another 4 mg lorazepam or 10 mg diazepam is recommended. Refractory GCSE is treated by anaesthetic doses of barbiturates, midazolam or propofol; the anaesthetics are titrated against an electroencephalogram burst suppression pattern for at least 24 h. The initial therapy of non‐convulsive SE depends on type and cause. Complex partial SE is initially treated in the same manner as GCSE. However, if it turns out to be refractory, further non‐anaesthetising i.v. substances such levetiracetam, phenobarbital or valproic acid should be given instead of anaesthetics. In subtle SE, in most patients, i.v. anaesthesia is required.     

The contribution of general practice based research to the development of national policy: case studies from Ireland and Australia

Background

This paper aims to describe the influence of general practice based research on the development of two specific policy initiatives, namely the Heartwatch Programme in Ireland and the Better Outcomes in Mental Health Care (BOiMHC) program in Australia. A case study approach was used to explore the extent to which relevant general practice based research shaped these initiatives.

Results

In both case studies, a range of factors beyond general practice based research shaped the initiative in question, including political will, the involvement of stakeholders (including key opinion leaders), and the historical context. Nonetheless, the research played an important role, and was not merely put to 'symbolic use' to support a position that had already been reached independently. Rather, both case studies provide examples of 'instrumental use': in the case of Heartwatch, the research was considered early in the piece; in the case of the BOiMHC program, it had a specific impact on the detail of the components of the initiative.

Conclusion

General practice based research can influence policy-making and planning processes by strengthening the foundation of evidence upon which they draw. This influence will not occur in a vacuum, however, and general practice researchers can maximise the likelihood of their work being 'picked up' in policy if they consider the principles underpinning knowledge transfer.

     

High ambient pressure of 41 bar increases the cerebral toxicity of penicillins

Sodium benzylpenicillin, cloxacillin, and azlocillin were infused intravenously in awake rats at 1 and 41 bar until they convulsed. The doses necessary to elicit convulsions were significantly lower at 41 than at 1 bar, i.e., with a 24% (P less than 0.0005) lower dose of benzylpenicillin and a 23% lower dose of azlocillin (P less than 0.005). The convulsion threshold of cloxacillin was also lower (13%), but not statistically significant. The results show that high pressure reduces the convulsion threshold for some penicillins. Hippocampal amino acid concentrations were also measured in animals exposed to 1 and 41 bar with and without benzylpenicillin treatment. Infusion of benzylpenicillin at 1 bar led to a decrease of 15% in the glutamate level (P less than 0.05), whereas at 41 bar it decreased the level of glutamate by 17% (P less than 0.05) as well as that of glutamine by 19% (P less than 0.05). The results suggest that treatment with penicillin at high ambient pressure may increase the turnover of transmitter glutamate in the rat hippocampus and thus increase the excitability. These effects should be considered when high doses of penicillins are administered to man at high ambient pressure.     

Cerebrospinal fluid proteins and free amino acids in patients with solvent induced chronic toxic encephalopathy and healthy controls

The concentrations of protein, albumin, IgG, and free amino acids in the cerebrospinal fluid of 16 patients with chronic toxic encephalopathy due to organic solvents were measured. The patient group consisted of all patients with this diagnosis in a neurological department in 1985. The diagnosis was based on neuraesthenic symptoms, pathological psychometric performance, and verified exposure to neurotoxic organic solvents. A control group of 16 patients with myalgias or backache, or both, and no signs of disease was used for comparison. The purpose was to study possible changes in the cerebrospinal fluid that might contribute to understanding the aetiology of solvent induced chronic toxic encephalopathy. A rise in protein, albumin, and IgG was found in the patient group compared with the control group, as well as reduced concentrations of phosphoethanolamine, taurine, homocarnosine, ethanolamine, alpha-aminobutyric acid, and leucine. Using a stepwise multiple regression analysis, taurine was negatively correlated to exposure to solvents. These findings may indicate membrane alterations in the central nervous system related to exposure to organic solvents.     

Raised bile acid concentrations in SIDS lungs at necropsy

Previous studies of the abnormal physical properties of lung surfactant derived from infants experiencing prolonged expiratory apnoea, or who have died of sudden infant death syndrome (SIDS), have led to a search for the agent responsible. Bronchoalveolar lavage (BAL) has been performed upon 12 infants under 12 months at necropsy and the rinsings analysed for up to 26 bile acids using high performance liquid chromatography, which requires nanomolar quantities. They were also analysed for simultaneously retrieved phospholipid and proteolipid-a minor component of lung surfactant-as markers of lavage efficiency. Total bile acid (TBA) was found to be higher in six SIDS cases, reaching a mean (SE) 8.54 (2.24) mumol/l in the BAL fluid compared with 4.66 (1.47) mumol/l in the six controls of similar age. When related to the concomitant surfactant yield, the TBA/ proteolipid and TBA/phospholipid ratios both showed highly significant differences between index lungs and controls, providing another postmortem marker of SIDS with potential for development as a test of risk. Since the bile:phospholipid ratio determines whether phospholipase A2 synthesises or hydrolyses phospholipid, the raised TBA/phospholipid ratio could be highly significant, causing this enzyme to function more like its role in the gut than in the lung.     

The effect of methioninesulfoximine, an inhibitor of glutamine synthetase, on the levels of amino acids in the intact and decorticated rat neostriatum

The glutamate terminals in rat rostral neostriatum were removed on one side by ipsilateral frontal cortical ablation. Intraperitoneal administration of L-methioninesulfoximine (MSO), an inhibitor of glutamine synthetase, induced different changes in amino acid concentration in the rostral neostriatum on the intact and decorticated sides. Glutamine was more reduced on the decorticated side than on the intact side. Glutamate changed less, but decreased more on the intact than on the lesioned side. There seems to be a correlation between the decrease in glutamine and the increase in alanine on both sides. GABA and taurine did not change significantly. The results indicate that the formation of glutamine probably formed from released glutamate is lower on the decorticated side than on the intact side.     

Which Carbohydrates Should We Recommend for Intravenous Nutrition?

In a short review solutions of glucose, fructose and invertose have been compared in regard to proteinsparing effects, side effects and infusion rates. It is concluded that fructose alone offers no advantage to glucose neither in the normal nor in the stressed organism. Compared with pure glucose and fructose solutions, higher amounts of carbohydrate can be administered as invertose, without increasing the risk of side effects.