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Prolonged use of sedative drugs frequently leads to oversedation of intensive care patients. Clinical assessment scales are not reliable in deeply sedated patients. Parameters obtained from spectral and bispectral analysis of electroencephalogram (EEG) records have been combined to create an index (BIS) to monitor anesthesia depth. The role of such parameters in monitoring the depth of the sedation in intensive care unit (ICU) patients has yet to be determined. We designed the present prospective study to redefine and calculate available spectral and bispectral parameters from raw EEG records and estimate their clinical relevance for the diagnosis of under- or oversedation levels in ICU patients. Forty adult patients receiving continuous midazolam and morphine sedation were included. We obtained 167 clinical evaluations of sedation level using Ramsay and COMFORT scales along with an EEG record of 300 s. Six spectral parameters-relative power of 4 frequency bands (beta, alpha, Theta, and delta), 95th percentile of the power spectrum (SEF95), and 50th percentile of the power spectrum (SEF50) and four bispectral parameters, real triple product, bispectrum (Bispectrum), bicoherence, and ratio 10-were calculated. The relevance of each of these parameters and combinations in predicting too light (Ramsay 1 and 2) or deep (Ramsay 5 and 6) sedation levels was assessed. These calculations were performed before and after exclusion of the agitated patients, whose COMFORT 4 score was above 2. The most relevant parameters for predicting levels of deep sedation (Ramsay 5 and 6) were ratio 10 (area under the curve = 0.763; 95% confidence interval, 0.679-0.833) and SEF95 (area under the curve = 0.687; 95% confidence interval, 0.597-0.767). The most relevant parameters for predicting light levels of sedation (Ramsay 1 and 2) were also ratio 10 (area under the curve = 0.829; 95% confidence interval, 0.695-0.917) and SEF95 (area under the curve = 0.798; 95% confidence interval, 0.650-0.898). There is a modest improvement in relevance of their linear combination in predicting sedation level. Results were similar after exclusion of agitated patients. We conclude that various calculated EEG descriptive parameters exhibited large interindividual variability. There was a strong correlation between EEG spectral and bispectral parameters. Bispectral analysis slightly improves the predictive power of simple spectral analysis in distinguishing too light or deep sedation levels in ICU patients.Spectral edge frequency 95 and Ratio 10 are the most relevant electroencephalogram (EEG) indexes for monitoring the level of sedation in intensive care unit patients but calculated EEG values exhibited large interindividual variability. Bispectral analysis of EEG provides a slight improvement over simple spectral analysis.

To explore memory impairments in temporal lobe epilepsy, we used two experimental models in the rats : (a) kainate-induced status epilepticus (SE) resulting in excitotoxic damage and in later spontaneous seizures ; and (b) amygdala kindling, known to induce no lesions (or only minor) and neuronal reorganization. Long-term effects of these models on memory were investigated with a spatial learning task in a radial-arm maze, and a social interaction test that implies degree of short-term memory. An histological analysis was made to determine neuronal damage or loss caused by epileptic activity in brain regions that could be related to memory functions. Kainate-induced epilepsy produced large memory deficits in animals tested 5 months after the injection. The rats showed severe lesions in amygdala and hippocampus and piriform and entorhinal cortex. Spatial memory was strongly diminished. The social memory test was severely impaired, probably due to the extent of amygdala injury, which is known to disturb social behavior. On the contrary, kindled rats showed no evident lesion in any brain region and displayed performances as good as those of controls in both tests. These experiments demonstrated that memory deficits appear to be related to the severity of neuronal damage in limbic areas, and the ability to develop seizures (permanence) is not solely responsible for these memory disturbances.

The capacity of thienylcyclohexylpiperidine (TCP), a non-competitive blocker of the N-methyl- d -aspartate (NMDA) receptor, to counteract the convulsant, lethal, and neuropathological effects of 2 × LD50 of soman (an irreversible inhibitor of cholinesterase) was investigated in guinea-pigs treated by pyridostigmine and atropine sulphate. The effects of a weak dose of TCP (1 mg/kg) used in the present study globally reproduced those previously obtained with a higher dose (2.5 mg/kg; [Neurotoxicology 15 (1994) 837]): TCP was again most protective when given curatively within the first hour of soman-induced seizures. In this condition, (a) paroxysmal activity ceased in 10–20 min, (b) all the animals survived, (c) the majority of them recovered remarkably well and did not show any brain damage 24 h after the intoxication, and (d) the minimal duration of seizure activity normally required for producing soman-induced brain damage in other pharmacological environments was increased from 10 to 40 min to 80 min. Strikingly, when TCP was given 120 min after seizure onset, it failed to show any anticonvulsant activity but still provided neuroprotection in the hippocampus. The present study also gives additional evidence (see [Neurotoxicology 21 (4) (2000) 521]) that in soman poisoning, (a) the development of brain damage depends on the occurrence of ECoG seizures, (b) the topographical distribution of lesions depends on seizure duration, and (c) an increase of the relative power in the lowest (delta) frequency band might be a reliable marker of neuronal degradation. All these findings confirm that (a) glutamatergic NMDA receptors are involved in the mechanisms of soman-induced seizures and brain damage, (b) non-competitive antagonists of NMDA receptors might be promising candidates for post-treatment of soman poisoning, and (c) ECoG parameters from ECoG tracings and power spectrum might serve as useful external predictors for soman-induced neuropathological changes.