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Description / Table of Contents: Abstract. Introduction. For many years, the main goal of premedication was prevention of the dangerous side effects sometimes encountered in anesthetics with anticholinergics, antiemetic antihistaminics, and opioids. Because the rules were always preoperative fasting, premedication was administered i.m. Thus, the onset of action was within 15 – 30 min from administration. In recent years, with the introduction of newer anesthetics with fewer side effects, anxiolysis became the main aim in premedication. Moreover, the oral route became popular since it obviously did not increase the acidity or volume of the gastric content. However, the uptake and thus onset of action of orally administered drugs may take longer and can differ considerably between individual patients. Therefore, the optimum interval between administration and induction of anesthesia remains controversial. The present study was carried out to examine the time course of drug action and the effects of different premedication regimens on the electroencephalogram (EEG). Patients and methods. After obtaining informed consent, in 38 unselected adult patients (ASA I and II, 〈65 years) scheduled for elective surgery, the EEG was recorded continuously before and after premedication. The patients were randomly assigned to four groups: M: midazolam, 0.2 mg/kg BW orally; N: nordazepam, 0.2 mg/kg BW orally; AP: atropine, 0.5 mg, plus promethazine, 50 mg i.m.; APP: atropine, 0.5 mg, plus promethazine, 50 mg, plus pethidine, 0.7 mg/kg BW i.m. The EEG was recorded for a reference period of 10 min before and a study period of 30 min after premedication. Automated EEG processing was performed with CATEEM® (computer-aided topographical electroencephalometry). Surface electrodes were placed according to the 10 – 20 system. Date were collected via an amplifier (resistance 10 MΩ) and a digitalization unit (filter 0.2 – 35 Hz, sampling rate 512 Hz, 12 bit A/D convertor). The original EEG signals were used in an interpolation algorythm to produce an additional 82 virtual recording points, allowing for high topographical resolution. After spectral analysis (fast Fourier transformation), the different frequency ranges of the EEG power spectrum are displayed in different colors. The screen displays the on-line map with color-based topographical power distribution. In order to achieve a pharmacodynamic time profile, the study period was subdivided into three periods of 10 min each. For clinical evaluation of vigilance, a 6-grade scoring system was used (1=awake, 6=not arousable). Results. All data are presented with respect to reference period. The power density of each frequency range for each electrode is integrated over the selected period and mean values are shown. Changes in power density with time are expressed as percentage change from reference period. Biometrical data showed no significant differences between groups. The median vigilance score 30 min after premedication (end of study period) was 4 in groups M, AP, and APP, and 3 in group N. In both benzodiazepine groups, a distinct increase in power density was found in the β-bands, while in groups AP and APP the increase was most pronounced in the δ and θ bands. In group M, there was a linear increase in β 1 power up to 310%, while in the β 2 range there was a 170% maximum within the second period of 10 min. In group N, there was a similar course with a lower increase in β 1 (220%) and β 2 (130%). Increases in both β-bands were most pronounced with frontal electrodes. While group M showed an increase in δ power (150%), together with moderate suppression in α (α 1 50%, α 2 40%), nordazepam caused only a slight increase in δ (124%) and a distinct increase in α 2 to 150%, predominantly in the frontal areas. Group APP showed a linear increase in both δ up to 210% and θ power to 190%. Maximum increases in δ (170%) and θ (140%) in group AP, however, were less pronounced and occurred in the second period. In both groups there was suppression in α 1 (AP: 20 – 40%, APP: 40 – 60%) and α 2 (AP: 30 – 60%, APP: 40 – 60%). Conclusion. Our results indicate that premedication with oral benzodiazepines results in β-activation, corresponding to the anxiolytic effect, while the degree of sedation as expressed by δ and θ bands may depend on the specific drug and dosage. The lower vigilance scores in group N may suggest a lower degree of sedative effect or too low a dosage. When benzodiazepines with fast uptake kinetics are administered orally, pharmacodynamic EEG effects may occur as soon as 30 min or less after premedication.

Description / Table of Contents: Abstract Gamma-hydroxybutyric acid (GHB) is a naturally occurring transmitter in the mammalian brain, related to sleep regulation and possibly to energy balance in diving or hibernating animals. It has been used for almost 35 years as an intravenous agent for induction of anaesthesia and for long-term sedation. Its convincing pharmacological properties, without serious adresse effects on circulation or respiration, are compromised by its unpredictable duration of action. This is not a major problem with long-term sedation during ICU treatment. GHB has been used with good results for sedation of patients with severe brain injury, where it compares favourably with barbiturates. In animal studies, it seems to possess a protective action against hypoxia on a cellular and whole organ level. However, in some experimental animals GHB has been shown to produce seizure-like activities, and the compound is being used to produce absence-like seizures. GHB has been used in our ICU for years to provide adequate sedation for patients under controlled ventilation or for patients figthing the respirator during spontaneous respiration. No serious side effects were observed in these patients, while in some patients under haemodialysis hypernatraemia and metabolic alkalosis developed; both were reversible after discontinuation of GHB and restriction of additional sodium input (Somsanit, the commercially available GHB preparation in Germany, contains 9.2 mmol sodium/g; the daily dose averages 20–40 g GHB, i.e. 180–370 mmol sodium). Patients and methods. In 31 patients after major abdominal surgery, sedation was established with GHB 50 mg/kg BW injected via perfusion pump over a 20-min period. No centrally acting medication had been given for at least 2 h. A computer-based multichannel EEG system (CATEEM, MediSyst, Linden) was used, allowing for fast Fourier transformation, spectral analysis and topographical brain mapping. EEG during induction of sedation was followed after a baseline EEG (10 min) had been recorded. Patients receiving long-term sedation were studied daily for an additional 15-min period. Corresponding well to the clinical findings, EEG pattern changed to a slow delta-theta or delta-only rhythm within 10 min of the start of injection. Alpha and beta power decreased, while delta activity exhibited an increase. All changes were most obvious in frontal and central areas of the brain. In about one out of three patients, a burst – suppression pattern developed. Since automatic processing of EEG may fail to detect special patterns like the looked-for 3/s spikes and waves, the raw EEG was analysed visually by an expert neurologist. Both processed and conventionally analysed EEG were free of any seizure-like electrical activity. Conclusion. We conclude that animal data may not apply to the use of GHB in humans, provided the dose is limited to the clinical needs. GHB is used in clinical practice in doses twice as high, or even higher, than the one we use for induction, without obvious side effects. However, the suppression of theta rhythm we observed in about half of the patients studied may indicate that even less than 50 mg/kg BW might be sufficient for adequate sedation.