Schlüsselwörter: Prämedikation – Atropin – Promethazin – Pethidin – Nordazepam – Midazolam – EEG – Pharmako-EEG-Elektroenzephalometrie
Key words: Premedication – Atropine – Promethazine – Pethidine – Meperidine – Nordazepam – Desmethyldiazepam – Midazolam – EEG – Pharmaco-EEG – Electroencephalometry
Springer Online Journal Archives 1860-2000
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.
Zusammenfassung. Die Prämedikation hat ihren Schwerpunkt von der i.m.-Gabe anticholinerger, antihistaminerger und analgetischer Komponenten hin zu oral verabreichten Anxiolytika verlagert. Um den Effekt unterschiedlicher Prämedikations-Regimes auf die zerebrale Aktivität zu untersuchen, wurden 32 Patienten vor elektiven Eingriffen mit je zwei verschiedenen peroralen bzw. i.m.-Medikamenten oder -Kombinationen mittels quantitativen Pharmako-EEGs (CATEEM®) untersucht. Es wurden folgende Gruppen gebildet: M: Midazolam 0,2 mg/kg KG p.o. (Dormicum®); N: Nordazepam 0,2 mg/kg KG p.o. (Tranxilium N®); AP: Atropin 0,5 mg und Promethazin 50 mg i.m. (Atosil®); APP: wie AP, zusätzlich Pethidin 0,7 mg/kg i.m. (Dolantin®). Nach einer Referenzzeitmessung (10 min) und Prämedikation wurde die zerebrale elektrische Aktivität für 30 min kontinuierlich registriert. Nach Benzodiazepinen trat – im Gegensatz zur i.m.-Medikation – die bekannte Zunahme des β-Rhythmus vor allem im frontopräzentralen Bereich auf. Dabei stieg die Aktivität im β 1-Bereich über 30 min kontinuierlich an (bei M stärker und früher als bei N). Für β 2 war ein Gipfel nach ca. 20 min zu beobachten. Dagegen folgte auf die i.m.-Prämedikation eine Zunahme der δ-Aktivität fronto-zentral. Während nach N die Aktivität im α-Band frontal anstieg, kam es nach M, AP und APP rasch zur Suppression des α-Rhythmus. Damit ist auch die kurzfristige orale Gabe schnell resorbierbarer Benzodiazepine sinnvoll. Innerhalb von 30 min zeigt das EEG deutliche pharmakodynamische Veränderungen.
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