ELECTROENCEPHALOGRAPHIC DEMONSTRATION OF CENTRAL-NERVOUS-SYSTEM EFFECTS OF DIFFERENT PREMEDICATION REGIMENS

Introduction: For many years, the main goal of premedication was preve ntion of the dangerous side effects sometimes encountered in anestheti cs with anticholinergics, antiemetic antihistaminics, and opioids. Bec ause the rules were always preoperative fasting, premedication was adm inistered i.m. Thus, the onset of action was within 15-30 min from adm inistration. In recent years, with the introduction of newer anestheti cs with fewer side effects, anxiolysis became the main aim in premedic ation. Moreover, the oral route became popular since it obviously did not increase the acidity or volume of the gastric content. However, th e uptake and thus onset of action of orally administered drugs may tak e longer and can differ considerably between individual patients. Ther efore, the optimum interval between administration and induction of an esthesia remains controversial. The present study was carried out to e xamine the time course of drug action and the effects of different pre medication regimens on the electroencephalogram (EEG). Patients and me thods: After obtaining informed consent, in 38 unselected adult patien ts (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 ora lly; N: nordazepam, 0.2 mg/kg BW orally; AP: atropine, 0.5 mg, plus pr omethazine, 50 mg i.m.; APP: atropine, 0.5 mg, plus promethazine, 50 m g, plus pethidine, 0.7 mg/kg BW i.m. The EEG was recorded for a refere nce period of 10 min before and a study period of 30 min after premedi cation. Automated EEG processing was performed with CATEEM(R) (compute r-aided topographical electroencephalometry). Surface electrodes were placed according to the 10-20 system. Date were collected via an ampli fier (resistance 10 MOMEGA) and a digitalization unit (filter 0.2-35 H z, sampling rate 512 Hz, 12 bit A/D convertor). The original EEG signa ls 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 topograph ical power distribution. In order to achieve a pharmacodynamic time pr ofile, the study period was subdivided into three periods of 10 min ea ch. For clinical evaluation of vigilance, a 6-grade scoring system was used 1 = awake, 6 = not arousable). Results: All data are presented w ith respect to reference period. The power density of each frequency r ange for each electrode is integrated over the selected period and mea n values are shown. Changes in power density with time are expressed a s 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, a nd APP, and 3 in group N. In both benzodiazepine groups, a distinct in crease in power density was found in the beta-bands, while in groups A P and APP the increase was most pronounced in the delta and theta band s. In group M, there was a linear increase in beta1 power up to 310 %, while in the beta2 range there was a 170% maximum within the second p eriod of 10 min. In group N, there was a similar course with a lower i ncrease in beta1 (220%) and beta2 (130%). Increases in both beta-bands were most pronounced with frontal electrodes. While group M showed an increase in delta power (150%), together with moderate suppression in alpha (alpha1 50%, alpha2 40%), nordazepam caused only a slight incre ase in delta (124%) and a distinct increase in alpha2, to 150%, predom inantly in the frontal areas. Group APP showed a linear increase in bo th delta up to 210% and theta power to 190%. Maximum increases in delt a (170%) and theta (140%) in group AP, however, were less pronounced a nd occurred in the second period. In both groups there was suppression in alpha1 (AP: 20-40%, APP: 40-60%) and alpha2 (AP: 30-60%, APP: 40-6 0%). Conclusion: Our results indicate that premedication with oral ben zodiazepines results in beta-activation, corresponding to the anxiolyt ic effect, while the degree of sedation as expressed by delta and thet a bands may depend on the specific drug and dosage. The lower vigilanc e scores in group N may suggest a lower degree of sedative effect or t oo low a dosage. When benzodiazepines with fast uptake kinetics are ad ministered orally, pharmacodynamic EEG effects may occur as soon as 30 min or less after premedication.