Effects of muscle relaxants on EEG, ABR and EMG in rabbits.

The effects of baclofen and pancuronium bromide on evoked electromyogram (EMG), cortical electroencephalogram (EEG) and auditory brainstem responses (ABR) were studied in pentobarbital anesthetized normal rabbits. Evoked EMG was measured in the gastrocnemius muscle by electrical stimulation of the sciatic nerve. Intravenous injection of baclofen decreased EEG and arterial blood pressure and light reflex, however, it had no significant influence on EMG or ABR at doses of 10 and 20 mg/kg/h. Pancuronium bromide immediately inhibited respiration, decreased EEG and EMG, however, it had no significant influence on arterial blood pressure, ABR, or light reflex, at doses of 0.4 and 1.0 mg/kg/h in anesthetized rabbits. ABR waves were observed until just before cardiac arrest with both of the muscle relaxants. It is suggested that ABR are not influenced by central or peripheral muscle relaxants, or by pentobarbital.

Assessment of antinociceptive drug effects in the presence of impaired motor performance.

The hot-plate (HP) and tail-flick (TF) tests are widely used to assess analgesic activity of drugs. These tests do not directly measure the intensity of the noxious stimulus perceived by the animal, but only the animal's response to it, and so may be affected by non-analgesic drugs. Sedatives and muscle relaxants, for example, may impair the ability to respond and hence be wrongly considered to have analgesic activity. We examined response of rats in the HP (55 degrees C, cutoff time 25 sec) and TF (cutoff time 5 sec) tests following administration of pentobarbitone, diazepam or pancuronium. These drugs all impaired motor performance as assessed by reduction in mean rotarod performance times to 6-32% of predrug values. However, HP and TF latencies were not appreciably prolonged. We also found that pancuronium did not alter effects of morphine on HP or TF latencies, despite reduction in rotarod performance to 38% of predrug values. Our results support the validity of HP and TF tests as analgesic assays even in the presence of substantial impairment of motor performance.

Static and dynamic pupillometry for determination of the course of gradual detoxification of opiate-addicted patients.

In order to assess the course of methadone (Heptadone) substitution therapy, 29 inpatients at the Vienna Psychiatric University Clinic (21 males, mean age = 27 years, SD 4 years; 8 females, mean age 29.75 years, SD 5.28 years) who were addicted to opium tea or to a mixture of opium and heroin were investigated by means of computer-assisted "static"- and "light-evoked dynamic" pupillometry. Pupillary measurements were carried out before the start of withdrawal, on the 2nd day 48 h after the administration of 10 mg methadone, and again after the maximum and half of the maximum dose of methadone had been administered. The constricted pupils (the effect of opiate) showed dilatation after the withdrawal syndrome appeared, but immediately after the start of the detoxification treatment, as well as 1 day after administration of the maximum methadone dose a decrease of pupillary diameter was observed. The narrowing of the pupil was followed by an increase in pupillary diameter, which peaked 48 h after the last minimal dose of methadone and nearly reached the normal level. The widening of the pupil reflects an increase of noradrenergic activity under conditions of opiate withdrawal. An increase of spontaneous fluctuations was observed during withdrawal and was only inhibited by the maximum dose of methadone. Finally, pupillary dynamics (shortening of latency time and increase of relative changes) improved during therapy. The pupillary measurement corresponded with clinical observations as well as with self-evaluation during treatment. Thus pupillometry seems to be a useful instrument for assessment of treatment of opiate-addicted patients.

Differential effect of pancuronium at the adductor pollicis, the first dorsal interosseous and the hypothenar muscles. An electromyographic and mechanomyographic dose-response study.

Cumulative dose-response curves were constructed from evoked compound electromyographic (EMG) recordings in man to compare the sensitivity to pancuronium of the adductor pollicis, the hypothenar and the first dorsal interosseous muscles. Also, the EMG and mechanomyography-based sensitivity of the adductor pollicis muscle were compared. The EMG and the mechanomyogram were evaluated in random sequence in each of 21 adult thiopental, fentanyl and diazepam anesthetized patients. The EMG-based ED50 were 36-38 micrograms.kg-1 with no differences between muscles. The EMG-based ED90 of the adductor pollicis and the hypothenar muscles were 62-65 micrograms.kg-1 compared to the 60 micrograms.kg-1 of the first dorsal interosseous muscle (P < 0.05). ED50 (34 micrograms.kg-1), and ED90 (56 micrograms.kg-1) obtained from the adductor pollicis mechanomyogram were significantly lower than those based on the EMG (P < 0.05). It is concluded that differences in sensitivity to pancuronium exist between the three muscles when evaluated from the EMG, and that the apparent sensitivity of a given muscle to a muscle relaxant may depend upon whether the response is evaluated using EMG or mechanomyography.