[Development and current status of combined spinal epidural anaesthesia]. / Entwicklung und gegenwärtiger Stand der kombinierten Spinal-Periduralanästhesie.

Combined spinal and epidural anaesthesia/analgesia is a method whereby drugs are applied intrathecally as a single dose and epidurally either continuously or intermittently via an epidural catheter. More than 50 years ago, first attempts were made to introduce this method into clinical practice but they found little general acceptance. Only during the last decades has tremendous progress been made in developing new, highly-sophisticated equipment: matching spinal and epidural needles and catheters, epidural needles with a separate conduit for the spinal needle or with an additional hole for the exit of the spinal needle as well as fixation devices for the spinal needle. A specific feature of the method is the only recently recognised epidural volume extension, which allows the use of low-dose drug combinations with sufficient analgetic properties but less cardiovascular compromise and fewer side-effects. This review describes the main and most important developmental steps and offers practical examples for its use in day-case surgery of the lower limb, in the "walking epidural" in obstetrics and in caesarean section. The method has become a valuable new tool in the armamentarium of the anaesthetist and part of daily routine in many clinics.

[The opioid tramadol demonstrates excitatory properties of non-opioid character--a preclinical study using alfentanil as a comparison]. / Das Opioid Tramadol hat zentral-exzitatorische Effekte von nicht-opioidartigem Charakter.Teil 1: Präklinische Ergebnisse im Vergleich zu Alfentanil.

Tramadol, an analgesic with mean potency one tenth that of morphine is used regularly for the treatment of chronic and postoperative pain. Previous reports have indicated that tramadol may induce seizure activity when given together with a selective serotonin reuptake inhibitor (SSRI). Therefore, its major mode of action may be questioned which purportedly is due to binding with the opioid receptor and partly due to the inhibition of monoamine reuptake. We therefore set out to study its potential in inducing seizure activity and to quantify its effect on EEG-power spectra and on the central modulation of sensory afferents in awake and trained dogs (n=7). In order to demonstrate if opioid receptors mediated these effects, incremental doses of tramadol were given which was followed by naloxone for possible reversal. After a wash-out period the same animals were exposed to graded doses of alfentanil, a pure mu-receptor agonist. Again this was followed by the opioid antagonist naloxone for reversal.The electroencephalogram (EEG) and the event-related evoked potentials (SEP) were used to demonstrate possible excitatory effects. In order to derive the SEP the front paw was stimulated electrically (Digi Stim II trade mark ) while the evoked potentials were picked up contralaterally from the somatosensory cortex using stick-on electrodes. 256 sweeps were averaged (Lifescan) and the peak-to-peak amplitude was measured to demonstrate CNS excitation compared to control (%). Additionally, the raw electroencephalogram was viewed for epileptogenic changes and its power computed into the various power bands alpha, beta, delta und theta using FFT over a time epoch of 60 s. Following control, graded doses of either tramadol (2-5-10 mg/kg i.v.) or alfentanil (10-30-60 microg/kg i.v.) were given every 15 min while the EEG and the SEP were recorded. Thereafter naloxone (20 microg/kg i.v.) was injected for reversal. Tramadol did not suppress the amplitude of the SEP at any dose. High doses (>5 mg/kg i.v.) resulted in an increase (+100%) of the amplitude of the evoked potential. This was accompanied by short-term muscle fibrillations, and a short-term spike-and-wave activity in the EEG followed by a long-lasting theta-dominance. These effects could not be reversed by naloxone. In contrast to tramadol, alfentanil induced a dose-related depression of amplitude in the SEP with a maximum of 82% suggesting a depressive effect of modulation of afferents in the sensory cortex. This effect was fully naloxone reversible and was followed by a rebound in amplitude of the SEP together with an increase in fast beta-waves in the EEG. Tramadol very little mediates its central action via the mu-opioid receptor as the present effects were not naloxone reversible. Consistent with the results is the very low affinity of tramadol to the opioid receptor which is several thousand times less than that of morphine. Most likely, inhibition of central norepinephrine and serotonin reuptake as well as the reduction in 5-HT-turnover may contribute to the effects of tramadol. Due to the monoamine reuptake inhibition an increase in transmission may result, triggering off excitatory phenomena with spike-and-wave activity in the CNS. Such excitatory effects, however, may only be seen when tramadol is used in doses exceeding the therapeutic range.

Studies on the abstinence-like overshoot following reversal of the potent 19-isoamyl derivative of etorphine with naloxone. A comparison with the opioids fentanyl and alfentanil.

Reversal of opioid-related respiratory depression is often accompanied by an "acute abstinence like syndrome" with hypertension, tachycardia, and pain. This overshoot was used to investigate the extent at which opioids of high potency but different structure are involved in naloxone-induced abstinence. In 10 awake and trained mongrel dogs two highly mu-selective compounds, alfentanil and fentanyl, were given in cumulative doses and at different occasions (30-60-120-240 micrograms/kg, and 6-12-24-48 micrograms/kg, respectively). Subsequently, a high dose of naloxone (100 micrograms/kg) was given at 5 min intervals while arterial blood gases, blood pressure, heart rate and the somatosensory evoked potential (SEP) were measured continuously. Following a wash-out period, the 19-isoamyl derivative of etorphine (M-140; 10,000 times more potent than normorphine and a 4.5 fold potency of ethylketocyclazocine in a bioessay preparation) was also given in increasing doses (0.2-0.4-0.8-3.2 micrograms/kg). Again, naloxone was given (100 micrograms/kg) at 5 min interval, while cardiovascular parameters, blood gases and SEPs were measured continuously. All three opioids induced a dose-related respiratory depression with hypercarbia and hypoxia, a dose-related bradycardia, and a modest hypotension. This was accompanied by a dose-related depression of the amplitude of the SEP, reflecting the degree of blockade of nociceptive afferents. Naloxone was sufficient to reverse respiratory impairment after fentanyl, alfentanil and M-140. However, in contrast to fentanyl and alfentanil, there was no cardiovascular or evoked potential overshoot following naloxone reversal of M-140. After alfentanil naloxone increased blood pressure, heart rate and amplitude of the SEP by 7%, 41% and 38%, respectively. After fentanyl this increase in blood pressure, heart rate and amplitude of the SEP was 17%, 43% and 96%, respectively. The study indicates that the more potent the opiate mu ligands are the more is naloxone liable to induce a hyperexcitatory state of the cardiovascular system and an increase of nociceptive stimuli to pain modulating centres. After M-140 reversal of mu-related respiratory depression by naloxone was possible. However, no precipitation on an acute abstinence-like syndrome affecting antinociception or inducing cardiovascular overshoot was observed. This may stem from an intense binding and slow dissociation of the ligand from the receptor site or may be due to high binding affinity to both the mu and the kappa receptor site. Opioids which interact with various receptor sites may be of clinical interest for substitution therapy in opioid dependent addicts.

[Constipation after tilidine/naloxone and tramadol in comparison to codeine. A dose response study in human volunteers]. / Die obstipierende Wirkung der Opioide Tilidin-N und Tramadol im Vergleich zu Codein. Eine vergleichende Gegenüberstellung zweier Wirkstoffkonzentrationen bei Probanden.

Tramadol, a mixed mu-opioid agonist and a monoamine-reuptake blocking analgesic, has been supposed to have little effect on propulsive gastrointestinal motility. However, this has not been specifically studied in man. Following institutional approval, 18 human volunteers were given 50 mg of tramadol, tilidine/naloxone, and codeine, respectively, in a double-blind randomised cross-over design. Additionally, 12 further volunteers were given 100 mg of each opioid in a double-blind, randomised fashion, followed by measurement of gastrocoecal transit time. Gastrointestinal transit time was measured using the lactulose H(2)-breath test. A threefold increase in end-expiratory hydrogen when compared to the control value was considered the end point of gastrocoecal transit. At the low dose (50 mg) the three opioids did not differ significantly with regard to their effect on gastrointestinal motility. Gastrocoecal transit time was 90.8 (+/- 10.1 SEM) min for tramadol, 100.6 (+/- 9.8 SEM) min for tilidine/naloxone, and 104.2 (+/- 8.7 SEM) min for codeine. Doubling the dose of each opioid resulted in an increase in mean gastrocoecal transit, namely 97.8 (+/- 11.2 SEM) min for tramadol, 129.2 (+/- 12.2 SEM) min for tilidine/naloxone and 135.9 (+/- 9.2 SEM) min for codeine. The increase in gastrocoecal transit time was significant (P < 0.01) for high doses of tilidine/naloxone and codeine in contrast to the effect of the low doses. This lesser constipation effect may be due to the reduced affinity of tramadol to the mu-opioid receptor. Sedation was significantly higher for codeine after 50 mg (P < 0.05) and 100 mg (P < 0.005) than for tilidine/naloxone and tramadol. Vertigo was significantly higher after 50 mg (P < 0.05) and 100 mg (P < 0.005) of tilidine/naloxone and codeine than after tramadol. Perspiration was significantly higher after tramadol 100 mg (P < 0.005) than after tilidine/naloxone and codeine. Sedation is considered a typical symptom of analgesics interacting with centrally located opioid receptor sites. The higher incidence of perspiration after tramadol suggests that monominergic pathways may be involved in thermoregulation. In conclusion, the opioids tilidine/naloxone and codeine at the doses used significantly prolong gastrointestinal transit time in the high-dose range. Since tramadol does not induce a dose-related increase in gastrocoecal transit time, it may be a useful analgesic in patients who are prone to developing constipation during high-dose opioid therapy.

Effect of transcutaneous electrical nerve stimulation on onset of axillary plexus block.

We examined the effect of high frequency transcutaneous electrical nerve stimulation on the onset of brachial plexus block. Three groups of patients scheduled for surgery of the hand had a local anaesthetic block performed with 40 ml mepivacaine 1.5% using the axillary approach. After injection of the local anaesthetic transcutaneous electrical nerve stimulation was applied for 15 min either to the median nerve or the ulnar nerve; no stimulation was applied in the control group. Before and for 45 min after, the injection of local anaesthetic touch perception, pin prick, motor strength and skin temperature were tested by a blinded investigator in the areas supplied by the median, musculocutaneous, radial and ulnar nerves. There were no differences in the onset of block between the groups. Thus, the frequency-dependent action of local anaesthetics could not be demonstrated.

[EEG power spectra and evoked potentials during alfentanil/midazolam analgesia-sedation in intensive care patients]. / EEG-Powerspektren und evozierte Potentiale unter Alfentanil/Midazolam-Analgosedierung bei Intensivpatienten.

In a prospective study, 10 patients (ASA II-IV) with different ailments received varying amounts of an alfentanil/midazolam mixture (consisting of 15 mg of alfentanil and 37.5 mg of midazolam) for analgesia and sedation in a typical ICU setting over a period of 3-14 days. Special interest focussed on potential residual activity of both drugs after termination of the treatment. Since both compounds interact with receptor sites in the CNS, neurophysiological measurements were performed before, during and after the sedation. Thus, EEG power spectra were used to evaluate the central effects of midazolam, while the late peak (greater than 50 ms) of the somatosensory-evoked potential (SEP) was used to determine the inhibitory effect of alfentanil on the propagation of efferent nerve volleys along the sensory tract. A residual activity of midazolam after long-term administration seems likely as the return in the fast beta-domain was slow, and the high power in the slow EEG frequency bands delta and theta still persisted 24 hours after treatment. However, rapid recovery of the amplitude of the late N100-peak in the evoked potential suggests no potential "overhang" of alfentanil even if administered for several days together with a benzodiazepine. Among the variables most suitable for the determination of a sufficient sedation, the spectral edge activity (the highest frequency component in the EEG incorporating 95% of the entire power spectrum) showed a close relationship to the applied dose. All patients except one, a former alcoholic with CT-verified widening of the cerebral ventricles, could be sufficiently sedated with alfentanil/midazolam.(ABSTRACT TRUNCATED AT 250 WORDS)