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Biomedical subjects

E Freye

Publications and source records attributed to E Freye.

At least 37 records · Page 2Linked to original sources
PubMed1998

[The opioid tramadol demonstrates excitatory properties of non-opioid character--a preclinical study using alfentanil as a comparison].

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.

English Abstract↗
PubMed1998

No inhibition of gastro-intestinal propulsion after propofol- or propofol/ketamine-N2O/O2 anaesthesia. A comparison of gastro-caecal transit after isoflurane anaesthesia.

BACKGROUND: Gastrointestinal motility may be considerably reduced by anaesthesia and or surgery resulting in postoperative ileus. Inhibition of propulsive gut motility is especially marked after an opioid-based technique. Little, however, is known of the gastrointestinal effects of the hypnotic propofol when given continuously over a longer period of time, which is the case in total intravenous anaesthesia (TIVA) and in intensive care sedation. We therefore set out to study the effects of a propofol-based nitrous oxide/oxygen anaesthesia (group PO) on gastro-caecal transit time. The results were compared with a propofol-ketamine technique (group PK) and an isoflurane-based anaesthesia (group I; each group n = 20). METHODS: Gastro-caecal transit was determined by measurement of endexpiratory hydrogen concentration (ppm). Following gastral installation of lactulose at the end of the operation, the disaccharide was degraded by bacteria in the caecum, resulting in the liberation of hydrogen which was expired. A 100% increase in endexpiratory hydrogen concentration compared to the preinduction period was considered the end-point of gastro-caecal transit. RESULTS: There was no significant difference with regard to gastro-caecal transit in the three groups of patients. In the propofol group mean gastro-caecal transit was 119 (+/- 50.6 SD) min, in the propofol-ketamine group it was 147 (+/- 57.4 SD) min, and in the isoflurane group transit time was 122 (+/- 48.6 SD) min. CONCLUSION: The data suggest that propofol, even when given as a continuous infusion, does not alter gastrointestinal tract motility more than a standard isoflurane anaesthesia. The data may be particularly relevant to patients who are likely to develop postoperative ileus. They also suggest that in an ICU setting propofol does not alter gut motility more than a sedation technique with the analgesic ketamine.

Adult↗
PubMed1997

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.

Alfentanil↗
PubMed1996

[Constipation after tilidine/naloxone and tramadol in comparison to codeine. A dose response study in human volunteers].

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.

Clinical Trial↗
PubMed1995

Clonidine: an adjunct in isoflurane N2O/O2 relaxant anaesthesia. Effects on EEG power spectra, somatosensory and auditory evoked potentials.

We investigated the effect of clonidine in 19 patients having lumbar disc surgery under nitrous oxide/isoflurane/relaxant anaesthesia. The EEG, spinal and cortical somatosensory evoked potentials, and the brainstem auditory evoked potentials were recorded. After equilibration of the general anaesthetic, two successive infusions of clonidine (5 micrograms.kg-1) were given. After the second infusion of clonidine, the plasma concentration increased from 0.2(SEM 0.05) to 6.4(SEM 0.06) ng.ml-1 (p < 0.05). In the EEG, delta-activity was maintained, but the beta-fraction, and the 95% and 50% spectral frequencies were reduced. Total EEG power progressively decreased from 296(152-397) microV2 to 108(51-240) microV2. The somatosensory evoked spinal potential (N13) decreased in amplitude, (1.77(SEM 0.35) microV to 1.59(SEM 0.35) microV, p < 0.05) and increased in latency (14.37(SEM 0.29) ms to 14.69(SEM 0.31) ms, p < 0.05). The central conduction time increased from 6.47(SEM 0.16) ms to 6.92(SEM 0.25) ms, ns. There was no effect on the cortical somatosensory potentials, or the brainstem auditory evoked potentials. According to the EEG spectral indices, anaesthesia appeared to deepen despite a reduction in the end expiratory isoflurane concentration from 0.53(SEM 0.07) to 0.28(SEM 0.06) vol%, which indicated a reduction in anaesthetic requirements following clonidine.

Adult↗
PubMed1994

[No inhibition of intestinal motility following ketamine-midazolam anesthesia. A comparison of anesthesia with enflurane and fentanyl/midazolam].

Postoperative intestinal atonia is a complication which is likely to occur in patients predisposed for constipation and in patients after intra-abdominal operations. The postoperative delay of bowel movement, however, is often also related to the type of anaesthesia being used. In order to evaluate the magnitude of an anaesthetic-induced postoperative delay of bowel movement, two types of intravenous-based anaesthesia using fentanyl/midazolam (1 mg/25 mg; dosage 0.1 ml/kg/h), and ketamine/midazolam (250 mg/25 mg; dosage 0.1 ml/kg/h) respectively were compared with a volatile anaesthetic technique (enflurane; mean concentration 1.5 vol%). METHODS. In three groups of patients (each n = 15) undergoing elective surgery of the lower extremities, induction of anaesthesia was accomplished with methohexital (1-1.5 mg/kg) to facilitate intubation. For the maintenance of muscle relaxation vecuronium bromide was used. All patients were given droperidol to prevent postoperative emesis, and they were artificially ventilated with N2O/O2 (60:40) to normal end-expiratory CO2 concentrations. No anticholinergic agents were used at the end of operation since they are known to interfere with bowel motility. In order to determine gastro-intestinal motility, the H2 exhalation test was used. For this purpose 40 g lactulose in 100 ml of water was given to all patients via a gastral tube shortly before extubation. Lactulose is broken down by bacteria once it enters the colon, and H2 is released, taken up by the vascular system and exhaled. Postoperatively, patients were asked to exhale into a 20-ml syringe every 10 min. The content was analysed for hydrogen (ppm), using an electrochemical sensor (GMI exhaled hydrogen monitor). From the time of lactulose instillation to a threefold increase in end-expiratory hydrogen concentration (compared to the preoperative value), gastro-coecal transit time was computed. RESULTS. All three groups of patients were comparable in age, height and body weight. Also, the duration of operation was comparable in all three groups. Mean gastro-coecal transit time was 204 (+/- 19.6, SD) min following enflurane, 302 (+/- 32.8 SD) min following fentanyl/-midazolam and 210 (+/- 28.8 SD) min following ketamine/midazolam anaesthesia. The gastro-intestinal inhibition after the opioid-based anaesthetic technique was significantly prolonged (p < 0.001, Kruskal-Wallis test). There was no significance between patients after ketamine-based anaesthesia and those who had the volatile anaesthetic. DISCUSSION AND CONCLUSION. When using intravenous anaesthesia with an opioid, gastro-intestinal inhibition, especially in patients prone to have constipation, is likely to develop postoperatively. In classical neuroleptanaesthesia and in analgosedation in the ICU, the simultaneous use of the butyrophenone droperidol seems to counteract the inhibition of opioid-related gastrointestinal motility. In cases of opioid-related gastrointestinal atonia a gastrokinetic compound may be necessary to overcome this effect on intestinal motility.

Adult↗
PubMed1994

[Interaction of S-(+)-ketamine with opiate receptors. Effects on EEG, evoked potentials and respiration in awake dogs].

To check for suspected opioid-receptor mediated hypnotic and antinociceptive effects of S(+)-ketamine, highly selective antagonists were used after the anaesthetic. METHODS. To determine the hypnotic effects of increasing doses of S(+)-ketamine (2-5-10-20 mg/kg given at 10-min intervals), EEG power spectra (delta, theta, alpha, beta) were derived (Lifescan), and antinociceptive potency was evaluated using the somatosensory evoked potential (SEP, Lifescan) in awake, trained dogs (n = 10). To check for an opioid-receptor-related interaction, an antagonist of the methoxymorphinane series (HS-275, 80 micrograms/kg i.v.) with higher selectivity than naloxone for the mu-receptor was given at the end. After washout the same animals were exposed to S(+)-ketamine. This time, however, the highly selective delta-antagonist naltrindole (160 micrograms/kg i.v.) was given. To show up any respiratory depression arterial blood gases were taken after each dose. RESULTS. S(+)-Ketamine induced a dose-related increase in power in the theta band (3-8 Hz), with a ceiling effect at 10 mg/kg. The changes were reversed by both antagonists. In the beta band (13-30 Hz) and in the delta domain, power decreased or increased, respectively, in a highly significant manner (P < 0.005) at 20 mg/kg. Both effects reversed after the antagonists with an overshoot in beta (+12% and +14%, respectively) and a decrease in delta (-45% and -62%, respectively) compared with control. S(+)-Ketamine induced a dose-dependent increase in peak latency and depression of the SEP amplitude by a maximum of over 50%. Latency changes were completely reversed only by HS-275. Amplitude height was only partly restored by both antagonists. A clinical relevant decrease in PaO2 and increase in PaCO2 increase were seen at 20 mg/kg. Hypoxia was reversed by both antagonists; hypercapnia was only partially reversed. CONCLUSION. The results confirm the suspicion that S(+)-ketamine induces an opioid theta- and delta-receptor-mediated deep hypnotic effect. Blockade of nociceptive impulses in afferent sensory nervous pathways suggests an efficient analgesic effect mediated partly by the opioid mu-receptor. Other mechanisms, such as an interaction with the NMDA receptor, have to be taken into consideration to account for the full antinociceptive effect. Respiratory depression may be of clinical importance when high dosages of S(+)-ketamine are given.

Animals↗
PubMed1993

Spinal evoked potential in patients undergoing thoracoabdominal aortic reconstruction: a prognostic indicator of postoperative motor deficit.

We studied 76 patients who had thoracoabdominal aortic reconstruction between January 1981 and March 1991. Evoked potential monitoring of the spinal cord (peridural bipolar catheter stimulation at level L4-L5, recording via a second bipolar catheter at level Th4) was used to predict intraoperatively a possible motor deficit. There was a close linear correlation of r = 0.892 between postoperative motor deficit (normal, paraparesis, paraplegia) and the time from declamping to reappearance of the potential. Forty-three of 76 patients received prostaglandin E1 (5 ng/kg/min) for pharmacologic protection of the spinal cord 15 minutes before onset of clamping and through the entire clamping period. Patients with protection had a loss of their potential significantly later (20.2 min; p < 0.05) than those patients who had not received any pharmacologic treatment (15.2 min). Pharmacologic protection also resulted in a reduced incidence of postoperative neurologic deficit and paraplegia when compared with patients receiving no treatment (25% vs 5%). These data suggest that spinal evoked potentials may be very useful for monitoring during these hazardous cases. They also suggest that pharmacologic protection before clamping may help preserve the function of the spinal cord during aortic clamping.

Aged↗
PubMed1993

Somatosensory evoked potential, a prognostic tool for the recovery of motor function following malperfusion of the spinal cord: studies in dogs.

The potential usefulness of somatosensory evoked potential monitoring during aortic cross-clamping is slowly being realized. In addition, the protection of endangered spinal nervous tissue during aortic cross-clamping has not been sufficiently evaluated. To test the pharmacologic protective efficacy of various agents, we recorded spinal evoked somatosensory potentials (bipolar epidural catheter) in dogs under controlled conditions (N2O/O2-enflurane anesthesia) following clamping of the aorta for 1 hour. There were 5 groups of animals: those treated with different medications, such as prostaglandin E1 (PGE1), prostacyclin (PGI2), superoxide dismutase (SOD), and PGE1 plus SOD for pharmacologic protection during ischemia, and the controls. The time to recovery of evoked potentials during the reperfusion period was 36 minutes in the controls, 15.9 minutes in the SOD group (p < 0.01), 12.5 minutes in the PGE1 group (p < 0.001), 10.8 minutes in the PGI2 group (p < 0.001), and 3.8 minutes in the combination group (p < 0.001). In addition, treatment resulted in a better neurologic outcome on the seventh postoperative day when compared with the control group. While in the control group only 1 animal could walk (9%), 7 of 12 in the PGE1 group (58%), 4 of 12 in the SOD group (33.8%), 8 of 12 in the PGI2 group (66.7%), and all animals in the combination group (100%) could walk. We computed an exponential correlation that related the mean time of potential recovery during reperfusion with Tarlov scoring (grade 0 = paraplegia; grade 1 = paraplegia with little movements; grade 2 = paraparesis; grade 3 = paraparesis with some problems; grade 4 = normal motor function) in the various groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Alprostadil↗
PubMed1993

Opioid receptors-mediated respiratory effects and antinociception after S(+)-ketamine.

Until recently only the racemic mixture of ketamine was available for anesthesia. Little is known, of the central nervous effects of the pharmacological more potent S(+)-isomer. In order to evaluate the effects on respiration, the electroencephalographic activity and on the somatosensory evoked potential (SEP), increasing doses of S(+)-ketamine (2-5-10-20 mg/kg) were given to trained and awake canines (n = 10) at 10 minutes interval. To demask any opioid-receptor mediated effect, the highly selective mu-antagonist naltrexone or the highly selective delta-antagonist naltrindole (NTI) was given after S(+)-ketamine. S(+)-ketamine depressed respiration in a dose-related manner (PaO2 decrease, PaCO2 increase). Hypoxia was fully reversed by NTI and naltrexone; however hypercapnia was only partly reversed. S(+)-ketamine induced a dose-related increase of power in the theta-band (3-8 Hz) with little increase of power in the alpha-domain (8-13 Hz). Both these changes were reversed by NTI and naltrexone. Compared to control, low doses (2-5 mg/kg) increased power (p < 0.05) in the beta-(13-30 Hz) and decreased power (p < 0.05) in the delta-(0.5-3 Hz) band. These effects changed with higher doses (5-10 mg/kg). When compared to control, power in the delta-domain was significantly higher (p < 0.05), while power in the beta-band decreased significantly following 20 mg/kg of S(+)-ketamine. NTI was capable to reverse all these effects, however, naltrexone was not. In the SEP, S(+)-ketamine induced a dose-related increase in peak latency and a depression of amplitude of more than 50% when compared to control. Latency changes and amplitude height was only partly restored by both antagonists. The present results corroborate the connotation, that the central effects of the S(+)-isomer of ketamine are related to the opioid delta- and mu-receptor. The respiratory depression may be of importance when S(+)-ketamine is used (in very high doses). The S(+)-isomer induced hypersynchronisation in the EEG, suggests a deep plane of anesthesia; the pronounced blockade of nociceptive stimuli in the sensory nervous pathways suggests an analgesic effect which is partly mediated by the opioid receptor.

Animals↗
PubMed1992

The delta receptor is involved in sufentanil-induced respiratory depression--opioid subreceptors mediate different effects.

It is generally accepted that analgesia induced by central analgesics is mediated through the mu-receptor. However, it still remains open to question as to whether or not the mu- and/or the delta-receptor site is mainly involved in the mediation of opioid-related respiratory impairment. Using a highly selective antagonist, naltrindole (NTI), or its benzofuran analogue naltriben (NTB), the hypothesis that competitive antagonism at the delta-receptor is able to attenuate sufentanil-related respiratory depression was tested in the dog. High dose (20 micrograms kg-1) sufentanil-induced respiratory impairment could be reversed by selective NTI-antagonism in a dose-related fashion (40-80-160 micrograms kg-1) increasing PaO2 from 57 to 81 mmHg and lowering PaCO2 from 52.1 to 49.2 mmHg. NTB-antagonism (40-80-160 micrograms kg-1) increased PaO2 from 48.4 to 91.2 mmHg and reduced PaCO2 from 46.9 to 37.6 mmHg. Simultaneously, somatosensory-evoked potentials (SEP) were used to quantify the opioid-induced attenuation and the reversal of afferent sensory input to pain modulating centres in the CNS. Sufentanil induced a significant depression (P < 0.01) of amplitude height of the SEP (13.9 to 0.9 microV in the NTI- and 8.8 microV to 1.3 microV in the NTB-group) which was only partially reversed by NTI (2.6 microV) and NTB (2.3 microV) respectively. The results suggest that delta-receptors are involved in sufentanil-related respiratory impairment. These receptors play a minor role in opioid-induced attenuation of sensory input to the brain. Highly selective delta-antagonists may be of clinical interest in reversing the respiratory depressant effect of potent opioids while maintaining analgesia.

Animals↗
PubMed1992

[Pharmacodynamic effects of S-(+)-ketamine on EEG, evoked potentials and respiration. A study in the awake dog].

Until recently, only the racemic mixture of ketamine has been used in anaesthesia. Little is known of the central nervous effects of the pharmacologically more potent S(+)-isomer. Information in regard to the putative receptor site involved in the mediation of its anaesthetic/analgesic effect is particularly sparse. METHODS. In order to evaluate the anaesthetic and antinociceptive properties of S(+)-ketamine, a dose-response relationship of the compound on the EEG, somatosensory-evoked potentials (SEP), and respiration was established. Increasing doses (2, 5, 10, 20 mg/kg) were given to trained and awake dogs (n = 10) at 10-min intervals. In order to detect a possible opioid receptor-related interaction, an antagonist of the methoxymorphinane series (cyprodime 80 g/kg i.v.) with higher selectivity than naloxone for the mu-receptor was given at the end. RESULTS. Compared to controls, S(+)-ketamine induced a dose-related increase in output in the theta-(3-8 Hz) band and an increase in output in the alpha-domain (8-13 Hz) following 20 mg/kg. Both effects were reversed completely by the opioid antagonist. At low doses (2-5 mg/kg) there was an increase in output (P less than 0.05) in the beta-(13-30 Hz) and a concomitant decrease in output (P less than 0.05) in the delta-(0.5-3 Hz) band. These effects were reversed with increasing doses (5-10 mg/kg). After 20 mg/kg, however, output in the delta-domain increased while power in the beta band decreased significantly (P less than 0.005) when compared to controls. Both effects were reversed by the opioid antagonist. Compared to controls, the reversal resulted in a 12% increase in output in the beta- and a 49% decrease in output in the delta-domain. In SEP, S(+)-ketamine induced a dose-related increase in peak latency and depression of amplitude of more than 50% when compared to controls. While latency changes were completely reversed, amplitude height was only partly restored by the antagonist. Respiration was depressed in a dose-related fashion (PaO2 decreased, PaCO2 increased). Hypoxaemia was fully reversed by the antagonist; hypercapnia was only partly reversed. CONCLUSION. The results support the presumption that the S(+)-isomer of ketamine induces opioid mu-receptor-mediated central effects. Hypersynchronisation of the EEG suggests a deep plane of anaesthesia after S(+)-ketamine. The pronounced blockade of impulses in the sensory nervous pathways suggests an efficient analgesic effect that is partly mediated by the opioid-receptor. The respiratory depression may be of importance when S(+)-ketamine is used in high dosages in man.

Animals↗
PubMed1991

Opioid-induced respiratory depression and analgesia may be mediated by different subreceptors.

Use of selective delta opioid antagonists provide evidence that the delta receptor within the brain seems an integrated part in the mediation of respiratory depression induced by a potent analgesic like fentanyl. Low doses of the delta antagonists RX-8008M (3-6 micrograms/kg) as well as ICI 174,864 (3-6 micrograms/kg) reversed fentanyl-related respiratory depression (arterial blood gases) in the unanesthetized canine. Opioid-induced blockade of afferent sensory nerve volleys (amplitude height of the somatosensory-evoked potential) could be reversed only by a high dose (9 micrograms/kg) of RX-8008M. Depression of amplitude height of the SEP could not be reversed by ICI 174,864 over the whole dose range (3-6-9 micrograms/kg). In comparison, naloxone (1-5-10 micrograms/kg) not only reversed depression of PaO2, it also reversed the blockade of afferent sensory nerve impulses in the low (5-micrograms/kg)-dose range. A highly selective delta antagonist may have a therapeutic value in reversing opioid-related respiratory depression, resulting in little or no attenuation of analgesia.

Analgesia↗
PubMed1991

[EEG power spectra and evoked potentials during alfentanil/midazolam analgesia-sedation in intensive care patients].

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)

Adult↗
PubMed1991

[Postoperative pain treatment].

The postoperative care of patients usually is characterized by the fact that the individual need of pain killers is not sufficiently recognized. An opioid given only when asked for, results in an underdosage as the patient does not receive the analgesic in time, so that he suffers pain. As there is insufficient knowledge with regard to the pharmacology of opioids which can be used for postoperative pain therapy, physicians and nurses usually tend to give a lower dose in order to avoid any possible side-effects. Considerations which lead to opioid underdosage include: the development of addiction and possible side-effects such as respiratory depression, heavy sedation, possible constipation and urinary retention. The aim in postoperative pain therapy is a time-contingent dosing after careful intravenous titration of the compound in the lower dose range during continuous supervision. Thus, the individual need in the recovery room can be estimated. Only such a procedure helps to keep the patient pain-free over a long period of time, reduces the workload of nurses during the night, results in the reduction of complications and finally may even reduce the hospital stay. Piritramide is a compound which has a number of potential advantages with regard to efficacy and side-effects in postoperative pain therapy. It has the highest analgesic potency among those compounds suitable for postoperative pain therapy; when compared with pethidine, pentazocine or nalbuphine it shows remarkable cardiovascular stability. In comparison to morphine, pethidine and pentazocine, piritramide has a lower incidence of nausea and vomiting. With a mean duration of action of up to six hours, piritramide has an advantage over pentazocine (3 hours), pethidine (2-3 hours) and morphine (5-6 hours). Compared to other mixed narcotic analgesics, piritramide does not induce dysphoric side-effects when given in the higher dose range and does not lead to addiction. It is derived from the same group of agents such as fentanyl or alfentanil which are used in neuroleptanaesthesia so that there is an increase in analgesia one to the interaction with the same receptor site. Piritramide has a fast onset of action, 2-5 minutes after intravenous injection and a peak action after 10 minutes. In comparison to pethidine it has no cardiovascular effects, in particular no myocardial depression or increased myocardial oxygen demand (MVO2). Last but not least, the cost-effectiveness is a financial factor of increasing importance to the institution that runs the hospital.

Analgesics, Opioid↗