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Biomedical subjects

E Freye

Publications and source records attributed to E Freye.

At least 73 records · Page 4Linked to original sources
PubMed1984

[Somatosensory evoked potentials under alfentanyl].

Somatosensory evoked potentials (SEP) at present seem to be the most reliable and accurate method for the investigation of compounds modulating pain sensation. Besides detecting changes in the duration and the potency of action of analgesics, their possible site of action in the sensory pathways may be derived by this method. In ten trials using two trained canines the efficacy and the duration of action of a new and short acting opioid, alfentanil was evaluated on SEP using cumulative doses (3, 30, 60, 120 micrograms/kg). Concomitantly arterial blood gases were analyzed for possible respiratory depressant effects. The results demonstrate that alfentanil induces a short lasting suppression of the N100 peak as well as a latency change of the N140 peak to N220, the latter lasting for more than 80 min. These effects saturate at doses higher than 30 micrograms/kg. The significant change in arterial blood gases - a fall in PaO2 and an increase in PaCO2 - are most prominent with 30 micrograms/kg and 120 micrograms/kg, respectively. It is of short duration and correlates with the suppression of the N100 peak. The latency changes seem to correlate with a marked sedatory effect. Due to the differential effects induced by the opioid, an interaction with different opioid subreceptor sites is postulated.

Alfentanil↗
PubMed1984

Nalbuphine reverses fentanyl-related EEG-changes in man.

Nalbuphine, chemically related to naloxone however, with mixed agonist-antagonist activity, was considered to be of clinical interest in reversing opioid anesthesia. In an open-end study 15 patients (mean age 40 years) undergoing orthopedic surgery received nalbuphine (0.1 mg/kg) after fentanyl (total dose 17.4 micrograms/kg over a mean of 95 min). In order to establish the state of vigilance, continuous EEG-recording of the posterior region of the cortex (P3-O1) was done with the aid of power spectral analysis using fast Fourier transformation (FFT). Additionally blood pressure and heart rate were measured. The observed effects were compared with the awake unpremedicated preoperative state. In the EEG nalbuphine reversed the anesthesia-related increase in power in the delta (0.25-4 Hz) and decrease in alpha (8-12 Hz), beta 3 (20-25 Hz) and beta 4 (25-32 Hz) domain. After the 45th minute delta significantly increased while power in the beta-band unsignificantly dropped. Power in the alpha-band remained elevated throughout the whole postoperative period. In regard to blood pressure measurements nalbuphine induced an increase in systolic, diastolic pressure and heart rate 15% above control. These parameters declined towards the 30th minute; only heart rate reached predrug values at the 45th minute. With the aid of EEG-power spectral analysis it was demonstrated that nalbuphine seems a valuable tool for the reversal of opioid-induced cortical depression.

Adult↗
PubMed1983

Naloxone reverses the hypnotic effect and the depressed baroreceptor reflex of halothane anaesthesia in the dog.

In order to evaluate the effect of an opioid antagonist on depressed intrinsic central vaso-motor drive (carotid sinus reflex) and high voltage slow delta waves in the EEG associated with halothane, naloxone was injected intravenously in a bolus of 100 or 200 micrograms.kg-1 on different days in the anaesthetized dog (0.64 Vol% halothane in oxygen). Only the 200 micrograms.kg-1 dose of naloxone reversed the halothane-induced depression of the blood pressure and heart rate response to clamping of both exteriorized common carotid arteries. The EEG changed from high voltage slow waves to low voltage fast waves, inducing a reduction of power in the delta band in spectral analysis. This effect was most pronounced during the 20th minute post naloxone injection. Naloxone did not reverse the halothane-related hypotension and bradycardia. Because of the late "cortical arousal" reaction during halothane-anaesthesia and the high dose necessary, naloxone appears to exert its action through a generalized increase in CNS excitation. An antagonisation of halothane-induced release of opiate-like peptides therefore is less likely.

Anesthesia, Inhalation↗
PubMed1983

Tifluadom (KC 5103) induces suppression and latency changes on somatosensory evoked potentials which are reversed by opioid antagonists.

Suppression of evoked potentials of the EEG are indicators of analgesia. Tifluadom induces latency changes which are reversed by the kappa-antagonist Mr 2266. Naloxone reverses peak suppression which indicates an additional interaction with the my-opioid-receptor. The specific benzodiazepine antagonist Ro 15-1788 is not effective in reversing peak-changes. Therefore nociceptive stimuli are modulated by tifluadom not only through the interaction with kappa- but also with my-opioid-receptors.

Animals↗
PubMed1983

Prevention of late fentanyl-induced respiratory depression after the injection of opiate antagonists naltrexone and S-20682: comparison with naloxone.

Compared with naloxone, two opiate antagonists (naltrexone and S-20682) were tested in the intact dog in order to reverse respiratory depression, induced by fentanyl 50 micrograms kg-1 i.v. Respiratory rate and arterial blood-gases were measured at 5, 30, 60, 120, 180 and 240 min after the additional i.v. injection of the antagonist (1 microgram kg-1). Only S-20682, but not naloxone or naltrexone, prevented late (240 min) fentanyl-induced depression of respiratory drive. A late respiratory depression coincided with an increase in amplitudes and a reduction of frequency in electrical cortical activity (EEG). Naltrexone exhibited an antagonistic effect of duration twice (60 min) that of naloxone.

Animals↗
PubMed1983

Effects of three narcotic antagonists (naltrexone, diprenorphine, and S-20682) on blood pressure, heart rate and electrical cortical activity.

Three narcotic antagonist drugs (EN-1639 or naltrexone, M-5050 or diprenorphine and the 6-oxo analogue of oxilorphan, S-20682) were evaluated in increasing doses (1-80 micrograms/kg) in the unanaesthetised dog for possible effects on blood pressure, heart rate, respiratory rate, arterial blood gases, and convulsive EEG changes. Compared to the control-awake situation, diprenorphine and S-20682 induced hypotension (maximum fall 15%), bradycardia (maximum 12%) and bradypnoea (maximum 25%). These effects were not increased at doses higher than 20 micrograms/kg. Despite the induced bradypnoea, there were no significant changes in arterial pO2 and pCO2. Simultaneously, with the cardio-respiratory changes, EEG activity shifted from high frequency, low amplitudes of the awake state, to low frequency, high amplitudes of a sleep-like state. Convulsive EEG changes were never recorded with any of the tested compounds. It is suggested that the observed cardiovascular changes are due to a reduced state of vigilance, since auditory stimuli induced an arousal reaction with a reversal of the depressed variables. In contrast, naltrexone induced only bradycardia in the observed dose range (maximum 25%). There were no effects on blood pressure, respiratory rate, arterial blood gases and EEG.

Animals↗
PubMed1983

Bremazocine: an opiate that induces sedation and analgesia without respiratory depression.

The benzomorphan analogue bremazocine has been shown to be a potent analgesic with a low dependence liability and with no respiratory depressant effects in preliminary pharmacologic screening. As this compound may prove to be of potential interest to anesthesiologists, it was tested in the conscious dog in increasing doses (1, 5, 10, 20, and 40 micrograms/kg) while blood pressure, heart rate, respiratory rate, arterial blood-gas tensions, electrical cortical activity, and somatosensory-evoked potentials (SS-EVP) were recorded. Bremazocine had no significant cardiovascular or respiratory effects. Power spectral analysis of the EEG showed a dose-related increase of power in the theta to delta band. SS-EVP was characterized by a decrease in amplitude of the P45 and P70 waves and an increase in the latency of the P 100 peak. EEG and peak latency changes could be reversed by the kappa-specific antagonist Mr 2266 (20 micrograms/kg), but not by the classic opiate antagonist naloxone (20 micrograms/kg). It is suggested that kappa receptor sites distinct from those interacting with common opioids (mu) are responsible for the observed changes associated with bremazocine.

Analgesics↗
PubMed1983

Plasma levels of alfentanil and etomidate in patients and their relation to compressed power spectral analysis of the EEG.

In 22 patients alfentanil-etomidate anesthesia was used for orthopedic procedures using for the induction period 300 micrograms/kg of the hypnotic and 100 micrograms/kg of the opioid. Maintenance of anesthesia consisted of 20 micrograms/kg of alfentanil given every 15 min and 20 micrograms/kg/min of etomidate given over an infusion. The patients were intubated and mechanically ventilated with pure oxygen. In order to access the state of vigilance with respect to etomidate and alfentanil plasma levels, EEG power spectra were computed from electrical cortical activity of the occipital region (P3-O1); respectively venous blood samples were assayed by means of gas chromatography for alfentanil and etomidate plasma concentration. In the EEG power spectrum, anesthesia replaced the high dominant alpha-peaks of the control-awake period by a disharmonious pattern over the whole frequency range (0.5-16.0 Hz). At the end of anesthesia vigilance recording indicated a correlation with plasma etomidate level. Once concentration had dropped below 100 ng/ml power spectra were characterized by a stable harmonious peak in the alpha-range (8.0-10.0 Hz). Plasma levels above 100 ng/ml induced a fluctuating pattern with peaks in the theta to delta band (0.5-8.0 Hz); the latter was characterized by drowsiness and a reduced respiratory drive. Opioid plasma levels above 100 ng/ml with etomidate levels below 80 ng/ml did not influence to the same extent. EEG power spectra seem to be a useful tool in pinpointing to a reduced state of vigilance. Such a state when present with opioid ingestion is often accompanied by respiratory depression.

Adult↗
PubMed1982

Perfusion of the fourth cerebral ventricle with the synthetic opioid peptide, FK 33-824, induces dose-related bradycardia and naloxone-reversible respiratory depression in the awake dog.

The importance of natural opioids in the central control of blood pressure, heart rate and respiratory function was evaluated with a synthetic analogue of Met-enkephalin, FK 33-824, which is more resistant to enzymatic degradation than the natural opioids. Increasing concentrations (20, 100, 200 and 400 micrograms/ml), perfused through the 4th cerebral ventricle of the conscious dog, induced a concentration-related depression of respiratory function - as reflected in arterial pCO2 and pO2 and heart rate. Naloxone (40 micrograms/ml) was able to reverse respiratory depression whereas bradycardia was naloxone-resistant even after massive (100 micrograms/kg) intravenous doses. Mean arterial blood pressure was not affected in the tested concentration range. Because respiration was reversed by naloxone, it is concluded that respiratory control is regulated by the mu-type opioid receptor. Heart rate, however, may be governed by the delta-type opioid receptor which is less susceptible to naloxone.

Animals↗
PubMed1982

[Naloxone-resistant EEG slowing induced by the synthetic opioid peptide FK 33-824 in the 4th cerebral ventricle of the dog].

In order to determine the importance of opioid peptides in the central control of wakefulness, the synthetic analogue of Met-Enkephalin, FK 33-824 (d-Ala-2-Phe-Met-(O)-ol-Enkephalin) which is more resistant to enzymatic degradation, was perfused in increasing concentrations (20, 100, 200, and 400 micgrograms/ml) through the fourth cerebral ventricle of the conscious dog. In the EEG (Power-spectral density in continuous acquisition) high concentrations (200--400 micgrograms/ml) induce slowing (theta--delta) with overlying beta-activity. This was reflected in the animals behaviour resulting in a sleep-like state which in spite of the administration of high doses of the antagonist Naloxone (100 micrograms/kg i.v.) sustained for 12 hours. A simultaneously dose-related respiratory depression (drop in arterial pO2 and an increase in arterial pCO2) was reversed by Naloxone. It is concluded that the opioid peptide FK 33-824 induces EEG-slowing which is mediated by a subpopulation of opiate-binding sites, possibly the kappa-receptors. These receptors are different from binding sites mediating respiratory depression (micro-receptors) as they interact with the opiate-antagonist Naloxone.

Animals↗
PubMed1982

Naloxone induces excitation of the cardiovascular system and a rise in myocardial oxygen consumption in fentanyl and meperidine-anesthetized dogs.

Naloxone, when administered for the purpose in reversing opiate-induced respiratory depression after morphine- or fentanyl-anesthesia may precipitate an increase in sympathetic tone with subsequent cardiovascular reactions. In order to investigate which variable of the cardiovascular system is affected most and to compare whether the effects after fentanyl anesthesia (0.05 mg/kg) differ markedly from those after sole equianesthetic meperidine-anesthesia (20 mg/kg), naloxone (5 microgram/kg) was given shortly (15 min.) after opiate injection. In the fentanyl group (n = 7) compared to the anesthetic level the antagonist induces an increase in heart-rate by 100%, in LV dP/dt max (inotropic state of the myocardium) by 90%, in mean peripheral blood pressure (afterload of the heart by 80%, in myocardial oxygen consumption by 50% and in left ventricular pressure by 42%. After 32 minutes all variables had returned to anesthesia values. In the meperidine-group (n = 7) naloxone induced an increase in heart-rate by 13%, in LV dP/dt max by 75%, in mean peripheral blood pressure by 65%, in myocardial oxygen consumption by 25% and in left ventricular pressure by 78%. After 25 minutes all increased variables had returned to prenaloxone values. The study indicates that the more potent the opiate agonist, the more naloxone is liable to induce a hyperexcitatory state of the cardiovascular system. This excitatory state is also reflected in an elevated myocardial oxygen consumption. Therefore caution is advised in administering naloxone to patients after sole opiate-anesthesia, who have an impaired myocardial oxygen supply. (Acta anaesth. belg., 1982, 33, 89-97).

Anesthesia, General↗
PubMed1982

Enflurane in cardiac surgery.

Due to its advantageous properties the volatile anesthetic enflurane is used as the main agent for all routine open heart cases in our department. The technique consists of the induction of the heavely premedicated patient with fentanyl (10 micrograms/kg i.v.) followed by pancuroniumbromide (100 micrograms/kg i.v.). For the maintenance of anesthesia, i.e. before, during, and after cardio-pulmonary bypass, enflurane together with nitrous-oxide (up to 66%) is used, in a concentration between 1.0-2.0 vol%. Compared to other volatile anesthetics we foster a technique with enflurane because it has following advantages: 1. Less negative inotropic effect on the myocardium. 2. Less tendency for ventricular arrhythmia. 3. Fast onset of action. 4. Fast recovery from the anesthetic state. 5. Spontaneous post-operative respiration. 6. Lesser incidence of toxic hepatitis (Acta anaesth. belg., 1982, 33, 141-155).

Anesthesia, Inhalation↗
PubMed1982

The potential use of thiamine in patients with cardiac insufficiency.

Incremental doses of vitamin B1 were injected into patients with myocardial and pulmonary insufficiency treated in the post-operative period in the ICU (intensive care unit) after repairment of abdominal aneurysm. Compared to the control situation thiamine in a total dose of 50 mg/Kg induced a rise of blood pressure by at least 20 mmHg and a moderate elevation of central venous pressure by 3 mmHg. Heart rate was not affected and the EEG exhibited arousal effects after B1 treatment. It is suggested that in the failing heart with increased sympathetic tone thiamine acts as a mild peripheral vasodilator followed by a diminished pump outflow impedance and a resultant increase in systolic blood pressure. The redistribution of volume to the low pressure side is associated with a rise in central venous pressure. Effects of B1 on the EEG suggest an arousal reaction probably due to an interaction with a neurotransmitter system such as acethylcholine.

Arousal↗
PubMed1981

Fentanyl in the fourth cerebral ventricle causes respiratory depression in the anesthetized but not in the awake dog.

Specific binding sites for opiate-induced bradycardia, hypotension and EEG-synchronization are located in areas bordering the IVth cerebral ventricle in the dog. To see if the clinically observed opiate-induced respiratory depression is mediated selectively from ponto-bulbar respiratory neurones, increasing concentrations of fentanyl (2.5-5-10-20 micrograms/ml) were perfused through the IVth cerebral ventricle in canines. Contrary to the awake state, fentanyl-perfusion during halothane-anesthesia (0.75 vol%/O2) induced a dose-related increase in arterial PCO2. This effect was reversed by subsequent naloxone-perfusion (20 micrograms/ml). The administration of halothane alone over the same period of time did not affect PCO2 in a similar manner. It is suggested that higher cortical centers which are involved in sensory awareness may modulate respiratory neurones in the medulla, since the depression of these higher centers by halothane resulted in opiate-induced respiratory impairment. An additive effect of fentanyl- and halothane-induced release of opiate-like peptides (enkephalins) on respiration should also be considered.

Anesthesia, Inhalation↗
PubMed1980

The effect of thiamine on the contractile responses of the isolated heart muscle.

Isolated papillary muscles of cats were exposed to increasing concentrations of thiamine during which the contractile response of myocardium to stimulation were measured. The results indicate that thiamine has no direct negative inotropic effect on the isolated heart muscle over a wide concentration range (0.1-1 mmol/l). Higher concentrations resulted in a concentration-related depression of all variables. The data indicate that thiamine in high doses as sometimes used in anesthesia (greater than 50 mg/kg) does not inhibit the contractile state of the myocardium. Blood pressure falls after massive doses of intravenous vitamin B1 are probably due to the synaptic blockade which is induced by the compound.

Animals↗
PubMed1980

[Chlormetiazole in anaesthesia (author's transl)].

The use of a vitamin derivate (chlormethiazole) in anaesthesia. Owing to its hypnotic properties and its wide margin of safety, "chlormethiazole" (a derivate of vitamin B1) was used in 30 patients which underwent varying surgical procedures. Since the drug exhibits no analgetic effect, fentanyl was added to maintain a sufficient depth of anesthesia. The patients were artificially ventilated with N2O/O2 at a rate of 3/1. Chlormethiazole, even when used in large doses (2400 mg) over a long period of time (5 hours was well tolerated. The technique therefore offers another opportunity to replace droperidol in classical neuroleptanaesthesia, which is often the cause for uncomfortable neurovegetative side-effects in the post-operative period.

Adolescent↗