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Mixtures of inhalation and i.v. anaesthetics at high pressure. A test of the multi-site hypothesis of general anaesthesia.

We have tested the hypothesis that anaesthetics having different pressure reversal characteristics act at different molecular sites with finite capacities and, therefore, do not necessarily have additive potencies when used in mixtures of varying composition. The additivity of the anaesthetic potencies has been tested at normal pressures and at pressures up to 100 ATA for eight combinations of the following mixtures: Althesin plus nitrous oxide; methohexitone plus nitrous oxide; thiopentone plus nitrous oxide; thiopentone plus propanidid. The anaesthetic potencies of the first two mixtures were not additive at increased pressures, whereas those of the latter two mixtures were additive. These data support the multi-site hypothesis of general anaesthesia.

Alfaxalone Alfadolone Mixture↗

[Anesthesia for cardiovascular surgery under extracorporeal circulation: the authors' own technic].

The A. describe a technique of general anaesthesia for open-heart surgery, induced with Althesin and Fentanyl, in 29 patients submitted to cardiac and aortic surgery, and relate the results obtained. The experience showed the effectiveness of the reduction of peripheral vascular resistances due to Althesin, as well as usefulness of collateral techniques (cortisonic drug, carbon dioxide mixture, hypothermia, beta-adrenergic block, coronary vasodilation) employed for these patients during cardiopulmonary bypass.

Adult↗

Contribution of pregnan steroid Althesin to the pathophysiology of epilepsy.

The original study with Althesin in the development of epilepsy was carried out in nine patients. EEG and SEEG records show that sensitivity to Althesin, which is a mixture of pregnandiol and pregnan acetate, precursors of sexual hormones, raises in the direction to the oldest brain formations. A physiological substance in provoking epilepsy was discovered.

Alfaxalone Alfadolone Mixture↗

[CT 1341 in continuous administration in 75 cases of prolonged general anesthesia in odontostomatology (constant flow assured by a double-lumen venous catheter and electric perfuser)].

The authors used during 75 prolonged general anaesthesia in maxillo-facial surgery CT. 1341 (Alfatesine) administered pure at constant flow rate through a double lumen venous cannula and electric perfuser. Four series of patients were thus distinguished depending on their use or not of N2O as the only analgesic and of gallamine. We do not agree with the classical assertion that CT. 1341 has a cumulative effect on some EEG results. The technique is quite inocuous and the authors propose a technique using CT. 1341 at a dose of 0.1 ml/kg for induction of anaesthesia with, later, 1 mg/kg of gallamine. Under a mixture of oxygen and nitrous oxide at 60 p. 100, the maintenance dose advised in 6.17 microliters per kilo, per minute of CT. 1341.

Adult↗

[Anesthesia with continuous infusion of alfatesine and phenoperidine. Uses in anesthesia of aged subjects in visceral surgery].

Anaesthesia was administered to one hundred and fifty eight patients by continuous infusion of a mixture of Alfatesine and phenoperidine. The patients were divided on two groups: group A consisted in 96 patients undergoing abdominal surgery and group B of 62 cases of various types of surgery, mainly orthopedics. The average age was 63 years (range 16-96). The operative risk scored 6 or more in 71 cases. The length of operation averaged 151 minutes (S.D. +/- 15). The mixture made of alfadione 25 ml and phenoperidine 5 mg in a glucose 5 per cent 250 ml solution was administered by mechanical pump. The induction dose was 50 ml of the mixture for patients under 50 years (rate 10 ml per minute), 40 ml per patients from 50 to 70 years (5 ml per minute), and 30 ml for patients over 70 years (5 ml per minute). The maintenance dose was adjusted to weight and age and ranged from 0,11 to 0,15 ml/kg/h for alfadione and from 0,022 to 0,030 mg/kg/h for phenoperidine. Routine tracheal intubation and artificial ventilation were performed in group A. The results are studied in relation to the effectiveness of the anaesthesia mixture, its side effects and influence on recovery. Generally, the results are good and emphasize the value of the technic in abdominal surgery for elderly patients. The methods of application are discussed in terms of medical background.

Adult↗

An animal model for the investigation of adverse responses to i.v. anesthetic agents and their solvents.

In man the number of adverse responses to the Cremophor-containing anaesthetic agents Althesin and propanidid (Epontol) has been reported to be greater than that encountered with thiopentone. The response of the mini-pig to repeated injection of a range of i.v. anaesthetics and their solvents has been investigated in an attempt to ascertain the possible role of Cremophor in the production of these responses. A second injection of Cremophor EL or the Cremophor/Micellophor-containing agents Althesin and propanidid (Epontol), given 7 days after the first, produced a high frequency of adverse responses. On only one occasion, when alphaxalone and alphadolone were given in a mixture of alcohol and propylene glycol, was an abnormal response seen on the first administration of any agent. The second administration of alphaxalone and alphadolone in the same solvent produced abnormal responses in two of four pigs. No such responses were seen when propanidid was administered in alcohol and propylene glycol or when this solvent mixture was given alone. No abnormal responses were seen following the repeated administration of thiopentone. A marked increase in arterial pressure, and an immediate but transient marked decrease in the numbers of circulating polymorphonuclear leucocytes, were consistent findings in animals showing adverse responses. No abnormal responses were found when the interval between two administrations of Althesin was extended to 3 weeks.

Alfaxalone Alfadolone Mixture↗

The influence of anaesthetics on the haematology of the patas monkey, Erythrocebus patas.

The effects of phencyclidine, ketamine and an alphaxalone-alphadolone mixture on the haematology of the patas monkeys have been compared. In animals sedated with phencyclidine or ketamine the only significant difference detected was in the mean cell volume. Statistically significant differences in white-cell count and blood coagulation and fibrinolytic activity were found in monkeys which had received alphaxalone-alphadolone. It is suggested that ketamine is a suitable alternative to phencyclidine for haematological studies in these monkeys.

Alfaxalone Alfadolone Mixture↗

[Impact of alfatesine anesthesia on cerebrospinal fluid pressure in man].

The variations in pressure of the cerebrospinal fluid was studied in 20 patients before and after induction of anesthesia with alfatesine (0.1 ml/Kg). 14 patients received no other complementary drug (group 1); in the six other cases, 1 g. of acetylsalicylic acid was administered as an analgesic complement (group II). All of the patients spontnaeously ventilated an O2 - N2O 50 p. 100 mixture. The C.S.F. pressure fell by 39 p. 100 on the average (p. less than 0.001) in group I and did not vary in group II. This fall is essentially related to cerebral vasoconstriction, therefore to the fall in cerebral blood flow caused by Alfatesine. In group II hypercapnia was noted in all of the patients; it abolishes the cerebral vasoconstriction due to Alfatesine; the cerebral blood flow did not fall neither did the C.S.F. pressure.

Acid-Base Equilibrium↗

Non-anesthetic steroids ameliorate the high pressure neurological syndrome in rats.

The hypothesis that non-anaesthetic compounds, structurally related to specific anaesthetics, can protect against the high pressure neurological syndrome was tested. Infusion of two structural analogues of alphaxalone (3 alpha-hydroxy-5 alpha pregnane-11,20 dione) during pressurisation of rats with helium and oxygen gas mixtures (total pressure 80-100 ATA; inspired oxygen partial pressure 0.5 ATA) ameliorated the severe tremors associated with the high pressure neurological syndrome without any shift in tremor frequency (11-14 Hz). The steroid analogues which were selected (delta 16 and 3 beta-hydroxy-alphaxalone) have no known general anaesthetic effects and present an unexpected structural approach to the pharmacology of the syndrome. It may now be possible to investigate, treat or prevent the syndrome by the use of selective drugs without more generalised anaesthetic effects.

Alfaxalone Alfadolone Mixture↗

Effects of steroid anaesthesia on some liver function tests in goats.

The effect of Saffan, a steroid anaesthetic, on the liver function of goats has been studied. Forty healthy animals were divided into 4 equal groups. The first 2 groups were given 2 and 4 mg Saffan/kg b. wt respectively. A mixture of Saffan (1 mg) and Xylazine (0.1 mg)/kg b. wt was given to the third group and Xylazine alone to the fourth group (0.1 mg/kg b. wt). Serum samples from all groups were analysed for glucose, total protein, total and direct bilirubin and the level of activity of transaminases. Administration of Saffan evoked more hyperglycemia than a mixture with Xylazine, or Xylazine alone. The hyperglycemic effect of both doses of Saffan (2 and 4 mg) was equivocal beyond 2 h. The effect then differed and glucose was increased 4-fold by 2 mg and 3-fold by 4 mg Saffan. Serum total protein, conjugated and total bilirubin, and GPT and GOT were not changed in the four experimental groups. This was good evidence of a normally functioning liver during the course of steroid anaesthesia administration in goats.

Alanine Transaminase↗

Biochemical effect of steroid anaesthesia on some liver function tests in goat.

Saffan, as a type of steroid anaesthetic, was tested to demonstrate the effect of its administration on liver function in goat. For this purpose, 40 healthy animals were divided into 4 equal groups. The 1st 2 groups were given 2 or 4 mg saffan/kg body weight (B.W.), respectively. A mixture of saffan (1 mg) and xylazine (0.1 mg)/kg B.W. was given to the 3rd group. Xylazine alone was offered to the 4th group in a concentration of 0.1 mg/kg B.W. Serum samples from all groups were analysed to measure the quantities of glucose, total protein, total and direct bilirubin as well as the activity levels of transaminases. Increased glucose levels resulted from administration of saffan which evoked more hyperglycaemia than its mixture with xylazine or xylazine alone. The hyperglycaemic effect of both doses of saffan was equivocal beyond 2 hours. The effect then differed, and glucose elevation reached the 4 fold level by 2 mg saffan and the 3 fold level by 4 mg. Total serum protein, direct and total bilirubin as well as GPT and GOT were not changed in the 4 experimental groups. This was a good indication to normal liver function in the course of administration of steroid anaesthetics to goat.

Alfaxalone Alfadolone Mixture↗

Saffan induced poikilothermia in cheetah (Acinonyx jubatus).

The steroidal anaesthetic agent Saffan (a 1,2% m/v mixture of alphaxalone and alphadolone) induced a state of poikilothermia in cheetahs. On a warm day (maximum temperature 29 degrees C) rectal temperatures rose in 7 of 8 male cheetahs given Saffan. The highest rectal temperature recorded was 41 degrees C. On a cool day (minimum temperature 19,5 degrees C) rectal temperature fell in 6 of 6 male cheetahs. The lowest rectal temperatures recorded was 36,2 degrees C. Saffan at 3 mg/kg intravenously in cheetahs is an excellent and safe hypnotic but should be used with caution on both hot and cold days.

Acinonyx↗

Anaesthesia for cystoscopy. A comparative study of 3 methods of intravenous anaesthesia: diazepam-fentanyl, thiomebumal and althesin.

Three different methods of anaesthesia for diagnostic cystoscopy are compared in randomly divided series of 100 males each. Group I received diazepam-fentanyl supplemented with Althesin in case of therapeutic transurethral procedures. Group II had thiomebumalnatrium-N2O-O2 and group III had althesin-N2O-O2. Group I had no premedication while the two others were premedicated with morphine-scopolamine mixture. The period during and after anaesthesia was observed independently by the urologist, the anaesthetist, the nurses on the ward and by interviewing the patient the day after the cystoscopy. The anaesthetist was the only one who knew the method to be used. Diazepam-fentanyl proved to give sufficient analgesia. This combination offered the shortest and most uncomplicated period of recovery. Five patients given diazepam-fentanyl remembered the cystoscopy as being painful. All these cases could be related to insufficient coordination of anaesthesia and cystoscopy, which seems to be of major importance for this method.

Aged↗

Ventilatory effects of oxygen-enriched mixtures in the dog under althesin anaesthesia.

In six dogs anaesthetized with Althesin, minute ventilation, respiratory rate, tidal volume, PaO2 and PaCO2 were measured while breathing air (F/O2 = 0.21), and then after correction of hypoxaemia (F/O2 = 0.35), and again while breathing 100% oxygen (F/O2 = 1.00). The administration of 35% oxygen corrected the hypoxaemia (PaO2 = 8.98 +/- 0.76 kPa in air; PaO2 = 16.39 +/- 1.59 kPa with 35% oxygen), but produced a significant and sustained depression of ventilation. The administration of 100% oxygen induced a further significant and sustained decrease in ventilation. It is concluded that hypoxaemia is not necessary for the ventilatory depressant action of oxygen in the anaesthetized dog and that, under Althesin anaesthesia, peripheral arterial chemoreceptors are active up to high PaO2 values.

Alfaxalone Alfadolone Mixture↗

[Constant outflow anesthesia with the combination of alfatesine and fentanyl].

In a previous work, the authors showed the value of administering Alfatesine, in interventions of long duration, at a constant rate by using an automatic syringe, and by combining it with destromoramide. In this new work the authors present an analagous study carried out in 47 subjects, in which dextromoramide was replaced by fentanyl. The automatic syringe used was the Braun Perfusor IV equipped with a 50 ml syringe containing 0.3 ml. of CT 13.41 and 0.006 mg. of fentanyl per ml. Induction was achieved at graduation 10, 14 ml of the mixture having been injected in approximately 60 seconds. Maintenance of anesthesia was ensured at graduation 6 corresponding to an hourly administration of 27 to 30 ml of the mixture (9 ml of CT 13.41 and 0.18 mg of fentanyl). The patients were adults of average weight 64 kg., who had undergone sometimes major orthopedic surgery, of an average duration of 161 mn. The results are looked at from the angle of quality of the anesthesia and of the awakening and of the side effects. They confirm the non-accumulation under these conditions of use and these doses of CT 13.41 used and reveals an analagous behaviour of fentanyl. Reserves are however made owing to the mode of elimination of fentanyl, on the use of such a technique in anuric patients or in renal insufficiency.

Adolescent↗

[Determination of alphaxalone in serum and urine by gas-liquid chromatography. Application in anaesthesiological pharmacology (author's transl)].

The authors propose a simple and reliable method for determination of alphaxalone [3 alpha-hydroxy(5 alpha)pregnane 11,20 dione] in serum and urine, during long-duration anaesthesia using Althesin, mixture of alphaxalone and alphadolone acetate [21 acetoxy, 3 alpha-hydroxy(5 alpha)pregnane 11,20 dione]. If assays of alphadolone appear difficult and without any precision, because of numerous interferences, the determination of alphaxalone in serum and urine seems interesting for pharmacokinetic and metabolic investigation. We confirm the quick rate of disappearance of alphaxalone from blood, associated with a very active metabolism in the liver. The results show that it exists a relation between the concentration of alphaxalone in blood and the value of anaesthesia judged on clinical and electrical criteria. We cannot however conclude that Althesin presents a cumulative effect, because we used important amounts of anaesthetic agent.

Alfaxalone Alfadolone Mixture↗

Effect of various anaesthetics on resting plasma concentrations of luteinizing hormone, follicle-stimulating hormone and prolactin in ovariectomized ewes.

Effects of various anaesthetics on plasma LH, FSH and prolactin levels were studied in ovariectomized ewes. In the first experimental series, conducted between June and November (late breeding season, early anoestrous season), the following treatments were given: saline (i.v.) (n = 7); single thiopentone injection (i.v.) (n = 4); induction of anaesthesia for 2 h with thiopentone (n = 5), ketamine/thiopentone mixture (n = 6), Alphathesin (n = 6) or induction with thiopentone and maintenance with halothane (n = 6). The major findings were: (1) halothane anaesthesia reduced mean plasma LH levels by preventing pulsatile secretion of LH; (2) Alphathesin had the least effect on tonic LH concentration; (3) a single thiopentone injection did not affect LH levels; (4) continuous thiopentone anaesthesia increased LH pulse amplitude; (5) plasma FSH concentration was not affected by any of the treatments; (6) ketamine/thiopentone-induced and Alphathesin-induced anaesthesia increased plasma prolactin levels. In a second experimental series four ovariectomized ewes were anaesthetized with thiopentone for 3 h in January. In contrast to the results obtained with thiopentone in August, treatment in January reduced plasma LH pulse amplitude and mean plasma LH levels. These latter results support the hypothesis that there may be seasonal variation in responses to barbiturate anaesthesia.

Alfaxalone Alfadolone Mixture↗