IT IS THE AIM OF THIS PAPER to introduce the technique of continuous intravenous infusion of the relatively new steroid anaesthetic Alfathesin, in conjunction with intermittent pentazocine (Talwin) analgesia. We shall attempt to demonstrate the advantages of Alfathesin and of this particular method of administration. Rationale for the techniqueAlfathesin. Having been introduced to Alfathesin, a mixture of the two steroids alphaxalone and alphadolone, at the 5th World Congress of Societies of Anesthesiology in Kyoto, Japan and having had occasion to assess it in some 200 surgical procedures in ambulatory patients, we have endeavoured to find a method of administration which would obviate some of the disadvantages while yet retaining the very real advantages of Alfathesin. The drawbacks of the agent which have in the past limited its use for maintenance of anaesthesia are its short duration and the absence of analgesia. To overcome the short action we have resorted to intermittent injection, but this technique is less than satisfactory because it is difficult to maintain a stable level of anaesthesia. The advantages of Alfathesin lie in its speed of action, its low toxicity and the paucity of undesirable side effects both during anaesthesia and on recovery.In contemplating the advisability of continuous infusion it was necessary to consider possible cumulative effects, if any. It is known from the work of British researchers I that, following intravenous injection, the plasma concentration of the agent recedes quickly after an initial peak, the half-life of Alfathesin in plasma being seven minutes. Serum protein binding is weak, although studies in animals show an affinity to albumin and beta lipo-proteins. The distribution of the two constituents of Alfathesin is similar to other steroids and no particular affinity in distribution towards fatty tissues has been observed. The agent undergoes metabolic degradation in the liver by means of combination with glycuronic acid. Only two cases of prolonged recovery from anaesthesia in the presence of hepatic insufficiency have been described in the literature.'-' The lack of cumulative effect is further evident from our own observation that no reduction in successive doses of Alfathesin was possible with the intermittent injection technique which was originally used. Based on these observations we felt justified in attempting the continuous infusion technique.Pentazocine. The absence of analgesic properties of Alfathesin made it imperative that another agent be added to provide such analgesia. This end has been achieved in Europe primarily by the use of dextromoramide (Palfium) or by
Dmzv.rnM is a derivative of benzodiazopine which has attracted the interest of anaesthetists since its introduction in 1961. Its sedative effect is intermediate between the neuroleptics and the tranquilizers which are often useful in anaesthesia, and we have studied its usefulness in patients undergoing pulmonary surgery.Our observations will be presented as a comparative study of two series of cases, in one of which diazepam was used (54 cases), and in the other of which a standard premedication was used with thiopentone induction for anaesthesia for pulmonary surgery (56 cases). METHODSThe patients were selected at random. There were 35 cases of pulmonary tuberculosis (diazepam 18, thiopentone 17), 68 cases of cancer (diazepam 34, thiopentone 34), and 7 cases of bronchiectasis (diazepam 2, thiopentone 5), making a total of 110 patients. These patients differed in age, sex, weight, pathology, and anaesthetic risk, and required different types of surgery.Although the patients were chosen at random, irrespective of the nature of the operation and the pathology, a strict procedure was followed in evaluating the anaesthetic risk (according to the classification of the American Society of Anesthesiologists), while making the observations and during the administration of the anaesthetic. ProcedureThe blood pressure was measttred by indirect stethoscopy, controlled occasionally by direct readings and recordings on an electrosphygmomanometer. The heart rate and ECC were observed and recorded on an oscilloscope and electrocardiograph. The tidal ventilation was monitored by a Wright respirometer. Finally, the blood pressure and heart rate before and after the induction of anaesthesia were accurately compared.The anaesthetic techniques were as follows: 1. Premedication. Either (a) our standard premedication with oral Noludar,| secobarbital, or Tuinal| (with or without diphenhydramine or promethazine) the night before, and meperidine or aneleridine, diphenydramine (Benadryl) and atropine intramuscularly one hour before induction, or (b) premedication with diazepam (per os and intramuscular).2. Induction of anaesthesia with intravenous thiopentone or diazepam.
TrimTv YEAtaS after Selye in 19411 discovered the hypnotic action of various steroids -a discovery which led to the work of Laubach, et aL e (1954)(1955) :~ on 21-hydroxy-pregnanedione sodium succinate (Hydroxydione-Viadril| -a new steroid anaesthetic known as "A1phadione," "Althesin" or "A1phathesin" (CT-1341), has now been made available following pharmacological study by K.J. Child, et al. in 1971. 4 "Alphathesin" is a mixture of two steroids -alphaxalone and alphado]one -each millilitre containing 9 mg and 3 mg respectively. The purpose of the second steroid alphadolone is to increase the solubility of alphaxalone which is dissolved in cremophor el ( polyoxyethylated castor off ).Studies in animals have shown that CT-1341 acts as a fast, short-duration and dose-related intravenous anaesthetic. Local tolerance is good, and side effects are not significant. PHARMACOLOGICAL AND CLINICAL PROPERTIESIn 1972, at the Fifth World Congress of Anesthesiology, in Kyoto, Japan, Professors John W. Dundee of Queen's University, Belfast, 5 Alex Forrester and coworkers of the Royal Infirmary of Glasgow, 6 and D.G. McDowall of Leeds, 7 presented papers on Alphathesin: one, on the general aspects of this new steroid anaesthetic; the second, a study on the peripheral vasculature comparing it with sodium thiopentone, and, finally, a third paper on the cerebral effects of Alphathesin. In the same year, the British Post-Graduate Medical Journal published a special issue, entirely devoted to steroid anaesthesia, s It dealt with the contents of a Symposium held at the Royal College of Physicians of London, on January 10 and 11, 1972. In that special issue the general and clinical pharmacology, as well as clinical uses of Althesin, are discussed.Induction of anaesthesia with Althesin is rapid and directly related to circulation time. The optimum dosage is in the vicinity of 50 ml to 60 ml per kilogram body weight. It appears that, like thiopentone and methohexitone, Alphathesin produces a drop in arterial blood pressure, venous pressure and systolic discharge. The cardiac output remains unchanged because of compensating tachycardia. Respiratory irregularities have been noted with all three anaesthetics, consisting usually of hyperventilation followed by a short period of apnoea and followed by fast shallow breathing. With A1phathesin pulmonary elasticity is apparently improved.A few muscular movements have been observed on induction of anaesthesia.
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