Certain pharmacological effects of a new non-depolarising muscle relaxant, AH 8165 (Glaxo), were studied in 50 patients. The adequate dose for muscle relaxation onset of action, duration of effect and reversibility with cholinesterase agents, were established. Changes in blood pressure, heart rate, intra-ocular pressure, blood gases and acid-base values were measured. In comparison with pancuronium bromide, the onset of action was much more rapid, but the duration of effect was the same. Reversal with anticholinesterase agents was good, and no residual hypoventilation could be detected postoperatively

Erasmus, F.R.

Ungerer, M.J.

AJOL - African Journals Online

14 December 1974 S.A. MEDICAL JOURNAL 2561Clinical Evaluation of a New Non-depolarisingMuscle RelaxantM. J. UNGERER, F. R. ERASMUSSUMMARY AH 8165Fig. 1. Chemical structure of AD 8165.MethodsThe drug was administered to 20 patients, who were allpremedicated with atropine only. After induction withsodium thiopentone, anaesthesia was deepened with halo-thane and nitrous oxide, and endotracheal intubationwas carried out after topical anaesthesia of the larynx with4 % lignocaine.The force of the thumb adduction was measured byusing a modification of the method described by Tyrrel!.'A nerve stimulator was used to deliver supramaximalstimuli at a rate of 0,5 Hz to the ulnar nerve at thewrist through 23-gauge needle electrodes inserted sub-cutaneously. A transducer (Statham UC (3-gold cell»surmounted by a load cell accessory (UL 4 - 5) to providea convenient working range (0 - 2,3 kg), was imbeddedin a perspex hand grip, with a perspex cradle accommo-dating the thumb. The hand was strapped in position withadhesive plaster. The transducer output was amfllified andrecorded on a Hewlett-Packard recorder.After steady baseline recordings had been obtained,AH 8165 was injected via a central venous line at threedifferent doses, viz. 0,25 mg/kg, 0,5 mg/kg and 1,0 mg/kg.The following observations were then made: .The time from injection to (i) the first detectablediminution of twitch height; (ii) the maximal effect onmuscle contraction; (iii) the first detectable sign of re-covery of the twitch response; and (iv) the recovery oftwitch response to 20% of control values. Direct intra-CH3_ M~ X8eN- N- N- N CHe EBN 3XS. Air. Med. l., 48, 2561 (1974).EVALUATIONCertain pharmacological effects of a new non-depolarisingmuscle relaxant, AH 8165 (Glaxo), were studied in 50patients. The adequate dose for muscle relaxation onset ofaction, duration of effect and reversibility with choline-sterase agents, were established. Changes in bloodpressure, heart rate, intra-ocular pressure, blood gasesand acid-base values were measured.In comparison with pancuronium bromide, the onset ofaction was much more rapid, but the duration of effect wasthe same. Reversal with anticholinesterase agents wasgood, and no residual hypoventilation could be detectedpostoperatively.The pharmacology of a new non-depolarising neuromus-cular blocking agent, 1,1'-azobis(3-methyl-2-phenyl-1H-imidazo (l,2-a)-pyridinium) dibromide (AR 8165) (Fig.1), has been studied in detail in different animal species.'It has been shown to produce a rapid onset of muscularblockade with a short duration of action, comparable tothe effects of succinylcholine. Encouraging results havealso been obtained in man.'"Permission was obtained from the Drug Control Councilto use AH 8165 (supplied by Glaxo-Allenbury) in acontrolled clinical trial.In this investigation, AH 8165 was administered to50 patients under general anaesthesia and in whomroutine general surgical and thoracic procedures wereperformed. The purpose of the study was explained toall patients and consent was obtained. The study wasconducted in two parts: (i) evaluation and (ii) clinical com-parison with pancuronium bromide.The purpose of the first part of the study was todetermine an adequate dose for muscle relaxation, therate of onset of action, the duration of effect and thereversibility with anticholinesterase agents.Department of Anaesthesiology, University of the OrangeFree State, Bloemfontein, OFSM. J. UNGERER, M.MED. (ANAES.), F.F.A. (S.A.)F. R. ER.!\SMUS, M.l\-IED. (A."IAES.), F.F.A. (S.A.)Date received: 2 April 1974.--2562 S.-A. MEDIESE TYDSKRIF 14 Desember 1974arterial pressure recordings were taken in 10 patients.Intra-ocular pressure was measured and recorded in 2patients scheduled for intra-ocular surgery, by placing anAmsler needle directly into the anterior chamber of theeye.At the end of the procedure, the effect of the musclerelaxant was reversed by the intravenous administrationof 2,5 mg prostigmine and 1,2 mg atropine.ResultsOnset and duration of action: Both the onset andduration of action were broadly dose-related but variedwidely (Table I). The speed of onset compares favourablywith that of succinylcholine (Fig. 2).Intra-ocular pressure: No changes in intra-ocularpressure could be detected during administration of AB8165, in contrast with the rise in pressure produced bysuccinylcholine (Fig. 3).COMPARISONFig. 3. Effects of succinylcholine and AB 8165 on intra-ocular pressure.IMlN.~MMHG., " ......k-....8l6S-..,8-MG......~ ......-...;..-~w:~-.........~iM;;;....Cardiovascular effects: At a dose of 0,25 mg/kg therelaxant had minimal effects on blood pressure, butcaused an increase in pulse rate of 12%. At a dose of0,5 mg/kg it caused a transient decrease in systolic bloodpressure of 12% and a 23% increase in pulse rate (Fig. 4).Reversibility with anticholinesterase agents: Reversalof neuromuscular blockade was clean and complete inall cases within 3 minutes after injection of prostigmineand atropine (Fig. 5)...IM~HFig. 2. Comparison of onset of action of AB 8165 withthat of succinylcholine.In the second part of the study a clinical comparison ofAH 8165 with pancuronium bromide was carried out.TABLE I. ONSET AND DURATION OF ACTION OF AH 8165Time from injection 0.25 mg/kg 0.5 mg/kg 1,0 mg/kg(7 patients) (7 patients) (6 patients)To first detectable action (sec)Range 14 - 25 12 - 18 6 - 12Mean 18,3 13,4 10,0To maximal effect (sec) Range 30 - 100 30 - 80 20 - 27Mean 51,0 50,7 24,7To first detectable sign of recovery (min)Range 4 -17 5 - 19 22 - 45Mean 8,7 13,0 30,0To 20% recovery (min) Range 9 - 20 15 - 36 35·75Mean 13,8 26,3 57,014 December 1974 S.A. MEDICAL JOURNAL 2563,-.r I .- 30' SECONDS-ItS'Fig, 4. Typical examples of the effects of AB 8165 onblood pressure and pulse rate.Fig. 5. Examples of the excellent reversal with anticho-linesterase of the neuromuscular block due to AB 8165.MethodsThrough experience gained in the first part of the study,it was decided that 0,75 mg/kg woulc!. be.a reasonabledose for muscle relaxation, and comparable to 0,1mg/kg of pancuronlum. AH 8165 was' given to 30 patientsand pancuronium bromide to 15 patients. 'After pre-oxygenation, anaesthesia was induced withsodium thiopentone, and immediately followed by either0,75 mg/kg AH 8165 or 0, I mg/kg pancuronium bromide.AU patients were ventilated with pure oxygen until therewas minimal resistance to expansion of the chest. -Endo-tracheal intubation was then accomplished. The timefrom injection until intubation, as well as the ease ofintubation, was noted.Anaesthesia was maintained with oxygen, nitrous oxideand 0,5 - 1% halothane. Increments of AH 8165 (10 - 20mg) or pancuronium bromide (I - 2 mg) were given whenrelaxation appeared to be wearing off. After conclusionof surgery neuromw:cular blockade was reversed with2,5 mg neostigmine and 1,2 mg atropine. The duration ofaction, degree of relaxation and ease of reversibility werenoted.In 14 patients arterial blood gases and acid-base valueswere measured immediately before induction and againone hour postoperatively, while the patients were spon-taneously breathing room air.ResultsEase of intubation: Intubation could be accomplishedwith ease after injection of 0,75 mg/kg of AH 8165 in26 patients, although movements of the cords, slightbucking or some movements of the extremities did occurin the majority of patients. In 4 patients intubatingconditions were regarded as unsatisfactory. These resultscompared favourably with the intubating conditionsattained aJter the injection of 0,1 mg/kg of pancuroniumbromide.Onset of action: Intubation was carried out at a meantime of 54, I (± 14,8) seconds after injection of AH 8165.This was considerably shorter than the 150 sec (± 32 sec)necessary after injection of pancuronium bromide beforeintubation could be carried out.Duration of action: This was taken as the time frominjection until an additional dose was necessary, or untilthe end of the operation. The duration of action of0,75 mg/kg was variable, but lasted a mean time of56 (± 29) min. The duration of action of pancuroniumbromide was 69,2 (± 22) min.Blood gas changes:.. No residual hypoventilation couldbe detected one hour postoperatively by means of bloodgas analyses (Table II).TABLE 11. PRE- AND POSTOPERATIVE BLOOD GAS VALUESIN 14 PATIENTS BEFORE AND AFTER ADMINISTRATION OFAH 8165P.02 P.C02Pre-op. Postop_ Pre-op_ Postop.Mean 76,07 74,57 34,36 32,93SO 7,5 11,98 2,60 2,83TABLE Ill. ACID-BASE CHANGES IN 14 PATIENTS AFTERAH 8165pH Std HCOl Base excessPre-op_ Postop. Pre-op_ Postop. Pre-op_ Postop_Mean 7,46 7,38 21,43 19,89 -2,78 -4,78SO 0,18 0,21 1,42 1,86 1,78 2,342564 S.-A. MEDIESE TVDSKRlf 14 D~sember 1974Acid-base changes: Small but insignificant decreasesin base excess, standard bicarbonate and pH occurred Inthe immediate postoperative period (Table fIr).DISCUSSIONThe onset of action of AH 8165 is more rapid than thatof pancuronium bromide, and is comparable to that of thefast-acting muscle relaxant, succinylcholine. However, AH8165 produces less ideal intubating conditions thansuccinylcholine. To constantly achieve optimal conditions.a higher dose would probably be needed, e.g. I mg/kg.If AH 8165 is not used for intubation, a smaller dose of0,5 mg/kg will provide satisfactory relaxation for surgery.Incremental doses of 10 mg prove adequate when relaxa-tion appears to be wearing off.The duration of action was not as short in humans aswas expected from experimental work, and is similar tothat of pancuronium bromide. It is therefore not thesolution to the problem of finding a short-acting non-depolarising muscle relaxant. Nevertheless, its rapid onsetof action, minimal cardiovascular effects, lack of changein intra-ocular pressure and excellent reversibility withanticholinesterase agents, should prove valuable inanaesthetic practice.REFERENCESI. Britain, R. T. and Tyers, M. B. (1973): Brit. I. Anaesth., 45, 837.2. Simpson, S. R., Savege, T. M., Foley, E. I., Ross, L. A., Strunin, L.WaJton, B., MaxweJl, M. P. and Harris, D. M. (1972): Lancet, I, 5J6:3. Coleman, A. I., O'Srien, A., Downing, I. W., Ieal, D. F., Moyes,D. G. and Leary, W. P. (1973): Anaesthesia, 28, 262.4. Slogg. C. Eo, Savege. T. M., Slmpson. I. C., Ross, L. A. andSimpson, B. R. (1973): Proc. Roy. Soc. Med., Iiti. 1023.5. TyrreJl, M. F. (1969): Anaesthesia, 24, 626.The Pharmacology of MalnutritionPART I. SALICYLATE BINDING STUDIES USING NORMALSERUM/PLASMA AND KWASHIORKOR SERUMC. EYBERG. G. P. MOODLEY, N. BUCHANANSUMMARYThe binding of salicylate to serum 'and plasma has beenreinvestigated. At normal pH, binding was saturated atabout 40 mg!100 ml of total serum salicylate. In kwashior-kor serum, binding was saturated at approximately 15mg/l00 ml. The implications of the latter finding are dis-cussed.S. Afr. Med. l., 48, 2564 (1974).We recently suggested that In infantile salicylism,the amount of salicylate in the cerebrospinal fluid (CSF)is of prime pathological importance. The CSF salicylateconcentration, in turn, is closely related to the free serumsalicylate concentration!-'Metabolic and Tutrition Researcb Unit, Department ofPaediatrics, Baragwanatb Hospital and University of theWitwatersrand, JohannesburgC. EYBERG, B.Se.G. P. MOODLEY, D.~I.T.~. BUCHA TAN. ~f.B. B.So, F.e.p. (S.A.)Date received: 3 June 1974.Reprint requests to: Dr T. Buchanan, Metabolic Unit, BaragwanathHospital, P.O. Bertsham, Johannesburg.Although salicylate binding has been extensively studiedover the past three decades: it was felt worth while toreinvestigate the problem, using a new dialysis system.At the same time, the binding of salicylate to hypo-albuminaemic kwashiorkor serum was studied. The resultsof these studies are reported here.MATERIALS AND METHODSPlan of StudyFresh pooled adult serum was loaded with sodiumsalicylate at various concentrations and then dialysed;the same procedure was followed with fresh pooledadult plasma. The effects of pH were studied by theaddition of hydrochloric acid or sodium bicarbonate, soas to obtain pH levels of 6,97; 7,5 and 8,[5.Pooled kwashiorkor serum was studied after it had beenloaded with sodium salicylate at various concentrationsand subsequently dialysed.MethodsDialysis was performed using a new equilibrium dialysissystem previously employed by our group! With this

English

Clinical Evaluation of a New Non-depolarising Muscle Relaxant

https://www.ajol.info/index.php/samj/article/download/171601/161003

Clinical Evaluation of a New Non-depolarising Muscle Relaxant

Abstract

Similar works

Full text

Available Versions

AJOL - African Journals Online