STUDIES OF DRUGS GIVEN BEFORE ANAESTHESIA VIE: MORPHINE 10 MG ALONE AND WITH ATROPINE OR HYOSCINE

Transcription

1 Brit. J. Anaesth. (9),, STUDIES F DRUGS GIVEN BEFRE ANAESTHESIA VIE: MRPHINE MG ALNE AND WITH ATRPINE R HYSCINE BY RICHARD S. J. CLARKE, JHN W. DUNDEE AND WILLIAM J. LVE Department of Anaesthetics, The Queen's University of Belfast, Northern Ireland SUMMARY Comparing the effects of morphine mg morphine-atropine and morphine-hyoscine it seems, from almost every standpoint, that this last combination is to be preferred. Pre-operatively, it produces better sedation and reduces the incidence of nausea and vomiting. During anaesthesia it reduces the frequency of hiccough out leading to an alarming amount of involuntary muscle movement. Postoperatively, there is a high incidence of nausea and vomiting following morphine alone which is much lower after morphine-hyoscine. -atropine is intermediate in most of its actions and, except when the tachycardia is particularly desired, has no particular value. In a recent paper Dundee, Moore and Clarke (9) studied the influence of hyoscine and atropine on the effect of pethidine mg. Contrary to expectations, they recorded a very high incidence of pre-operative emetic effects when pethidine was given alone which was significantly reduced by atropine or hyoscine. In addition to this, both antisialogogues reduced the incidence of troublesome hiccough found when pethidine was given as sole premedication before methohexitone anaesthesia. As might have been expected because of its antanalgesic action (Dundee, Nicholl and Moore, 9), the addition of hyoscine increased the frequency of spontaneous muscle movements following intravenous barbiturates. Hyoscine also greatly prolonged recovery from anaesthesia and both antisialogogues had a transient anti-emetic effect in the postoperative period This paper describes a similar study morphine mg and also attempts to evaluate its effect alone and in combination atropine or hyoscine. In view of the extensive use of morphine for over years, it is surprising that there appears to be no comparative study of these premedicants. In addition, many of the newer synthetic analgesics have been introduced the claim that they have less severe side effects than morphine and it is hoped that the data obtained in this study can be used as a baseline for comparison other analgesics. METHDS The procedure and method of evaluation was exactly as described by Dundee, Moore and Clarke (9) and patients scheduled for minor gynaecological procedures were given either morphine mg alone, morphine mg atropine. mg, or morphine mg hyoscine. mg. Part of this study was carried out on a double-blind basis. Anaesthesia was induced methohexitone. mg/kg and maintained per cent nitrous oxide in oxygen, further doses of barbiturate being given as required. Table I shows the number of patients given each combination, and the numbers in the "detailed" and "index" series. In the former, pre-operative visits were made at,, and 9 minutes after premedication had been given, whereas patients were seen once only, between and 9 minutes, in the "index" series. Some of the patients in the latter series were given other anaesthetics for a different study and therefore do not appear in the anaesthetic and postoperative group. The patients in each premedication group are broadly comparable as regards age and weight and the average duration of anaesthesia was similar in each group.

2 STUDIES F DRUGS GIVEN BEFRE ANAESTHESIA VIH Pre-operative evaluation Detailed studies atropine hyoscine Indices only atropine hyoscine TABLE I Details of patients. No. of patients Anaesthesia and postoperative evaluation atropine hyoscine age (yr) weight (kg) duration of anaesthesia (min). ±.9. ±..9 ±. TABLE II Comparison of morphine, morphine atropine and morphine hyoscine (percentage) 9 minutes after intramuscular injection. Drowsiness Good Fair SUght Apprehension Marked Excitement or restlessness Pain at injection site Dizziness Marked Emetic symptoms Nausea Vomiting Tachycardia - - Hypotension mm Hg + Efficacy score Mean Toxicity score Mean Net mean score atropine hyoscine

3 BRITISH JURNAL F ANAESTHESIA RESULTS (y' =., elf= ; P>.) but morphine It is evident from table H that morphine hyoscine was significantly better than either of hyoscine is a much better hypnotic than either ^ other premedications (P<.). Although morphine alone or morphine atropine. The there was n significant difference in the disrelief of apprehension is also better after hyoscine. tribution of the toxicity scores the three The series of patients receiving morphine and forms of premedication, the higher mean score atropine showed a lower incidence of dizziness f r morphine and atropine can be attributed to than those receiving either of the other pre- ^ high incidence of tachycardia and the low medications; whereas it was only in the patients mean score f r morphine and hyoscine can be who had been given morphine hyoscine that attributed to its absence. there was a significant reduction in pre-operative Th e ove rall effect of the premedication, judged emetic effects. Tachycardia was commonest after ^v ^ net mean scores, also showed morphine morphine and atropine and least frequent after ^^ hyoscine significantly better than morphine morphine and hyoscine. atropine ( y =.; df=; P<.) or Judging by the distribution of scores for the morphine alone ( /* = 8.; df=; P<.). "desired effects", morphine atropine was alone was significantly better than not significantly better than morphine alone morphine atropine (y a =.; df=; TABLE III Percentage incidence of overall effects of the three premedications as judged by net scores (efficacy score less toxic score). verall effect Net scores atropine hyoscine Good + & + ' Fair + & + Poor & - Undesirable or less TABLE IV Dosage and course of anaesthesia (percentage) methohexitone after morphine, morphine atropine, and morphine hyoscine. dosage (mg/kg)' Induction Total Course of anaesthesia Excitatory phenomena Respiratory upset Hypotension mm Hg + Grade of anaesthesia a b Condition at end Awake Safe Unsafe.. ±. atropine..8 ±. 9 9 hyoscine.. ±

4 EFFECT c/ MRPHINE MRIPHINE-ATRPINE MRPHINE-HYSCINE oo li DRWSINESS oo APPREHENSIN DIZZINESS J so - D f""! r*t*i K. o oo Cd EMETIC EFFECTS H HEART RATE o J MINUTES AFTER INJECTIN FIG. Comparison of morphine, morphine atropine and morphine hyoscine at,, and 9 minutes after injection. Drowsiness Apprehension Dizziness Emetic effects Heart rate Solid column Good or fair Moderate or marked Marked Vomiting + b.p.m. Hatched column Nausea - b.p.m.

5 BRITISH JURNAL F ANAESTHESIA P<.). Table III summarizes the above findings and shows why morphine hyoscine is par excellence the premedication of our choice as far as pre-operative effects are concerned. Figure shows that, regard to both desired and toxic effects, the peak of morphine activity was not reached for 9 minutes, although there was little change after minutes. The incidence of good or fair drowsiness at minutes was slightly increased by atropine and markedly by hyoscine and the tachycardia following morphine atropine was at its peak in minutes. n the basis of their effects on the course of anaesthesia, morphine hyoscine is again the most satisfactory premedication (table IV). There is a higher incidence of excitatory phenomena when hyoscine is given but a lower incidence of respiratory upset (largely hiccough). Hypotension is equally common all these premedications. The distribution of the grades of anaesthesia shows that all premedications were followed by uneventful or only slight disturbance in a high proportion of cases. Although morphine atropine appears to be slightly better than morphine alone, only morphine hyoscine is significantly better on ridit analysis (P<.) and the difference between morphine atropine and morphine hyoscine is not statistically significant. It is difficult to assess the effect of the three premedications on recovery. The morphine-hyoscine series had the lowest percentage of patients awake minutes after the end of anaesthesia but because of the low incidence of complications this group received the lowest total dose of methohexitone. Therefore it does appear that morphine hyoscine delayed recovery relative to the other two forms of premedication. The overall incidence of emetic sequelae during the first hours after anaesthesia was significantly less after morphine and hyoscine than after morphine alone (y s =.8; df=; P<.) but there was no significant difference between morphine and morphine plus atropine (-/ I =.9; df=) or between morphine atropine and morphine hyoscine (x =.; df=). With regard to the first postoperative hour, patients receiving either of the antisialogogues showed a much lower incidence of emetic sequelae than those receiving morphine alone (P<.). Further analysis shows that hyoscine is superior to atropine in this respect (-/ =.98; df=; P<.). It is worth noting that either antisialogogue reduced the severity of sickness in those patients who exhibited emetic symptoms. DISCUSSIN In a review of the evolution of premedication Shearer (9) dates the introduction of morphine from about 8 and it appears to have sustained its popularity (alone or atropine or hyoscine) out criticism for half a century. There is no doubt that this study shows morphine to be a good pre-operative sedative as compared TABLE V Percentage incidence of emetic sequelae and average emetic scores following methohexitone anaesthesia and different premedications. atropine hyoscine 8 First hour Time after the end of the operation - hours N N N 8 8 V=vomiting (including retching); N=nausea alone. First hours Nil 8 9 score...8 score sick patients only...

6 STUDIES F DRUGS GIVEN BEFRE ANAESTHESIA VIH atropine or an inert placebo given under similar conditions (Clarke, Dundee and Moore, 9). Guedel (9) and Minnitt and Gillies (9) state that atropine antagonizes the depressant effects of morphine on metabolism. This may explain the lesser degree of drowsiness and greater apprehension this combination as compared morphine alone. Cullen (9) claims that hyoscine counteracts the respiratory depression of morphine and "contributes a satisfying measure of psychic sedation and amnesia". ur results confirm that it definitely adds to the hypnotic effect of morphine and accelerates the onset of sedation. In almost every respect hyoscine adds to the beneficial pre-operative effects of morphine. Preoperative emetic effects and tachycardia are reduced by its use, but dizziness (which is usually mild and does not worry sedated patients unduly) is increased slightly. Mushin (9) lists the ability of drugs to prevent undesirable side effects of anaesthetics as the first aim of premedicatdon. In this respect both antisialogogues were beneficial in reducing the incidence of hiccough when methohexitone was given after morphine premedication. This was also found in the companion study pethidine (Dundee, Moore and Clarke, 9), and hyoscine is better than atropine in this respect. The increase in excitatory phenomena hyoscine was also found in the pethidine study, but was not of any great clinical significance. Contrary to Goodman and Gilman (9) and others, Riding (9) found that atropine reduced the incidence of postoperative nausea and vomiting when morphine was given as preanaesthetic medication. This study supports the latter findings, but shows that the anti-emetic effect was short lasting. This also applied when pethidine and pethidine atropine were given before methohexitone (Dundee, Moore and Clarke, 9). The anti-emetic effect of hyoscine, although apparently more powerful than that of atropine, also wears off before the emetic effect of the opiate, again confirming the findings of previous studies (Dundee, Armstrong and Alexander, 9; Dundee, Moore and Clarke, 9). It is not the purpose of this paper to draw a detailed comparison between the effects of morphine and pethidine, but it must be stated that morphine mg has been shown to be a very suitable drug for pre-anaesthetic medication, and that its desired effects are enhanced and toxic actions reduced by the addition of hyoscine. The main drawback to its use is the high incidence of prolonged postoperative vomiting and nausea which is not reduced to a sufficient degree by either of the antisialogogues studied. ACKNWLEDGMENTS ur thanks are due to the nursing, theatre and gynaecological staff of Musgrave Park Hospital, Balmoral, out whose co-operation this study would not have been possible. REFERENCES Clarke, R. S. J., Dundee, J. W., and Moore, J. (9). Studies of drugs given before anaesthesia. IV: Atropine and hyoscine. Brit. J. Anaesth.,, 8. Cullen, S. C (9). Anesthesia in General Practice, st ed., p.. Chicago: Year Book. Dundee, J. W., Armstrong, C. A. G., and Alexander, J. P. (9). Clinical studies of induction agents. VIII: A comparison of the effects of atropine and hyoscine on the course and sequelae of thiopentone anaesthesia. Brit. J. Anaesth.,, 9. Moore, J., and Clarke, R. S. J. (9). Studies of drugs given before anaesthesia. V: Pethidine mg alone and atropine or hyoscine. Brit. J. Anaesth.,,. Nicholl, R. M., and Moore, J. (9). Alterations in response to somatic pain associated anaesthesia. VIII: The effects of atropine and hyoscine. Brit. J. Anaesth.,,. Goodman, L. S., and Gilman, A. (9). The Pharmacological Basis of Therapeutics, nd ed., p.. New York: Macmillan. Guedel, A. E. (9). Inhalation Anesthesia, st ed., p.. New York: Macmillan. Minnitt, R. J., and Gillies, J. (98). Textbook of Anaesthetics, th ed., p. 8. Edinburgh: Livingstone. Mushin, W. W. (9). Administration of drugs before anaesthesia. Brit. med. J.,, 8. Riding, J. E. (9). Postoperative vomiting. Proc. roy. Soc. Med., S,. Shearer, W. M. (9). The evolution of premedication. Brit. J. Anaesth.,,.

7 8 BRITISH JURNAL F ANAESTHESIA ETUDE DES DRGUES DNNEES AVANT L'ANESTHESIE VIII: MG DE MRPHINE SEULE, ET AVEC L'ATRPINE U L'HYSCINE SMMAIRE Comparant les effets de la morphine seule, de la morphine-atropine et de la morphine-hyoscine, il semble de presque tous les points de vue qu'il faut pr frer la derniere association. Avant l'operation, elle produit une meilleure sedation et retluit l'incidence des nausdes et vomissements. Pendant Tanesthesie, elle rexluit la frequence du hoquet sans mener a une quantity alarmante de mouvements musculaires involontaires. Apres l'operarion, il y a une forte incidence de nausees et vomissements apres la morphine seule, elle est beaucoup plus faible apres la morphinehyoscine. La morphine-atropine est intermediaire dans la plupart de ses effets et, sauf si la tachycardie est particulierement desiree, elle n'a pas de valeur particuliere. UNTERSUCHUNG VN MEDIKAMENTEN ZUR VRBEHANDLUNG BEI NARKSE VIII: MRPfflN ALLEIN, MG, UND MIT ATRPIN DER HYSCIN ZUSAMMEN ZUSAMMENFASSUNG Vergleicht man die Wirkungen von mg Morphin mit Morphin-Atropin und Morphin-Hyoscin, dann scheint, von fast jedem Standpunkt aus betrachtet, die letzgenannte Kombination den Vorzug zu verdienen. Sic erreicht vor der peration eine bessere Sedierung und verringert das Auftreten von belkeit und Erbrechen. Wahrend der Narkose vermindert es die Haufigkeit des Singultus, ohne zu einem alarmierenden Mafl an unwillkiirlicher motorischer Aktivitat zu fiihren. Postoperativ tritt nach Morphin allein oft belkeit und Erbrechen auf, was nach Morphin- Hyoscin viel seltener geschiehl Morphin-Atropin steht mit den meisten seiner Wirkungen in der Mine. Es hat keinen besonderen Vorteil, aufler wenn eine Tachykardie besonders erwiinscht ist. Exposes d'anesthesiologie a l'usage des practiciens et des ituditmu. By P. Huguenard and P. Jaquenoud. nd series. Published by Masson et Cie, Paris, 9. Pp. ; 9 figures. The authors of this book are well known, and they have had the assistance of eight collaborators, most of whose names are also familiar to British anaesthetists. The first series, published in 9, was rather on the lines of Adriani's Techniques and Procedures, although oriented more towards the formulation of questions and answers suitable for higher examinations in anaesthesia. This second series is along similar lines, and deals particular problems which beset anaesthetists (the special requirements of the newborn, the aged, the alcoholic; postoperative confusion, renal insufficiency; shock; pulmonary complications; syncope). This section is followed by one on pharmacology, which is a subject in which the French have always been regarded as preeminent; the items dealt are sympathomimetic and parasympathomimetic drugs, opioids, tranquillizers, plasma expanders and halogenated anaesthetics (two and a half pages are devoted to halothane, while chloroform is given no less than six). Then follows a section on physiology (pain, sleep and arousal, stress and operation, secretion of urine, the mechanics of respiration). Finally, there are chapters on tracheotomy, artificial ventilation of the lungs and the prevention of bleeding during operation. No one will expect such a book to be very profound, nor is this one. It does, however, contain a great deal of information, chiefly in note form, propounded all the dogma of a catechism and the faith of an enthusiast. Any candidate for the final FFARCS examination a smattering of the French language will find both this book and its predecessor extremely useful, for it contains much that is valuable and will direct his attention to subjects of importance which so often crop up in the course of examinations. The authors arc to be congratulated on making so much basic information so readily available. M. H. Armstrong Davison BK REVIEWS Principles and Practice of bstetric Anaesthesia (nd edition). By J. Selwyn Crawford, Leverhulme Senior Research Fellow in Anaesthetics and Deputy Director of the Research Department of Anaesthetics at the Royal College of Surgeons of England. Published by Blackwell Scientific Publications, xford. Pp.. Price s. In a review of the first edition of this monograph I wrote, amongst other things, that in the presentation of scientific data in relation to the mother and child Dr. Crawford had succeeded in combining lucidity accuracy and, later, that he was above all stimulating in his approach. Now, five years on, and a wealth of added knowledge available in this hitherto backward area of anaesthetic practice, Dr. Crawford's original text has increased almost threefold in size and I see no reason to revise my first opinion. The expansion is welcome, not only as a source of information but also as an indication of the worthwhile progress that has been made in our knowledge and understanding of maternal and foetal physiology, of the action of drugs on mother and child, and of the value and safety of individual anaesthetic and resuscitative techniques. Thus it exemplifies the increasing interest that anaesthesia at birth engenders amongst obstetricians, paediatricians and anaesthetists. A particular value of this book is the information it contains from both sides of the Atlantic. Although, as Dr. Crawford states, the difference between American and British obstetric practice makes nonsense of any attempt to be didactic about clinical analgesia and anaesthesia, such disparity is not of importance in relation to scientific investigations. This is a very good and useful book. It is frequently a personal book since the identity of the author is often in evidence sometimes in the expression of an opinion, sometimes in the use of words but it is none the worse for this, particularly in relation to clinical technique. Dr. Crawford has continued to build on solid foundations and he can undoubtedly look forward to renewed and well-deserved success this edition. W. D. Wvlie