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THE INTERACTION OF SUXAMETHONIUM WITH PROPANIDID AND THIOPENTONE
Brit. J. Anaesth. (1970), 42, 636
THE INTERACTION OF SUXAMETHONIUM WITH PROPANIDID AND THIOPENTONE BY
D. M. Ross SUMMARY
Several reports have indicated that propanidid prolongs the duration of apnoea following injection of suxamethonium (Howells et al., 1964; Clarke, Dundee and Daw, 1964; Clarke, Dundee and Hamilton, 1967; Doenicke et al., 1968). No reports have been seen concerning the effect of propanidid on muscle pain after suxamethonium. The incidence of muscle pain following the use of thiopentone and suxamethonium has varied widely according to published reports (ChurchillDavidson, 1954; Foster, 1960; Newnam and Loudon, 1966). A study was undertaken to compare the interaction of propanidid or thiopentone with suxamethonium and to determine whether the duration of apnoea was related to the incidence of musde pains or fasciculation. METHODS
A double-blind trial could not be undertaken because of the dissimilarity of the two induction agents. Patients were allocated to one of two groups, the allocation being made according to the last digit of their case number. Propanidid was given to the patients whose case-number final digit was even and thiopentone to those in which it was odd. The trial was designed on a latin square basis such that there were approximately even numbers of patients of either sex in each group, and to a lesser extent similar
numbers of patients over the age of 40 were evenly divided between the two groups (see table I). Propanidid and thiopentone were each used in 2.5 per cent solutions, as it was felt that a more uniform rate of injection could thus be achieved. Furthermore Clarke, Dundee and Hamilton (1967) stated that propanidid 2.5 per cent is equipotent with thiopentone 2.5 per cent. TABLE I
Age (yr) Under 40 Over 40 Total
Female
Male
Total
21 22
13 28
34 50
43
41
84
The dosage in all cases was 250 mg of either induction agent. This injection, given over a period of 6-10 seconds through a No. 1 needle, was immediately followed by suxamethonium 50 mg which had been stored in a refrigerator until its time of use. The duration of apnoea was noted following the injection of the suxamethonium. This was measured from the onset of apnoea to the onset of respiratory efforts (Clarke, Dundee and Daw, D. M. Ross, M3., B.S., F.F.A.RX.S., Department of Anaesthetics, North Staffordshire Hospital Centre. Present appointment: Consultant Anaesthetist, Coventry Group of Hospitals.
Downloaded from http://bja.oxfordjournals.org/ at University of Sydney on May 2, 2015
An investigation was carried out in adults aged 20-60 years comparing the interaction of propanidid or thiopentone with the muscle relaxant suxamethonium. An attempt was made to correlate the apnoea time with the incidence and severity of muscle pains. No correlation was found between the apnoea times and the incidence of muscle pains. The overall incidence of muscle pains was 19 per cent. The older age-groups of both sexes had a significantly shorter apnoea time with propanidid Than with thiopentone, when the drugs were used in combination with suxamethonium; this was also true of the young females. On the other hand, there was no difference in the young males between propanidid and thiopentone and their interaction with suxamethonium, but young men had a higher incidence of muscle pains than anybody else.
SUXAMETHONIUM WITH PROPANIDID AND TfflOPENTONE
RESULTS
Respiratory effects. Considering all patients the duration of apnoea produced by suxamethonium following induction with propanidid was, in general, briefer than that produced by suxamethonium
following induction with doiopentone (fig. la). The average apnoea time following propanidid and suxamethonium was less dian 2 minutes compared with an average time of 3 minutes following thiopentone and suxamethonium. This differnce is statistically significant (P<0.0025). Age and sex groups. The frequency response curve of the apnoea times of males and females, receiving die combination of propanidid and suxamethonium showed a different pattern from that of patients receiving thiopentone and suxamethonium (figs. lb, lc). In patients over 40 years who received propanidid and suxamethonium dierc was a significantly shorter period of apnoea dian diere was in diose who received diiopentone and suxamethonium (P<0.005) (figs. 3a, 3b 3c). This difference was also noted in females under 40 years (fig. 2c). The frequency curve of the duration of apnoea in young males (fig. 2b) was similar whedier they received propanidid or thiopentone, in marked contrast to the curves in all die other age or sex groups. The difference in the response of the young males from that of all other series is significant at die 10 per cent level (x a =4.5841; d i . 3). This is a comparison of die sum of die curves of figure 2b with the propanidid frequency response curve of figure la. Muscle pains. The overall incidence of muscle pains was 19 per cent. The incidence was 11 per cent in males and 8 per cent in females. The latin square design of diis study enables die effects of a number of possible contributing factors to be isolated: namely, die age of die patient; die sex of the patient; die induction drug; the duration of apnoea; or combinations of two or more of these factors. Age. There were 50 patients in the older age group of whom 7 had muscle pain, whereas 9 of the 34 younger patients had muscle pain. This difference is not statistically significant (/s=2.84;P>0.1). Sex groups. Seven of 43 females and 9 of 41 males experienced muscle pains. This difference is not statistically significant (y*=0.015; P>0.9).
Downloaded from http://bja.oxfordjournals.org/ at University of Sydney on May 2, 2015
1964). The timing of the apnoea was done with the aid of a stopwatch and performed doubleblind by an independent observer who did not know what drugs were being used, or indeed the purpose of the riming. During the period of apnoea the lungs were inflated with a nitrous oxide and oxygen mixture, care being taken not to overventilate. No supplementary anaesthetic agents were administered during the period of apnoea but as soon as respiratory efforts were noted halothane was added to the gas mixture, and the lungs ventilated with this combination until stable anaesdiesia was established. Throughout the operative procedure the patient spontaneously breathed this anaesdietic mixture through a Magill circuit (Type A; Mapleson, 1954). All anaesthetics were administered by the same person. The operations were all completed by 4.30 pjn. but patients were not allowed out of bed until the next morning. Each patient was interviewed during the latter part of die morning of the first postoperative day and was asked in general terms how he felt. A patient who did not complain of pain was then asked the direct question, "Have you any aches or pains apart from in the wound site?" If the response was in the affirmative then the severity of pain was assessed. In patients who spontaneously complained the pain was also assessed according to whether it was moderate or severe. Pain was classified as severe, moderate or absent. If the pain was such as to add materially to the patient's discomfort then it was classed as severe. All other aches or pains were classed as moderate. Eighty-four patients (43 females) aged between 20 and 60 were included in the series. The types of operation for which they were anaesthetized were such that the duration did not exceed 30 minutes, and were of such a nature as to allow the patient to be up and out of bed the next morning; for example, carotid angiography and inguinal hernia. The patients received no premedication.
637
BRITISH JOURNAL OF ANAESTHESIA
638 20
lb
la ALL CASES
Ic
ALLMALES
ALL FEMALES
< u
o
10
1
2
3 - 4
5
6
1
2
3
20
4
5
a
MINUTES
MINUTES -
2c FEMALES UNDER 40
2b MALES UNDER 40
10 O
3 4 MINUTES
5
6
3a MALES & FEMALES OVER 40
20
2
2
3 4 MINUTES
3c
3b MALES OVER 40
3 4 MINUTES FEMALES OVER 40
<
s
10
-
2 2
3 4 MINUTES
5
2
3 4 M I N U TES '
5
1
2
3 4 MINUTES
FIGS. 1, 2, 3
Duration of apnoea after the administration of suxamethonium 50 mg. The upper graphs show the response when thiopentone or propanidid was used as the induction drug. The middle and lower graphs show the apnoea frequency curves according to the patients' ages and sexes. It will be seen that the apnoea frequency curve after thiopentone or propanidid in the young males (2b) has a different pattern from all the others. Propanidid # - • Thiopentone X-
Effect of the induction drug. Forty-two patients received propanidid, of whom 9 experienced muscle pains, compared with 7 of 42 patients who received thiopentone. The difference is not statistically significant (x 1 = 0.30; P>0.5). Apnoea time. Of the 42 patients in whom apnoea lasted less than 2 minutes 6 experienced muscle pains, whereas of the 42 patients in whom apnoea lasted more than 2 minutes 10 ex-
perienced muscle pain. The difference is not significant ( x '=1.235; PXJ.2). If there was an association between the occurrence of muscle pain and duration of apnoea then the incidence of muscle pain would have increased among patients with longer periods of apnoea and this increase would have been greater as the apnoea time progressed. The durations of apnoea are, considering the subgroups, arranged in 1-minute periods of
Downloaded from http://bja.oxfordjournals.org/ at University of Sydney on May 2, 2015
2a MALES & FEMALES UNDER 40
< u
SUXAMETHONIUM WITH PROPANIDID AND THIOPENTONE 30
639
unrelated to the incidence or severity of the fasciculations, neither were the fasciculations influenced by the induction agent, the age or the sex of the patient.
: 20
DISCUSSION
Downloaded from http://bja.oxfordjournals.org/ at University of Sydney on May 2, 2015
The results show that a 250 mg dose of propanidid 2.5 per cent, when compared with an equipotent dose, namely 250 mg, of thiopentone 10 5 2.5 per cent, does not potentiate the respiratory eftects of suxamethonium 50 mg. Moreover, in z the patients over 40 years the length of apnoea following induction of anaesthesia with propanidid and suxamethonium was significantly 1 2 3 4 5 6 shorter than that following thiopentone and APXOEA TIME IN MINUTES suxamethonium 50 mg. These findings may in part be explained by the fact that in this study a FIG. 4 The frequency distribution of apnoea and postoperative 2.5 per cent solution of propanidid was used muscle pains after suxamethonium. throughout, for Ellis (1967), working with the Apnoea time (all cases) # # rat phrenic nerve-diaphragm preparation, has Incidence of pain related to time (all cases) X X stated that the myoneural block produced by propanidid and suxamethonium was in proporapnoea and the distribution of the apnoea times tion to the dose of propanidid. of each 1-minute period also showed no statisThe reports of the incidence of muscle pains tically abnormal distribution (^ a =2.998; dJ. 4; following the use of suxamethonium vary widely. P>0.2) (see fig. 4). This may well be in part related to the time No correlation was found between any interval between injection of the induction drug individual factor and the incidence of muscle and suxamethonium. Craig (1964) emphasized pains. However, when combinations of factors are this point and in his study of female patients the examined the frequency of muscle pains was incidence of muscle pains was only 14 per cent found to be twice as high in the young males (5 when suxamethonium was given immediately out of 13) as it was for the older males (4 out of after thiopentone. This compares with 16 per 28) and in fact was appreciably higher than for cent in the females in this series. It must be conthe rest of the population (11 out of 71). The cluded that if, as Craig suggests, thiopentone difference in response of young men compared offers considerable protection against muscle with all other patients was significant at the 10 pains, then so does propanidid. per cent level (x 2 =2.417; P<0.1). Doenicke and associates (1968) showed that It is thus of interest that just as the apnoea rapid injection of propanidid results in a higher time response for young males differed from the blood concentration of propanidid and that the rest of the population tested so also did the drug is also more rapidly broken down in the incidence of muscle pains, even if it did not serum following rapid injection. A dose of 250 mg reach the customary levels of statistical signifi- of 2.5 per cent propanidid can be rapidly injected cance. This failure to reach customary levels was and it might be expected that the higher serum due in part to the rather small numbers of this levels so produced would be able to afford an equal degree of protection against muscle pains particular subset of the population studied. as does thiopentone when the induction agent is rapidly followed by the relaxant. Of the patients Fasciculations. No relationship was found between the in this series who experienced muscle pains, only severity or the incidence of fasciculations and the two were severe. The rest only experienced apnoea times. The incidence of muscle pains was moderate degrees of pain. It was not possible to
BRITISH JOURNAL OF ANAESTHESIA
640 correlate the evidence of muscle pains with the duration of apnoea nor the incidence or severity of fasciculations. There is no obvious reason why the young men should differ from the older patients in the response to suxamethonium and muscle pain, though Crawford (1969) has suggested that protein binding capacity is related to the level of sex hormones. If suxamethonium is transported in the body by plasma proteins, as may be expected in view of its ionization charges, this may be the explanation of the observed differences.
REFERENCES
Churchill-Davidson, H. C. (1954). Suxamethonium chloride and muscle pains. Brit. med. J., 1, 74. Clarke, R. S. J., Dundee, J. W., and Daw, R. H. (1964). Clinical studies of induction agents. XI: The influence of some intravenous anaesthetics on the respiratory effects and sequelae of suxamethonium. Brit. J. Anaesth., 36, 307. Hamilton, R. C (1967). Interaction between induction agents and muscle relaxantv Anaesthesia, 22, 235. Craig, H. J. L. (1964). The protective effect of thiopentone against muscle pain and stiffness which follows the use of suxamethonium chloride. Brit. J. Anaesth., 36, 612. Crawford, J. S. (1969). Drug binding by serum albumin. Brit. J. Anaesth,, 41, 543. Doenicke, A., Krumey, I., Kugler, J., and Klempa, J. (1968). Experimental studies of the breakdown of Epontol: determination of propanidid in human s:rum. Brit. J. Anaesth., 40, 415. Ellis, F. R. (1967). The neuromuscular effects of propanidid. Brit. J. Anaesth., 39, 515. (1968). The neuromuscular interaction of propanidid with suxamethonium and tubocurarine. Brit. J. Anaesth,, 40, 818. Foster, C. A. (1960). Muscle pains that follow administration of suxamethonium. Brit. med. J., 2, 24.
INTERACTION DU SUXAMETHONIUM AVEC PROPANIDID FT THIOPENTONE SOMMAIRE
Une itude a tti faite chez des adultes de 20-60 ans, comparant I'interaction de propanidid et thiopentone avec le myorelaxant suxamethonium. On a essayi d'e'tablir le rapport entre le temps d'apnee et l'incidence et la severite des douleurs musculaires. L'incidence ginirale des douleurs musculaires hit 19 pourcent. Les patients plus ages des deux sexes presenterent une apnee significativement plus courte avec propanidid qu'ayec thiopentone, lorsque les medicaments itaient administres en association au suxamethonium; il en fut de merne chez les femmes jeunes. Mais il n'y cut pas de difference entre propanidid et thiopentone dans leur interacti6n avec suxamethonium chez les jeunes sujets de sexe masculin, mais ceux-ci manifesterent plus de douleurs musculaires que tous les autres patients. DIE WECHSELWIRKUNG VON SUXAMETHONIUM MIT PROPANIDID UND THIOPENTON ZUSAMMENFASSUNG
An Erwachsenen im Alter von 20-^60 Jahren wurde eine Untersuchung durchgefuhrt, bei der die Wechselwirkung von Propanidid und Thiopenton mit dem Muskelrelaxans Suxamethonium verglichen wurde. Es wurde der Versuch gemacht, die Zeit der Apnoe mit dem Auftreten und der Schwere von Muikelschmerzen zu korrelieren. Eine Korrelation zwischen den Zeiten von Apnoe und dem Auftreten von Muskelschmerzen wurde nicht festgestellt. Insgesamt traten bei 19 Prozent der Untersuchten Muskelschmerzen auf. Bei den alteren Altersgruppen beider Geschlechter ergab sich mit Propanidid eine significant kurzere Zeit der Apnoe als mit Thiopenton, wenn die Wirkstoffe in Kombination mit Suxamethonium angewendet wurden; dasselbe wurde bei den jungen weibUchen Probandcn festgestcllL Bei den jungen mSnnlichen Probanden jedoch ergab sich kein Unterschied zwischen Propanidid und Thiopenton und ihrer Wechselwirkung mit Suxamethonium; aber bei den jungen Mannern war das Auftreten von Muskelschmerzen haufigcr als in alien anderen.
Downloaded from http://bja.oxfordjournals.org/ at University of Sydney on May 2, 2015
ACKNOWLEDGEMENTS
To Professor J. S. Robinson for his help and encouragement with this project, and to Dr P. J. Tomlin for the statistical analysis of the results. To Dr L. Bowcock, Department of Medical Illustration, for the preparation of the figures.
Howells, T. H., Odell, J. R., Hawkins, T. J., and Steane, P. A. (1964). An introduction to FBA.1420: a new non-barbiturate intravenous anaesthetic. Brit. J. Anaesth., 36, 295. Mapleson, W. W. (1954). The elimination of rebreathing in various semiclosed anaesthetic systems. Brit. J. Anaesth., 26, 323. Newnam, P. T. F., and Loudon, J. M. (1966). Muscle pains following administration of suxamethonium: the aetiological role of muscle fitness. Brit. J. Anaesth., 38, 533.
THE INTERACTION OF SUXAMETHONIUM WITH PROPANIDID AND THIOPENTONE BY
D. M. Ross SUMMARY
Several reports have indicated that propanidid prolongs the duration of apnoea following injection of suxamethonium (Howells et al., 1964; Clarke, Dundee and Daw, 1964; Clarke, Dundee and Hamilton, 1967; Doenicke et al., 1968). No reports have been seen concerning the effect of propanidid on muscle pain after suxamethonium. The incidence of muscle pain following the use of thiopentone and suxamethonium has varied widely according to published reports (ChurchillDavidson, 1954; Foster, 1960; Newnam and Loudon, 1966). A study was undertaken to compare the interaction of propanidid or thiopentone with suxamethonium and to determine whether the duration of apnoea was related to the incidence of musde pains or fasciculation. METHODS
A double-blind trial could not be undertaken because of the dissimilarity of the two induction agents. Patients were allocated to one of two groups, the allocation being made according to the last digit of their case number. Propanidid was given to the patients whose case-number final digit was even and thiopentone to those in which it was odd. The trial was designed on a latin square basis such that there were approximately even numbers of patients of either sex in each group, and to a lesser extent similar
numbers of patients over the age of 40 were evenly divided between the two groups (see table I). Propanidid and thiopentone were each used in 2.5 per cent solutions, as it was felt that a more uniform rate of injection could thus be achieved. Furthermore Clarke, Dundee and Hamilton (1967) stated that propanidid 2.5 per cent is equipotent with thiopentone 2.5 per cent. TABLE I
Age (yr) Under 40 Over 40 Total
Female
Male
Total
21 22
13 28
34 50
43
41
84
The dosage in all cases was 250 mg of either induction agent. This injection, given over a period of 6-10 seconds through a No. 1 needle, was immediately followed by suxamethonium 50 mg which had been stored in a refrigerator until its time of use. The duration of apnoea was noted following the injection of the suxamethonium. This was measured from the onset of apnoea to the onset of respiratory efforts (Clarke, Dundee and Daw, D. M. Ross, M3., B.S., F.F.A.RX.S., Department of Anaesthetics, North Staffordshire Hospital Centre. Present appointment: Consultant Anaesthetist, Coventry Group of Hospitals.
Downloaded from http://bja.oxfordjournals.org/ at University of Sydney on May 2, 2015
An investigation was carried out in adults aged 20-60 years comparing the interaction of propanidid or thiopentone with the muscle relaxant suxamethonium. An attempt was made to correlate the apnoea time with the incidence and severity of muscle pains. No correlation was found between the apnoea times and the incidence of muscle pains. The overall incidence of muscle pains was 19 per cent. The older age-groups of both sexes had a significantly shorter apnoea time with propanidid Than with thiopentone, when the drugs were used in combination with suxamethonium; this was also true of the young females. On the other hand, there was no difference in the young males between propanidid and thiopentone and their interaction with suxamethonium, but young men had a higher incidence of muscle pains than anybody else.
SUXAMETHONIUM WITH PROPANIDID AND TfflOPENTONE
RESULTS
Respiratory effects. Considering all patients the duration of apnoea produced by suxamethonium following induction with propanidid was, in general, briefer than that produced by suxamethonium
following induction with doiopentone (fig. la). The average apnoea time following propanidid and suxamethonium was less dian 2 minutes compared with an average time of 3 minutes following thiopentone and suxamethonium. This differnce is statistically significant (P<0.0025). Age and sex groups. The frequency response curve of the apnoea times of males and females, receiving die combination of propanidid and suxamethonium showed a different pattern from that of patients receiving thiopentone and suxamethonium (figs. lb, lc). In patients over 40 years who received propanidid and suxamethonium dierc was a significantly shorter period of apnoea dian diere was in diose who received diiopentone and suxamethonium (P<0.005) (figs. 3a, 3b 3c). This difference was also noted in females under 40 years (fig. 2c). The frequency curve of the duration of apnoea in young males (fig. 2b) was similar whedier they received propanidid or thiopentone, in marked contrast to the curves in all die other age or sex groups. The difference in the response of the young males from that of all other series is significant at die 10 per cent level (x a =4.5841; d i . 3). This is a comparison of die sum of die curves of figure 2b with the propanidid frequency response curve of figure la. Muscle pains. The overall incidence of muscle pains was 19 per cent. The incidence was 11 per cent in males and 8 per cent in females. The latin square design of diis study enables die effects of a number of possible contributing factors to be isolated: namely, die age of die patient; die sex of the patient; die induction drug; the duration of apnoea; or combinations of two or more of these factors. Age. There were 50 patients in the older age group of whom 7 had muscle pain, whereas 9 of the 34 younger patients had muscle pain. This difference is not statistically significant (/s=2.84;P>0.1). Sex groups. Seven of 43 females and 9 of 41 males experienced muscle pains. This difference is not statistically significant (y*=0.015; P>0.9).
Downloaded from http://bja.oxfordjournals.org/ at University of Sydney on May 2, 2015
1964). The timing of the apnoea was done with the aid of a stopwatch and performed doubleblind by an independent observer who did not know what drugs were being used, or indeed the purpose of the riming. During the period of apnoea the lungs were inflated with a nitrous oxide and oxygen mixture, care being taken not to overventilate. No supplementary anaesthetic agents were administered during the period of apnoea but as soon as respiratory efforts were noted halothane was added to the gas mixture, and the lungs ventilated with this combination until stable anaesdiesia was established. Throughout the operative procedure the patient spontaneously breathed this anaesdietic mixture through a Magill circuit (Type A; Mapleson, 1954). All anaesthetics were administered by the same person. The operations were all completed by 4.30 pjn. but patients were not allowed out of bed until the next morning. Each patient was interviewed during the latter part of die morning of the first postoperative day and was asked in general terms how he felt. A patient who did not complain of pain was then asked the direct question, "Have you any aches or pains apart from in the wound site?" If the response was in the affirmative then the severity of pain was assessed. In patients who spontaneously complained the pain was also assessed according to whether it was moderate or severe. Pain was classified as severe, moderate or absent. If the pain was such as to add materially to the patient's discomfort then it was classed as severe. All other aches or pains were classed as moderate. Eighty-four patients (43 females) aged between 20 and 60 were included in the series. The types of operation for which they were anaesthetized were such that the duration did not exceed 30 minutes, and were of such a nature as to allow the patient to be up and out of bed the next morning; for example, carotid angiography and inguinal hernia. The patients received no premedication.
637
BRITISH JOURNAL OF ANAESTHESIA
638 20
lb
la ALL CASES
Ic
ALLMALES
ALL FEMALES
< u
o
10
1
2
3 - 4
5
6
1
2
3
20
4
5
a
MINUTES
MINUTES -
2c FEMALES UNDER 40
2b MALES UNDER 40
10 O
3 4 MINUTES
5
6
3a MALES & FEMALES OVER 40
20
2
2
3 4 MINUTES
3c
3b MALES OVER 40
3 4 MINUTES FEMALES OVER 40
<
s
10
-
2 2
3 4 MINUTES
5
2
3 4 M I N U TES '
5
1
2
3 4 MINUTES
FIGS. 1, 2, 3
Duration of apnoea after the administration of suxamethonium 50 mg. The upper graphs show the response when thiopentone or propanidid was used as the induction drug. The middle and lower graphs show the apnoea frequency curves according to the patients' ages and sexes. It will be seen that the apnoea frequency curve after thiopentone or propanidid in the young males (2b) has a different pattern from all the others. Propanidid # - • Thiopentone X-
Effect of the induction drug. Forty-two patients received propanidid, of whom 9 experienced muscle pains, compared with 7 of 42 patients who received thiopentone. The difference is not statistically significant (x 1 = 0.30; P>0.5). Apnoea time. Of the 42 patients in whom apnoea lasted less than 2 minutes 6 experienced muscle pains, whereas of the 42 patients in whom apnoea lasted more than 2 minutes 10 ex-
perienced muscle pain. The difference is not significant ( x '=1.235; PXJ.2). If there was an association between the occurrence of muscle pain and duration of apnoea then the incidence of muscle pain would have increased among patients with longer periods of apnoea and this increase would have been greater as the apnoea time progressed. The durations of apnoea are, considering the subgroups, arranged in 1-minute periods of
Downloaded from http://bja.oxfordjournals.org/ at University of Sydney on May 2, 2015
2a MALES & FEMALES UNDER 40
< u
SUXAMETHONIUM WITH PROPANIDID AND THIOPENTONE 30
639
unrelated to the incidence or severity of the fasciculations, neither were the fasciculations influenced by the induction agent, the age or the sex of the patient.
: 20
DISCUSSION
Downloaded from http://bja.oxfordjournals.org/ at University of Sydney on May 2, 2015
The results show that a 250 mg dose of propanidid 2.5 per cent, when compared with an equipotent dose, namely 250 mg, of thiopentone 10 5 2.5 per cent, does not potentiate the respiratory eftects of suxamethonium 50 mg. Moreover, in z the patients over 40 years the length of apnoea following induction of anaesthesia with propanidid and suxamethonium was significantly 1 2 3 4 5 6 shorter than that following thiopentone and APXOEA TIME IN MINUTES suxamethonium 50 mg. These findings may in part be explained by the fact that in this study a FIG. 4 The frequency distribution of apnoea and postoperative 2.5 per cent solution of propanidid was used muscle pains after suxamethonium. throughout, for Ellis (1967), working with the Apnoea time (all cases) # # rat phrenic nerve-diaphragm preparation, has Incidence of pain related to time (all cases) X X stated that the myoneural block produced by propanidid and suxamethonium was in proporapnoea and the distribution of the apnoea times tion to the dose of propanidid. of each 1-minute period also showed no statisThe reports of the incidence of muscle pains tically abnormal distribution (^ a =2.998; dJ. 4; following the use of suxamethonium vary widely. P>0.2) (see fig. 4). This may well be in part related to the time No correlation was found between any interval between injection of the induction drug individual factor and the incidence of muscle and suxamethonium. Craig (1964) emphasized pains. However, when combinations of factors are this point and in his study of female patients the examined the frequency of muscle pains was incidence of muscle pains was only 14 per cent found to be twice as high in the young males (5 when suxamethonium was given immediately out of 13) as it was for the older males (4 out of after thiopentone. This compares with 16 per 28) and in fact was appreciably higher than for cent in the females in this series. It must be conthe rest of the population (11 out of 71). The cluded that if, as Craig suggests, thiopentone difference in response of young men compared offers considerable protection against muscle with all other patients was significant at the 10 pains, then so does propanidid. per cent level (x 2 =2.417; P<0.1). Doenicke and associates (1968) showed that It is thus of interest that just as the apnoea rapid injection of propanidid results in a higher time response for young males differed from the blood concentration of propanidid and that the rest of the population tested so also did the drug is also more rapidly broken down in the incidence of muscle pains, even if it did not serum following rapid injection. A dose of 250 mg reach the customary levels of statistical signifi- of 2.5 per cent propanidid can be rapidly injected cance. This failure to reach customary levels was and it might be expected that the higher serum due in part to the rather small numbers of this levels so produced would be able to afford an equal degree of protection against muscle pains particular subset of the population studied. as does thiopentone when the induction agent is rapidly followed by the relaxant. Of the patients Fasciculations. No relationship was found between the in this series who experienced muscle pains, only severity or the incidence of fasciculations and the two were severe. The rest only experienced apnoea times. The incidence of muscle pains was moderate degrees of pain. It was not possible to
BRITISH JOURNAL OF ANAESTHESIA
640 correlate the evidence of muscle pains with the duration of apnoea nor the incidence or severity of fasciculations. There is no obvious reason why the young men should differ from the older patients in the response to suxamethonium and muscle pain, though Crawford (1969) has suggested that protein binding capacity is related to the level of sex hormones. If suxamethonium is transported in the body by plasma proteins, as may be expected in view of its ionization charges, this may be the explanation of the observed differences.
REFERENCES
Churchill-Davidson, H. C. (1954). Suxamethonium chloride and muscle pains. Brit. med. J., 1, 74. Clarke, R. S. J., Dundee, J. W., and Daw, R. H. (1964). Clinical studies of induction agents. XI: The influence of some intravenous anaesthetics on the respiratory effects and sequelae of suxamethonium. Brit. J. Anaesth., 36, 307. Hamilton, R. C (1967). Interaction between induction agents and muscle relaxantv Anaesthesia, 22, 235. Craig, H. J. L. (1964). The protective effect of thiopentone against muscle pain and stiffness which follows the use of suxamethonium chloride. Brit. J. Anaesth., 36, 612. Crawford, J. S. (1969). Drug binding by serum albumin. Brit. J. Anaesth,, 41, 543. Doenicke, A., Krumey, I., Kugler, J., and Klempa, J. (1968). Experimental studies of the breakdown of Epontol: determination of propanidid in human s:rum. Brit. J. Anaesth., 40, 415. Ellis, F. R. (1967). The neuromuscular effects of propanidid. Brit. J. Anaesth., 39, 515. (1968). The neuromuscular interaction of propanidid with suxamethonium and tubocurarine. Brit. J. Anaesth,, 40, 818. Foster, C. A. (1960). Muscle pains that follow administration of suxamethonium. Brit. med. J., 2, 24.
INTERACTION DU SUXAMETHONIUM AVEC PROPANIDID FT THIOPENTONE SOMMAIRE
Une itude a tti faite chez des adultes de 20-60 ans, comparant I'interaction de propanidid et thiopentone avec le myorelaxant suxamethonium. On a essayi d'e'tablir le rapport entre le temps d'apnee et l'incidence et la severite des douleurs musculaires. L'incidence ginirale des douleurs musculaires hit 19 pourcent. Les patients plus ages des deux sexes presenterent une apnee significativement plus courte avec propanidid qu'ayec thiopentone, lorsque les medicaments itaient administres en association au suxamethonium; il en fut de merne chez les femmes jeunes. Mais il n'y cut pas de difference entre propanidid et thiopentone dans leur interacti6n avec suxamethonium chez les jeunes sujets de sexe masculin, mais ceux-ci manifesterent plus de douleurs musculaires que tous les autres patients. DIE WECHSELWIRKUNG VON SUXAMETHONIUM MIT PROPANIDID UND THIOPENTON ZUSAMMENFASSUNG
An Erwachsenen im Alter von 20-^60 Jahren wurde eine Untersuchung durchgefuhrt, bei der die Wechselwirkung von Propanidid und Thiopenton mit dem Muskelrelaxans Suxamethonium verglichen wurde. Es wurde der Versuch gemacht, die Zeit der Apnoe mit dem Auftreten und der Schwere von Muikelschmerzen zu korrelieren. Eine Korrelation zwischen den Zeiten von Apnoe und dem Auftreten von Muskelschmerzen wurde nicht festgestellt. Insgesamt traten bei 19 Prozent der Untersuchten Muskelschmerzen auf. Bei den alteren Altersgruppen beider Geschlechter ergab sich mit Propanidid eine significant kurzere Zeit der Apnoe als mit Thiopenton, wenn die Wirkstoffe in Kombination mit Suxamethonium angewendet wurden; dasselbe wurde bei den jungen weibUchen Probandcn festgestcllL Bei den jungen mSnnlichen Probanden jedoch ergab sich kein Unterschied zwischen Propanidid und Thiopenton und ihrer Wechselwirkung mit Suxamethonium; aber bei den jungen Mannern war das Auftreten von Muskelschmerzen haufigcr als in alien anderen.
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ACKNOWLEDGEMENTS
To Professor J. S. Robinson for his help and encouragement with this project, and to Dr P. J. Tomlin for the statistical analysis of the results. To Dr L. Bowcock, Department of Medical Illustration, for the preparation of the figures.
Howells, T. H., Odell, J. R., Hawkins, T. J., and Steane, P. A. (1964). An introduction to FBA.1420: a new non-barbiturate intravenous anaesthetic. Brit. J. Anaesth., 36, 295. Mapleson, W. W. (1954). The elimination of rebreathing in various semiclosed anaesthetic systems. Brit. J. Anaesth., 26, 323. Newnam, P. T. F., and Loudon, J. M. (1966). Muscle pains following administration of suxamethonium: the aetiological role of muscle fitness. Brit. J. Anaesth., 38, 533.