CARDIAC EFFECTS OF ATROPINE AND GALLAMINE IN PATIENTS RECEIVING SUXAMETHONIUM

Br.J. Anaesth. (1980), 52, 1137

CARDIAC EFFECTS OF ATROPINE AND GALLAMINE IN PATIENTS RECEIVING SUXAMETHONIUM J. VlBY-MOGENSEN, K . WlSBORG AND O . S0RENSEN

Severe arrhythmia and asystole are well-known complications of repeated doses of suxamethonium (Martin, 1958; Bullough, 1959; Lupprian and Churchill-Davidson, 1960; Mathias and Evans-Prosser, 1968). In previous studies, we have examined the protective effect of atropine and gallamine when given before halothane (VibyMogensen et al., 1976; Wisborg, Christensen and Viby-Mogensen, 1977). Only atropine in doses causing considerable tachycardia protected against bradycardia and gallamine did not give sufficient protection even in doses causing severe tachycardia and a high frequency of unpleasant side-effects. These results seem inconsistent with those reports in which atropine and small doses of non-depolarizing neuromuscular blockers have been found to protect against severe arrhythmia following repeated doses of suxamethonium (Verner and Comty, 1959; Lupprian and Churchill-Davidson, 1960; Mathias, EvansProsser and Churchill-Davidson, 1970; Karhunen, Heinonen and Tammisto, 1972; Stoelting, 1977). However, our studies were conducted in patients who did not receive a barbiturate, whereas the patients in the other studies did, and did not receive halothane. Williams and others (1961) and Shoenstadt and Whitcher (1963) found that thiopentone protected against severe

changes in cardiac rhythm following suxamethonium. We have studied the effect of a second dose of suxamethonium after preoperative administration of atropine, gallamine or an i.v. combination in patients in whom anaesthesia was induced with thiopentone and maintained with halothane. PATIENTS AND METHODS

Patients

Eighty healthy patients who underwent minor surgical procedures and gave consent to the study were allocated randomly to four groups. Premedication was given i.m. lh before induction of anaesthesia and the drugs under study were given i.v. 3 min before injection of thiopentone (table I). Anaesthesia (fig. 1)

Three minutes before induction atropine or gallamine or both was administered i.v. according to group. Anaesthesia was induced by slow injection of thiopentone 4—5 mg kg"' i.v. until the 3

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JORGEN Vmy-MoGENSEN, M.D., Department of Anaesthesia, Herlev Hospital, University of Copenhagen, DK 2730 Herlev, Denmark.

KAJ WISBORG, MJ>.; OLE SORENSEN, MJX;

Department of Anaesthesia, Gentofte Hospital, University of Copenhagen, Denmark. 0007-0912/80/111137-06 801.00

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FIG. 1. Time sequence of anaesthesia and administration of drugs. © Macmillan Publishers Ltd 1980

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Eighty healthy patients were randomly allocated to four groups. Atropine 0.01 mg kg ' i.v. (group I), gallamine 0.3 mg kg" ' i.v. (group II), atropine 0.01 mg kg" ' i.m. and gallaminc 0.3 mg kg" ' i.v. (group III), or atropine 0.01 mg kg" ' i.v. and gallamine 0.3 mg kg" ' i.v. (group IV) were given before operation. After induction of anaesthesia with thiopentonc, suxamethonium 1 mg kg" ' was given i.v. The lungs were ventilated with halothane in nitrous oxide in oxygen. Five minutes later the same dose of suxamethonium was repeated. E.c.g. was monitored continuously. No serious bradycardia was observed following a second injection of suxamethonium in any group. The results suggest that thiopentone protects against suxamethonium-induced bradycardia during halothane anaesthesia.

1138

BRITISH JOURNAL OF ANAESTHESIA TABLE I. Premedication, dose of atropine and gallamine, number of patients, sex and age distribution in each of the four groups

Group I

II III

I.v. 3 min before induction

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Mean age No. of patients

Male

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20

13

20

10

20

13

31.2 (18-57) 29.6 18-46). 30.6 (18-52)

Atropine 0.01 mgkg-' Gallamine 0.3 mgkg-'

20

13

32.8 (18-59)

80

49

31.0 (18-59)

I + II + III + IV

eyelash reflex was abolished. Ventilation of the lungs was assisted or controlled throughout the study with halothane 1 % in 50% nitrous oxide in oxygen using a non-rebreathing technique. One minute after the injection of thiopentone was completed and exactly 5 min after, suxamethonium 1 mg kg"' was given i.v. The trachea was not intubated nor surgery performed during the observation period. Measurements E.c.g. lead II was monitored continuously throughout the procedure. Heart rate was determined from the e.c.g. (Wisborg, Christensen and Viby-Mogensen, 1977). Blood samples were taken for measurement of serum potassium concentration, P&co, and PaOj before injection of atropine or gallamine, or both, and again 3 min after each injection of suxamethonium. Serum potassium was measured by the flame photometric method and blood-gases measured with a Radiometer ABL 1 acid-base machine. Arterial pressure was recorded every 5 min. In order to exclude changes in cardiac rate and rhythm caused by gross alterations in PaCO2, the results include only those patients in whom PS^-Q, was between 3.3 and 6.7 kPa (25 and 50 mm Hgj throughout the procedure. Statistical analyses were performed using the £2-test, Fisher exact probability test, KruskalWallis test and Wilcoxon matched-paired signedranks test. Significance was assigned at a level of 0.05.

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RESULTS AND DISCUSSION

Cardiac rate and rhythm Preinduction period. There were no significant differences between the control values of the groups (fig. 2). After injection of atropine or gallamine, or both, the heart rate increased significantly in all groups (P<0.01). One minute after injection the heart rate in group IV was significantly greater than in other groups. The maximum changes in heart rate during this period are shown infigure3. Increases in heart rate to more than 120 beat min"' were found in one patient in group II, in four patients in groups I and III, and in eight patients in group IV. However, these differences were not significant. Five patients in group I, and one patient in group IV had episodes of nodal rhythm after the injection of atropine or gallamine or both. Induction and first injection of suxamethonium. Only minor changes in heart rate were found after the first injection of suxamethonium. No serious arrhythmia was found. In group I, one patient had nodal rhythm continuing from the period before induction to 30 s after the injection of thiopentone. In group III, two patients developed nodal rhythm 27 and 43 s after the injection of suxamethonium which continued throughout the observation period. The remaining patients had regular sinus rhythm at all times. Second injection of suxamethonium. After the second injection of suxamethonium, mean heart rate decreased in all groups (fig. 2). The lowest

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ATROPINE, GALLAMINE AND SUXAMETHONIUM

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FIG. 3. Maximum changes in heart rate after injection of atropine or gallamine, or both. Each line represents the findings in one patient.— = Nodal rhythm or nodal extrasystoles.

rates occurred 30 s after injection in groups I and II, and 45 s after injection in groups III and IV. Compared with the values just before injection of the second dose of suxamethonium, the decrease in heart rate was significant only in group I Thirty seconds after the second injection of

suxamethonium, the heart rates in groups I and II were significantly less than the heart rates in groups III and IV. The maximum decreases in heart rate after the second injection of suxamethonium are shown in figure 4, with the number of patients who had episodes of nodal rhythm. No patient had serious

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BRITISH JOURNAL OF ANAESTHESIA Group I atropine 0 0 1 mg kg'1 121 " 140

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FIG. 4. Maximum decreases in heart rate after second injection of suxamethonium. Each line represents the findings in one patient.— = Nodal rhythm or nodal extrasystoles.

bradycardia (less than 20 beat min ') or ventricular arrhythmia.

In earlier similar investigations we found that atropine and gallamine, given during halothane anaesthesia in the same doses used in this investigation, did not provide sufficient protection against co,, P&O2 and serum potassium Only minor variations occurred, and no signifi- severe bradycardia following a second dose of cant differences were found between the groups. suxamethonium (Viby-Mogensen et al., 1976; Wisborg, Christensen and Viby-Mogensen, 1977). Figures 5, 6, and 7 illustrate the changes in Arterial pressure The changes in arterial pressure were small, and heart rate seen after a second dose of suxamethono systolic arterial pressure of less than 12 kPa nium in patients from a previous study who received halothane and nitrous oxide only, com(90 mm Hg) was found. pared with changes seen in patients from this None of the methods used provided absolute investigation in whom thiopentone 4—5 mg kg"' protection against a decrease in heart rate after the preceded the administration of halothane. The second injection of suxamethonium (fig. 4). mean heart rate, before the injection of atropine or However, the decrease in heart rate was significant gallamine, or both, was not significantly different only in group I (atropine 0.01 mg kg" 1 i.v.) and no in the four groups. After induction (fig. 5), the patient developed severe bradycardia. Since all mean heart rate was significantly faster in patients four methods investigated were able to protect who received thiopentone. Forty-five seconds against extreme bradycardia, we must consider if after the second injection of suxamethonium, one method is superior. Both with and without corresponding to the slowest heart rate infigure5, premedication with atropine i.m., gallamine the rate was still significantly faster in the patients 0.3mgkg~' i.v. 3 min before the injection of who received thiopentone. The decrease in heart thiopentone provided greater protection. Atropine rate after a second dose of suxamethonium in 0.01 mg kg"' i.v. alone (group I) did not give the patients receiving thiopentone was either not sigsame degree of protection (figs 2 and 4) and nificant (gallamine group) or was significantly less administration of both atropine and gallamine i.v. (atropine group) than the decrease seen in patients (group IV) caused unnecessary tachycardia which who did not receive thiopentone. None of the could be dangerous in certain patients (Viby- patients who received thiopentone developed severe bradycardia (heart rate less than 20 Mogensen et al., 1976).

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FIG. 5. Significance of thiopentone induction on bradycardia following a repeated dose of suxamethonium during halothane anaesthesia in patients given atropine 0.01 mg kg" ' i.v. or gallamine 0.3 mg kg" ' i.v. before operation. (No. of patients = 80; 20 in each group.) Mean values ± SEM are shown. SI and SII = suxamethonium 1 mg kg~ ' i.v. (first and second injecoon).

beat min '), whereas four and five patients in the two other groups (figs 6, 7) did so. There are two possible explanations for the fact that atropine and gallamine in the doses investigated provided sufficient protection against severe bradycardia after a second dose of suxmethonium in patients induced with thiopentone

but not in patients induced with halothane and nitrous oxide. The most obvious is that the difference is attributable to the vagolytic properties of thiopentone (Andersen and Eikard, 1978). However, patients in whom anaesthesia was induced with halothane and nitrous oxide were Inhalation induction I v induction 121-1401 [-121 "140-1

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FIG. 6. Maximum decrease in heart rate after second injection of suxamethonium in two groups of patients (20 each) given atropine 0.01 mgkg" 1 i.v. and anaesthetized with halothane and nitrous oxide. One group of patients received an inhalation induction, the other received thiopentone 4-5 mg kg" ' i.v. for induction. Each line represents one patient.— = Nodal rhythm or nodal extrasystoles.

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FIG.7. Maximum decrease in heart rate after second injection of suxamethonium in two groups of patients (20 each) pretreatcd with gallamine 0.3 mg kg" ' i.v. and anaesthetized with halothane and nitrous oxide. One group of patients received an inhalation induction, the other received thiopentone 4-5mgkg"' i.v. for induction. Each line represents one patient.— = Nodal rhythm or nodal extrasystoles; = ventricular extrasystoles.

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BRITISH JOURNAL OF ANAESTHESIA

1142 exposed to halothane for a longer period (10-15 min) at the time of injection of the second dose of suxamethonium than patients induced with thiopentone (5-10 min). Therefore, a more pronounced influence of halothane on the heart cannot be excluded in that group. ACKNOWLEDGEMENTS

REFERENCES

On a reparti quatre-vingts malades sains en quatre groupes au hasard. Avant l'opcration, on leur a administre 0,01 mg kg" ' d'atropine i.v. (groupe I), 0 3 mg kg"' de gallamine i.v. (groupe II), 0,01 mg kg"' d'atropine i.m. ct 0,3 mg kg"' de gallamine i.v. (group III), ou 0,01 mg kg"' d'atropine i.v. et 0 3 mg kg" ' dc gallamine i.v. (group IV). Apres les avoir anesthesies avec de la thiopentone, on leur administra 1 mg kg "' de suxamethonium i.v. On leur ventila les poumons avec de l'halothane en protoxyde d'azote dans de l'oxygene. On repeta la meme dose de suxamethonium cinq minutes plus tard. Un controle du e.c.g. se poursuivit sans arm. On n'observa aucune arrythmie grave a la suite de la seconde injection dc suxamethonium dans les groupes I and II. On peut deduire des resultats que la thiopentone protege contre la bradycardie induite par le suxamethonium au cours de l'ancsthcsie par halothane.

Andersen, J. R., and Eikard, B. (1978). Arrhythmias during halothane anaesthesia. Ill: The influence of barbiturates. Ada Anaesthesiol. Scand., 22, 430. Bullough, J. (1959). Intermittent suxamethonium injections. EINWIRKUNGEN VON ATROPIN UND GALLAMIN Br. Med. J., 1, 786. AUF DAS HERZ VON PATIENTEN, DIE Karhunen, U., Heinonen, J., and Tammisto, T. (1972). The SUXAMETHONIUM BEKOMMEN effect of tubocuranne and alcuroruum on suxamethoniuminduced changes in cardiac rate and rhythm. Ada ZUSAMMENFASSUNG Anaesthesiol. Scand., 16, 3. Achtzig gesunde Patienten wurden willkurlich in vier Gruppen Lupprian, K. G., and Churchill-Davidson, H. C. (1960). Effect aufgctcilt. Atropin 0.01 mg kg" 1 intravenos (Gruppe I), of suxamethonium on cardiac rhythm. Br. Med. J., 2, 1774. Gallamin 0.3 mg kg"' intravenos (Gruppe II), Atropin Martin, K. H. (1958). Die Wirkung des Succinylcholins auf den Hcrzrhythmus. Atti XI Congresso Societa Italiana di 0.01 mg kg" ' intramuskular und Gallamin 0.3 mg kg" ' intravenos (Gruppe III), order Atropin 0.01 mgkg"' intravenos Anesthesiologia, Venezia, September 1958, p. 362. und Gallamin 0.3 mg kg" ' intravenos (Gruppe IV) wurden Mathias, J. A., and Evans-Prosser, C. D. G. (1968). An vor der Operation verabreicht. Nach Einleitung der Narkose investigation into the site of action of suxamethonium on cardiac rhythm; in Progress in Anacstheriology. Proceedings ofdurch Thiopenton wurdc 1 mg kg"' Suxamethonium intrathe Fourth World Congress of Anaesthesiologists (eds. T. B. venos verabreicht. Die Lungen wurden mit Halothan in Stickstoffoxydul und Sauerstoff beluftet. Funf Minuten spater Boulton, R. Bryce-Smith, M. K. Sykes, G. B. Gillctt and A. wurde dicselbe Dosis Suxamethonium wieder verabreicht. Das L. Revcll), p. 1153. Amsterdam, London, New York: EKG wurde standig uberwacht. Nach einer zweiten Injektion Elsevier Publishing Co. von Suxamethonium bei den Gruppen I und II wurde keine Churchill-Davidson, H. C. (1970). The role of the crnste Arrhythmic beobachtet. Die Ergebnisse deuten an, dass non-depolanzing drugs in the prevention of suxamethonium Thiopenton bei der Halothan-Narkose einen Schutz gegen bradycardia. Br. J. Anaesth., 42, 609. Suxamethonium-induzierte Bradykardie bietet. Schoenstadt D. A., and Whitcher, C. E. (1963). Observations on the mechanism of succinyldicholine-induced cardiac EFECTOS CARDIACOS DE LA ATROPINA Y DE LA arrhythmias. Anesthestology, 24, 358. GALAMINA EN PACIENTES BAJO Stocking, R. K. (1977). Comparison of gallamine and atropine ADMINISTRACION DE SUXAMETONIO as pretreatment before anesthetic induction and succinylcholine administration. Ancsth. Anaig. (Cleve.), 56, 493. SUMARIO Verner, I., and Comty, C. (1959). Intermittent suxamethonium Se distribuyo al azar a ochenta pacientes sanos en cuatro injections. Br. Med. J., 1, 1239. grupos. Antes dc la operacion, sc administro 0,01 mg kg" ' de Viby-Mogensen, J.,Wisborg, K., Gabrielsen, J., and Spotoft, atropina i.v. (grupo I), 0 3 mgkg" 1 dc galamina i.v. (grupo H. (1976). Halothane anaesthesia and suxamethonium. I: II), 0,01 mg kg" ' de atropina i.m. y 0,3 mg kg" ' de galamina The significance of preoperative atropine administration. A i.v.(grupo III), 6 0,01 mg kg" ' de atropina i.v. y 0 3 mg kg" ' double-blind study. Ada Anaesthestol. Scand., 20, 129. dc galamina i.v. (grupo IV). Despucs de la induccion de la Williams, C. H., Deutsch, S., Unde, H. W., Bullough, J. W., anestesia mediante tiopentona, se administro 1 mgkg"' dc and Dripps, R. D. (1961). Effects of intravenously adsuxametonio i.v. Se ventilaron los pulmones con halotano en ministered succinyldicholine on cardiac rate, rhythm, and arterial blood pressure in anesthetized man. Anesthesiology, oxido nitroso en oxigeno. Se repino la misma dosis de suxametonio cinco minutos despucs. Se vigilo continuamente 22, 947. el e.c.g. No se observo arritmia grave despues de la segunda Wisborg, K., Christcnsen, V., and Viby-Mogensen, J. (1977). inyeccion de suxametonio en los grupos I y II. Los resultados Halothane anaesthesia and suxamethonium. II: The signifisugieren que la tiopentona protege contra la bradicardia cance of .preoperative gallamine administration. Ada inducida por el suxametonio durante la anestesia por halotano. Anaesthesiol. Scand., 21, 266.

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We would like to thank our colleagues in the ENT department (Heads: Professor N. Risktcr, M.D., G. Salomon, M.D., and Mirko Tos, M.D.), the surgical department D (Heads: Tyge Cl. Gertz, MJ). and L. Kuld Hansen, M.D.), and the nurses in the anaesthetic department and the operating theatres.

EFFETS CARDIAQUES DE L'ATROPINE ET DE LA GALLAMINE CHEZ DES MALADES AUXQUELS ON ADMINISTRE DU SUXAMETHONIUM