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ANAESTHESIA FOR CARDIOVERSION: A comparison of diazepam, thiopentone and propanidid
Br.J. Anaesth. (1976), 48, 257
ANAESTHESIA FOR CARDIOVERSION: A comparison of diazepam, thiopentone and propanidid R. ORKO SUMMARY
Following the introduction of direct current countershock for the restoration of sinus rhythm, thiopentone seems to have been the most popular anaesthetic agent for this procedure (Lown, Amarasingham and Newman, 1962; Lown et al., 1963). However, since Muenster and colleagues (1967) reported a greater frequency of ventricular extrasystoles in patients anaesthetized with thiopentone than in those given diazepam, the latter has become a popular anaesthetic agent for cardioversion (Winters et al., 1968; Somers et al., 1971; Vinge, Wyant and Lopez, 1971). Johnstone and Barron (1968) found that propanidid has a quinidine-like anti-arrhythmic effect and considered it to be superior to thiopentone for the induction of anaesthesia. Propanidid has a useful brevity of action (Clarke, 1969). However, it has not been compared with other anaesthetics for cardioversion. The course of anaesthesia, the success rate of conversion of arrhythmia and the occurrence of ventricular arrhythmias in patients anaesthetized with diazepam, thiopentone or propanidid for the application of d.c. countershock have been compared. PATIENTS AND METHODS
One hundred and fifty unselected patients undergoing elective cardioversion were divided randomly into three groups. Group I was anaesthetized with diazepam, group II with thiopentone and group III with propanidid. The groups were comparable (tables I and II). Digoxin treatment was discontinued 2 days before the d.c. shock. In patients who were receiving quinidine, the dose was adjusted so that the serum RIITTA ORKOJ M.D.J Department of Anaesthesia, University
Central Hospital, Helsinki, Finland.
concentration was within the range 1-3 mg/litre (Hartel et al., 1970). The patients fasted overnight and arrived at the cardiovascular laboratory without premedication. Atropine 0.01 mg/kg was given i.v. 2 min before anaesthesia. Diazepam (Valium) was given over a period of about 1 min until the patient's speech became sluggish and ptosis was obvious. Thiopentone (Hypnostan) and propanidid (Epontol), both in 2.5% solutions, were also injected over about 1 min. When the patient did not respond to questions, the level of anaesthesia was considered adequate for the application of d.c. shock. All patients were given 100% oxygen through a "non-rebreathing valve and facepiece from 1 min before the induction of anaesthesia to the time of countershock. Controlled ventilation was instituted if the duration of apnoea exceeded 30 sec. The author administered all the anaesthetics. In group I the patients were drowsy only. In groups II and III, the duration of anaesthesia was timed from the start of the anaesthetic injection to the moment at which the patient responded to a command. About 2-3 min after the anaesthetic injection began,the d.c. shock or shocks were given with theaid of a d.c. defibrillator (Electrodyne C-100 M or Olli defibrillator). One electrode was placed between the scapular angle and the spine, the odier over the left sternal border. The energy discharge initially was 100 Wsec and it was increased successively, when necessary, to 200 and 300 Wsec. A maximum of three countershocks was given on each occasion. Arterial systolic pressure was determined by indirect sphygmomanometry. The e.c.g. was recorded for a 2-min period during the 4 h r before the patient's arrival at the laboratory, during the 2 min
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Three groups of 50 patients were anaesthetized with diazepam 0.32 mg/kg or thiopentone 3.7 mg/kg or propanidid 4.6 mg/kg for elective cardioversion. Propanidid caused more hypotension than diazepam or thiopentone. Apnoea was most frequent following thiopentone and excitatory sideeffects were most prominent following propanidid; the electric countershock worsened the excitatory phenomena. The success rate of conversion was higher in the diazepam group than in the other groups, but the difference was not statistically significant. Diazepam failed to produce amnesia in about 33% of the patients. Thiopentone is suitable and pleasant for cardioversion. Diazepam is recommended in poor-risk patients and in emergency situations.
BRITISH JOURNAL OF ANAESTHESIA
258
TABLE I. Age, sex and weight, haemoglobin and serum potassium concentrations of the patients studied. Arterial systolic pressure and heart rate before premedication are shown also. Mean values with range or SD. Fifty patients in each group
Group
Age (yr)
Sex (M/F)
Diazepam Thiopentone Propanidid
55 ±9.3 55 ±12.0 54+11.1
32/18 32/18 28/22
Weight (kg)
Haemoglobin (g/100 ml)
Serum potassium (m-equiv/litre)
Systolic pressure (mm Hg)
Heart rate (beats/min)
4.4 (3.8-5.1) 4.4 (3.7-5.2) 4.5 (3.8-5.2)
134±19.1 140 ±22.0 138 ±23.9
88 + 23.8 82 ±18.5 82 ±15.2
75 ±12.9 14.0(10.7-20.1) 77 ±13.6 14.5 (9.7-17.3) 73 ±14.1 14.4 (10.9-17.7)
TABLE II. Diagnosis, typeof arrhythmia and drug treatment. Fifty patientsin each group
Group Diazepam Thiopentone Propanidid
Other RHD RHD or (O) (U) IHD HHD unknown 13 11 18
0 2 4
9 11 4
4 3 1
Arrhythmia
Drug treatment
Atrial Atrial fibrillation nutter
Other antiarrhythmia AntiDigoxin Quinidine drug coagulant
24 23 23
47 49 50
3 1 0
23 17 26
50 48 48
14 7 7
40 47 44
RHD = rheumatic heart disease; IHD = ischaemic heart disease: HHD = hypertonic heart disease; O = operated; U = unoperated.
before the induction of anaesthesia and from the start of the anaesthetic injection until 3min after the d.c. shock. The heart rate was calculated and possible ventricular arrhythmias were noted from the e.c.g. records. The analysis of arrhythmias was performed without any knowledge of the group to which the patient belonged. Problems during anaesthesia and the immediate recovery period were noted. The patients were observed at the laboratory for 30 min after the procedure. On the next day most of the patients were visited by the anaesthetist and a note was made as to whether or not the sinus rhythm had been maintained. The patients were asked if they recalled the procedure. Student's t test or the Chi-square test was used for analysis of the results, unless indicated otherwise. The criterion for statistical significance was taken as P<0.05.
Electrocardiographic findings Conversion of the arrhythmia was achieved in 42 patients (84%) in the diazepam group, 36 (72%) in the thiopentone group and 35 (70%) in the propanidid group (table III). The differences are not statistically significant. Twenty-four hours after the countershock, sinus rhythm was present in 40 of the 42 patients in group I, in 35 of the 36 in group II and in all 35 patients in group III. The final success rates were 80%, 70% and 70%. An average of 1.9 countershocks per patient was required to achieve conversion in groups I and III, whereas group II required an average of 2.1 countershocks. The difference between these values is not statistically significant. TABLE I I I . Conversion of arrhythmia with the aid of d.c. countershock. Fifty patients in each group
Successful conversion
RESULTS
The mean dose of diazepam required to achieve drowsiness was 0.32 ( + SD 0.09) mg/kg. The dose of thiopentone was 3.7 ±1.1 mg/kg and of propanidid 4.6+ 1.4 mg/kg. The duration of anaesthesia in the thiopentone group was 4.7 + 2.0 min and in the propanidid group 4.9+ 1.8 min, the difference being not statistically significant.
Energy level required (Wsec) Group Diazepam Thiopentone Propanidid
100 200 300 18 12 10
10 8 17
14 16 8
Total
Unsuccessful conversion
42 36 35
8 14 15
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Diagnosis
DIAZEPAM, THIOPENTONE, PROPANIDID FOR CARDIOVERSION
259
TABLE IV. Occurrence of ventricular extrasystoles (VES) before and during the procedure Number of VES/min Diazepam
Propanidid
0
\-±
5 or more
0
1-4
5 or more
0
1-4
5 or more
32
16
2
36
11
3
33
15
2
31
16
3
33
14
3
38
9
3
31
16
3
32
15
3
37
11
2
32
15
3
30
16
4
37
13
0
Table IV shows data on the prevalence of ventricular extrasystoles. The statistical analysis of these data was based on the increases and decreases in the number of patients showing ventricular extrasystoles. Within the groups, there were no statistically significant changes in the prevalence of ventricular extrasystoles. The comparison between the groups did not reveal any statistically significant differences either (hypergeometrical distribution). Ventricular tachycardia, fibrillation or standstill did not occur in any patient.
Arterial pressure and heart rate The values of systolic pressure and heart rate, measured 2 min after the administration of atropine (table V) compared with values obtained before premedication (table I) show no change in arterial pressure and a marked increase in heart rate. The percentage changes in arterial pressure and heart rate at various stages (table VI) and the reference values representing 100% (table V) show a remarkable stability of systolic pressure in the diazepam group. Two minutes after the start of anaesthesia, the decrease in arterial pressure in the propanidid group was significantly different from that in the diazepam
TABLE V. Arterial pressure and heart rate before the injection of anaesthetic {2 min after the injection of atropine 0.01 mg/kg). Mean values + SEM
Systolic pressure (mmHg) Heart rate (beats/min)
Diazepam
Thiopentone
Propanidid
134 + 3.9
146 ±3.3
139 ±2.1
114 ±3.5
113 ±2.9
116 ±4.2
group (P< 0.001). The difference between the thiopentone and the diazepam groups was significant (P<0.05), whereas the difference between the propanidid and the thiopentone groups was not. Immediately after countershock, there were significant differences between the groups in the changes in arterial pressure (diazepam v. propanidid, P< 0.001; diazepam v. thiopentone, P<0.05; thiopentone v. propanidid, P<0.01). Three minutes after the shock, arterial pressure had returned to near the initial value in all groups and there were no statistically significant differences between the groups. In most of the patients in the diazepam and the thiopentone groups, the decreases in arterial pressure were less than 20%. Decreases of 20-30% were found
TABLE VI. Changes in arterial pressure and heart rate during the procedure. The values are per cent (mean + SEAT). 100 per cent is the value following atropine but before the administration of the anaesthetic
Heart rate (beats/min)
Systolic pressure (mm Hg) Thiopentone
Propanidid
Diazepam
Thiopentone
Propanidid
97 ±1.7
89±1.2|
85±1.8f
108±2.1f
107±2.3J
lll±3.1f
101 ±1.5 99 ±1.8
96 + 1.5* 98 ±1.5
91 + 1.It 98±1.4
89 +4.01 86±3.3f
88 + 3.4t 85±1.9t
93 ±3.8 89±2.5f
Diazepam 2 min after start of anaesthesia After shock 3 min after shock
I P<0.001; JP<0.01; *P<0.05.
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Before premedication After premedication During anaesthesia. before shock After shock
Thiopentone
260 in none of the patients in the diazepam group, in four in the thiopentone group, and in 11 in the propanidid group. Decreases of more than 30% were seen in two patients in the thiopentone group and in seven in the propanidid group. However, in this respect, the differences between the groups were not statistically significant (hypergeometrical distribution). The changes in heart rate throughout the procedure followed a similar pattern in all groups (table VI). No statistically significant differences were found between the groups.
BRITISH JOURNAL OF ANAESTHESIA DISCUSSION
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The mean doses of diazepam and thiopentone were similar to the amounts given by Fox, Wynands and Bhambhami (1968) in their comparison of these drugs as induction agents. Nutter and Massumi (1965) and Muenster and colleagues (1967) have used diazepam in doses of 5-20 mg and 15-20 mg, respectively, for cardioversion. These doses are smaller than in the present study: thiopentone 3.7 mg/kg; propanidid 4.6 mg/kg: a potency ratio of 1.2 : 1. This ratio is similar to that found by Wynands and Fox (1966). The potency ratio for thiopentone and propanidid is 1.1 : 1 (Clarke et al., 1968). Side-effects The incidences of ventricular extrasystoles in the The frequency of side-effects is shown in table VII. present series differ from those reported by Muenster The incidence of apnoea exceeding 30 sec was and others (1967), who found that ventricular significantly less in the diazepam group than in the extrasystoles appeared in 11 of 18 patients anaesthepropanidid group (P<0.01) or in the thiopentone tized with thiopentone, but in none of 19 patients group (P< 0.001). The difference between the anaesthetized with diazepam. When results from the thiopentone and the propanidid groups was not patients in the present study who showed no extrasignificant. systoles before the procedure were analysed, there were no significant differences between the groups in the appearances of ventricular extrasystoles during the TABLE VII. Occurrence of side-effects during anaesthesia. procedure. The patients in the present study received Fifty patients in each group oxygen and atropine (Orko, 1974), whereas Muenster's Laryngeal patients did not. Apnoea Excitation irritation Johnstone and Barron (1968) reported that propanidid has an anti-arrhythmic effect. This was seen in Diazepam 2 0 0 the present study, although there was no statistically Thiopentone 25 4 1 Propanidid 15 19 1 significant difference between the propanidid and the other two groups. The success rate of conversion was not very high in Excitatory side-effects, such as muscular tension this series. There were no statistically significant or involuntary movements, or both, were observed differences between the groups. It is probable that the most commonly in the propanidid group. The choice of anaesthetic agent has no significant influence difference, as compared with either the thiopentone upon the success rate of conversion of arrhythmia or the diazepam group, was statistically significant (Muenster et al., 1967; Heinonen, Orko and Louhija, (P<0.001), whereas the difference between the 1973). thiopentone and the diazepam groups was not The arterial pressure in the diazepam group was significant. The electric countershock seemed to almost unchanged, which is in accordance with worsen the excitatory side-effects. previous observations (Nutter and Massumi, 1965; Signs of laryngeal irritation were observed in one McClish, 1966; Brown and Dundee, 1968; Winters patient in the thiopentone group and in one in the et al., 1968; Knapp and Dubow, 1970; Wyant and propanidid group. No other side-effects, such as Studney, 1970; Somers et al., 1971). In this respect hiccup, retching, vomiting or sweating were observed diazepam may be considered a safe agent for patients during anaesthesia or the immediate recovery period. with cardiac disease. However, relatively small In the diazepam group 15 patients, out of 41 doses have been used in all the studies, including the interviewed, recalled the electric countershock, present study, and it is evident that diazepam in compared with one out of 40 in the thiopentone group larger doses may have some depressant effect on the and three out of 38 in the propanidid group (diazepam circulatory function (Rao et al., 1973). v. thiopentone, P< 0.001; diazepam v. propanidid, The decreases in arterial pressure in the thiopentone P<0.01 (hypergeometrical distribution)). and the propanidid groups are comparable with the
DIAZEPAM, THIOPENTONE, PROPANIDID FOR CARDIOVERSION
ACKNOWLEDGEMENT
I wish to thank Laakeruonti Oy of F. Hoffmann-La Roche & Co. A.G. for supplies of Valium. REFERENCES
Brown, S. S., and Dundee, J. W. (1968). Clinical studies of induction agents. XXV: Diazepam. Br. J. Anaesth., 40, 108.
Clarke, R. S. J. (1969). The eugenols—propanidid; in Newer Intravenous Anesthetics, 1st edn, p. 43. Boston: Little, Brown and Co. Dundee, J. W., Barron, D. W., and McArdle, L. (1968). Clinical studies of induction agents. XXIV: The relative potencies of thiopentone, methohexitone and propanidid. Br. J. Anaesth., 40, 593. Dalen, J. E., Evans, G. L., Banas, J. S., Brooks, H. L., Paraskos, J. A., and Dexter, L. (1969). The hemodynamic and respiratory effects of diazepam (Valium). Anesthesiology, 30, 259. Dundee, J. W., and Clarke, R. S. J. (1964). Clinical studies of induction agents. IX: A comparative study of a new eugenol derivative FBA. 1420 with G. 29, 505 and standard barbiturates. Br.J. Anaesth., 36, 100. Wyant, G. M. (1974). Intravenous Anaesthesia, 1st edn, p. 262. Edinburgh and London: Churchill Livingstone. Fox, G. S., Wynands, J. E., and Bhambhami, M. (1968). A clinical comparison of diazepam and thiopentone as induction agents to general anaesthesia. Can. Anaesth. Soc.J., 15,281. Glassman, E. (1971). Direct current cardioversion. Am. Heart J., 82, 128. Hartel, G., Louhija, A., Konttinen, A., and Halonen, P. I. (1970). Value of quinidine in maintenance of sinus rhythm after electric conversion of atrial fibrillation. Br. Heart J., 32, 57. Heinonen, J., Orko, R., and Louhija, A. (1973). Anaesthesia for cardioversion: a comparison of Althesin and thiopentone. Br. J. Anaesth., 45, 49. Johnstone, M., and Barron, P. T. (1968). The cardiovascular effects of propanidid. Anaesthesia, 23, 180. Knapp, R. B., and Dubow, H. (1970). Comparison of diazepam with thiopental as an induction agent in cardiopulmonary disease. Anesth. Analg. (Cleve.), 49, 722. Lown, B., Amarasingham, R., and Newman, J. (1962). New method for terminating cardiac arrhythmias. J.A.M.A., 182, 548. Perlroth, M. G., Kaidney, S., Abe, T., and Harken, D. E. (1963). "Cardioversion" of atrial fibrillation. N. Engl. J. Med., 269, 325. McClish, A., (1966). Diazepam as an intravenous induction agent for general anaesthesia. Can. Anaesth. Soc. J., 13, 562. Muenster, J. J., Rosenberg, M. S., Carleton, R. A., and Graettinger, J. S. (1967). Comparison between diazepam and sodium thiopental during d.c. countershock. J.A.M.A., 199, 758. Nutter, D. O., and Massumi, R. A. (1965). Diazepam in cardioversion. N. Engl. J. Med., 273, 650. Orko, R. (1974). Anaesthesia for cardioversion: thiopentone with and without atropine premedication. Br.J. Anaesth., 46, 947. Rao, S., Sherbaniuk, R. W., Prasad, K., Lee, S. J. K., and Sproule, B. J. (1973). Cardiopulmonary effects of diazepam. Clin. Pharmacol. Ther., 14, 182. Somers, K., Gunstone, R. F., Patel, A. K., and D'Arbela, P. G. (1971). Intravenous diazepam for direct-current cardioversion. Br. Med. J., 4, 13.
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findings of Wynands and Fox (1966), but not with those of Dundee and Clarke (1964), who used smaller doses of propanidid. The periods of hypotension after propanidid in the present study were brief and unlikely to be dangerous. No signs of hypersensitivity were observed in any of the patients. The different frequency of apnoea in the thiopentone and the propanidid groups might be because only apnoea exceeding 30 sec was considered. There were shorter periods of apnoea immediately after the hyperventilation in some of the patients in the propanidid group. There was significantly less apnoea in the diazepam group than in the other two groups and the same observation has been made by Fox, Wynands and Bhambhami (1968). However, diazepam may depress breathing occasionally (Dalen et al., 1969; Rao et al., 1973) and it should be given by anaesthetists preferably (Dundee and Wyant, 1974), although some authors (Glassman, 1971; Somers et al., 1971) are of the opinion that an anaesthetist is not necessary when diazepam is used for cardioversion. Amnesia produced by diazepam has been reported frequently (McClish, 1966; Brown and Dundee, 1968). In the present study 37% of the patients anaesthetized with diazepam recalled the electric countershock. This is unacceptable in elective cardioversion. The lack of sufficient amnesia did not seem to be related to the given dose per kg. No patient in the series of Muenster and others (1967) recalled the event although the exact dose per kg was not stated. The interval between the injection of diazepam and the electric countershock was the same in both studies. In the present study the individual variations in the effect of diazepam were great, and it was difficult to find the optimal dosage for every patient. Diazepam may be considered the drug of choice for cardioversion in poor-risk patients and in emergency situations, because it does not seem to depress the circulation. However, patients anaesthetized with diazepam may recall the unpleasant procedure. For patients in better physical condition thiopentone would seem to be preferable. Hypotension and excitatory side-effects produced by propanidid make it less suitable.
261
BRITISH JOURNAL OF ANAESTHESIA
262 Vinge, L. N., Wyant, G. M., and Lopez, J. F. (1971). Diazepam in cardioversion. Can. Anaesth. Soc. J., 18, 166. Winters, W. L., McDonough, M., Hafer, J., and Dietz, R. (1968). Diazepam, a useful hypnotic drug for directcurrent cardioversion. J.A.M.A., 204, 926. Wyant, G. M., and Studney, L. J. (1970). A study of diazepam (Valium) for induction of anaesthesia. Can. Anaesth. Soc.J., 17, 166. Wynands, J. E., and Fox, G. S. (1966). A clinical comparison of propanidid and thiopentone as induction agents to general anaesthesia. Can. Anaesth. Soc.J., 13, 505.
RESUME
On a anesthesie pour choc electrique externe a froid, trois groupes de 50 patients a l'aide de diazepam (0,32 mg/kg), de thiopentone (3,7 mg/kg) ou de propanidide (4,6 mg/kg). La propanidide a provoque une hypotension plus grande que le diazepam ou le thiopentone. L'apnee a ete plus frequente apres l'administration de thiopentone et les effets secondaires excitatoires ont ete plus prononces apres la propanidide; le contrechoc electrique a aggrave le phenomene excitatoire. Le taux de reussite de la conversion a ete plus eleve dans le groupe traite au diazepam que dans les autres groupes, mais la difference n'a pas ete d'une importance statistique consequente. Dans 33% des cas, le diazepam n'a produit aucune amnesic Le thiopentone convient bien et est plaisant dans les cas de chocs electriques externes. Le diazepam est recommande pour les patients presentant peu de risques et pour les cas d'urgence. NARKOSE BEI HERZWENDUNGSCHIRURGIE: VERGLEICHSERWERTUNGEN VON DIAZEPAM, THIOPENTON UND PROPANIDID ZUSAMMENFASSUNG
Drei 50-Patientengruppen wurden zwecks Herzwendungschirurgie mit Diazepam (0,32 mg/kg), Thiopenton (3,7 mg/ kg) und Propanidid (4,6 mg/kg) narkotisiert. Es wurde
ANESTESIA PARA LA CARDIOVERSION: UNA COMPARACION DEL DIAZEPAM, LA TIOPENTONA Y LA PROPANIDIDA SUMARIO
Se anestesio a tres grupos de 50 pacientes con diazepam (0,32 mg/kg), tiopentona (3,7 mg/kg) o propanidida (4,6 mg/ kg) para una cardioversion electiva. La propanidida produjo mas hipotension que el diazepam y la tiopentona. La apnea fue mas frecuente despues del diazepam o la tiopentona y los efectos secundarios excitables fueron mas prominentes despues de la propanidida; el contrachoque electrico empeoro los fenomenos excitables. El porcentaje de logro de conversion fue mas alto en el grupo del diazepam que en los otros grupos, pero la diferencia no fue significante estadisticamente. El diazepam fallo en provocar la amnesia en alrededor del 33% de los pacientes. La tiopentona es adecuada y agradable para la cardioversion. Se recomienda el diazepam en pacientes de exiguo riesgo y en situaciones de emergencia.
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ANESTHESIE POUR CHOC ELECTRIQUE EXTERNE: COMPARAISON DU DIAZEPAM, DU THIOPENTONE ET DE LA PROPANIDIDE
festgestellt, dass Propanidid ein grosseres Ausmass von Hypotonie ausloste, als Diazepam, oder Thiopenton. Nach Anwendung von Thiopenton ergab sich Apnoe am Haufigsten; Reizwirkungen als Komplikation waren auffallend nach Propanidid; electrisch ausgeloster Gegenschock verschlimmerte die Reizwirkungen. Die Erfolgsergebnisse bei der Herzwendungschirurgie waren bei Patienten, denen Diazepam verabreicht worden war, besser als bei denen der anderen zwei Gruppen angehdrigen. Jedoch war der Unterschied nicht von statistischer Bedeutung. Bei ungefahr 33% der Patienten verursachte Diazepam keinerlei Amnesic Thiopenton erwie sich als erfolgreiches und angenehmes Mittel zum Gebrauch in der Herwendungschirurgic Diazepam wird fiir Patienten mit schlechtem Risiko, sowie fiir Notfalle empfohlen.
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PROCEEDINGS OF THE ANAESTHETIC RESEARCH SOCIETY
ANAESTHESIA FOR CARDIOVERSION: A comparison of diazepam, thiopentone and propanidid R. ORKO SUMMARY
Following the introduction of direct current countershock for the restoration of sinus rhythm, thiopentone seems to have been the most popular anaesthetic agent for this procedure (Lown, Amarasingham and Newman, 1962; Lown et al., 1963). However, since Muenster and colleagues (1967) reported a greater frequency of ventricular extrasystoles in patients anaesthetized with thiopentone than in those given diazepam, the latter has become a popular anaesthetic agent for cardioversion (Winters et al., 1968; Somers et al., 1971; Vinge, Wyant and Lopez, 1971). Johnstone and Barron (1968) found that propanidid has a quinidine-like anti-arrhythmic effect and considered it to be superior to thiopentone for the induction of anaesthesia. Propanidid has a useful brevity of action (Clarke, 1969). However, it has not been compared with other anaesthetics for cardioversion. The course of anaesthesia, the success rate of conversion of arrhythmia and the occurrence of ventricular arrhythmias in patients anaesthetized with diazepam, thiopentone or propanidid for the application of d.c. countershock have been compared. PATIENTS AND METHODS
One hundred and fifty unselected patients undergoing elective cardioversion were divided randomly into three groups. Group I was anaesthetized with diazepam, group II with thiopentone and group III with propanidid. The groups were comparable (tables I and II). Digoxin treatment was discontinued 2 days before the d.c. shock. In patients who were receiving quinidine, the dose was adjusted so that the serum RIITTA ORKOJ M.D.J Department of Anaesthesia, University
Central Hospital, Helsinki, Finland.
concentration was within the range 1-3 mg/litre (Hartel et al., 1970). The patients fasted overnight and arrived at the cardiovascular laboratory without premedication. Atropine 0.01 mg/kg was given i.v. 2 min before anaesthesia. Diazepam (Valium) was given over a period of about 1 min until the patient's speech became sluggish and ptosis was obvious. Thiopentone (Hypnostan) and propanidid (Epontol), both in 2.5% solutions, were also injected over about 1 min. When the patient did not respond to questions, the level of anaesthesia was considered adequate for the application of d.c. shock. All patients were given 100% oxygen through a "non-rebreathing valve and facepiece from 1 min before the induction of anaesthesia to the time of countershock. Controlled ventilation was instituted if the duration of apnoea exceeded 30 sec. The author administered all the anaesthetics. In group I the patients were drowsy only. In groups II and III, the duration of anaesthesia was timed from the start of the anaesthetic injection to the moment at which the patient responded to a command. About 2-3 min after the anaesthetic injection began,the d.c. shock or shocks were given with theaid of a d.c. defibrillator (Electrodyne C-100 M or Olli defibrillator). One electrode was placed between the scapular angle and the spine, the odier over the left sternal border. The energy discharge initially was 100 Wsec and it was increased successively, when necessary, to 200 and 300 Wsec. A maximum of three countershocks was given on each occasion. Arterial systolic pressure was determined by indirect sphygmomanometry. The e.c.g. was recorded for a 2-min period during the 4 h r before the patient's arrival at the laboratory, during the 2 min
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Three groups of 50 patients were anaesthetized with diazepam 0.32 mg/kg or thiopentone 3.7 mg/kg or propanidid 4.6 mg/kg for elective cardioversion. Propanidid caused more hypotension than diazepam or thiopentone. Apnoea was most frequent following thiopentone and excitatory sideeffects were most prominent following propanidid; the electric countershock worsened the excitatory phenomena. The success rate of conversion was higher in the diazepam group than in the other groups, but the difference was not statistically significant. Diazepam failed to produce amnesia in about 33% of the patients. Thiopentone is suitable and pleasant for cardioversion. Diazepam is recommended in poor-risk patients and in emergency situations.
BRITISH JOURNAL OF ANAESTHESIA
258
TABLE I. Age, sex and weight, haemoglobin and serum potassium concentrations of the patients studied. Arterial systolic pressure and heart rate before premedication are shown also. Mean values with range or SD. Fifty patients in each group
Group
Age (yr)
Sex (M/F)
Diazepam Thiopentone Propanidid
55 ±9.3 55 ±12.0 54+11.1
32/18 32/18 28/22
Weight (kg)
Haemoglobin (g/100 ml)
Serum potassium (m-equiv/litre)
Systolic pressure (mm Hg)
Heart rate (beats/min)
4.4 (3.8-5.1) 4.4 (3.7-5.2) 4.5 (3.8-5.2)
134±19.1 140 ±22.0 138 ±23.9
88 + 23.8 82 ±18.5 82 ±15.2
75 ±12.9 14.0(10.7-20.1) 77 ±13.6 14.5 (9.7-17.3) 73 ±14.1 14.4 (10.9-17.7)
TABLE II. Diagnosis, typeof arrhythmia and drug treatment. Fifty patientsin each group
Group Diazepam Thiopentone Propanidid
Other RHD RHD or (O) (U) IHD HHD unknown 13 11 18
0 2 4
9 11 4
4 3 1
Arrhythmia
Drug treatment
Atrial Atrial fibrillation nutter
Other antiarrhythmia AntiDigoxin Quinidine drug coagulant
24 23 23
47 49 50
3 1 0
23 17 26
50 48 48
14 7 7
40 47 44
RHD = rheumatic heart disease; IHD = ischaemic heart disease: HHD = hypertonic heart disease; O = operated; U = unoperated.
before the induction of anaesthesia and from the start of the anaesthetic injection until 3min after the d.c. shock. The heart rate was calculated and possible ventricular arrhythmias were noted from the e.c.g. records. The analysis of arrhythmias was performed without any knowledge of the group to which the patient belonged. Problems during anaesthesia and the immediate recovery period were noted. The patients were observed at the laboratory for 30 min after the procedure. On the next day most of the patients were visited by the anaesthetist and a note was made as to whether or not the sinus rhythm had been maintained. The patients were asked if they recalled the procedure. Student's t test or the Chi-square test was used for analysis of the results, unless indicated otherwise. The criterion for statistical significance was taken as P<0.05.
Electrocardiographic findings Conversion of the arrhythmia was achieved in 42 patients (84%) in the diazepam group, 36 (72%) in the thiopentone group and 35 (70%) in the propanidid group (table III). The differences are not statistically significant. Twenty-four hours after the countershock, sinus rhythm was present in 40 of the 42 patients in group I, in 35 of the 36 in group II and in all 35 patients in group III. The final success rates were 80%, 70% and 70%. An average of 1.9 countershocks per patient was required to achieve conversion in groups I and III, whereas group II required an average of 2.1 countershocks. The difference between these values is not statistically significant. TABLE I I I . Conversion of arrhythmia with the aid of d.c. countershock. Fifty patients in each group
Successful conversion
RESULTS
The mean dose of diazepam required to achieve drowsiness was 0.32 ( + SD 0.09) mg/kg. The dose of thiopentone was 3.7 ±1.1 mg/kg and of propanidid 4.6+ 1.4 mg/kg. The duration of anaesthesia in the thiopentone group was 4.7 + 2.0 min and in the propanidid group 4.9+ 1.8 min, the difference being not statistically significant.
Energy level required (Wsec) Group Diazepam Thiopentone Propanidid
100 200 300 18 12 10
10 8 17
14 16 8
Total
Unsuccessful conversion
42 36 35
8 14 15
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Diagnosis
DIAZEPAM, THIOPENTONE, PROPANIDID FOR CARDIOVERSION
259
TABLE IV. Occurrence of ventricular extrasystoles (VES) before and during the procedure Number of VES/min Diazepam
Propanidid
0
\-±
5 or more
0
1-4
5 or more
0
1-4
5 or more
32
16
2
36
11
3
33
15
2
31
16
3
33
14
3
38
9
3
31
16
3
32
15
3
37
11
2
32
15
3
30
16
4
37
13
0
Table IV shows data on the prevalence of ventricular extrasystoles. The statistical analysis of these data was based on the increases and decreases in the number of patients showing ventricular extrasystoles. Within the groups, there were no statistically significant changes in the prevalence of ventricular extrasystoles. The comparison between the groups did not reveal any statistically significant differences either (hypergeometrical distribution). Ventricular tachycardia, fibrillation or standstill did not occur in any patient.
Arterial pressure and heart rate The values of systolic pressure and heart rate, measured 2 min after the administration of atropine (table V) compared with values obtained before premedication (table I) show no change in arterial pressure and a marked increase in heart rate. The percentage changes in arterial pressure and heart rate at various stages (table VI) and the reference values representing 100% (table V) show a remarkable stability of systolic pressure in the diazepam group. Two minutes after the start of anaesthesia, the decrease in arterial pressure in the propanidid group was significantly different from that in the diazepam
TABLE V. Arterial pressure and heart rate before the injection of anaesthetic {2 min after the injection of atropine 0.01 mg/kg). Mean values + SEM
Systolic pressure (mmHg) Heart rate (beats/min)
Diazepam
Thiopentone
Propanidid
134 + 3.9
146 ±3.3
139 ±2.1
114 ±3.5
113 ±2.9
116 ±4.2
group (P< 0.001). The difference between the thiopentone and the diazepam groups was significant (P<0.05), whereas the difference between the propanidid and the thiopentone groups was not. Immediately after countershock, there were significant differences between the groups in the changes in arterial pressure (diazepam v. propanidid, P< 0.001; diazepam v. thiopentone, P<0.05; thiopentone v. propanidid, P<0.01). Three minutes after the shock, arterial pressure had returned to near the initial value in all groups and there were no statistically significant differences between the groups. In most of the patients in the diazepam and the thiopentone groups, the decreases in arterial pressure were less than 20%. Decreases of 20-30% were found
TABLE VI. Changes in arterial pressure and heart rate during the procedure. The values are per cent (mean + SEAT). 100 per cent is the value following atropine but before the administration of the anaesthetic
Heart rate (beats/min)
Systolic pressure (mm Hg) Thiopentone
Propanidid
Diazepam
Thiopentone
Propanidid
97 ±1.7
89±1.2|
85±1.8f
108±2.1f
107±2.3J
lll±3.1f
101 ±1.5 99 ±1.8
96 + 1.5* 98 ±1.5
91 + 1.It 98±1.4
89 +4.01 86±3.3f
88 + 3.4t 85±1.9t
93 ±3.8 89±2.5f
Diazepam 2 min after start of anaesthesia After shock 3 min after shock
I P<0.001; JP<0.01; *P<0.05.
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Before premedication After premedication During anaesthesia. before shock After shock
Thiopentone
260 in none of the patients in the diazepam group, in four in the thiopentone group, and in 11 in the propanidid group. Decreases of more than 30% were seen in two patients in the thiopentone group and in seven in the propanidid group. However, in this respect, the differences between the groups were not statistically significant (hypergeometrical distribution). The changes in heart rate throughout the procedure followed a similar pattern in all groups (table VI). No statistically significant differences were found between the groups.
BRITISH JOURNAL OF ANAESTHESIA DISCUSSION
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The mean doses of diazepam and thiopentone were similar to the amounts given by Fox, Wynands and Bhambhami (1968) in their comparison of these drugs as induction agents. Nutter and Massumi (1965) and Muenster and colleagues (1967) have used diazepam in doses of 5-20 mg and 15-20 mg, respectively, for cardioversion. These doses are smaller than in the present study: thiopentone 3.7 mg/kg; propanidid 4.6 mg/kg: a potency ratio of 1.2 : 1. This ratio is similar to that found by Wynands and Fox (1966). The potency ratio for thiopentone and propanidid is 1.1 : 1 (Clarke et al., 1968). Side-effects The incidences of ventricular extrasystoles in the The frequency of side-effects is shown in table VII. present series differ from those reported by Muenster The incidence of apnoea exceeding 30 sec was and others (1967), who found that ventricular significantly less in the diazepam group than in the extrasystoles appeared in 11 of 18 patients anaesthepropanidid group (P<0.01) or in the thiopentone tized with thiopentone, but in none of 19 patients group (P< 0.001). The difference between the anaesthetized with diazepam. When results from the thiopentone and the propanidid groups was not patients in the present study who showed no extrasignificant. systoles before the procedure were analysed, there were no significant differences between the groups in the appearances of ventricular extrasystoles during the TABLE VII. Occurrence of side-effects during anaesthesia. procedure. The patients in the present study received Fifty patients in each group oxygen and atropine (Orko, 1974), whereas Muenster's Laryngeal patients did not. Apnoea Excitation irritation Johnstone and Barron (1968) reported that propanidid has an anti-arrhythmic effect. This was seen in Diazepam 2 0 0 the present study, although there was no statistically Thiopentone 25 4 1 Propanidid 15 19 1 significant difference between the propanidid and the other two groups. The success rate of conversion was not very high in Excitatory side-effects, such as muscular tension this series. There were no statistically significant or involuntary movements, or both, were observed differences between the groups. It is probable that the most commonly in the propanidid group. The choice of anaesthetic agent has no significant influence difference, as compared with either the thiopentone upon the success rate of conversion of arrhythmia or the diazepam group, was statistically significant (Muenster et al., 1967; Heinonen, Orko and Louhija, (P<0.001), whereas the difference between the 1973). thiopentone and the diazepam groups was not The arterial pressure in the diazepam group was significant. The electric countershock seemed to almost unchanged, which is in accordance with worsen the excitatory side-effects. previous observations (Nutter and Massumi, 1965; Signs of laryngeal irritation were observed in one McClish, 1966; Brown and Dundee, 1968; Winters patient in the thiopentone group and in one in the et al., 1968; Knapp and Dubow, 1970; Wyant and propanidid group. No other side-effects, such as Studney, 1970; Somers et al., 1971). In this respect hiccup, retching, vomiting or sweating were observed diazepam may be considered a safe agent for patients during anaesthesia or the immediate recovery period. with cardiac disease. However, relatively small In the diazepam group 15 patients, out of 41 doses have been used in all the studies, including the interviewed, recalled the electric countershock, present study, and it is evident that diazepam in compared with one out of 40 in the thiopentone group larger doses may have some depressant effect on the and three out of 38 in the propanidid group (diazepam circulatory function (Rao et al., 1973). v. thiopentone, P< 0.001; diazepam v. propanidid, The decreases in arterial pressure in the thiopentone P<0.01 (hypergeometrical distribution)). and the propanidid groups are comparable with the
DIAZEPAM, THIOPENTONE, PROPANIDID FOR CARDIOVERSION
ACKNOWLEDGEMENT
I wish to thank Laakeruonti Oy of F. Hoffmann-La Roche & Co. A.G. for supplies of Valium. REFERENCES
Brown, S. S., and Dundee, J. W. (1968). Clinical studies of induction agents. XXV: Diazepam. Br. J. Anaesth., 40, 108.
Clarke, R. S. J. (1969). The eugenols—propanidid; in Newer Intravenous Anesthetics, 1st edn, p. 43. Boston: Little, Brown and Co. Dundee, J. W., Barron, D. W., and McArdle, L. (1968). Clinical studies of induction agents. XXIV: The relative potencies of thiopentone, methohexitone and propanidid. Br. J. Anaesth., 40, 593. Dalen, J. E., Evans, G. L., Banas, J. S., Brooks, H. L., Paraskos, J. A., and Dexter, L. (1969). The hemodynamic and respiratory effects of diazepam (Valium). Anesthesiology, 30, 259. Dundee, J. W., and Clarke, R. S. J. (1964). Clinical studies of induction agents. IX: A comparative study of a new eugenol derivative FBA. 1420 with G. 29, 505 and standard barbiturates. Br.J. Anaesth., 36, 100. Wyant, G. M. (1974). Intravenous Anaesthesia, 1st edn, p. 262. Edinburgh and London: Churchill Livingstone. Fox, G. S., Wynands, J. E., and Bhambhami, M. (1968). A clinical comparison of diazepam and thiopentone as induction agents to general anaesthesia. Can. Anaesth. Soc.J., 15,281. Glassman, E. (1971). Direct current cardioversion. Am. Heart J., 82, 128. Hartel, G., Louhija, A., Konttinen, A., and Halonen, P. I. (1970). Value of quinidine in maintenance of sinus rhythm after electric conversion of atrial fibrillation. Br. Heart J., 32, 57. Heinonen, J., Orko, R., and Louhija, A. (1973). Anaesthesia for cardioversion: a comparison of Althesin and thiopentone. Br. J. Anaesth., 45, 49. Johnstone, M., and Barron, P. T. (1968). The cardiovascular effects of propanidid. Anaesthesia, 23, 180. Knapp, R. B., and Dubow, H. (1970). Comparison of diazepam with thiopental as an induction agent in cardiopulmonary disease. Anesth. Analg. (Cleve.), 49, 722. Lown, B., Amarasingham, R., and Newman, J. (1962). New method for terminating cardiac arrhythmias. J.A.M.A., 182, 548. Perlroth, M. G., Kaidney, S., Abe, T., and Harken, D. E. (1963). "Cardioversion" of atrial fibrillation. N. Engl. J. Med., 269, 325. McClish, A., (1966). Diazepam as an intravenous induction agent for general anaesthesia. Can. Anaesth. Soc. J., 13, 562. Muenster, J. J., Rosenberg, M. S., Carleton, R. A., and Graettinger, J. S. (1967). Comparison between diazepam and sodium thiopental during d.c. countershock. J.A.M.A., 199, 758. Nutter, D. O., and Massumi, R. A. (1965). Diazepam in cardioversion. N. Engl. J. Med., 273, 650. Orko, R. (1974). Anaesthesia for cardioversion: thiopentone with and without atropine premedication. Br.J. Anaesth., 46, 947. Rao, S., Sherbaniuk, R. W., Prasad, K., Lee, S. J. K., and Sproule, B. J. (1973). Cardiopulmonary effects of diazepam. Clin. Pharmacol. Ther., 14, 182. Somers, K., Gunstone, R. F., Patel, A. K., and D'Arbela, P. G. (1971). Intravenous diazepam for direct-current cardioversion. Br. Med. J., 4, 13.
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findings of Wynands and Fox (1966), but not with those of Dundee and Clarke (1964), who used smaller doses of propanidid. The periods of hypotension after propanidid in the present study were brief and unlikely to be dangerous. No signs of hypersensitivity were observed in any of the patients. The different frequency of apnoea in the thiopentone and the propanidid groups might be because only apnoea exceeding 30 sec was considered. There were shorter periods of apnoea immediately after the hyperventilation in some of the patients in the propanidid group. There was significantly less apnoea in the diazepam group than in the other two groups and the same observation has been made by Fox, Wynands and Bhambhami (1968). However, diazepam may depress breathing occasionally (Dalen et al., 1969; Rao et al., 1973) and it should be given by anaesthetists preferably (Dundee and Wyant, 1974), although some authors (Glassman, 1971; Somers et al., 1971) are of the opinion that an anaesthetist is not necessary when diazepam is used for cardioversion. Amnesia produced by diazepam has been reported frequently (McClish, 1966; Brown and Dundee, 1968). In the present study 37% of the patients anaesthetized with diazepam recalled the electric countershock. This is unacceptable in elective cardioversion. The lack of sufficient amnesia did not seem to be related to the given dose per kg. No patient in the series of Muenster and others (1967) recalled the event although the exact dose per kg was not stated. The interval between the injection of diazepam and the electric countershock was the same in both studies. In the present study the individual variations in the effect of diazepam were great, and it was difficult to find the optimal dosage for every patient. Diazepam may be considered the drug of choice for cardioversion in poor-risk patients and in emergency situations, because it does not seem to depress the circulation. However, patients anaesthetized with diazepam may recall the unpleasant procedure. For patients in better physical condition thiopentone would seem to be preferable. Hypotension and excitatory side-effects produced by propanidid make it less suitable.
261
BRITISH JOURNAL OF ANAESTHESIA
262 Vinge, L. N., Wyant, G. M., and Lopez, J. F. (1971). Diazepam in cardioversion. Can. Anaesth. Soc. J., 18, 166. Winters, W. L., McDonough, M., Hafer, J., and Dietz, R. (1968). Diazepam, a useful hypnotic drug for directcurrent cardioversion. J.A.M.A., 204, 926. Wyant, G. M., and Studney, L. J. (1970). A study of diazepam (Valium) for induction of anaesthesia. Can. Anaesth. Soc.J., 17, 166. Wynands, J. E., and Fox, G. S. (1966). A clinical comparison of propanidid and thiopentone as induction agents to general anaesthesia. Can. Anaesth. Soc.J., 13, 505.
RESUME
On a anesthesie pour choc electrique externe a froid, trois groupes de 50 patients a l'aide de diazepam (0,32 mg/kg), de thiopentone (3,7 mg/kg) ou de propanidide (4,6 mg/kg). La propanidide a provoque une hypotension plus grande que le diazepam ou le thiopentone. L'apnee a ete plus frequente apres l'administration de thiopentone et les effets secondaires excitatoires ont ete plus prononces apres la propanidide; le contrechoc electrique a aggrave le phenomene excitatoire. Le taux de reussite de la conversion a ete plus eleve dans le groupe traite au diazepam que dans les autres groupes, mais la difference n'a pas ete d'une importance statistique consequente. Dans 33% des cas, le diazepam n'a produit aucune amnesic Le thiopentone convient bien et est plaisant dans les cas de chocs electriques externes. Le diazepam est recommande pour les patients presentant peu de risques et pour les cas d'urgence. NARKOSE BEI HERZWENDUNGSCHIRURGIE: VERGLEICHSERWERTUNGEN VON DIAZEPAM, THIOPENTON UND PROPANIDID ZUSAMMENFASSUNG
Drei 50-Patientengruppen wurden zwecks Herzwendungschirurgie mit Diazepam (0,32 mg/kg), Thiopenton (3,7 mg/ kg) und Propanidid (4,6 mg/kg) narkotisiert. Es wurde
ANESTESIA PARA LA CARDIOVERSION: UNA COMPARACION DEL DIAZEPAM, LA TIOPENTONA Y LA PROPANIDIDA SUMARIO
Se anestesio a tres grupos de 50 pacientes con diazepam (0,32 mg/kg), tiopentona (3,7 mg/kg) o propanidida (4,6 mg/ kg) para una cardioversion electiva. La propanidida produjo mas hipotension que el diazepam y la tiopentona. La apnea fue mas frecuente despues del diazepam o la tiopentona y los efectos secundarios excitables fueron mas prominentes despues de la propanidida; el contrachoque electrico empeoro los fenomenos excitables. El porcentaje de logro de conversion fue mas alto en el grupo del diazepam que en los otros grupos, pero la diferencia no fue significante estadisticamente. El diazepam fallo en provocar la amnesia en alrededor del 33% de los pacientes. La tiopentona es adecuada y agradable para la cardioversion. Se recomienda el diazepam en pacientes de exiguo riesgo y en situaciones de emergencia.
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ANESTHESIE POUR CHOC ELECTRIQUE EXTERNE: COMPARAISON DU DIAZEPAM, DU THIOPENTONE ET DE LA PROPANIDIDE
festgestellt, dass Propanidid ein grosseres Ausmass von Hypotonie ausloste, als Diazepam, oder Thiopenton. Nach Anwendung von Thiopenton ergab sich Apnoe am Haufigsten; Reizwirkungen als Komplikation waren auffallend nach Propanidid; electrisch ausgeloster Gegenschock verschlimmerte die Reizwirkungen. Die Erfolgsergebnisse bei der Herzwendungschirurgie waren bei Patienten, denen Diazepam verabreicht worden war, besser als bei denen der anderen zwei Gruppen angehdrigen. Jedoch war der Unterschied nicht von statistischer Bedeutung. Bei ungefahr 33% der Patienten verursachte Diazepam keinerlei Amnesic Thiopenton erwie sich als erfolgreiches und angenehmes Mittel zum Gebrauch in der Herwendungschirurgic Diazepam wird fiir Patienten mit schlechtem Risiko, sowie fiir Notfalle empfohlen.
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LONDON MEETING
OCTOBER 31,1975
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PROCEEDINGS OF THE ANAESTHETIC RESEARCH SOCIETY