CARDIAC ARRHYTHMIAS OCCURRING DURING HALOTHANE ANAESTHESIA IN CATS

Brit. J. Anaesth. (1966), 38, 13

CARDIAC ARRHYTHMIAS OCCURRING DURING HALOTHANE ANAESTHESIA IN CATS BY I. F. H.

PURCHASE

School of Veterinary Medicine, Cambridge SUMMARY

The incidence of cardiac arrhythmias in cats during halothane anaesthesia is high, and the arrhythmias observed during thirty-seven periods of anaesthesia have been classified into four types. The effect of the concentration of halothane, the blood pressure, the arterial blood gases and sensory stimulation on the occurrence of the ventricular extrasystoles with contradirectional interference are described. It is suggested that, under certain conditions, halothane may produce cardiac arrythmias in cats through a direct action on the myocardium. Muir, Hall and Iittlewort (1959) reported cardiac arrhythmia in fourteen of sixteen cats anaesthetized with 1.5-3.0 per cent halothane. Electrocardiograms from the cats showed that the arrhythmia consisted of ventricular extrasystoles with a phasic variation in the amplitude of the R waves, indicating the presence of "interference dissociation". The arrhythmia disappeared rapidly on increasing the concentration of halothane in the inspired gases, but reappeared about 5 minutes later. A decrease in the inspired concentration of halothane had no immediate effect on the arrhythmia. Overventilation with an accompanying reduction in plasma bicarbonate also caused the arrhythmia to disappear. When 5 per cent carbon dioxide was added to the ventilating gases, however, overventilation had no effect. This report is an account of an investigation in which the incidence and nature of the arrhythmia, as well as some of the factors apparently responsible for its appearance, were studied. METHODS

Anaesthesia was induced in the cats either with intravenous thiopentone (10 mg/kg) followed by a paralyzing dose of suxamethonium (1-2 mg) or with halothane-oxygen alone administered to the cat in a perspex tank. No premedication was used. A No. 2 or 3 Magill oral tube was inserted into the trachea under direct vision, and anaesthesia Present address: National Nutrition Research Institute, C S IR, P.O. Box 395, Pretoria, South Africa.

was maintained with halothane vaporized from a Fluotec vaporizer in a stream of oxygen, or oxygen and nitrous oxide, delivered through a Tpiece. The cats breathed spontaneously after recovery from the suxamethonium. The period of anaesthesia varied from 40 to 120 minutes. Electrocardiograms were recorded from eleven cats undergoing minor surgery and during twentysix periods of anaesthesia in twenty experimental cats. Blood pressure and electrocardiograms were recorded on a three-channel recorder (Cambridge Instrument Company). The blood pressure was controlled by means of a technique similar to that of Moe and associates (1948). A cannula was introduced into the carotid artery and pressure was applied to a blood reservoir connected to the cannula from an oxygen cylinder and reduction valve. The terminology used to describe the electrocardiograms is that suggested by Miller and Sharret (1957) and Schott (1960), and the electrocardiograms were analyzed according to the method used by them. The oxygen saturation of arterial haemoglobin was determined with a Haemorefiector (P. J. Kipp & Zonen). Pco3 was estimated according to the technique of Siggaard Andersen and associates (1960). Arterial blood samples were withdrawn into 2-ml syringes the deadspace of which had been filled with heparin saline. A correction for heparin dilution was made (Siggaard Andersen, 1961).

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BRITISH JOURNAL OF ANAESTHESIA the stage in the myocardial depression produced by halothane administration which immediately preceded nodal rhythm. It consisted of atrioventricular (AV) dissociation accompanied by incomplete antegrade block and complete retrograde AV block. Interference between sinus and AV nodal beats occurred when the ventricles were beating faster than the atria. The condition was essentially transient, resolving either into nodal or into sinus rhythm, and was observed infrequently.

RESULTS

(A) Types of Arrhythmia encountered. When the thirty-seven electrocardiograms were scrutinized, it was found that the irregularities of rhythm which occurred could be classified into four types: Type I. Dissociation with interference (Schott, 1960). This condition (fig. 1) occurred during inhalation of high concentrations of halothane and was

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FIG. 1 Dissociation with interference in the lead II electrocardiogram from a cat breathing halothaneoxygen. The atria are beating regularly, but the ventricles irregularly, due to the capture beats R7 and R14. The ventricles are beating faster than the atria, and thus the P wave merges with the R wave (R2 and R3; R9 and RIO). This is continued until the P wave emerges from the R wave with a lengthening R-P interval. R6 occurs 0.12 sec before P6, and as P6 is not inverted, retrograde block must be present. P6 follows long enough after R6 to enable the impulse to reach the ventricles after the refractory period, and a ventricular capture or interference beat (R7) therefore occurs. The AV conduction is considerably prolonged to 0.16 sec in this beat. P7R8 is the beginning of a new cycle of the same length (8 beats) as the preceding one. The length of the cycle depends on the relative frequency of atrial and ventricular beats. The figures between beats refer to the time interval in hundredths of a second.

FIG. 2 Nodal rhythm in a cat breathing halothane-oxygen. A strip of lead II is shown. The P waves can be discerned after the R waves. (Inverted lead II is fairly common in cats.)

CARDIAC ARRHYTHMIAS DURING HALOTHANE ANAESTHESIA IN CATS

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FIG. 3 Extrasystoles in a cat under halothane anaesthesia in a strip of lead II is shown with the accompanying blood pressure tracing. Beats 2, 6 and 10 are ventricular extrasystoles which are coupled to nodal beats. Each pair of coupled beats is followed by a compensatory pause (R3-4 and R7-8) which allows a marked fall in blood pressure. The succeeding b:at (R4 and R8) has an enhanced action, probably due to enhanced ventricular filling. The overall effect is a phasic change in blood pressure.

Type II. Nodal rhythm. Nodal rhythm was frequently observed during inhalation of high concentrations of halothane in oxygen (fig. 2). Type III. Ventricular extrasystoles. In the early stages of halothane anaesthesia or during very light anaesthesia, when the response to painful stimuli was brisk, ventricular extrasystoles were precipitated by surgical stimulation or hypircapnia. These extrasystoles became multifocal at times and the electrocardiograms were indistinguishable from those described below under type IV as ventricular extrasystoles occurring during sinus domination. The mode of precipitation was the only feature which distinguished this arrhythmia from those described in type IV. Type IV. Ventricular extrasystoles with or without contradirectional interference. The term "contradirectional interference" is used in this report following the recommendation

of Miller and Sharret (1957). "Interference dissociation" was the term used by Muir and his colleagues (1959). This was the arrhythmia most commonly encountered during halothane anaesthesia in cats and the one investigated in detail in this study. Three forms of this arrhythmia were encountered, two occurring during sinus domination and the other during AV dissociation. The first form rarely exhibited contradirectional interference, while the second typically did so during sinus domination, and the third during AV dissociation. The first form consisted of isolated ventricular extrasystoles (fig. 3). If the hypoxia and hypercapnia resulting from respiratory depression were not alleviated, the number of extrasystoles increased until the second form supervened. In this form the extrasystoles seemed usually to originate from a single focus. A close inspection of a portion of a typical electrocardiogram (fig.4)

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FIG. 4 Ventricular irregularities during sinus rhythm in a cat under halothane anaesthesia (lead II) In this tracing there is always a P wave preceding the QRS complexes. The atria are beatinR regularly, but only beats 1, 2, 9, 16, 17 and 18 are sinus beats. The rest are fusion beats showing contradirecuonal interference, and the exact shape of the QRS complexes in such beats depends on the temporal relationship between the sinus and ectopic beats which make up the complex Thus the apparent conduction time (P-Q interval) in beat 3 is 0.06 sec, which means that the ectopic focus dominates the complex, and this is shown as interference "high" in the ventricle In contrast, the conduction time in beat 10 is 0.08 sec, with the result that interference is "low" in the ventricle and there is a biphasic complex.

reveals that there were some normal sinus beats with normal P-Q intervals. The other beats with varying contours usually occurred after a shortened P-Q interval, and were considered to be the result of fusion of a nodal and an ectopic beat. The contour of the ventricular complex depended on the temporal relationship between these beats. In the particular case shown it appears that only one ectopic focus existed. In other cases where there appear to be two or more ectopic foci (fig. 6) the electrocardiogram was so bizarre as to defy logical analysis. The third form occurring during AV dissociation appeared similar to the second form on superficial examination (fig. 5). On closer examination, however, it could be seen that the majority of ventricular complexes were not preceded by a P wave and that, although the atria were beating at a fairly regular rate, the ventricular beat was irregular. Contradirectional interference occurred between nodal and ectopic complexes. Where a P wave preceded a QRS complex this could have been fortuitous rather than the result of a normal sinus beat, because ectopic and nodal beats were present after normal P-Q intervals (e.g., beats 20 and 21). The cardiac action was enhanced in those beats in which the P wave

preceded the QRS complex, with a resulting increase in blood pressure. The blood pressure tracing in this condition (fig. 5) could easily be confused with that obtained during isolated extrasystoles (fig. 3). In both cases there was a phasic change in blood pressure, but the increase in blood pressure in this third form of the arrhythmia (fig. 5) was due to enhanced cardiac action resulting from a normal temporal relationship between atrial and ventricular beats. The fall in blood pressure which accompanied isolated extrasystoles was due to the compensatory pause that followed the extrasystolic beats. (B) Incidence of Type W Arrhythmias. Twenty-six periods of anaesthesia in cats breathing halothane vaporized in a mixture of nitrous oxide and oxygen were monitored with an electrocardiograph. The experimental animals were divided into three groups: (i) Cats breathing anaesthetic mixtures containing more than 50 per cent oxygen. During periods of anaesthesia lasting 80 minutes, none of the seven cats in this group developed type IV arrhythmias (ii) Cats breathing anaesthetic mixtures containing more than 50 per cent oxygen, but with

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Ventricular irregularities during nodal rhythm in a cat under halothane anaesthesia. A strip of lead II is shown with the accompanying blood pressure tracing. The atria are beating regularly, but the ventricular beat is irregular due to ectopic beats. The ventricular complexes can be divided into three types: (a) nodal or sinus beats (Nos. 5, 6, 11, 12, 13 and 21); (b) ectopic beats (Nos. 1, 8, 9, 10, 14, 15, 16, 17 and 19); (c) fusion beats showing contradirectional interference (Nos. 2, 3, 4, 7, 18, 20 and 22). The shape of the fusion beats varies, depending on the timing and the conduction paths of the two separate complexes which fuse to form the beat.

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5 In those beats in which the P waves precede the ventricular complexes there is improved cardiac action and a resulting increase in the blood pressure. This is true of both nodal beats (e.g., Nos. 5 and 6) and fusion beats (e.g., Nos. 2 and 3). In beats 3 and 20 there is adequate time for orthograde conduction (0.08 sec) but an ectopic complex dominates, indicating depression of orthograde conduction. The position of the P wave before any beat may thus be fortuitous. In certain beats (e.g., No. 13) there is a strong indication that retrograde conduction is depressed. There is a prolonged R-P interval (0.12 sec) with a normal P wave. This confirms the other observations concerning the effect of halothane on retrograde conduction, and as a result retrograde conduction has not been shown in beats 1, 8-10, 14-17, and 19.

BRITISH JOURNAL OF ANAESTHESIA

FIG. 6 Extrasystolcs originating from a number of foci shown in a lead II electrocardiogram from a cat under halothane anaesthesia.

carbon dioxide added for 10-minute periods. This group included two cats breathing 20 per cent carbon dioxide, two breathing 10 per cent carbon dioxide, one breathing 5 per cent carbon dioxide, and one subjected to total rebreathing. Only the two cats breathing 10 per cent carbon dioxide developed type IV arrhythmias. (iii) Cats breathing anaesthetic mixtures containing 25 per cent oxygen with the balance consisting of nitrous oxide and halothane. Of thirteen cats in this group, nine developed type IV arrhythmias.

(ii) Oxygen and carbon dioxide tension. On two occasions an increase in halothane concentration which abolished the arrhythmia was accompanied by a decrease in haemoglobin saturation and an increase in carbon dioxide tension. (iii) Arterial pressure. The blood pressure did not fall when the halothane concentration was increased to abolish the arrhythmia (fig. 7). As soon as the arrhythmia disappeared there was a rise in mean blood pressure, probably due to the return of cardiac action toward normal caused by a return to normal rhythm.

(c) Factors affecting the development of Type IV Arrhythmias. Concentration of halothane. Type IV arrhythmias appeared over a wide concentration range (1.0-3.0 per cent). Extrasystoles occurring during sinus domination appeared at low concentrations (generally less than 2 per cent). Those occurring during AV dissociation were more common at higher concentrations. An increase in the halothane concentration temporarily abolished type IV arrhythmias, which disappeared within 20-30 seconds (fig. 7) and reappeared about 5 minutes later. The following factors were investigated in cats exhibiting type IV arrhythmia to seek an explanation for their disappearance when the halothane concentration was increased. (i) Cardiac rhythm. The rhythm returned to normal sinus rhythm in the majority of cases. On two occasions the heart was beating in nodal rhythm when the irregularities disappeared.

Arterial pressure. The development of arrhythmias was favoured by higher arterial pressures. Cats with mean pressures below 60 mm Hg during administration of 1.0 or 1.5 per cent halothane seldom showed arrhythmias. Acute changes in blood pressure were able to abolish an existing arrhythmia. In three cats the arrhythmia disappeared when the blood pressure was suddenly decreased. On restoring the pressure to normal the arrhythmia reappeared in one cat, but failed to do so in the other two, even when die blood pressure was further raised to beyond the control level. Arterial blood gases. Type IV arrhythmias invariably occurred when the PcOj increased beyond a level of about 55 mm Hg and the haemoglobin saturation decreased to about 90 per cent during anaesthesia with halothane in oxygen and nitrous oxide. If the Pco2 was elevated for 10 minutes by adding carbon dioxide to the inspired gases when the oxygen saturation was high, type IV arrhyth-

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FIG. 8 The effect of hypercapnia during halothane anaesthesia as seen in blood pressure tracings and lead II electrocardiograms from a cat anaesthetized with halothane-oxygen for 70 minutes. A Before administration of carbon dioxide. B After 20 minutes inhalation of 20 per cent carbon dioxide.

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2O SECONDS FIG. 9 The effect of sciatic stimulation during halothane anaesthesia as seen in a blood pressure tracing and lead II electrocardiogram from a cat anaesthetized with halothaneoxygen for 90 minutes. The sciatic nerve was stimulated at the marker (S) for 48 seconds with a 20-volt tetanic stimulus. The absence of ventricular anythmias is confirmed by the blood pressure tracing (cf. fig. 7).

mias were produced in a third of the cats (see under B). In three cats which had been breathing 1.5 per cent halothane in oxygen for 1 hour, 20 per cent carbon dioxide was added to the inspired gases, but no arrhythmia appeared within 20 minutes (fig. 8). When the oxygen saturation decreased, due to respiratory depression in cats anaesthetized with halothane in 25 per cent oxygen and 75 per cent nitrous oxide, hypercapnia frequently precipitated arrhythmias. Confirmation of the above observations was obtained in three cats in which arrhythmias had developed during administration of 1.5 per cent halothane in 1:3 oxygen/nitrous oxide mixture. When the oxygen/nitrous oxide mixture was replaced by oxygen, the haemoglobin saturation increased in each case from about 92 to 99 per cent in ten minutes. The arrhythmia then disappeared. Reversion to oxygen/nitrous oxide again produced the arrhythmia, and the haemoglobin saturation decreased to below 95 per cent. Sensory stimulation. Stimulation of the sciatic nerve (with a 20-volt tetanic stimulus) in two cats which had breathed 1.5 per cent halothane in oxygen for one hour did net alter the cardiac rhythm (fig. 9).

DISCUSSION

The arrhythmias encountered during halothane administration consisted of those resulting from depression of atrioventricular conduction (dissociation with interference and nodal rhythm) and ventricular extrasystoles. These two types occurred under differing conditions and reacted differently to changes in halothane concentration. The arrhythmias resulting from disturbances in AV conduction occurred under deep halothane anaesthesia. Nodal rhythm represented a greater disturbance in conduction than AV dissociation, because of the absence of ante- and retrograde conduction,* and could be produced by increasing the inspired concentration of halothane. This indicated that a direct action of halothane on the myocardium could be responsible for the changes in conduction. Ventricular extrasystoles occurred in 69 per cent of cats breathing nitrous oxide/oxygen/halothane, as it did in 88 per cent of the cats breathing similar mixtures reported on by Muir, Hall and Littlewort (1959). The incidence in man appears to bs far lower, being only 25 per cent in the combined cases of Stephen and associates (1957), * In cats, retrograde conduction is depressed.

CARDIAC ARRHYTHMIAS DURING HALOTHANE ANAESTHESIA IN CATS Burnap, Galla and Vandam (1958), and Wyant and associates (1958); this can probably be attributed to different conditions. Extrasystoles observed during light anaesthesia, when there is a brisk response to painful stimuli, may be caused by the effects of sympathetic discharge as has been described in man (Dundee and Black, 1960). There is some evidence that deeper halothane anaesthesia depresses sympathetic activity (Price et al., 1960). In the present experiments there was a low incidence of extrasystoles in the six cats exposed for 10 minutes to varying concentrations of carbon dioxide during halothane anaesthesia, while none developed in those exposed to 20 per cent carbon dioxide for 20 minutes. Stimulation of the sciatic nerve in cats, which produces a sympathetic discharge and ventricular extrasystoles during chloroform anaesthesia (Levy, 1912), was not observed to alter the cardiac rhythm during halothane anaesthesia. These findings could be explained by assuming a reduced or absent sympathetic response during halothane administration, and if this is indeed the case some other cause than increased sympathetic discharge must be sought to explain the appearance of extrasystoles. Halothane produces depression of AV conduction leading to dissociation with interference and nodal rhythm in the isolated cat heart, and when in addition the heart is exposed to a combination of hypoxia and hypercapnia, extrasystoles may be produced (Purchase, 1966, in press). These findings suggest that halothane may produce changes in conduction directly, so that when hypoxia and hypercapnia are also present extrasystoles may occur without an intact sympathetic system. An increase in the concentration of anaesthetic in the inspired gases abolished extrasystoles in cats during halothane anaesthesia and has also been reported during chloroform anaesthesia (Levy and Lewis, 1911). The extrasystoles disappeared more or less permanently during chloroform anaesthesia, however, and only temporarily during halothane anaesthesia. The disappearance of the extrasystoles on increasing halothane concentration did not appear to be associated with a reduction in arterial pressure or an alteration in the blood gases.

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ACKNOWLEDGMENTS

This work was carried out during the tenure of a Wellcome Fellowship of the Animal Health Trust, and forms part of a thesis submitted to the University of Cambridge. I wish to thank Dr. L. W. Hall for his help and advice and Miss J. M. Bierne for her technical assistance. REFERENCES

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