ARRHYTHMIAS PRODUCED BY COMBINATIONS OF HALOTHANE AND SMALL AMOUNTS OF VASOPRESSOR

Transcription

1 ARRHYTHIAS PRODUCED BY COBINATIONS O HALOTHANE AND SALL AOUNTS O VASOPRESSOR WILLIA I. HIRSHO, 1 D..D., RICHARD G. TAYLOR, 2 B.D.S.,.S., D..D. and JOHN C. SHEEHAN, 3.D. WHEN epinephrine in relatively large amounts is administered to dogs narcotised with halothane significant ventricular arrhythmias occur. The conditions under which these experiments have been carried out are, however, far removed from clinical situations since large amounts of vasopressor were used, as much as 5"I mg. injected directly into the vena cava (Hall & orris, (I958). Regardless of dosage, it is obvious that great care must be taken when the above mentioned agents, both of which potentiate myocardial irritability, are used in combination. ew objective clinical studies of combined usage have been reported although at the present time epinephrine in varying amounts is being used in patients anaesthetised with halothane for purposes ranging from intentional cardiac stimulation Dawson et al. (I96O) to its use as a local vasoconstrictor either injected or topically applied. The purpose of this study was to determine whether detectable cardiac arrhythmias, as determined by the electrocardiograph, occurred in patients anaesthetised with halothane when epinephrine or neo-cobefrin in small amounts was injected in a local anaesthetic vehicle. aterials and methods.--ifty-nine healthy patients, ranging in age from 16 to 45 years who were to undergo similar oral surgical procedures under general anaesthesia were studied. All patients received a complete pre-operative history, physical examination, and routine laboratory studies including chest X-ray, haematocrit, white blood cell count, differential, and urinalysis. If any abnormal findings were recorded, the patient was not utilised in the study. or the purposes of the experiment patients were divided into four groups: Group I: Twenty patients who received 4 ml. of local anaesthetic solution containing no epinephrine or neo-cobefrin. Group II: Twenty-four patients who received 4 ml. of local anaesthetic solution containing epinephrine I to lo%ooo concentration. Group III: Ten patients who received 4 ml. of local anaesthetic solution containing neo-cobefrin I to 20,000 concentration. Group IV: ive patients who received 4 ml. of local anaesthetic solution containing epinephrine I to 5%o00 concentration. All patients were anaesthetised in a similar manner by the same anaesthesiologist using a pentothal sodium-anectine induction. Great care was taken to avoid hypercarbia or hypoxia both of which may produce arrhythmias. All patients were intubated by means of a nasoendotracheal tube. The pentothal 1 Associate Visiting Surgeon for Oral Surgery, Boston City Hospital. 2 Director, Department of Dentistry, Boston City Hospital; Professor of Oral Surgery, Tufts University School of Dental edicine. 3 Associate Director, Department of Anaesthesiology, Boston City Hospital. 131

2 132 BRITISH JOURNAL O ORAL SURGERY sodium was then discontinued and anaesthesia maintained by means of a halothane, nitrous oxide, and oxygen combination, the halothane being delivered by a luotec (Rx) vaporisor at a concentration of between 0. 7 and 0"9 per cent. Electrocardiographic readings at lead 2 (right arm and left leg) using a standard Sanborn viso cardiette were taken prior to induction and following anaesthetic stabilisation of the patient. our ml. of local anaesthetic solution was then infiltrated supraperiosteally 2 ml. on the right and 2 ml. on the left in the region of the canine fossa to enhance haemostasis. The average time taken to complete the injection was 30 seconds and on its completion continuous electrocardiographic readings were made for five or six minutes. Periodic recordings were then taken every few minutes until anaesthesia was completed and the patient extubated. If at any time an arrhythmia was noted, surgery was stopped, halothane administration was discontinued and the patient was hyperventilated with oxygen. An arrhythmia for the purposes of this study was said to have occurred if any variation from the normal rhythm of the heart beat was observed. igure I represents a normal electrocardiograph in which the various complexes from lead 2 were recorded. Changes in the character of these complexes indicated an arrhythmia. Results.--In the control group no arrhythmias were observed after anaesthetic stabilisation. Occasional changes in rate and rhythm occurred during intubation and were attributed to vagal stimulation. In group II, two (8"3 per cent.) of the 24 patients who received epinephrine 1:1o%ooo developed arrhythmias. Both subjects developed a sinus tachycardia, a rate of slightly over ioo beats per minute, with premature ventricular beats. In igure 2 may be seen a series of 2, 4, and 3 normal tracings each followed by a premature QRS complex of nodal origin. Note that the 'P' wave has been lost, and the inverted 'T' wave is distorted. The notching in the QR segment may have been superimposed on the succeeding 'P' wave. In igure 3 is another example where the normal E.K.G. tracing changed to a bigeminate type of arrhythmia shortly after infiltration of the vasopressor. Note the broad and notched 'P' wave. The pulse rate was about IOO per minute. Of the IO patients in group III who received a local anaesthetic solution containing neo-cobefrin I:2O,OOO, six (6o per cent.), developed arrhythmias. These changes were similar to those encountered with epinephrine I :lo%ooo. In igure 4, which was typical of the group III, premature ventricular beats were seen. Some of the QRS complexes were high and 'P' wave loss was observed. There was again distortion of the.inverted 'T' wave. Of the five patients in group IV who received a local anaesthetic solution containing epinephrine i :5%oo0, two developed complex tracings in which the origin of the impulses was from multiple loci. igure 5 shows the transition of the normal tracing to such an arrhythmia. The pulse rate was about 9o and there were tall and short QRS complexes. Some of the 'T' waves were inverted and the 'P' waves were irregular. The tracing showed a variety of patterns indicative of myocardial irritability.

3 ARRHYTHIAS PRODUCED BY COBINATIONS O HALOTHANE Because of the marked distortion of these tracings it was decided to discontinue the use of local anaesthetic solution containing epinephrine 1:5o,ooo in this study. In Table I is presented a summary of the results. I33 -L.4-2~- ~;2 2 ~; ;L;. ;k ;; 2 ;2;.;.;.~i[;2;;';2.~... i~- ~ *..... _T2~72 ro. i Typical essentially normal electrocardiograph tracing. ro. 2 Example of an arrhythmia occurring shortly after injection of epinephrine I :IOO,OOO. IG. 3 Another example of an arrhythmia occurring with epinephrine i :ioo,ooo. ~_~ Discussion.--The results of this small study indicate that ventricular arrhythmias occurred quite frequently in halothane anaesthetised patients when epinephrine or neo-cobefrin was injected supraperiosteally in small amounts. Short periods of arrhythmia are not necessarily of great significance and have been encountered frequently when halothane has been administered alone particularly with concentrations above I per cent. These arrhythmias, as with those encountered in our study, could rapidly be reversed by reducing the concentration of the agent. It has been demonstrated by Hall & Norris (1958) that large amounts of epinephrine injected directly into the vena cava of dogs frequently produces significant arrhythmias and in many instances death of the animal. The amount of epinephrine to produce these changes varies widely with the individual animal, the experimental species, the route of administration, and the rate of injection. In their study amounts of the order of 5 mg. per kg. injected directly into the vena cava

4 134 BRITISH JOURNAL O ORAL SURGERY were necessary to produce the changes described. If the epinephrine was administered intramuscularly, approximately 159 x the dosage was required to produce similar changes, and they have estimated that the fatal intravenous dose in man would be I/3 of a milligram, that is, 35 micrograms. On this basis then, they see no absolute contraindication to the combined usage of epinephrine and fluothane in reasonable amounts and concentrations in healthy patients. In an earlier study Raventos (I956) reported that with even very large intravenous doses of epinephrine ventricular fibrillation did not always occur. IG. 4 An example of an arrhythmia occurring with neo-cobefrin 1:2o,ooo. q IG. 5 An arrhythmia occurring with epinephrine 1:5o,ooo. He found that the mean dose required to produce arrhythmias in the unpremedicated animal was 88 micrograms. If given intramuscularly or subcutaneously much larger doses could be tolerated. In some dogs as much as 200 ml. of I/IOO,OOO epinephrine or 5 ml. of I to I,OOO epinephrine given intramuscularly failed to produce any arrhythmias. Very few clinical studies, in humans, have been performed wherein epinephrine has been used during halothane anaesthesia. But of considerable interest is the fact that on a number of occasions the patients general condition necessitated the use of epinephrine as an emergency measure. Dawson et al. (I96o) have reported five occasions in which a persistent reduction in cardiac output after cardiac manipulation necessitated the injection of "5 to I ml. of I to io,ooo solution of epinephrine directly into the cavity of the right ventricle. In all instances an increase in heart rate and restoration of blood pressure

5 _ <s/conds ARRHYTHIAS PRODUCED BY COBINATIONS O HALOTHANE 135 TABLE I SUARY O ARRHYTHIAS Sex Agent Time of injection Time Arrhyth. noted Duration of Arrhyth. l ain characteristics Neo -Cobefrin 1:20,000 1: :20,000 1:20~000 1:20,000 1:20~000 9:13 8:49 10:12 9:1o 11:55 8:28 9:15 3/4 9:51 I/3 I:13 I/I0 9:11 I/~ 11:57 1/6 8:31 5/6 I Ventricular following irreg. Numbers of normal beats, ectopic loci bigeminate rhythm I "I00,000 I : I00,000 9:31 8:55 9:32 5/6 8:57 5/ prematnrities nodal escape bigeminate rhythm 1:50~0OO 1:50~000 9:30 9:I9 9:32 3/4 9:20 I/ bigeminate rhythm too complex to analyse INCIDENCE O ARRHYTHIAS Combinations Total subjects Number of arrhythmias Percentage of arrhythmias Halothane 20 Halothane 1:50~000 4o Halothane C- I : 100) "3 Halothane C- Neo-Cobefrin 1:20~000 IO 6o

6 136 BRITISH JOURNAL O ORAL SURGERY followed. In only two patients were a few ventricular extrasystoles noted. They did not report that ventricular tachycardia or fibrillation occurred after the injection of epinephrine. In a recent study Katz et al. (1962) reported on the administration of relatively large amounts of epinephrine, "5 mg. of a I to 6%ooo solution administered subcutaneously over a 3o-minute period. Very few arrhythmias were observed. In fact there was practically no difference between the control and experimental groups. They concluded that this was due to the long injection period which resulted in slow absorption and low plasma epinephrine levels. They also stressed the importance of maintaining adequate ventilation thereby preventing arrhythmias that might have been due to hypoxia or hypercarbia. In the light of these findings it is interesting to surmise why we should have encountered a relatively large number of arrhythmias when using such small amounts of epinephrine. There are, of course, a number of possibilities. One is the rate of injection. All injections in the study reported here were completed within 3 seconds and even with the smaller dosage this could be responsible for the increased number of arrhythmias encountered. Secondly, the rate of absorption by injection in the oral cavity approaches that of the intravenous route and is much greater than from the subcutaneous route used in the experiments of Katz eta!. (1962). There is the third possibility. Since aspirating syringes were not used in our experiment, a small percentage of the cases may have received the local anaesthetic solution containing the epinephrine, intravenously, which could have caused some of the arrhythmias. We do not believe that the combined usage of halothane and small amounts of epinephrine is absolutely contraindicated as long as adequate precautions are observed; these would include: I. aintaining the lowest concentration of halothane. 2. Never using epinephrine in concentrations greater than I:IOO,OOO and preferably 1:2o0,0o0, which would probably give equally good vasoconstriction. 3. Injecting small amounts periodically rather than depositing the entire volume at one time. 4. Not using the combination in patients with cardiac conduction disorders. 5. onitoring patients with E.K.G. is desirable but probably not essential. Summary.--The results of a clinical study concerning the incidence of ventricular arrhythmias in patients anaesthetised with halothane and who received small amounts of epinephrine and neo-cobefrin in a local anaesthetic vehicle is reported. An appreciable number of arrhythmias, which were rapidly reversible was encountered in all groups except the control group. Suggestions for the safe usage of the combination have been made. ACKNOWLEDGEENT This investigation was supported in part by USPHS research grant Teacher Training DT-I6 (C3)from the National Institute of Dental Research, National Institutes of Health, Bethesda, aryland. REERENCES DAWSON, B., THEYE, R. A. & KIRKLIN, J. W. (196o). Anaesth. Analg. Curr. Res. 39, 59. HALL, K. D. ~9' NORRIS,. H. (1958). Anaesthesiology, 19, 631. KATZ, R. L. ATTEO, R. S. C~' PAPPEN, E.. (1962). Anaesthesiology, 23, 5. RAVENTOS, J. (1956). Brit. J. Pharmacol. II, 394.