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TRIAL OF COMBINED INTRAMUSCULAR AND INTRAVENOUS LIGNOCAINE IN PROPHYLAXIS OF VENTRICULAR TACHYARRHYTHMIAS
817 SUMMARY OF FINDINGS IN REPRODUCIBILITY TESTS
reliability of the D.R.M. During a period of three months, three of the six D.R.M.S became so defective that they had to be returned to the manufacturer. We conclude that, until these defects in calibration and functional stability are corrected, the meter cannot be recommended for evaluating diagnostic glucose-tolerance tests and for monitoring the bloodsugar levels during treatment of diabetic coma. We thank Ames Company for instruction and use of the reflectance meters, and Mr. P. Thoft-Christensen for statistical
analyses. Requests for reprints should be addressed
to
J. D.
REFERENCES
line can also be resolved (fig. 6) into two statistically different lines using 180 mg. per 100 ml. as the dividing value-namely, y==0-80x+ll’17 for values below 180 mg. per 100 ml., and y=0-65x+57-47 for values above 180 mg. per 100 ml. Both these lines differ significantly from the 45’line. The table summarises the results of 110 double determinations performed with meters i-vi. The reproducibility was satisfactory, as seen from the mean differences between duplicate blood-sugar determinations. The calculated coefficient of variation was 4-0% for blood-sugar values below 180 mg. per 100 ml. and 3-2% for values above 180 mg. per 100 ml. Discussion
Dextrostix is
semiquantitative method for bloodsugar determination, and according to the manufacturer the reflectance meter makes this glucose-oxidase method quantitative. This suggestion has been supported by several investigations, &bgr;-I0 most of which compared the reflectance meter with a reduction method for blood-sugar determination, and only a limited number of blood-sugars above 300 mg. per a
included. 7-9 We included several bloodwith samples sugar values above 300 mg. per 100 ml., and the D.R.M. was compared with an autoanalyser glucose-oxidase method. For the D.R.M. method to be acceptable, blood-sugar determinations by the two methods should yield a regression line close to the 45’line, when the results are plotted against each other. This might be so for meter no. i, but with this meter only few blood-sugar values above 300 mg. per 100 ml. were estimated. For all other meters the lines are regression only just acceptable below 180 100 ml. and mg. per quite unacceptable above 180 mg. 100 ml. 180 per mg. per 100 ml. is used as the dividing of the point results, because the meter scale for the highest blood-sugar values ranges from 180 to 1000 mg. per 100 ml. The D.R.M. has three meter scales for blood-sugar measurements-one from 10 to 70 mg. per 100 ml., another from 70 to 180 mg. per 100 ml., and a third from 180 to 1000 mg. per 100 ml.but even so the meter is only provided with a single reference strip (110 mg. per 100 ml.), corresponding to the middle range of values. Our results indicate the necessity of at least a further reference stick in the range from 180 to 1000 mg. per 100 ml., as has also been recommended by Balazs et a1. and Schersten 10 on a more theoretical background. During this trial we have also evaluated the functional stability and 100 ml.
were
1. 2. 3. 4. 5. 6. 7. 8. 9.
10.
Alberti, K. G. M. M., Middleton, G. G., Cairo, F. J. Lancet, 1965, ii, 319. Beckett, A. G. ibid. 1965, ii, 591. Cohen, S. L., Legg, S., Bird, R. ibid. 1964, ii, 883. Mackay, N., Gordon, A., Neilson, J. M. ibid. 1965, ii, 269. Rennie, I. D. B., Keen, H., Southon, A. ibid. 1964, ii, 884. Balazs, N., Bradshaw, R., Welborn, T. ibid. 1970, i, 1232. Deckert, T., Futtrup, L. Ugeskr. Laeg. 1971, 43, 2121. Jarrett, R. J., Keen, H., Hardwick, C. Diabetes, 1970, 19, 724. Mazzaferri, E. L., Skillman, T. G., Lanese, R. R., Keller, M. P. Lancet, 1970, i, 331. Scherstén, B. Laekartidn. 1971, 68, 4001.
TRIAL OF COMBINED INTRAMUSCULAR AND INTRAVENOUS LIGNOCAINE IN PROPHYLAXIS OF VENTRICULAR TACHYARRHYTHMIAS SHEILA DARBY
M. A. BENNETT
J. C. CRUICKSHANK
B. L. PENTECOST
General
Hospital, Birmingham 4
The prophylactic effect of lignocaine in suppressing ventricular ectopic activity, ventricular tachycardia, and fibrillation was assessed in 203 patients admitted to hospital with acute myocardial infarction. 103 received an initial intramuscular dose of 200 mg. lignocaine followed by an intravenous infusion at 2 mg. per minute, while 100 controls received no routine prophylactic antiarrhythmic therapy. Both groups were continuously No sigmonitored for 48 hours after admission. nificant difference was found in the frequency of ventricular extrasystoles, while ventricular tachycardia and fibrillation were commoner in the treated group, suggesting that at this dose level lignocaine was ineffective as a prophylactic measure.
Sum ary
Introduction AN effective and safe antiarrhythmic drug regimen is needed for routine administration to patients with myocardial infarction. Results of trials with lignocaine have been conflicting. 1-4 We found no reduction in the incidence of ventricular tachyarrhythmias after the routine administration of 60 mg. lignocaine by intravenous injection followed by a 48-hour infusion of lignocaine 0-5 or 1-0 mg. per minute.These were relatively small doses, and since we encountered no serious problems attributable to lignocaine we decided to try a higher dose.
818 Patients and Methods Patients were assessed in the emergency department of the hospital, and those considered likely to have had a myocardial infarction in the preceding 48 hours were randomly consigned to one of two groups. Those in group A received an immediate intramuscular injection of 200 mg. lignocaine, and patients in group B were given no routine antiarrhythmic treatment. Patients who had a blood-pressure of less than 90 mm. Hg, bradycardia of less than 50 per minute, atrioventricular block of second or third degree, or pulmonary oedema were excluded, as were patients who experienced ventricular tachycardia or fibrillation before they could be admitted to the trial. On arrival at the coronary-care unit patients in group A received an intravenous infusion of 2 mg. lignocaine per minute for 48 hours. In both groups the appearance of frequent ventricular extrasystoles (more than 5 per minute), and salvoes of ventricular extrasystoles, or of the R-on-T phenomenon was treated with additional lignocaine or procaine amide. Patients who developed advanced atrioventricular block, cardiogenic shock, pulmonary oedema, or recurrent sinus or nodal bradycardia resistant to atropine were withdrawn from the trial. Rhythm monitoring was achieved by means of nurses’ observation of the oscilloscope displaying a vi lead. The heart rhythm was continuously recorded on electromagnetic tape and the presence of serious arrhythmias could be confirmed by playing back the recordings. Results
322 patients were admitted to the trial over a period of 15 months, of whom 119 were subsequently rejected because they did not meet the criteria of infarction.33 Of the remaining 203 patients, 103 were in group A and 100 in group B. The two groups were comparable with respect to age, sex, and site of infarction (table i). Table n shows the delay between the onset of symptoms thought to represent infarction and admission to the study, 42% and 46% of patients being admitted within 3 hours of infarction in groups A and B,
respectively. In group A, 11 patients did not complete 48 hours of infusion: 4 developed cardiogenic shock, 3 had
profound sinus bradycardia not improved by reducing lignocaine dosage but responsive to atropine, while 4 TABLE I--CHARACTERISTICS OF PATIENTS
TABLE III-INCIDENCE OF VENTRICULAR ARRHYTHMIAS
In group A, 3
lignocaine. v.E.s.
=
of V.T. progressed to v.F. despite intravenous In the control group 1 episode of v.2. progressed to v.F.
episodes
Ventricular extrasystoles. v.2. Ventricular tachycardia. v.F. = Ventricular fibrillation. * Figures in italic type show number of episodes. =
TABLE IV-NON-VENTRICULAR ARRHYTHMIAS
others had to be discharged early from the unit beof pressure on beds. 3 further patients had severe hypotension after the intramuscular lignocaine but improved rapidly, and lignocaine infusion subsequently had no untoward effect. The frequency of sporadic and frequent ventricular premature beats was approximately equal in the two groups, and incidents were spread throughout the 48 hours (table ill). 2 of the patients in group A developed frequent ventricular extrasystoles between the intramuscular injection and the setting up of the infusion. Ventricular tachycardia and fibrillation were both more common in the treated group, but this was not statistically significant at the 5% level. In view of the increased number of patients with preceding angina, hypertension, or diabetes in group A, the results were analysed after withdrawal of such patients from each group. There was still no statistical significance between the two. One of the patients withdrawn from the treated group because of sinus bradycardia later developed ventricular tachycardia. In table in ventricular tachycardia refers to a sustained arrhythmia requiring termination by drug therapy or electrical cardioversion. All episodes of ventricular tachycardia and fibrillation developed within the first 24 hours of admission and most within the first 12 hours. Of the 3 episodes of ventricular fibrillation in the control group, 2 occurred in the emergency department while the patient was awaiting transfer to the unit, and in the third patient ventricular fibrillation occurred immediately on arrival at the unit. Episodes of ventricular cause
TABLE V-MORTALITY
TABLE II-INTERVAL BETWEEN ONSET OF SYMPTOMS AND ADMISSION TO STUDY
819
fibrillation in the treated group all occurred while the patient was being monitored on the unit. There was no significant difference between the two groups as regards atrioventricular conduction defects,
pulmonary oedema, or supraventricular tachyarrhythmias. Sinus bradycardia, however, was more frequent in the treated group (table iv), although this incidence was not statistically significant at the 5% level. The mortality rate both early and late was similar in groups A and B (table v).
Preliminary Communications STIMULATION OF GASTRIN RELEASE BY CATECHOLAMINES J. ARDILL J. R. HAYES T. L. KENNEDY
R. G. SHANKS
K. D. BUCHANAN
Department of Medicine, Queen’s University of Belfast
Discussion
and
injection of 200 mg. lignocaine produces therapeutic blood-levels in 10-15 minutes.5 Therapeutic levels are also achieved by a constant infusion of the drug at a rate of 2 mg. per minute.6 None of the patients in group A who experienced ventricular tachycardia or fibrillation did so before adequate blood-levels would be expected to have been reached. The results are similar to those of the lowdose trial,3 and produce no support for the routine use of lignocaine in the prophylaxis of serious ventricular arrhythmias after cardiac infarction. In those studies claiming effective protection against arrhythmias 1,2,44 ventricular fibrillation was rare, suggesting that the patients were highly selected, probably on the basis of delay before admission to the trial. Antiarrhythmic effect has been demonstrated through a reduction in ventricular premature beats, but we could not confirm this either, possibly because rhythm monitoring mainly depended on nurse observation of the oscilloscope. It is, however, the serious and life-threatening sustained ventricular tachycardia and ventricular fibrillation rather than ventricular extrasystoles that most concern clinicians. A defect in this study, as in all other trials in coronary-care units, is that allocation to the control group does not rule out the use of antiarrhythmic drugs if ventricular ectopic activity subsequently develops, although the results of one study7 suggest that it would not be unethical to withhold drug treatment in such cases. We cannot say that the routine use of lignocaine will not be of benefit when monitoring facilities are not available. When lignocaine is ineffective in controlling an arrhythmia an antiarrhythmic effect can often be gained by steadily increasing the dose of lignocaine infused.8 This technique is only practicable where there is some pre-existing arrhythmia the frequency of which may be used as an index of therapeutic efficacy. High rates of infusion are probably best restricted to centres where blood-levels of the drug may be determined immediately. We would certainly hesitate to use doses higher than 2 mg. per minute for routine prophylaxis, for, although there was no evidence of an increase in the frequency of cardiac failure or heart block, the incidence of sinus or nodal bradycardia was higher in the treated group, suggesting that we were approaching a dose level when the unwanted effects of lignocaine might occur.
Royal Victoria Hospital, Belfast
An intramuscular
We thank Dr. K. W. Cross for statistical help and Sister P. Lamb and the staff of the coronary-care unit for their help.
Requests for reprints should be addressed
to
References at foot of next column
B. L. P.
Plasma-gastrin levels measured by radioimmunoassay were found to be elevated in two patients with phæochromocytoma. Both the administration of phenoxybenzamine and the later removal of the tumour reduced the fasting plasma-gastrin level to normal. The intravenous infusion of adrenaline in dogs produced a rise in plasma-gastrin level. It is concluded that catecholamines stimulate gastrin release. Summary
INTRODUCTION
CATECHOLAMINES have been shown to inhibit the release of insulin 1,2 and stimulate the release of glucagon.2 We have investigated the effect of catecholamines on gastrin release by studying patients with phseochromocytoma before and after oc-adrenergic blockade and after removal of the tumour. We have also investigated the effect of the intravenous infusion of adrenaline on plasma-gastrin levels in dogs. PATIENTS
Two
patients
with
phxochromocytoma were studied. Case 1.-A woman, aged 35, had had a colectomy for Crohn’s disease when aged 18. In April, 1971, her bloodpressure was 190/125 mm. Hg and her pulse-rate was consistently above 110 per minute. Plasma-catecholamines were 24-3 g. per litre and urinary catecholamines 1000 g. per 24 hours. A phaeochromoctyoma was removed from the hilum of the left kidney. Case 2.-A girl, aged 16, had a recurrence of phaeochromocytoma, the original tumour having been removed in 1968. The blood-pressure was 150/110 mm. Hg and the pulse-rate consistently above 110 per minute. Plasmacatecholamines were 4 g. per litre and urinary catecholThree tumour nodules amines 650 g. per 24 hours. removed had the histological appearance of phaeochromocytoma and had a high catecholamine content. METHODS
Plasma-gastrin
was
measured
by radioimmunoassay.
DR. DARBY AND OTHERS: REFERENCES
1. Morgensen, L. Acta med. scand. 1970, suppl. no. 513. 2. Kostuk, W. J., Beanlands, D. S. in Lidocaine in the Treatment of Ventricular Arrhythmias (edited by D. B. Scott and D. G. Julian); 3. 4. 5.
p. 82. Edinburgh, 1971. Bennett, M. A., Wilner, J. M., Pentecost, B. L. Lancet, 1970, ii, 909. Pitt, A., Lipp, H., Anderson, S. T. ibid. 1971, i, 612. Scott, D. B. in Lidocaine in the Treatment of Ventricular Arrhythmias (edited by D. B. Scott and D. G. Julian); p. 153. Edinburgh, 1971.
Prescott, L. F., Nimmo, J. ibid. p. 168. Chopra, M. P., Thadani, U., Portal, R. W., Aber, C. P. Br. med. J. 1971, iii, 668. 8. Harrison, D. C., Alderman, E. L. in Lidocaine in the Treatment of Ventricular Arrhythmias (edited by D. B. Scott and D. G. Julian); p. 178. Edinburgh, 1971.
6. 7.
reliability of the D.R.M. During a period of three months, three of the six D.R.M.S became so defective that they had to be returned to the manufacturer. We conclude that, until these defects in calibration and functional stability are corrected, the meter cannot be recommended for evaluating diagnostic glucose-tolerance tests and for monitoring the bloodsugar levels during treatment of diabetic coma. We thank Ames Company for instruction and use of the reflectance meters, and Mr. P. Thoft-Christensen for statistical
analyses. Requests for reprints should be addressed
to
J. D.
REFERENCES
line can also be resolved (fig. 6) into two statistically different lines using 180 mg. per 100 ml. as the dividing value-namely, y==0-80x+ll’17 for values below 180 mg. per 100 ml., and y=0-65x+57-47 for values above 180 mg. per 100 ml. Both these lines differ significantly from the 45’line. The table summarises the results of 110 double determinations performed with meters i-vi. The reproducibility was satisfactory, as seen from the mean differences between duplicate blood-sugar determinations. The calculated coefficient of variation was 4-0% for blood-sugar values below 180 mg. per 100 ml. and 3-2% for values above 180 mg. per 100 ml. Discussion
Dextrostix is
semiquantitative method for bloodsugar determination, and according to the manufacturer the reflectance meter makes this glucose-oxidase method quantitative. This suggestion has been supported by several investigations, &bgr;-I0 most of which compared the reflectance meter with a reduction method for blood-sugar determination, and only a limited number of blood-sugars above 300 mg. per a
included. 7-9 We included several bloodwith samples sugar values above 300 mg. per 100 ml., and the D.R.M. was compared with an autoanalyser glucose-oxidase method. For the D.R.M. method to be acceptable, blood-sugar determinations by the two methods should yield a regression line close to the 45’line, when the results are plotted against each other. This might be so for meter no. i, but with this meter only few blood-sugar values above 300 mg. per 100 ml. were estimated. For all other meters the lines are regression only just acceptable below 180 100 ml. and mg. per quite unacceptable above 180 mg. 100 ml. 180 per mg. per 100 ml. is used as the dividing of the point results, because the meter scale for the highest blood-sugar values ranges from 180 to 1000 mg. per 100 ml. The D.R.M. has three meter scales for blood-sugar measurements-one from 10 to 70 mg. per 100 ml., another from 70 to 180 mg. per 100 ml., and a third from 180 to 1000 mg. per 100 ml.but even so the meter is only provided with a single reference strip (110 mg. per 100 ml.), corresponding to the middle range of values. Our results indicate the necessity of at least a further reference stick in the range from 180 to 1000 mg. per 100 ml., as has also been recommended by Balazs et a1. and Schersten 10 on a more theoretical background. During this trial we have also evaluated the functional stability and 100 ml.
were
1. 2. 3. 4. 5. 6. 7. 8. 9.
10.
Alberti, K. G. M. M., Middleton, G. G., Cairo, F. J. Lancet, 1965, ii, 319. Beckett, A. G. ibid. 1965, ii, 591. Cohen, S. L., Legg, S., Bird, R. ibid. 1964, ii, 883. Mackay, N., Gordon, A., Neilson, J. M. ibid. 1965, ii, 269. Rennie, I. D. B., Keen, H., Southon, A. ibid. 1964, ii, 884. Balazs, N., Bradshaw, R., Welborn, T. ibid. 1970, i, 1232. Deckert, T., Futtrup, L. Ugeskr. Laeg. 1971, 43, 2121. Jarrett, R. J., Keen, H., Hardwick, C. Diabetes, 1970, 19, 724. Mazzaferri, E. L., Skillman, T. G., Lanese, R. R., Keller, M. P. Lancet, 1970, i, 331. Scherstén, B. Laekartidn. 1971, 68, 4001.
TRIAL OF COMBINED INTRAMUSCULAR AND INTRAVENOUS LIGNOCAINE IN PROPHYLAXIS OF VENTRICULAR TACHYARRHYTHMIAS SHEILA DARBY
M. A. BENNETT
J. C. CRUICKSHANK
B. L. PENTECOST
General
Hospital, Birmingham 4
The prophylactic effect of lignocaine in suppressing ventricular ectopic activity, ventricular tachycardia, and fibrillation was assessed in 203 patients admitted to hospital with acute myocardial infarction. 103 received an initial intramuscular dose of 200 mg. lignocaine followed by an intravenous infusion at 2 mg. per minute, while 100 controls received no routine prophylactic antiarrhythmic therapy. Both groups were continuously No sigmonitored for 48 hours after admission. nificant difference was found in the frequency of ventricular extrasystoles, while ventricular tachycardia and fibrillation were commoner in the treated group, suggesting that at this dose level lignocaine was ineffective as a prophylactic measure.
Sum ary
Introduction AN effective and safe antiarrhythmic drug regimen is needed for routine administration to patients with myocardial infarction. Results of trials with lignocaine have been conflicting. 1-4 We found no reduction in the incidence of ventricular tachyarrhythmias after the routine administration of 60 mg. lignocaine by intravenous injection followed by a 48-hour infusion of lignocaine 0-5 or 1-0 mg. per minute.These were relatively small doses, and since we encountered no serious problems attributable to lignocaine we decided to try a higher dose.
818 Patients and Methods Patients were assessed in the emergency department of the hospital, and those considered likely to have had a myocardial infarction in the preceding 48 hours were randomly consigned to one of two groups. Those in group A received an immediate intramuscular injection of 200 mg. lignocaine, and patients in group B were given no routine antiarrhythmic treatment. Patients who had a blood-pressure of less than 90 mm. Hg, bradycardia of less than 50 per minute, atrioventricular block of second or third degree, or pulmonary oedema were excluded, as were patients who experienced ventricular tachycardia or fibrillation before they could be admitted to the trial. On arrival at the coronary-care unit patients in group A received an intravenous infusion of 2 mg. lignocaine per minute for 48 hours. In both groups the appearance of frequent ventricular extrasystoles (more than 5 per minute), and salvoes of ventricular extrasystoles, or of the R-on-T phenomenon was treated with additional lignocaine or procaine amide. Patients who developed advanced atrioventricular block, cardiogenic shock, pulmonary oedema, or recurrent sinus or nodal bradycardia resistant to atropine were withdrawn from the trial. Rhythm monitoring was achieved by means of nurses’ observation of the oscilloscope displaying a vi lead. The heart rhythm was continuously recorded on electromagnetic tape and the presence of serious arrhythmias could be confirmed by playing back the recordings. Results
322 patients were admitted to the trial over a period of 15 months, of whom 119 were subsequently rejected because they did not meet the criteria of infarction.33 Of the remaining 203 patients, 103 were in group A and 100 in group B. The two groups were comparable with respect to age, sex, and site of infarction (table i). Table n shows the delay between the onset of symptoms thought to represent infarction and admission to the study, 42% and 46% of patients being admitted within 3 hours of infarction in groups A and B,
respectively. In group A, 11 patients did not complete 48 hours of infusion: 4 developed cardiogenic shock, 3 had
profound sinus bradycardia not improved by reducing lignocaine dosage but responsive to atropine, while 4 TABLE I--CHARACTERISTICS OF PATIENTS
TABLE III-INCIDENCE OF VENTRICULAR ARRHYTHMIAS
In group A, 3
lignocaine. v.E.s.
=
of V.T. progressed to v.F. despite intravenous In the control group 1 episode of v.2. progressed to v.F.
episodes
Ventricular extrasystoles. v.2. Ventricular tachycardia. v.F. = Ventricular fibrillation. * Figures in italic type show number of episodes. =
TABLE IV-NON-VENTRICULAR ARRHYTHMIAS
others had to be discharged early from the unit beof pressure on beds. 3 further patients had severe hypotension after the intramuscular lignocaine but improved rapidly, and lignocaine infusion subsequently had no untoward effect. The frequency of sporadic and frequent ventricular premature beats was approximately equal in the two groups, and incidents were spread throughout the 48 hours (table ill). 2 of the patients in group A developed frequent ventricular extrasystoles between the intramuscular injection and the setting up of the infusion. Ventricular tachycardia and fibrillation were both more common in the treated group, but this was not statistically significant at the 5% level. In view of the increased number of patients with preceding angina, hypertension, or diabetes in group A, the results were analysed after withdrawal of such patients from each group. There was still no statistical significance between the two. One of the patients withdrawn from the treated group because of sinus bradycardia later developed ventricular tachycardia. In table in ventricular tachycardia refers to a sustained arrhythmia requiring termination by drug therapy or electrical cardioversion. All episodes of ventricular tachycardia and fibrillation developed within the first 24 hours of admission and most within the first 12 hours. Of the 3 episodes of ventricular fibrillation in the control group, 2 occurred in the emergency department while the patient was awaiting transfer to the unit, and in the third patient ventricular fibrillation occurred immediately on arrival at the unit. Episodes of ventricular cause
TABLE V-MORTALITY
TABLE II-INTERVAL BETWEEN ONSET OF SYMPTOMS AND ADMISSION TO STUDY
819
fibrillation in the treated group all occurred while the patient was being monitored on the unit. There was no significant difference between the two groups as regards atrioventricular conduction defects,
pulmonary oedema, or supraventricular tachyarrhythmias. Sinus bradycardia, however, was more frequent in the treated group (table iv), although this incidence was not statistically significant at the 5% level. The mortality rate both early and late was similar in groups A and B (table v).
Preliminary Communications STIMULATION OF GASTRIN RELEASE BY CATECHOLAMINES J. ARDILL J. R. HAYES T. L. KENNEDY
R. G. SHANKS
K. D. BUCHANAN
Department of Medicine, Queen’s University of Belfast
Discussion
and
injection of 200 mg. lignocaine produces therapeutic blood-levels in 10-15 minutes.5 Therapeutic levels are also achieved by a constant infusion of the drug at a rate of 2 mg. per minute.6 None of the patients in group A who experienced ventricular tachycardia or fibrillation did so before adequate blood-levels would be expected to have been reached. The results are similar to those of the lowdose trial,3 and produce no support for the routine use of lignocaine in the prophylaxis of serious ventricular arrhythmias after cardiac infarction. In those studies claiming effective protection against arrhythmias 1,2,44 ventricular fibrillation was rare, suggesting that the patients were highly selected, probably on the basis of delay before admission to the trial. Antiarrhythmic effect has been demonstrated through a reduction in ventricular premature beats, but we could not confirm this either, possibly because rhythm monitoring mainly depended on nurse observation of the oscilloscope. It is, however, the serious and life-threatening sustained ventricular tachycardia and ventricular fibrillation rather than ventricular extrasystoles that most concern clinicians. A defect in this study, as in all other trials in coronary-care units, is that allocation to the control group does not rule out the use of antiarrhythmic drugs if ventricular ectopic activity subsequently develops, although the results of one study7 suggest that it would not be unethical to withhold drug treatment in such cases. We cannot say that the routine use of lignocaine will not be of benefit when monitoring facilities are not available. When lignocaine is ineffective in controlling an arrhythmia an antiarrhythmic effect can often be gained by steadily increasing the dose of lignocaine infused.8 This technique is only practicable where there is some pre-existing arrhythmia the frequency of which may be used as an index of therapeutic efficacy. High rates of infusion are probably best restricted to centres where blood-levels of the drug may be determined immediately. We would certainly hesitate to use doses higher than 2 mg. per minute for routine prophylaxis, for, although there was no evidence of an increase in the frequency of cardiac failure or heart block, the incidence of sinus or nodal bradycardia was higher in the treated group, suggesting that we were approaching a dose level when the unwanted effects of lignocaine might occur.
Royal Victoria Hospital, Belfast
An intramuscular
We thank Dr. K. W. Cross for statistical help and Sister P. Lamb and the staff of the coronary-care unit for their help.
Requests for reprints should be addressed
to
References at foot of next column
B. L. P.
Plasma-gastrin levels measured by radioimmunoassay were found to be elevated in two patients with phæochromocytoma. Both the administration of phenoxybenzamine and the later removal of the tumour reduced the fasting plasma-gastrin level to normal. The intravenous infusion of adrenaline in dogs produced a rise in plasma-gastrin level. It is concluded that catecholamines stimulate gastrin release. Summary
INTRODUCTION
CATECHOLAMINES have been shown to inhibit the release of insulin 1,2 and stimulate the release of glucagon.2 We have investigated the effect of catecholamines on gastrin release by studying patients with phseochromocytoma before and after oc-adrenergic blockade and after removal of the tumour. We have also investigated the effect of the intravenous infusion of adrenaline on plasma-gastrin levels in dogs. PATIENTS
Two
patients
with
phxochromocytoma were studied. Case 1.-A woman, aged 35, had had a colectomy for Crohn’s disease when aged 18. In April, 1971, her bloodpressure was 190/125 mm. Hg and her pulse-rate was consistently above 110 per minute. Plasma-catecholamines were 24-3 g. per litre and urinary catecholamines 1000 g. per 24 hours. A phaeochromoctyoma was removed from the hilum of the left kidney. Case 2.-A girl, aged 16, had a recurrence of phaeochromocytoma, the original tumour having been removed in 1968. The blood-pressure was 150/110 mm. Hg and the pulse-rate consistently above 110 per minute. Plasmacatecholamines were 4 g. per litre and urinary catecholThree tumour nodules amines 650 g. per 24 hours. removed had the histological appearance of phaeochromocytoma and had a high catecholamine content. METHODS
Plasma-gastrin
was
measured
by radioimmunoassay.
DR. DARBY AND OTHERS: REFERENCES
1. Morgensen, L. Acta med. scand. 1970, suppl. no. 513. 2. Kostuk, W. J., Beanlands, D. S. in Lidocaine in the Treatment of Ventricular Arrhythmias (edited by D. B. Scott and D. G. Julian); 3. 4. 5.
p. 82. Edinburgh, 1971. Bennett, M. A., Wilner, J. M., Pentecost, B. L. Lancet, 1970, ii, 909. Pitt, A., Lipp, H., Anderson, S. T. ibid. 1971, i, 612. Scott, D. B. in Lidocaine in the Treatment of Ventricular Arrhythmias (edited by D. B. Scott and D. G. Julian); p. 153. Edinburgh, 1971.
Prescott, L. F., Nimmo, J. ibid. p. 168. Chopra, M. P., Thadani, U., Portal, R. W., Aber, C. P. Br. med. J. 1971, iii, 668. 8. Harrison, D. C., Alderman, E. L. in Lidocaine in the Treatment of Ventricular Arrhythmias (edited by D. B. Scott and D. G. Julian); p. 178. Edinburgh, 1971.
6. 7.