828 To dismiss them as clinically irrelevant at this stage would, we feel, be premature. We wholeheartedly endorse George’s plea for individualisation of dosage, adding the caveat that a dose should be the lowest required to achieve the desired therapeutic effect. ROY DAVIES* T. G. PICKERING A. MORGANTI G. BIANCHETTI P. L. MORSELLI Hypertension and Cardiovascular Center, J. ROMANKIEWICZ New York Hospital Cornell Medical Center, New York, N.Y. 10021, U.S.A. J. H. LARAGH *

Present address: Middlesex Hospital, London W1N 8AA.

HYPOTENSION AFTER INTRAVENOUS CIMETIDINE

SIR,—A 34-year-old male was admitted with an 85% burn of both 3rd and 2nd degree caused by an explosion. On the third day after admission he had a gastrointestinal bleed, the gastric pH was 1 8, and he was therefore given cimetidine (300 mg as a bolus intravenous injection given over 4 min). The gastric pH did not rise above 3.0and the dose was increased after 4 doses of 300 mg to 600 mg, again given intravenously over 4 min. After the second 600 mg dose the blood-pressure fell dramatically from an average of 100/50 to 30/0 mm Hg. This occurred on three further occasions and was not at first attributed to cimetidine. Blood-pressure declined when the patient had a heart-rate of 130 beats/min and this did not change at the time of hypotension. Central venous pressure was 20-25 cm of water and showed no changes coincident with the hypotension. The rapid intravenous infusion of plasma in varying quantities reversed the hypotension and although the patient was in a positive cumulative fluid balance of 10-12 it was felt that he might have a reduced intravascular volume. Additional colloid was given and the hypotensive episodes coincident with cimetidine gradually decreased in severity, although bloodpressure did not return fully to normal. Intravenous injection of the diluent had no effect. Gentamicin and carbenicillin were also given for infection with gram-negative organisms and morphine alkaloids were given for relief of pain. The second patient was a 49-year-old male admitted for respiratory intensive care 6 days after clinical signs of tetanus appeared. The patient was ventilated and treated with large doses of diazepam intravenously, and with pancuronium bromide and penicillin. On the fifth day after admission the patient had a gastrointestinal bleed and 300 mg cimetidine was given intravenously over 5 min. The gastric pH rose from 1.5 to 3.0 and after two doses of 300 mg, 600 mg cimetidine was given intravenously After the first dose of 600 mg the bloodpressure fell abruptly from 170/100 to 120/60. The patient’s blood-pressure had varied considerably both spontaneously and when he was disturbed and the fall in blood-pressure was not initially attributed to cimetidine. However, subsequent doses of cimetidine produced similar effects. Hypotension lasted 5-25 min. 300 mg cimetidine reduced blood-pressure less than 600 mg and for a shorter time. A variety of other drugs for control of blood-pressure had been given but were stopped when cimetidine was given. Heart-rate or central venous pressure did not change during hypotensive episodes. It is difficult to explain the mechanism of cimetidine-induced hypotension; in the second patient considerable alterations in sympathetic activity were evident, with swings in bloodpressure and heart-rate and profuse sweating, but in the first patient the usual blood-pressure of 100/50 was maintained despite large doses of plasma. Cimetidine in a number of clinical disorders might act as a partial histamine agonist, producing vasodilation, but this has not been previously reported. The possibility that excessive secretion of histamine might have occurred in both the patients, and that cimetidine had a vasodilator effect, seems unlikely. Cimetidine did not induce hypotension in 50—60 other patients in the intensive-care unit.

now infuse the drug rather than give bolus injections, and have not seen any haemodynamic changes.

We

Respiratory Intensive Care Unit, Toronto General Hospital, Toronto, Ontario, Canada

W. A. MAHON M. KOLTON

CIMETIDINE AND BRADYCARDIA

SIR,—Reding et al.’ described a patient who developed bradycardia and atrioventricular dissociation while on oral cimetidine. We have seen two cases of bradycardia associated with cimetidine. A 39-year-old man with a radiologically proven gastric ulcer responded well to a 4 week course of cimetidine (1 g daily) but symptoms recurred on a maintenance dose of 400 mg at night. 2 days after restarting a 1 g daily dose he developed malaise and dizziness which persisted until he was seen as an outpatient 4 weeks later. Examination was normal except that the pulse-rate was 48/min (previously 76/min) and an electrocardiogram confirmed a sinus bradycardia. The symptoms disappeared and his pulse-rate rose to 72/min on stopping cimetidine. A 62-year-old man was admitted with a melama after taking aspirin. 4 h after being given cimetidine (200 mg intravenously) a sinus bradycaria was noted (42/min). There was no electrocardiographic or enzyme evidence of myocardial infarction. Cimetidine (1 g) was given orally for the next 3 days and bradycardia persisted. On the third day the patient complained of thirst and had glycosuria (blood-sugar 14.2 mmol/1). He had no history of diabetes mellitus, his bloodsugar was normal on admission, and he was not receiving Intravenous glucose. Cimetidine-induced , hyp.erglyca:mia has been noted by us previously (Feb. 18, p. 383), and therefore the drug was discontinued. Over the following 10 h his pulse rose from 44/min to 64/min. 3 days later the patient was challenged with an intravenous bolus of 200 mg cimetidine. His heart-rate fell from 70/min to 44/min over 3 h and subsequently returned to normal over 10 h. Cimetidine may induce sinus bradycardia by blocking the H2-receptor sites present in the heart.2 We thank Dr G. W. Scott for tients under his care.

allowing

us to

report details of paD. B.

JEFFERYS J. A. VALE

Guy’s Hospital, London SE1

NOMIFENSINE OVERDOSE

SIR,—Nomifensine3is one of a number of new antidepresNo reports of overdosage have been published and we report here one case in which the patient made an uneventful sants.

recovery.

28-year-old woman was admitted to hospital 3 h after tak5 g (sixty 25 mg capsules) of nomifensine. She had a history of attempted suicide and had previously received antidepressant drugs and electroconvulsive therapy. Her drug treatment had been changed by her general practitioner from imipramine to nomifensine a few days before the overdose because of failure to respond. On admission she was conscious; pulse, blood-pressure, and respiration were normal, and there were no abnormal neurological signs. A stomach wash-out was done but no capsules could be identified in the washings. Although clinically not severely poisoned, she was transferred to the intensive therapy unit for further observation. Apart from a sinus tachycardia of 140/min which rapidly resolved, A

ing

1. 2.

1

P. Lancet, 1977, ii, 1227. Black, J. W., and others. Nature, 1972, 236, 385. 3. Symposium on Nomifensine Br. J. Pharmac. 1977, 4, Suppl. 2 (edited by P. A. Nicholson and P. Turner).

Reding, P., Devroede, C., Barbier,

829 Observations remained nor24 h and 2 days later she was transferred to a psychiatric unit. Plasma-nomifensine concentrations were 2780 flg;1 on admission and 1915 g/1 the following morning. Peak levels of 20-50 g/1 were found after a single dose of 100 mg nomifensine.4 A comprehensive toxicological screen of plasma and urine from the patient detected no drugs apart from nomifensine. In this case the history was accurate, overdosage with nomifensine was confirmed analytically, and the ingestion of other drugs was excluded. In most of the cases of nomifensine poisoning reported to the manufacturers,s other drugs were taken and toxicological analyses were not done. We would be interested to hear from other clinicians who have encountered similar cases of nomifensine overdosage and we would be willing to make toxicological investigations. an

electrocardiogram was normal.

mal for the

next

S. MONTGOMERY P. CROME R. BRAITHWAITE

Department of Psychiatry and Poisons Unit, Guy’s Hospital, London SE 1

RHEUMATOID ARTHRITIS AND ORAL CONTRACEPTION

SiR,-In its report of a reduced incidence of rheumatoid arthritis associated with oral contraceptives (March 18, p. 569) the R.C.G.P. Oral Contraception Study does not give the method of statistical analysis, an important omission especially since the difference between numbers of first cases of rheumatoid arthritis seems small (37 in oral contraceptive takers/extakers and 57 in controls). Did the diagnoses of rheumatoid arthritis fit the definite or classical pattern as laid down by the American Rheumatism Association? This is a critical question. If the diagnosis is correct then we have annual incidence figures of the order of 0-3 5 per 1000. This is much lower than the population studies, which suggest an incidence of 2-6%. I have always felt that the figures for the incidence of rheumatoid arthritis given in the textbooks are too high, and the R.C.G.P. study would confirm this view. Department of Rheumatology and Rehabilitation, King’s College Hospital, London SE5 9RS

***This letter has been shown

to

Dr

HEDLEY BERRY

Kay, whose reply fol-

lows.-ED. L

SiR,—The statistical test was fully described by Mr Richard Peto in appendix III in our interim report.’ It is not practical to summarise this test here but we will send a photocopy to anyone who finds it inconvenient to refer to the original. In the context of a general morbidity study, we were unable to obtain sufficient detail about the specific criteria used for the diagnosis of rheumatoid arthritis to the extent recommended by international agreement. Our aim, therefore, was to determine that similar criteria were used in each of our contraceptive categories, and that comparisons between these groups were valid. This was the purpose of our special inquiry. We would not claim, however, that the diagnostic criteria were sufficiently strict for comparisons to be made with other populations, especially if they had different characteristics. Nevertheless, Wood2 has estimated an annual incidence of at least 0.2 per 1000 for both sexes, so that our estimate of approximately 0.5 per 1000, based on a population of women of reproductive age, is of a similar order of magnitude. We suspect that 4. Chamberlain, J., Hill, H. M. ibid. p. 117. 5. Hoechst Pharmaceuticals. Unpublished. 1. Royal College of General Practitioners. Oral

the figure Dr Berry quotes rather than incidence.

Oral Contraception Study, R.C.G.P. Manchester Research Unit, 8 Barlow Moor Road, Manchester M20 0TR

Contraceptives

London,1974. 2. Wood, P. H. M. in Copeman’s Text Book of the Rheumatic Diseases by J. T. Scott); chap. 3. Edinburgh, 1978.

(edited



CLIFFORD R. KAY SALLY J. WINGRAVE

PROSTAGLANDINS AND ACTINIC CANCER

SIR,-Professor Greaves (Jan. 28, p. 189) has proposed that prostaglandin E (P.G. E), by reducing proliferative activity in the epidermis, may protect the skin against the mutagenic effects of ultraviolet irradiation. If this is so we should expect find an increased incidence of solar keratosis in patients with psoriasis, since such patients have an increase in the rate of epidermal proliferation, and they have decreased P.G.E levels both in affected and unaffected skin.l,2 An Australian study has shown that psoriasis is associated, not with an increase, but with a considerable decrease in the incidence of solar keratosis.3 Of 819 men over the age of 45 without psoriasis 88% had solar keratosis, whereas of 51 men of the same age with psoriasis only 2 had solar keratosis. Whether this decreased risk of actinic malignancy in psoriasis is due to enhanced immunosurveillance as a result of the low P.G.E levels4 or to some other mechanism needs to be tested. to

Department of Dermatology,

Royal Infirmary, Bristol BS2 8HW

E. M. SAIHAN

J. L. BURTON

METHOD OF TOTAL VEIN INJECTION FOR VARICOSE VEINS

SIR,-Many of the large number of methods for the injection treatment of varicose veins demand multiple injections with prolonged bandaging to obtain satisfactory results. The method described here aims at injection of the whole varicosity, the vein being injected in the empty state, and when combined with careful bandaging, ensures in many cases a most satisfactory result. The patient lies with the affected limb raised at about 30° The leg is supported. A sphygmomanometer is placed round the upper thigh. The pressure in the manometer is raised to 50 mm Hg and the patient is instructed to move the foot up and down. The veins in the whole leg slowly distend and varicosities become easily recognisable. A satisfactory distension is achieved in three minutes. Using a radiopaque ’Teflon’ ’E-Z’ catheter (size 16 or possibly a little larger) with a needle length of 0.55 in a venepuncture is made in the prominent lower vein just above the ankle. When blood appears in the catheter the manometer is released; in about two minutes the raised limb has emptied the superficial veins. The leg may be stroked upwards to aid vein collapse. The needle assembly is then removed completely from the catheter, which is passed up the collapsed vein. There is often some difficulty in negotiating communicators but with some patience the catheter can be easily inserted up the vein to the region of the knee. It is possible to pass the catheter above this level but injection is best restricted to veins below knee level. The injection syringe is now connected to the catheter and as the catheter is slowly withdrawn the injection is made into the vein. A support tubegrip can be placed above the knee as the manometer is placed in position and this tubegrip can be unwound down the leg as the injection proceeds. The whole limb should then be carefully supported with sorKassis, V., Weismann, K., Heiligstadt, H. Sondergaard, J. Arch. derm. Res. 1977, 259, 207. 2. Aso, K., Denau, G., Krulig, L., Wilkinson, D. I., Farber, E. M. J. invest. Derm. 1975, 64, 326. 3. Kocsard, E. Aust. J. Derm., 1976, 17, 65. 4. Smith, E. B., Mason, W. V., Goodwin, J. S. Lancet, 1978, i, 561. 1.

and Health.

(2-6%) is an estimate of prevalence

Nomifensine overdose.

828 To dismiss them as clinically irrelevant at this stage would, we feel, be premature. We wholeheartedly endorse George’s plea for individualisation...
310KB Sizes 0 Downloads 0 Views