- Email: [email protected]
THE TREATMENT OF SEVERE ASPIRIN POISONING
329
of fluid and electrolyte balance, and must be carried out under close clinical and biochemical control. Treatment along the lines indicated can almost always bring the serum concentration under toxic level in less than twenty-four hours. Therefore, in our opinion, in bromide poisoning only if is indicated hxmodialysis has cardiac the patient decompensation, if renal function is considerably impaired, or if the poisoning is exceedingly severe or combined with poisoning by depressants of respiratory reflexes.
problems
Summary
.
A case of severe bromide poisoning is reported. The rate of spontaneous elimination of bromide is compared with that induced by forced halogen excretion
and by haemodialysis. Even after effective htmodialysis, the concentration of bromide in the cerebrospinal fluid is slow to fall. From the study of elimination-rates, indications are given for treatment of bromide poisoning by forced
halogen excretion
or
by haemodialysis. REFERENCES
Brun, C. (1949) Nord. Med. 42, 1774. Gjørup, P. A. (1955) Ugeskr. Lœg. 117, 749. Jørgensen, H. E., Wieth, J. O. (1963) Lancet, i, 81. Merrill, J. P., Weller, J. M. (1952) Ann. intern. Med. 37, 186. Schreiner, G. E. (1958) Arch. intern. Med. 102, 896. Todd, J. C., Sanford, A. H., Wells, B. B. (1953) Clinical Diagnosis by Laboratory Methods; p. 460. Philadelphia and London. von Frey, E. (1911) Z. exp. Pharm. Ther. 8, 29.
THE TREATMENT OF
SEVERE ASPIRIN POISONING D. C. DUKES M.B., B.Sc. Birm.
J. D. BLAINEY M.D.
Lond., M.R.C.P.
MEDICAL REGISTRAR THE ARTIFICIAL KIDNEY UNIT, THE GENERAL
PHYSICIAN
HOSPITAL, BIRMINGHAM, 4
G. GUMMING M.B., B.Sc., Ph.D. Birm., A.R.I.C. LECTURER IN MEDICINE IN THE UNIVERSITY OF BIRMINGHAM
G. WIDDOWSON B.Sc. Birm., A.R.I.C. BIOCHEMIST, THE GENERAL HOSPITAL,
BIRMINGHAM
ASPIRIN and the other salicylates are the third most common cause of death from acute poisoning in this country, being exceeded in frequency only by carbon monoxide and the barbiturates (Ministry of Health 1962). In 1961 the total number of deaths from salicylate poisoning was 290 (Registrar General 1962) but a better idea of the size of the problem is given by the estimate that 15% of hospital admissions for poisoning are due to the taking of aspirin and other salicylate compounds (Ministry of Health 1962). In 1959 20,100 cases of all types of poisoning were admitted to hospital, and it may be assumed that this number will continue to increase. The serious toxic effects of acetylsalicylic acid and other salicylates depend on their concentration in the tissues, and the effective treatment of salicylate poisoning requires the removal of the drug as rapidly as possible. Haemodialysis with the artificial kidney (Doolan et al. 1951) is now an accepted method of treatment of severe salicylate poisoning, but the number of cases involved would impose an impossible burden upon existing artificial-kidney units if all required dialysis. Forced diuresis has been suggested as a logical method of treating salicylate poisoning (Cumming 1961, Clemmeson et al. 1962) and Gutman, Yu and Sirota (1955) have shown that the excretion of free salicylate is increased in alkaline urine. No direct com-
treatment of patients with dialysis or forced alkaline diuresis has yet been reported. In this study of patients with acute aspirin poisoning, measurements have been made of the quantity of salicylate removed when hxmodialysis and forced diuresis were used simultaneously. The results are compared with those obtained in a second group of patients, treated by forced alkaline diuresis alone.
parison of
Methods Eleven patients were treated in all, six with the Travenol Kolff " twin-coil " artificial kidney and five by forced alkaline diuresis without dialysis. In all the patients, some
form of
salicylate (either acetylsalicylic acid or calcium amounts varying from 26 to aspirin) 98 g. (80 to 300 5-grain tablets) between three and fourteen hours before admission, as far as was known. None of the patients in either group was hypotensive. had been taken in
In the
dialysed group the bladder was emptied every minutes, the urine being pooled for analysis. During dialysis the patients were weighed on an Avery bed-weighing machine, and the rate of intravenous infusion of alternate bottles of 0-9% sodium-chloride solution and of 5% dextrose was adjusted to maintain a weight increase of 1-5 kg. as a 30
diuresis. The concentrations of total salicyl in compounds serum, urine, and dialysis fluid were determined by theAutoAnalyzer ’,i using a modification of the method of Trinder for convenience in dealing with a large number of specimens. Five patients were treated by forced diuresis alone. The clinical state of each patient on admission was comparable with that of the patients treated by hxmodialysis. It was reassessed by the same observer at hourly intervals according to (a) impairment of consciousness, (b) restlessness, (c) overbreathing (it was found impracticable to measure ventilation accurately in the uncooperative subject), (d) tachycardia, (e) vomiting, (f) sweating, (g) deafness, and (h) tinnitus. In these five patients the dose of salicylate, the time-interval between its ingestion and treatment, and the initial serum-salicylate levels were of the same order as in the patients treated by ha:modialysis. A catheter was placed in the bladder and the urine collected hourly, the rate of infusion being adjusted to produce a urine flow of approximately 500 ml. per hour. 500 ml. of 0-9% sodium-chloride solution, 5% dextrose, and 2% sodium bicarbonate (1/6 M sodium lactate in case 1) were infused in rotation, at an initial rate of about 2 litres an hour. Hourly measurements were made of serum and urine salicylate; urine pH was measured with an ‘ E.LL.’ pH meter. The arterial pH, Pco2 and standard bicarbonate were determined hourly by the capillary method of Astrup (1961). Alkali was omitted from the infusion when a urinary pH of 8-0 was attained. stimulus
to
(1954),
Results Patients Treated
by Hcemodialysis
six patients recovered rapidly, freedom from symptoms (apart from tinnitus and mild deafness) being attained towards the end of dialysis. Patient 6, an intelligent schoolboy who had been transferred from another hospital in coma after a series of convulsions, was well enough before the end of his treatment to demand an explanation of the principles of haemodialysis. The table relates the change in serum-salicylate concentration to clinical improvement in each patient during the first All
8 hours of observation and compares the total urinary excretion of salicylate with the extraction of salicylate by dialysis. Any error in the measurement of the very low concentrations of salicylate (2-4 mg. per 100 ml.) in the dialysis fluid (100 litres) is magnified when the extraction of salicylate is calculated. Therefore, the values for 1.’
AutoAnalyzer ’ is the trade name of Company, Chauncey, New York, U.S.A.
the Technicon Instruments
330 TABLE RELATING CLINICAL STATE TO REMOVAL OF SALICYLATE IN THE FIRST EIGHT HOURS IN PATIENTS TREATED BY HaeMODIALYSIS AND BY FORCED ALKALINE DIURESIS
a-impairment of consciousness. b-restlessness.
Summary of clinical state c--overbreathing. d-tachycardia.
e-vomiting. f-sweating.
g-deafness. h-tinnitus.
salicylate recovery shown in the table may be approximate; but it appears that salicylate was removed from the blood twice as fast by haemodialysis as by diuresis, with a urine output of 100-800 ml. per hour. Urine pH was not measured in the dialysed cases, and no attempt was made
Intravenous therapy, however, can be started without delay, and the results show that forced diuresis by itself, although it does not remove salicylate so quickly, is an effective means of treating salicylate poisoning (see table). Its success depends on reasonable renal function and a to make the urine alkaline. satisfactory blood-pressure : in their absence, haemodialysis is necessary. In case 4 the urine was deeply pigmented, containing Our regime of treatment starts with aspiration of the and no was brown-stained attempt many granular casts, stomach contents as soon as aspirin poisoning is diagnosed. made to force a diuresis. The urine returned to normal in 48 hours. The pigment, which was not a hsemoglobin Lavage with large volumes of fluid is unnecessary, because derivative, remains unidentified, although such pigmenta- little more aspirin is removed by this means; and it may tion of the urine has occasionally been described in be dangerous, because it increases the risk of aspiration pneumonia (Cumming 1961). While the gastric aspiration salicylate intoxication. is being performed, an intravenous drip is started, and the Patients Treated by Forced Alkaline Diuresis level is measured. The volume of fluid All five patients recovered rapidly. In each case clinical serum-salicylate required is considerable, for fluid is lost rapidly with improvement was evident 4-5 hours after starting the sweating and overbreathing and the aim is to produce infusion, which was then slowed. Except in case 8, the a urine flow of at least 500 ml. per hour. 2% sodium patients before the start of treatment had a normal or bicarbonate (or 1/6 M sodium lactate), 0-9% sodium raised arterial pH, normal standard bicarbonate, and chloride, and 5% dextrose are infused in rotation, and reduced PC021 indicating hyperventilation as the cause of up to 2 litres an hour is given for the first three hours, these disturbances. Alkali was given to these patients with to the maintenance of normal jugular venous the sole object of rendering the urine alkaline, in order to subject pressure and the absence of crepitations at the lung bases, produce the maximum excretion of salicylate. Infusion of The bladder is emptied hourly; if the patient cannot do alkali was accompanied by a rise in the arterial pH and this voluntarily, an indwelling catheter is passed. standard bicarbonate and by a rise in the urine pH. The Alkali is omitted from the infusion when the urine low initial Pc02 was slowly corrected as hyperventilation attains a pH of 8-0 (if a pH meter is not available, British diminished with treatment. Diuresis began after about Drug Houses indicator paper of suitable range can be 2 litres of fluid had been infused, and clinical improvement used). A chart is kept of the patient’s clinical state, fluid progressed as the plasma-salicylate concentration fell. input, and urine output. A positive water balance is Another paper will give details of the changes resulting required to stimulate diuresis, and an intake of 6-8 litres from this treatment. is necessary to produce 3-4 litres of urine in the first Discussion 8 hours’ treatment. Intravenous therapy is controlled The results confirm previous reports of the effectiveness according to the patient’s clinical state and the serumof hsemodialysis in removing salicylate from the poisoned salicylate level, which should be measured hourly. patient (Doolan et al. 1951, Schreiner et al. 1955, Determination of arterial pH, Pc02, and standard bicar’ Schreiner 1958, Thomsen and Dalgard 1958, Magness bonate is probably an unnecessary refinement, provided and Murray 1961, Jorgensen and Wieth 1963) and show that not more than 2 litres of alkali is given, for the kidney that the amount removed is considerably increased when is able to excrete alkali rapidly. With an initial serumis combined with forced diuresis (see table). salicylate level of 80-90 mg. per 100 ml., 8 hours’ treathsemodialysis To this extent support is lent to a suggestion made in the ment is enough to produce a level of 30-40 mg. This is recent report from the Ministry of Health (1962) that the comparable to what can be achieved with the artificial artificial kidney may be a useful adjunct to proposed kidney within 8 hours of diagnosis, taking into account regional poisoning treatment centres. On the other hand, delays due to transport of the patient and the cross’ the number of artificial-kidney units is limited; and, even matching of blood for priming the machine. if the apparatus is not already in use, delay may occur We suggest that, when renal function is adequate, forced between diagnosis of poisoning and the start of treatment, alkaline diuresis is a satisfactory treatment for severe particularly if the patient has to be brought from a salicylate poisoning. It should not be attempted in the distance. presence of hypotension, which is an indication for urgent
i
331 or where renal function is suspect for any other reason. Haemodialysis is also indicated if adequate diuresis is not obtained in 3 hours. If the number of deaths from aspirin poisoning is to be reduced, promptness of treatment is vital; and we regard this condition as a medical emergency which demands the closest supervision.
htemodialysis,
Summary The removal of salicylate by hasmodialysis and simultaneous forced diuresis has been measured in six patients with acute aspirin poisoning, and has been compared with the effects of forced alkaline diuresis in five patients with poisoning of the same severity. In each patient clinical improvement was related to reduction in serum-salicylate level. If delays in obtaining use of the artificial kidney are taken into account, forced alkaline diuresis is shown to be comparable in efficiency to hasmodialysis in producing clinical and biochemical improvement over the eight-hour
period following diagnosis. A method is described for treating poisoning by forced alkaline diuresis. We wish
acute
aspirin
thank Prof. W. M. Arnott, Dr. W. T. Cooke, Dr. D. R. M. Malins for allowing us to include patients under their care in this study, and Mr. P. Dawson-Edwards and Mr. L. J. Lawson for the surgical care of the patients treated by hamiodialvsis. to
Humphreys, and Dr. J.
REFERENCES
Astrup, P. (1961) Clin. Chem. 7, 1. Clemmesen, C., Myschetzky, A., Lassen, N. A. (1962) Lancer, i, 162. Cumming, G. (1961) Medical Management of Acute Poisoning. London. Doolan, P. D., Walsh, W. P., Kyle, L. H., Wishinsky, N. (1951) J. Amer. med. Ass. 146, 105. Gutman, A. B., Yü, T. F., Sirota, J. H. (1955) J. clin. Invest. 34, 711. Jørgensen, H. E., Wieth, J. O. (1963) Lancet, i, 81. Magness, J. L., Murray, J. B. (1961) J.-Lancet, 81, 253. Ministry of Health (1962) Emergency Treatment in Hospital of Cases of Acute Poisoning. H.M. Stationery Office. Registrar General (1962) Statistical Review of England and Wales for 1961, Part I. H.M. Stationery Office. Schreiner, G. E. (1958) Arch. intern. Med. 102, 896. Berman, L. B., Griffin, J., Feys, J. (1955) New Engl. J. Med. 253, —
213.
Thomsen, Å. C., Dalgård, O. Z. (1958) Amer. J. Med. 25, Trinder, P. (1954) Biochem. J. 57, 301.
484.
ADULT ENDOMYOCARDIAL FIBROSIS IN BRITAIN A. A.
FARUQUE
M.B. Dacca REGISTRAR IN PATHOLOGY, GENERAL HOSPITAL, WEST HARTLEPOOL, CO. DURHAM
ENDOMYOCARDIAL fibrosis is relatively common in tropical Africa but is rare in other parts of the world, particularly among white adults. Isolated cases have been reported from many places, and from as early as 1883 (Nauwerk) ; but most of these reports contained few clinical or pathological details. Though a few cases have been reported in expatriate Englishmen (Edge 1946, Gray 1951), the disease seems rare in ,Britain; search has revealed reports of twelve examples of endomyocardial fibrosis or similar conditions in this country. In the majority of these cases the patients had lived abroad for a considerable period, or the cardiac abnormality was detected at postmortem examination without there having been any clinical evidence of cardiac involvement; one patient was a native of Jamaica. Two out of the four cases described by Evans (1957) and that described by Lennox (1948) had apparently normal endocardium, and the abnormality was suggested only microscopically. Data on the twelve cases are summarised in the accompanying table. It is difficult to say whether all these cases are
examples of the disease so clearly described from Africa with distinct clinical and pathological features. Two cases of endomyocardial fibrosis came to necropsy in this department within a period of eight months. Oni patient, a woman of 71, had characteristic features o involvement of right ventricle, and had been considere( as a case of Ebstein’s congenital anomaly of the heart the other, a woman of 22, had features of left ventricula] involvement, and had been thought to have an atria septal defect from childhood. Case-reports
Case 1 A married woman, aged 71, developed swelling of both legf and breathlessness in September, 1954. Mitral stenosis wa; diagnosed, and she was treated with digitalis and mersalyl, bu without much benefit. She was admitted to hospital in June 1955. There was no history of rheumatic fever, or othe! illnesses of note. She had an acromegalic type of feature witt prominent lower jaw and heavy upper lip, but she was no acromegalic. There was no enlargement of her hands or feet and no history of headache; and X-ray of the skull showed< small sella turcica. She said that she resembled her father. He] blood pressure was 150/95 mm. Hg, and the jugular venom pressure was raised. The apex-beat was slapping, and there wa! a slow auricular fibrillation with apex rate of 70 per minute. Ar apical systolic and a short rumbling diastolic murmur wer< heard. X-ray showed generalised cardiac enlargement but nc pulmonary congestion. Electrocardiography confirmed auricula] fibrillation with digitalis effect. No ascites was detectable, bu’ the liver was palpable down to the umbilicus. Breath sound: were vesicular with scattered basal rales. The patient’s condition improved with rest, digitalis, and diuretics and she wa: discharged from hospital after 6 weeks. Although the murmu] suggested mitral stenosis, there were other features agains1 this diagnosis-notably hilar congestion. Ebstein’s congenita: heart-disease was provisionally diagnosed. When the patient was readmitted in March 1958, she was troubled with severe ankle oedema and increasing dyspncea despite continued treatment. The physical signs had no1 changed significantly, but she had lost considerable weight and her abdomen was distended and her legs showed varicose ulcers. Laboratory investigations showed hypochromic anaemis (Hb 60%) with normal leucocyte-count, blood-urea, serumcholesterol, basal metabolic rate, glucose-tolerance test, and 17-urinary ketosteroids, and a negative Wassermann reaction. Her last admission was in November, 1961, with extreme dyspnoea and oedema, and she died on Dec. 3, 1961. R. T. Cooke) There were pronounced oedema in the legs and moderate ascites. The liver was large and showed nutmeg pattern; the spleen was large, firm, and congested; the kidneys showed much surface granularity and thinning of the cortex with small scattered cysts. The lungs showed oedema and early bronchopneumonia. Heart-weight 520 g.; the left ventricle was of small average size, and the right ventricle formed the apex (wall 8 mm. thick). The right atrium was enormously dilated, its volume being roughly equal to that of the rest of the heart. The mitral valve admitted two fingers easily; the tricuspid valve was much dilated. There was extensive fibrosis of the endocardium of both ventricles which produced severe contracture of the papillary muscles of the tricuspid valve particularly, but also of the mitral valve. Considerable fibrosis of the Small endocardium of left and right atria was also seen. of both calcified and non-calcified, deposits yellow material, were present in the endocardium of all the cavities except right atrium. In all cavities except the left ventricle antemortem thrombus was attached to the endocardium. There was no septal defect, and the position of the valve rings was normal. The coronary arteries showed calcification of the wall with atheromatous patches, but the lumen was reasonably wide open.
Necropsy (Dr.
--_-c’_----..1
.t::.1_____:- _.C’
....1_-
_._..J-
of fluid and electrolyte balance, and must be carried out under close clinical and biochemical control. Treatment along the lines indicated can almost always bring the serum concentration under toxic level in less than twenty-four hours. Therefore, in our opinion, in bromide poisoning only if is indicated hxmodialysis has cardiac the patient decompensation, if renal function is considerably impaired, or if the poisoning is exceedingly severe or combined with poisoning by depressants of respiratory reflexes.
problems
Summary
.
A case of severe bromide poisoning is reported. The rate of spontaneous elimination of bromide is compared with that induced by forced halogen excretion
and by haemodialysis. Even after effective htmodialysis, the concentration of bromide in the cerebrospinal fluid is slow to fall. From the study of elimination-rates, indications are given for treatment of bromide poisoning by forced
halogen excretion
or
by haemodialysis. REFERENCES
Brun, C. (1949) Nord. Med. 42, 1774. Gjørup, P. A. (1955) Ugeskr. Lœg. 117, 749. Jørgensen, H. E., Wieth, J. O. (1963) Lancet, i, 81. Merrill, J. P., Weller, J. M. (1952) Ann. intern. Med. 37, 186. Schreiner, G. E. (1958) Arch. intern. Med. 102, 896. Todd, J. C., Sanford, A. H., Wells, B. B. (1953) Clinical Diagnosis by Laboratory Methods; p. 460. Philadelphia and London. von Frey, E. (1911) Z. exp. Pharm. Ther. 8, 29.
THE TREATMENT OF
SEVERE ASPIRIN POISONING D. C. DUKES M.B., B.Sc. Birm.
J. D. BLAINEY M.D.
Lond., M.R.C.P.
MEDICAL REGISTRAR THE ARTIFICIAL KIDNEY UNIT, THE GENERAL
PHYSICIAN
HOSPITAL, BIRMINGHAM, 4
G. GUMMING M.B., B.Sc., Ph.D. Birm., A.R.I.C. LECTURER IN MEDICINE IN THE UNIVERSITY OF BIRMINGHAM
G. WIDDOWSON B.Sc. Birm., A.R.I.C. BIOCHEMIST, THE GENERAL HOSPITAL,
BIRMINGHAM
ASPIRIN and the other salicylates are the third most common cause of death from acute poisoning in this country, being exceeded in frequency only by carbon monoxide and the barbiturates (Ministry of Health 1962). In 1961 the total number of deaths from salicylate poisoning was 290 (Registrar General 1962) but a better idea of the size of the problem is given by the estimate that 15% of hospital admissions for poisoning are due to the taking of aspirin and other salicylate compounds (Ministry of Health 1962). In 1959 20,100 cases of all types of poisoning were admitted to hospital, and it may be assumed that this number will continue to increase. The serious toxic effects of acetylsalicylic acid and other salicylates depend on their concentration in the tissues, and the effective treatment of salicylate poisoning requires the removal of the drug as rapidly as possible. Haemodialysis with the artificial kidney (Doolan et al. 1951) is now an accepted method of treatment of severe salicylate poisoning, but the number of cases involved would impose an impossible burden upon existing artificial-kidney units if all required dialysis. Forced diuresis has been suggested as a logical method of treating salicylate poisoning (Cumming 1961, Clemmeson et al. 1962) and Gutman, Yu and Sirota (1955) have shown that the excretion of free salicylate is increased in alkaline urine. No direct com-
treatment of patients with dialysis or forced alkaline diuresis has yet been reported. In this study of patients with acute aspirin poisoning, measurements have been made of the quantity of salicylate removed when hxmodialysis and forced diuresis were used simultaneously. The results are compared with those obtained in a second group of patients, treated by forced alkaline diuresis alone.
parison of
Methods Eleven patients were treated in all, six with the Travenol Kolff " twin-coil " artificial kidney and five by forced alkaline diuresis without dialysis. In all the patients, some
form of
salicylate (either acetylsalicylic acid or calcium amounts varying from 26 to aspirin) 98 g. (80 to 300 5-grain tablets) between three and fourteen hours before admission, as far as was known. None of the patients in either group was hypotensive. had been taken in
In the
dialysed group the bladder was emptied every minutes, the urine being pooled for analysis. During dialysis the patients were weighed on an Avery bed-weighing machine, and the rate of intravenous infusion of alternate bottles of 0-9% sodium-chloride solution and of 5% dextrose was adjusted to maintain a weight increase of 1-5 kg. as a 30
diuresis. The concentrations of total salicyl in compounds serum, urine, and dialysis fluid were determined by theAutoAnalyzer ’,i using a modification of the method of Trinder for convenience in dealing with a large number of specimens. Five patients were treated by forced diuresis alone. The clinical state of each patient on admission was comparable with that of the patients treated by hxmodialysis. It was reassessed by the same observer at hourly intervals according to (a) impairment of consciousness, (b) restlessness, (c) overbreathing (it was found impracticable to measure ventilation accurately in the uncooperative subject), (d) tachycardia, (e) vomiting, (f) sweating, (g) deafness, and (h) tinnitus. In these five patients the dose of salicylate, the time-interval between its ingestion and treatment, and the initial serum-salicylate levels were of the same order as in the patients treated by ha:modialysis. A catheter was placed in the bladder and the urine collected hourly, the rate of infusion being adjusted to produce a urine flow of approximately 500 ml. per hour. 500 ml. of 0-9% sodium-chloride solution, 5% dextrose, and 2% sodium bicarbonate (1/6 M sodium lactate in case 1) were infused in rotation, at an initial rate of about 2 litres an hour. Hourly measurements were made of serum and urine salicylate; urine pH was measured with an ‘ E.LL.’ pH meter. The arterial pH, Pco2 and standard bicarbonate were determined hourly by the capillary method of Astrup (1961). Alkali was omitted from the infusion when a urinary pH of 8-0 was attained. stimulus
to
(1954),
Results Patients Treated
by Hcemodialysis
six patients recovered rapidly, freedom from symptoms (apart from tinnitus and mild deafness) being attained towards the end of dialysis. Patient 6, an intelligent schoolboy who had been transferred from another hospital in coma after a series of convulsions, was well enough before the end of his treatment to demand an explanation of the principles of haemodialysis. The table relates the change in serum-salicylate concentration to clinical improvement in each patient during the first All
8 hours of observation and compares the total urinary excretion of salicylate with the extraction of salicylate by dialysis. Any error in the measurement of the very low concentrations of salicylate (2-4 mg. per 100 ml.) in the dialysis fluid (100 litres) is magnified when the extraction of salicylate is calculated. Therefore, the values for 1.’
AutoAnalyzer ’ is the trade name of Company, Chauncey, New York, U.S.A.
the Technicon Instruments
330 TABLE RELATING CLINICAL STATE TO REMOVAL OF SALICYLATE IN THE FIRST EIGHT HOURS IN PATIENTS TREATED BY HaeMODIALYSIS AND BY FORCED ALKALINE DIURESIS
a-impairment of consciousness. b-restlessness.
Summary of clinical state c--overbreathing. d-tachycardia.
e-vomiting. f-sweating.
g-deafness. h-tinnitus.
salicylate recovery shown in the table may be approximate; but it appears that salicylate was removed from the blood twice as fast by haemodialysis as by diuresis, with a urine output of 100-800 ml. per hour. Urine pH was not measured in the dialysed cases, and no attempt was made
Intravenous therapy, however, can be started without delay, and the results show that forced diuresis by itself, although it does not remove salicylate so quickly, is an effective means of treating salicylate poisoning (see table). Its success depends on reasonable renal function and a to make the urine alkaline. satisfactory blood-pressure : in their absence, haemodialysis is necessary. In case 4 the urine was deeply pigmented, containing Our regime of treatment starts with aspiration of the and no was brown-stained attempt many granular casts, stomach contents as soon as aspirin poisoning is diagnosed. made to force a diuresis. The urine returned to normal in 48 hours. The pigment, which was not a hsemoglobin Lavage with large volumes of fluid is unnecessary, because derivative, remains unidentified, although such pigmenta- little more aspirin is removed by this means; and it may tion of the urine has occasionally been described in be dangerous, because it increases the risk of aspiration pneumonia (Cumming 1961). While the gastric aspiration salicylate intoxication. is being performed, an intravenous drip is started, and the Patients Treated by Forced Alkaline Diuresis level is measured. The volume of fluid All five patients recovered rapidly. In each case clinical serum-salicylate required is considerable, for fluid is lost rapidly with improvement was evident 4-5 hours after starting the sweating and overbreathing and the aim is to produce infusion, which was then slowed. Except in case 8, the a urine flow of at least 500 ml. per hour. 2% sodium patients before the start of treatment had a normal or bicarbonate (or 1/6 M sodium lactate), 0-9% sodium raised arterial pH, normal standard bicarbonate, and chloride, and 5% dextrose are infused in rotation, and reduced PC021 indicating hyperventilation as the cause of up to 2 litres an hour is given for the first three hours, these disturbances. Alkali was given to these patients with to the maintenance of normal jugular venous the sole object of rendering the urine alkaline, in order to subject pressure and the absence of crepitations at the lung bases, produce the maximum excretion of salicylate. Infusion of The bladder is emptied hourly; if the patient cannot do alkali was accompanied by a rise in the arterial pH and this voluntarily, an indwelling catheter is passed. standard bicarbonate and by a rise in the urine pH. The Alkali is omitted from the infusion when the urine low initial Pc02 was slowly corrected as hyperventilation attains a pH of 8-0 (if a pH meter is not available, British diminished with treatment. Diuresis began after about Drug Houses indicator paper of suitable range can be 2 litres of fluid had been infused, and clinical improvement used). A chart is kept of the patient’s clinical state, fluid progressed as the plasma-salicylate concentration fell. input, and urine output. A positive water balance is Another paper will give details of the changes resulting required to stimulate diuresis, and an intake of 6-8 litres from this treatment. is necessary to produce 3-4 litres of urine in the first Discussion 8 hours’ treatment. Intravenous therapy is controlled The results confirm previous reports of the effectiveness according to the patient’s clinical state and the serumof hsemodialysis in removing salicylate from the poisoned salicylate level, which should be measured hourly. patient (Doolan et al. 1951, Schreiner et al. 1955, Determination of arterial pH, Pc02, and standard bicar’ Schreiner 1958, Thomsen and Dalgard 1958, Magness bonate is probably an unnecessary refinement, provided and Murray 1961, Jorgensen and Wieth 1963) and show that not more than 2 litres of alkali is given, for the kidney that the amount removed is considerably increased when is able to excrete alkali rapidly. With an initial serumis combined with forced diuresis (see table). salicylate level of 80-90 mg. per 100 ml., 8 hours’ treathsemodialysis To this extent support is lent to a suggestion made in the ment is enough to produce a level of 30-40 mg. This is recent report from the Ministry of Health (1962) that the comparable to what can be achieved with the artificial artificial kidney may be a useful adjunct to proposed kidney within 8 hours of diagnosis, taking into account regional poisoning treatment centres. On the other hand, delays due to transport of the patient and the cross’ the number of artificial-kidney units is limited; and, even matching of blood for priming the machine. if the apparatus is not already in use, delay may occur We suggest that, when renal function is adequate, forced between diagnosis of poisoning and the start of treatment, alkaline diuresis is a satisfactory treatment for severe particularly if the patient has to be brought from a salicylate poisoning. It should not be attempted in the distance. presence of hypotension, which is an indication for urgent
i
331 or where renal function is suspect for any other reason. Haemodialysis is also indicated if adequate diuresis is not obtained in 3 hours. If the number of deaths from aspirin poisoning is to be reduced, promptness of treatment is vital; and we regard this condition as a medical emergency which demands the closest supervision.
htemodialysis,
Summary The removal of salicylate by hasmodialysis and simultaneous forced diuresis has been measured in six patients with acute aspirin poisoning, and has been compared with the effects of forced alkaline diuresis in five patients with poisoning of the same severity. In each patient clinical improvement was related to reduction in serum-salicylate level. If delays in obtaining use of the artificial kidney are taken into account, forced alkaline diuresis is shown to be comparable in efficiency to hasmodialysis in producing clinical and biochemical improvement over the eight-hour
period following diagnosis. A method is described for treating poisoning by forced alkaline diuresis. We wish
acute
aspirin
thank Prof. W. M. Arnott, Dr. W. T. Cooke, Dr. D. R. M. Malins for allowing us to include patients under their care in this study, and Mr. P. Dawson-Edwards and Mr. L. J. Lawson for the surgical care of the patients treated by hamiodialvsis. to
Humphreys, and Dr. J.
REFERENCES
Astrup, P. (1961) Clin. Chem. 7, 1. Clemmesen, C., Myschetzky, A., Lassen, N. A. (1962) Lancer, i, 162. Cumming, G. (1961) Medical Management of Acute Poisoning. London. Doolan, P. D., Walsh, W. P., Kyle, L. H., Wishinsky, N. (1951) J. Amer. med. Ass. 146, 105. Gutman, A. B., Yü, T. F., Sirota, J. H. (1955) J. clin. Invest. 34, 711. Jørgensen, H. E., Wieth, J. O. (1963) Lancet, i, 81. Magness, J. L., Murray, J. B. (1961) J.-Lancet, 81, 253. Ministry of Health (1962) Emergency Treatment in Hospital of Cases of Acute Poisoning. H.M. Stationery Office. Registrar General (1962) Statistical Review of England and Wales for 1961, Part I. H.M. Stationery Office. Schreiner, G. E. (1958) Arch. intern. Med. 102, 896. Berman, L. B., Griffin, J., Feys, J. (1955) New Engl. J. Med. 253, —
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484.
ADULT ENDOMYOCARDIAL FIBROSIS IN BRITAIN A. A.
FARUQUE
M.B. Dacca REGISTRAR IN PATHOLOGY, GENERAL HOSPITAL, WEST HARTLEPOOL, CO. DURHAM
ENDOMYOCARDIAL fibrosis is relatively common in tropical Africa but is rare in other parts of the world, particularly among white adults. Isolated cases have been reported from many places, and from as early as 1883 (Nauwerk) ; but most of these reports contained few clinical or pathological details. Though a few cases have been reported in expatriate Englishmen (Edge 1946, Gray 1951), the disease seems rare in ,Britain; search has revealed reports of twelve examples of endomyocardial fibrosis or similar conditions in this country. In the majority of these cases the patients had lived abroad for a considerable period, or the cardiac abnormality was detected at postmortem examination without there having been any clinical evidence of cardiac involvement; one patient was a native of Jamaica. Two out of the four cases described by Evans (1957) and that described by Lennox (1948) had apparently normal endocardium, and the abnormality was suggested only microscopically. Data on the twelve cases are summarised in the accompanying table. It is difficult to say whether all these cases are
examples of the disease so clearly described from Africa with distinct clinical and pathological features. Two cases of endomyocardial fibrosis came to necropsy in this department within a period of eight months. Oni patient, a woman of 71, had characteristic features o involvement of right ventricle, and had been considere( as a case of Ebstein’s congenital anomaly of the heart the other, a woman of 22, had features of left ventricula] involvement, and had been thought to have an atria septal defect from childhood. Case-reports
Case 1 A married woman, aged 71, developed swelling of both legf and breathlessness in September, 1954. Mitral stenosis wa; diagnosed, and she was treated with digitalis and mersalyl, bu without much benefit. She was admitted to hospital in June 1955. There was no history of rheumatic fever, or othe! illnesses of note. She had an acromegalic type of feature witt prominent lower jaw and heavy upper lip, but she was no acromegalic. There was no enlargement of her hands or feet and no history of headache; and X-ray of the skull showed< small sella turcica. She said that she resembled her father. He] blood pressure was 150/95 mm. Hg, and the jugular venom pressure was raised. The apex-beat was slapping, and there wa! a slow auricular fibrillation with apex rate of 70 per minute. Ar apical systolic and a short rumbling diastolic murmur wer< heard. X-ray showed generalised cardiac enlargement but nc pulmonary congestion. Electrocardiography confirmed auricula] fibrillation with digitalis effect. No ascites was detectable, bu’ the liver was palpable down to the umbilicus. Breath sound: were vesicular with scattered basal rales. The patient’s condition improved with rest, digitalis, and diuretics and she wa: discharged from hospital after 6 weeks. Although the murmu] suggested mitral stenosis, there were other features agains1 this diagnosis-notably hilar congestion. Ebstein’s congenita: heart-disease was provisionally diagnosed. When the patient was readmitted in March 1958, she was troubled with severe ankle oedema and increasing dyspncea despite continued treatment. The physical signs had no1 changed significantly, but she had lost considerable weight and her abdomen was distended and her legs showed varicose ulcers. Laboratory investigations showed hypochromic anaemis (Hb 60%) with normal leucocyte-count, blood-urea, serumcholesterol, basal metabolic rate, glucose-tolerance test, and 17-urinary ketosteroids, and a negative Wassermann reaction. Her last admission was in November, 1961, with extreme dyspnoea and oedema, and she died on Dec. 3, 1961. R. T. Cooke) There were pronounced oedema in the legs and moderate ascites. The liver was large and showed nutmeg pattern; the spleen was large, firm, and congested; the kidneys showed much surface granularity and thinning of the cortex with small scattered cysts. The lungs showed oedema and early bronchopneumonia. Heart-weight 520 g.; the left ventricle was of small average size, and the right ventricle formed the apex (wall 8 mm. thick). The right atrium was enormously dilated, its volume being roughly equal to that of the rest of the heart. The mitral valve admitted two fingers easily; the tricuspid valve was much dilated. There was extensive fibrosis of the endocardium of both ventricles which produced severe contracture of the papillary muscles of the tricuspid valve particularly, but also of the mitral valve. Considerable fibrosis of the Small endocardium of left and right atria was also seen. of both calcified and non-calcified, deposits yellow material, were present in the endocardium of all the cavities except right atrium. In all cavities except the left ventricle antemortem thrombus was attached to the endocardium. There was no septal defect, and the position of the valve rings was normal. The coronary arteries showed calcification of the wall with atheromatous patches, but the lumen was reasonably wide open.
Necropsy (Dr.
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