ORAL POTASSIUM THERAPY

1190 the following morning, give the medicine again morning, midday, and evening on the day before the X-ray.

ORAL POTASSIUM THERAPY

C. T. G. FLEAR

Radiographs of the abdomen taken before the intra,pyelograms were subsequently studied independently by our consultant radiologist, Dr. T. Lodge, and by me. An arbitrary classification of 0, A, B, C, I) 0 and A were films showing no fæces was agreed on : or only a minimal amount ; C and D were films in which a large quantity of faeces was present, D amounting almost to megacolon ; B was between these extremes. As with all independently observed phenomena in which no absolute standard is possible, in comparing the

M.B., B.Sc. Birm.

venous

results an observer error was found. However, since I had marked higher than the radiologist on 20 occasions (with a difference on one grade 17 times and a difference of two grades 3 times), and the reverse had only happened on 4 occasions, with a difference of one grade each time, it was obvious that there was no fundamental lack of agreement. It was therefore decided to abide by the on the 3 occasions when radiologists’ markings there was a difference of two, in which cases the mean was taken.

except

Results The final results -

the

gut

was

found

given in table 11. heavily loaded with

are

On 11 occasions faeces (classifica-

TABLE II—RELATIONSHIP BETWEEN AMOUNT OF FÆCEB SEEN ON RADIOGRAPHY AND DRUG GIVEN

No. of children treated with

Classification of radiograph

i i

Diodyl sodium sulphosuccinate

Syrup of figs

D) after the child had received dioctyl sodium sulphosuccinate, whereas- this happened only once when the child had been given syrup of figs. Even though the groups are not quite the same in number (24 compared with 22 children), this result is significant. tion C and

Summary Two controlled

designed

to

assess

experiments are described. These were the efficacy of dioctyl sodium sulpho-

succinate. In the first experiment children with fpccal impaction selected by random sampling were given either dioctyl sodium sulphosuccinate by mouth and enemata, or a standard mixture of purgatives by mouth and plain water enemata. The results in the two groups were almost identical, the only complete failure being in a child given dioctyl sodium sulphosuccinate. In the second experiment children were given either dioctyl sodium sulphosuccinate or syrup of figs as a simple aperient before intravenous pyelography. The efficacy of the drugs was assessed by examining the control films taken before an intravenous pyelogram. In the dosage in which it was administered dioctyl sodium sulphosuccinate had no value as an aperient. It is a pleasure to acknowledge the help given by Sister J. L. Isaacs and her nurses : Sister B. Mallinder and the X-ray staff ; and Miss C. I. Crawford and the dispensary staff. The medical and surgical consultants kindly allowed access to their patients. My thanks are particularly due to Prof. R. S. Illingworth, who suggested the investigation and criticised this paper. REFERENCES

Benaglia, A. E., Robinson, E. J., Utley, E., Cleverdon, M. A. (1943) J. industr. Hyg. 25, 175. Wilson, J. L., Dickinson, D. G. (1955) J. Amer. med. Ass. 158, 261.

MEDICAL REGISTRAR

MOLLY HILL M.B. Birm. HOUSE PHYSICIAN

GARFIELD THOMAS M.Sc. Mane., F.R.I.C. BIOCHEMIST

QUEEN ELIZABETH HOSPITAL, BIRMINGHAM THE need for potassium supplementation has become realised in congestive cardiac failure, hepatic cirrhosis, steatorrhoea, and other conditions in which there is increasing evidence of considerable potassium depletion, often long-standing. It is usual to give this potassium by mouth because intravenous administration of large amounts of potassium is both.difficult and dangerous where the potassium depletion -is neither acute nor associated with shortage of fluid, and where cedema may be present. We draw attention to some of the difficulties attendant on giving potassium by mouth and discuss the potassium content of various drinks. The response to oral potassium varies greatly from patient to patient, and because of this no attempt will be made to indicate the precise incidence of each of the different symptoms experienced. Among them may be listed epigastric discomfort and burning, nausea, vomiting, distension, meteorism, looseness of bowel action or frank diarrhoea, stiffness of the fingers, mental clouding, and a metallic taste. These complaints may lead to the patient refusing therapy. Not infrequently medication is followed by vomiting, and the potassium taken is thereby lost, and in some instances we had to chart the giving of each separate dose of the potassium, and to record whether or not this is followed by vomiting, to estimate

accurately

a

patient’s daily potassium supplementation.

Several different potassium compounds have been tried, and these are listed in table 1. 32 consecutive cases of congestive cardiac failure were started off on potassium chloride in addition to the usual therapy (rest in bed, 5 of these patients did digitalis, mercurial diuretics, &c.). not have any symptoms due to the potassium chloride, 15 tolerated it despite symptoms, and 12 were completely unable to tolerate it. 2 of those who originally were tolerant later became intolerant. The 14 patients unable TABLE I-PREPARATIONS OF POTASSIUM TO BE TAKEN BY MOUTH

Compound

Preparation

Composition

* These solutions will not keep. * Potassium bicarbonate

2656}

Tartaric acid.... Citric acid ....

Sucrose

16-87 11-25

9.40

....

Granulated on a hot-plate. Potassium acid tartrate gr. 20. Citric acid gr. 0-25. Essence of lemon minim Water to 1 fluid oz. -

11/18.

tg.pei-100 tablets

1191 chloride were tried on other potassium 11of them a form of potassium and for compounds, was found which could be tolerated, supplementation though about half these patients still had distressing to take

potassium

symptoms.

-

reported that the administration of calcium carbonate together with potassium chloride may obviate epigastric burning (Schemm and Camara 1954). We have not found this to be so ; all the compounds of potassium so far tried by us have given rise to symptoms in some patients, even to the extent of intolerance. Of the various compounds tried the mixture termed potassium effervescens (table I) was by far the most easily It has been

tolerated. of potassium is sometimes associated with Where this is present ammonium chloride is often given as well as potassium. It may be given either The tablets do as enteric-coated tablets or as a solution. not often given rise to symptoms, but they are rarely, if ever, absorbed and are found unchanged in the faeces. The ammonium-chloride solution often gives rise to nausea or vomiting. These symptoms we found in 19 of 30 consecutive patients with congestive cardiac failure. 5 of the patients refused the solution, and many of the others vomited some of the doses.

Deficiency

alkalosis.

are unlikely to be due rise in the serum-potassium level. In more’than 100 patients with either congestive heart-failure or steatorrhoea a high serum-potassium level coinciding with symptoms has not been observed, even though many of these patients had poor output of urine while under treatment with potassium. The symptoms produced by either potassium salts or ammonium chloride appear to be independent of the dosage. The dosage of potassium we have given has usually been about 60-100 m.eq. daily, but more has been given without any ill effects. The most that we have given has been 400 m.eq. daily for several weeks. It has been our experience that the more ill patients have the most side-effects and are least likely to tolerate either potassium or ammonium chloride. Often these are the patients in whom their use is most indicated. In healthy people symptoms were not caused

Symptoms caused by potassium

to

a

by potassium salts, except epigastric pain produced by potassium chloride and occasional nausea by potassium bicarbonate. These symptoms could be minimised by taking food immediately before or after the potassium salts. In ill patients, however, this did not help ; the food was sometimes vomited and appetite often impaired. Clearly it would be helpful if it were possible to give at least some of the extra potassium by more natural

TABLE II-COMPOSITION OF VARIOUS DRINKS AND FOODSTUFFS

*

Diet-kitchen recipe : 100 g. of dried apricots stewed, homogenised, sieved, and made to 20 t Diet-kitchen recipe : 300 g. of tomatoes boiled, sieved, and made up to 330 ml.

oz.

1192 With this in mind we have analysed various drinks for their sodium, potassium, and chloride concentration. These are summarised in table 11, and of them the pure fruit-juices contain the most potassium with least sodium. We have given up to a litre a day of pure fruit-juices to several patients and been able thereby substantially to reduce the daily amounts of potassium given as salts. The drinks did not interfere with the patient’s appetite, and no side-effects were observed. means.

Schemm, F. R., Cámara,

Preliminary

(1954) Circulation, 10,

17-OXOSTEROIDS

(mg.

Urinary 17-oxosteroid per pig per 24 hr. ±S.E.)

Group

10 animals and 15-22 estimations per group.

for 17-ketosteroids), which has been measured Dr. R. D. Bulbrook and Dr. F. C. Greenwood, who have kindly allowed us to use some of their data here. Table i gives figures for the output of such steroids (which do not include aldosterone) in guineapigs which have been castrated or have been treated with large doses of stilboestrol (implants of 15-mg. tablets renewed every three to four months) for more than a year. The output of 17-oxosteroids is increased equally in intact and castrated guineapigs treated with stilbcestrol, and there is other evidence (particularly from the increase produced by adrenocorticotrophin) that the 17-oxosteroid output is one index of adrenal-cortical activity. The excretion of 17-oxogenic steroids is also increased in parallel fashion. (2) The evidence for loss of potassium in treated guineapigs is given in table 11, which records the over. new name

REFERENCE A. A.

TABLE I—DAILY OUTPUT OF URINARY

by

430.

Communications

POSSIBLE ALDOSTERONISM IN

STILBŒSTROL-TREATED GUINEAPIGS THE evidence is so far indirect ; but the similarities between the condition of primary aldosteronism or Conn’s syndrome in man and the effects of large doses of stilbopstrol in male guineapigs seem suggestive enough to report. In the human disease excessive secretion of aldosterone by the adrenal cortex is associated with loss of potassium.l2 There are also changes in the kidneys of the patients (vacuolation of the epithelia] cells of the renal tubules 3) like those produced in the early stages of potassium deficiency in rats.4 Later the kidneys of

TABLE

II—NIGHTLY

OUTPUT

URINARY

OF

SODIUM

AND

POTASSIUM

whether normal potassium intake is restored or not, show a different lesion—cystic It is this late result of dilatation of the tubules.4 5 potassium deficiency that we believe is reproduced in the treated guineapigs, and our suggestion that the cause may be excessive secretion of aldosterone is based on evidence that the stilbœstro] treatment causes adrenal overactivity and loss of potassium. A further similarity between human patients and the treated guineapigs is that both have polydipsia and polyuria.

potassium-deficient rats,

Nightly output (m.eq. per pig ±S.E.) Group Sodium

Potassium

excretion of sodium and potassium mea. four nights weekly for five weeks in 4 normal guineapigs and 4 guineapigs which had been treated with stilboestrol 05-20 mg. by mouth daily for three months. Despite the large variation in the nightly excretion of sodium the mean figure is virtually the same in the two groups. There was less variation in the potassium output which was significantly greater (almost doubled) in the treated animals than in the controls. The mean bodyweight of the two groups did not differ by more than 5% during the course of the urine collections. The food intake was not measured but had borne a constant relation to body-weight in other experiments. (3) Both intact and castrated guinea pigs in which stilbœstrol is implanted die, during the second year of treatment, from renal failure with a raised blood-

night urinary

sured

EVIDENCE

(1) The evidence for adrenal overactivity depends on urinary excretion of 17-oxosteroids (the chemists’

the

1. Conn, J. W. J. Lab. clin. Med. 1955, 45, 3. 2. Chalmers, T. M., FitzGerald, M. G., James, A. H., Scarborough, H. Lancet, 1956, i, 127. 3. Conn, J. W. J. Lab. clin. Med. 1955, 45, 661. 4. Follis, R. H. jun., Orent-Keiles, E., McCollum, E. V. Amer. J. Path. 1942, 18, 29. 5. Fourman, P., McCance, R. A., Parker, R. A. Brit. J. exp. Path. 1956, 37, 40.

on

urea level, voluminous pericardia! effusion, and abnormal kidneys.

The first visible -change in the is in the glomeruli, where the intercapillary cells proliferate and the intercapillary substance increases relatively early-after about three months. Later, about a year after the start of treatment, more widespiead changes appear, whose main feature is dilatation, often cystic, of some of the tubules throughout the renal cortex. with atrophy of other tubules and interstitial fibrosis (see

kidneys

Kidney of guineapig, aged 22

mos.,

castrated and treated with and eosin. x 31/2.)

(Haematoxylin

stilboestrol for -

17

months.

6.

Trevan, D. Lancet, July 7, 1956. p. 22.