SULPHONAMIDE, SULPHATES AND ORDINARY DIET

A CLINICAL INVESTIGATION INTO THE EFFECTS OF THEIR SIMULTANEOUS ADMINISTRATION

By W. McN. NIBLOCK, m.a., m.b., B.chir., f.r.c.s. (Eng.)

CAPTAIN, I.M.S.

Second Resident Medical Officer, Presidency General

Hospital, Calcutta

In 1936 the publication of the work of Cole- brook and Kenny and others on the action of prontosil caused the English-speaking medical world to adopt the new chemotherapy with enthusiasm. That this enthusiasm was some- times untempered by caution can be judged by the large number of reports published in 1937

describing toxic complications following the use of sulphonamide*. Among these complications sulphgemoglo-

binaemia figured prominently though not the most frequently; that it is still most readily brought to mind may be due to two factors. The first is the mistaken idea (which dies hard) that

cyanosis indicates sulphsemoglobinsemia, and the second is that the restrictions that have been

* The term sulphonaraide is used generically for

purposes of simplification in this article.

458 THE INDIAN MEDICAL GAZETTE [Aug., 1941

recommended regarding diet and drugs exert a popular appeal to doctors, nurses and even

patients. Nor is this surprising, as the majority of writers on the subject of sulphonamide seldom fail to mention that patients must not be given sulphur-containing compounds, especially the saline purgatives, and eggs' and onions must be excluded from the diet. One writer has even

gone the length of issuing a warning against the use of hypodermic injections of the sulphates of atropine and morphia while sulphonamide is

being exhibited. .

Lately, however, a few dissentient voices have been heard deploring the prohibition of such valuable remedies as the sulphates and such an important dietetic article as eggs. Smith (1940) gave thirty cases pentothal sodium (which con- tains 12 per cent sulphur) although they were receiving sulphapyridine at the same time, and noted no untoward results. One case actually received no less than 3 grains of sulphur in this way while receiving intravenous sulphapyridine. He also states that he gives saline purgatives to cerebral cases receiving sulphonamides when- ever indicated and has seen no complications.

Tisdall (1940) has published the sulphur con- tent of various foods, which may be tabulated as follows :?

Table I

Sulphur content of foods (after Tisdall)

Sulphur content Foodstuff in parts per

million Boiled onions .. .. 23

Cauliflower .. .. .. 29

Boiled Brussels sprouts .. ? ? ; 77 White flour .. .. .. 108

Wholemeal flour .. .. 123

Eggs .. .. .. 170 Cheddar cheese .. .. 230

While admitting that eggs do contain a fairly high proportion of sulphur, Tisdall argues that the amount of sulphur ingested in 24 hours by an invalid through eggs and through bread would not be materially different. On the other hand, Campbell and Morgan

(1939) were able to produce sulphsemoglobinaemia experimentally by giving 3 grammes of sulpho- namide and 4 grammes of confection of sulphur to individuals for two days. Sulphur in un-

combined form was therefore not used in the

series to be described.

Plan of investigation The object of this investigation was to observe

the effect, if any, of combining the administra- tion of sulphonamide with therapeutic doses of sulphates and standard hospital diets. One hundred cases were taken without selec-

tion, and, apart from about fifteen cases which had to be discarded for reasons not relevant to the investigation, they were consecutive.

Sixty-one cases were young adult males because of the type of hospital accommodation available.

Every opportunity, however small, was taken to administer drugs containing sulphates, but excessive dosage was avoided.

Method of administration

(?) Sulfonamide.?Thirty-two cases received an initial dose of 2 grammes of

' M. & B. 693 '

by mouth followed by a further 2 grammes after 4 hours. Thereafter 1 gramme was given 4

hourly night and day until 16 to 20 grammes had been given. Forty-seven cases received 1

gramme of various sulphonamide preparations, either orally or by injection, three times a day until between 9 and 24 grammes had been

given. Children received doses proportionate to their age.

(?) Sulphates.?These were given in the fol-

lowing forms, and many cases received more than one form :?

Dose. Saturated solution of sodium and magnesium sulphate .. to 1 oz.

Mistura alba* .. .. ^ to 2 oz. Mistura ferri aperiens* .. \ to 1 oz.

Mistura quininae sulphata .. \ to 1 oz.

Pulv. ipecac, co. .. 10 gr. Atropine sulphate (injection) 100 to?V?r* Morphine sulphate ( ? ) 1 to \ gr. Hyoscine co.* ( ? )

containing atropine sul-

phate .. . . t!(T gr- * For formulae see Presidency General Hospital

Pharmacopoeia, the Extra Pharmacopoeia Vol. 1>

Thompson's Compendium, etc.

(c) Diet.?The majority of cases were at first given a

' milk diet', which includes 2 eggs daily (the eggs average f oz. each). They then pro- gressed to higher diets containing 2 eggs on

alternate days. Onions are a favourite ingre- dient and flavouring medium in these diets.

Results

No case of sulphaemoglobinaemia was observed. Cyanosis was observed in two cases of pneu- monia, and in one of acute pleurisy. The cya- nosis was unaffected by the administration both of methylene blue as recommended by Wendel (1939) and of glucose intravenously as recom- mended by Brooks (1940). No abnormal spectroscopic bands were observed in the blood. It was therefore concluded that neither methae- moglobinaemia nor sulphaemoglobinaemia were

present in these cases.

Case 1.?G. M., male, aged 67 years. Past history of treatment in hospital for heart failure. Admitted ?.n 17th January, 1941, with bilateral bronchopneumonia of 48 hours' duration. Slight cyanosis present admission. Treatment included M. & B. 693 2 gramas and then 1 gramme four-hourly. Dover's powder 10 grains on 17th and mistura alba 1 oz. on mornioS of 18th. Marked cyanosis noted on morning of I9tn* M. & B. 693 discontinued. Died on 21st January 0

cardiac failure.

Case 2.?E. F., male, aged 19 years. Admitted on

9th December, 1940, with history of fever, pain in tne

chest and rusty expectoration for three days.

Aug., 1941] TOXEMIA OF PREGNANCY : MITRA 459

Table II - i

Analysis of cases, showing types of sulphates given

Type of cases

?eptic surgical conditions

^fectecl operation wounds ..

~ePsis associated with filariasis

pUr. nose and throat conditions gonorrhoea ^?^laria ..

Respiratory diseases k ePsis coincident with other Medical conditions.

Sulphates given during sulphonamide therapy

S.S.Sod.et Mag. Sulph.

i oz.

4-hourly h oz.

daily

10 4 1 8 2

3

28

Less than ^ oz. daily

24

Mist. Alba

1 oz.

daily

21

Less daily ,

15

Mist. Quin.

1 oz. t.d.s.

Mist. Ferri

aperiens

1 oz. t.d.s.

Totals

32 4

11 19 10 6 13 5

100

rp Examination revealed right lobar pneumonia,

foment included M. & B. 693 2 : 2 : 1 : 1 grammes

jT-hourly, and then i gramme, t.d.s., until 13th

^comber. Mistura alba 1 oz. every morning. On 15th

j0i Cember he developed a fresh patch in the left upper

aj^e and M. & B. 693 i gramme, t.d.s., and mistura

oz. every morning were again given.

gnosis was observed on 16th December, and

for fi was discontinued. The cyanosis persisted

l94j Ve days. Recovery. Discharged on 18fh January,

2iHas-F, 3.?J. p.j male, aged 36 years. Admitted on

the i arch> 1941, complaining of fever and pain in

fihrJ t for eight hours. Examination revealed acute

ranni0118 Pleurisy on the left side, but an effusion

2 .

g .

f?rmed later. Treatment included M. & B. 693

2o" " : : 1 ?' 1, etc., grammes four-hourly until

sodi mmes had been given. Saturated solution of

Whil an.d magnesium sulphate $ oz. every morning

aft0t? ?"eceiving M. & B. 693. Mild cyanosis appeared

J?0f. fourth day, taking about ten days to subside.

Very. Discharged on 14th April, 1941.

cases were given quinine sulphate by

all s^mu^aneously with sulphonamide. They

r offered from vomiting and their speed of

te ]?Very was noticeably slower than the expec-

the S^ee^- With the exception of these cases,

Wit} ^^istration of sulphates simultaneously

Prnr! su^P^?namide had no adverse effect upon

Php^rCSS or sPee^ recovery, and no toxic

rpn Il01Inena (other than the cyanosis already 0rded) were observed.

Conclusions

c0iV Experience with 100 cases leads to the

P^ents receiving sulphonamide

tj0n n?t be subjected to special dietary restric-

the?' Th?y may also be given sulphates in

exercfe^i? doses provided proper care is

be^T gnosis occurs, sulphonamide should

inillg(^continued until its cause has been deter-

(4) As there are alternatives to oral admin- istration of quinine sulphate, this drug should not be used at the same time as sulphonamide.

Permission to publish this series of cases is

kindly given by Major J. C. Drummond, i.m.s., Surgeon Superintendent, Presidency General

Hospital, Calcutta.

REFERENCES

Brooks, M. M. (1940) .. Nature, 145, 707. Campbell, D., and Mor- Lancet, ii, 123.

GAN, T. N. (1939). Colebrook, L., and Ibid., i, 1279. Kenny, M. (1936).

Smith, E. J. R. (1940). Brit. Med. J., ii, 488. Tisdall, O. R. (1940) .. Ibid., i, 743. Wendel, W. B. (1939). J.Clin.Investigation, 18,179.