MERCURIAL DIURETIC IN THERAPV

WITH SPECIAL REFERENCE TO

CONTROL OF ASCITES IN HE-

PATIC CIRRHOSIS AND ITS

TOXIC MANIFESTATION

WITH CASE REPORTS

By M. BHATTACHARYYA, b.a., m.b., d.t.m.,

D.C.H., M.R.C.P.

Assam Medical College, Dibrugarh

Cirrhosis of liver, when fully established,

precludes any chance of cure, and therapeutic measures are directed towards amelioration of

the distressing symptoms. Of the three g oups

of symptomatology due to parenchymal failure,

excretory failure and portal obstruction (Him" sworth 1950), the last group attract the atten- tion of the patients predominantly. The

distended abdomen full of fluid with or without

generalised swelling of the body demands im- mediate relief. Portal obstruction due to

intrahepatic fibrosis, hypoproteinaemia due to

deficient function of the liver, accumulation of antidiuretic hormones in the body due to in-,

adequate disposal by the liver and retention

of sodium salt in the body due to not-definitely- known causes, are responsible for ascites and oedema (Himsworth, 1950, Karmachandani, 1951). Portal obstruction cannot be removed

by medical means, increased intake of protein cannot keep up the plasma protein as the liver is unable to work, nor can intravenous protgin administration can keep up a lasting plasma

W, 1954] MERCURIAL DIURETIC IN THERAPY .... : BHATTACHARYYA 481

Protein level, destruction of the excess of anti- diuretic mormone in the body is not possible and the only medical therapeutic measure we are left with for combating fluid reten.ion is the depletion of the excess of salt in the body, ^lakemore (1947), Linton, et al (1948), and

^erbode and Holman (1951), obtained better

results in patients with extra-hepatic portal obstruction and in young patients with minimal liver damage than in those with intrahepatic ?bstruction, by direct portcaval and splenorenal anastomosis. Portis (1953) while quoting the

above results opines "sufficient time has not

^et elapsed for defini.ive evaluation of the

rosults of operation." It is for this reason that

clrrhotic cases with ascites are kept on salt fiee ^iet with therapeutic measures for eliminating the salt from the body. Mercurial salts affect the renal tubules and inhibiting their'absorptive Power of salt, produce profuse diuresis with

c?ncomitant exertion of salt. Tapping as !i

therapeutic measure in cirrhosis has draw-

backs ; the patient who is already at a disad-

vantage with regard to protein metabolism, ^?ses a large amount of protein in ascitic fluid

aud the abdominal cavity is exposed to the Potential risk' of extraneous infection. Hence, Unless the amount of abdominal fluid is very

^arge tapping is rarely resorted to, and salt

restriction with mercurial diuretics reinforced

by ammonium chloride, remains the mainstay lri combating the fluid retention "in the body.

Atkinson, Paton and Sherlock (1954) des-

cribed cases of ascites in hepatic cirrhosis

successfully controlled with salt restriced diet

aud mercurial diuretic given intramuscularly twice a week, reinforced, when necessary, with

attimonium chloride, and they quo'ed Langon aud Schemm, Patoon et al and Eisenmenger (1952) confirming their results. Patients can

he kept on mecurial diuretic for a long time ;

aud after a period of 10-40 months on salt

restricted diet and mercurial diuretics, the

Patients can tolerate unrestricted salt intake Without developing ascites (Eisemenger 1952). ^To complications were met with in this series

though the rare but possible ones are low-salt syndrome, hypokalaemia and hepatic coma :

the last during ammonium administration.

"Acute nephritis is a contra-indication to

Mercurial diuretic though it can occasional!}" he given in nephrotic syndrome... .Albuminu- ria, per se, is not a contra-indication as it is a

common finding in congestive failure and may

disappear when the failure responds to the

treatment" (Hayward 1954). Good results may be obtained "in chronic nephrosis, nephrotic type of glomerulo-nephritis and ascites due to

cirrhosis and portal obstruction" (Goodman and Gilman, 1940).

Intravenous injection of mercurial diuretic

may cause sudden heart failure and very rarely sudden fatal coma may develop in twenty-four hours after mercurial injection. Allerg'c reac- tions consisting of rash, fever, rigor etc. mny occur occasionally (Micks 1950). In a ulc

mercurial poisoning oliguria and anuria may occur (Goodman and Gilman, 1940).

Present work

Of the last 48 consecutive cases of hepatic cirrhosis with asci es admitted into the Medical

Ward II, Assam Medical College Hospital, 15 were treated with salt restricted diet but with-

out mercurial diuretic wi;h 4 deaths in the

hospital from the following causes.

J.B. 27 M?died of cholaemia.

D. 34 F?died of amoebic dystentery. B. 14 M?died of amoebic dystentery. N.B. 37 M?died of broncho-pneumonia.

i The rest, 11 cases, were discharged relie-

ved of ascites.

The remaining 33 patients were treated with mersalyl and salt restricted diet with 6 deaths

in the hospital from the following causes :

P.H. 35 M?died of diarrhoea.? Hookworm.

Y. 38 M?died of Bacillary dysentery. S.G. 30 M?died of diarrhoea.

T. 30 F?died of Bacillary dysentery. B. 30 M?died of Cholaemia.

D.M. 30 M?died of Haematemesis.

The rest were discharged from the hospital relieved of ascites. There were 4 patients in

this group who showed albumin in the urine ;

none of them had any had untoward effect with

mercurial diuretic and were discharged relieved of ascites.

Unusual reactions

The following two cases behaved unusually to the mercurial injections.

Case No. 1.?R. G. 25 F, housewife, admitted into hospital on the 28th of January, 1954,

482 THE INDIAN MEDICAL GAZETTE [Aug., 19&

Complaints.?Gradual weakness, 1 year. Loose motions, 1 year. Swelling of the abdomen and the legs, 9 months. Occasional feverish feeling, 9 months. Since the birth of a child one year

back, which died three days later, she was

having loss of appetite, nausea, specially in

the morning and increasing weakness. Her

abdomen began to swell up about 9 months

back and was followed by swelling of the feet and legs.. She' was having 2-3 stools a day during this period. She was occasionally feel-

ing feverish for the last 1 year. There was no

history of haematemesis nor malaena nor any

particular change in the colour of her stools

and urine.

Past History.?3 abortions at 3 to 4 months of pregnancy. No Jaundice.

Personal History.?Average Indian diet ; no

excess of spice, no alchohol.

On Examination.?Fair build, poor nutrition, cheeks and eyes sunken, distended abdomen

and oedematous lower extremities, pitting on

pressure. Average intelligence. Icteric tinge on soft palate and under surface of tongue. Moderately anaemic, teeth and gum unhealthy. Tongue, moist and clean. Glands, not palpa- ble. B.P., 110/65; temperature from 97?F to

98?F (during the hospital stay)

Pulse, 86/min ; Respiration, 20/min.

, Gastro-intestinal Tract : Abdomen greatly distended with full flanks and everted umbili-

cus ; the veins visible radiating from umbilicus ;

filling from below upwards above the umbilicus and from above down-wards below it. Fluid

thrill and shifting dullness present. Liver en-

larged. Spleen enlarged. Cardiovascular System :

Pulse, tension low, apex beat in the fourth left

interocostal space in the mid-clavicular line.

Soft systolic murmur in the pulmonary and mitral areas not conducted, and diminishing on exertion.

Respiratory system : N.A.D. Upper border of

liver, right fifth inter costal space in the mid

clavicular line.

Nervous system : N.A.D.

Genito-urinary system : Scanty urine of high colour and strong smell.

Laboratory Examination.?Blood Hb 40 per

cent. (Hellige) W.B.C., 5725/cmm Poly 64 per

cent, Lympho 30 per cent, Mono 5 per cent,

Eosino 1 per cent.

Urine.?Sp. Gr. 1015., Reaction alkaline

albumin -j?1?{-, bile Nil.

Stool.?N.A.D.

Patient was put on salt free high protein diet, iron mixture, multivite pellet, crude liver

extract 2 cc. I.M. alternate days, Hydrops0' tein by mouth and a diuretic mixture contain' ing Pot. Citras Gr. 15 and Ext. Punarnava HQ- m30 per ounce T.D.

7.2.54: Weight 86 lbs.

8.2.54: Alb. in urine +

10.2.54: Epistaxis, not much.

14.2.54: Weight 84 lbs.

15.2.54: Had a cut injury on the chin due to

fall and A.T.S. 1500 units given.

18.2.54: Alb. in urine, trace. Liver, 3 fingers below costal margin approximately* not tender, ? irregular. Spleen, About 2 fingers below umbilicus, not tender-

Ammonium chloride Gr. 15 T;D. in mixture

started. Alkaline diuretic stopped.

19.2.54: Inj Mersalyl (Evans) 2 CC. I.M. ̂

the buttock in the early morning- 4-30 P.M. Patient restless, com'

plained of pain at the side of injec tion. Headache. Pulse 100/min. Re'

gular. 5-30 P.M. Patient stuporse, had

a convulsion, tonic in character with the body arched back. Pupils not

dilated, sluggish reaction to lig^- Lower extremities, increased tone-

? Tendon jerks diminished. Plants

response extensor in type. Upper extremities, slightly increased tone*

tendon reflexes diminished. Abdc minal reflex, slight response.

rigor, no articarial rash. Had no

urine since noon. Catheterised. total amount of urine since mornin# 30 ounce. Catheterised specimen ^

urine; Acid, Alb?urine almost boiled solid. No R.B.C., no cast, no bile*

Tenp., 100.4?F; respiration, 22 Per minute; pulse, 104/min. 6-15 P.M-" 25 per cent Mag. Sulph. solution ^

ounce per rectum after an enftf1*1 and 30 cc. 50 per cent Dextrose 1$'

*W, 19541 MERCURIAL DIURETIC IN THERAPY .... : BHATTACHARYYA 483

Patient vomited 7 times between

5-30 and 6-30 P.M., vomit contain-

ing greenish fluid with food materials. 9 P.M.: No convulsion since 5-30

P.M., no vomiting since 6-30 P.M.

Patient quiet. Pulse 60/min, regular. B.P. 144/90.

20.2.54: 2 A.M.: Pulse 98/inin, regular, ten- sion low.

Breathing stertorous. Heart beat

weak.

Lung full of crepitation: Coramin

was administered.

3 A.M., patient expired.

The course was rapid and took place in the

evening and night. Any increase in Jaundice

could not be detected. No biochemical exa-

mination could be done. Postmortem was

refused.

Case No. 2.?A 22 F, admitted on the 4th

^larch, 1954 with generalised swelling of the

body with ascites. Urine acid, no abnormality. Hb. 50 per cent, B.P. 110/70. Pulse 100/min. Heart with soft systolic murmur in pulmonary area and mitral area. Apex beat left fifth

space mid-clavicular line. Stool, hookworm ova found.

6.3.54?Had an injection of Mersalyl I.M. 1 cc. in the morning preceded by ammonium chloride administration on the 5th March.

Patient developed headache, giddiness and

rigor with a vomit before 11 A.M. on the day of the injection, with pain at the site of injec- tion. Calcium lactate was given orally. To-

wards the evening she was alright. She had

plenty of urine that day. Tenderness at the

site of injection was slight on the 7th, and nil

on 8th March.

Discussion

In the 1st case the symptomatology points to acute uraemia with hypertensive encephalo- pathy resulting from acute tubular necrosis?

"Lower nephron nephrosis". Lack of postmor- tem examination in the case is regretted. The symptoms referable to hepatic damage

were of one year's duration and on admission, the patient had signs and symptoms of advanced Uver damage. The progress of liver damage

was sufficiently rapid. As the symptoms of

liver damage were observed by the patient after delivery, it is probable that the increased

demands by the foetus resulted in cystin defi-

ciency with concomitant sub-acute massive

necrosis of the liver leading to post necrotic

scarring with lobular hyperplasia (Himsworth, 1950). "Toxic substances absorbed from the

bowel which the severely damaged liver has

failed to destroy" (Luckes quoted by Hadfield, 1953) or the "toxins" or "intermediate products of digestion" absorbed from gut, which are not detoxicated by the damaged liver, find their

way via the venous plexus of Retzius, due to the obstruction offered by the liver, into the

kidneys (Blond and Haler, 1950) or the accu-

mulated bilirubim in the plasma interfered

with the nutrition of the renal tubular epithe- lium and that in the case under review, the

single injection of mersalyl was the last straw on the camel's back and "promoted renal tubular damage". But such catastrophies are very rare as is obvious from the review of literature in

the beginning of this paper, whereas cases of

hepatic damage as in sub-acute massive necrosis of liver or post-necrotic scarring with lobular hyperplasia from nutritional (cystin) deficiency (Himsworth 1950) with liability to exposure to such factors as promote renal damage like

mercurial salts, carbontetra chloride etc. are

not infrequent. Here hypersensitivity to mer-

cury is a possibility but signs of hypersensiti- vity like rash, difficulty in breathing or joint pains etc. were lacking, nor is it known why the increased susceptibility should have been

confined to renal tubules alone. The predis- posing factors to such fatality even on a single dose of mercurial diuretic are to be explored. This case shows that though cases of cirrho-

sis of liver with ascites have been treated with

good result without fatalities, even with repea- ted injections of mercurial dirretic (Atkinson et al, 1954; Langon and Schemm, Patoon et al,) and for a period of 10 to 40 months (Eisen-

menger, 1952) and that "albuminuria per se"

is not a contra indication (Hayward 1954), we should always be alive to such possibilities, as in this case.

The second case appears to be one of hyper- sensitivity to mercury.

Summary

The position of mercurial diuretic in deplet- ing the excess of water from the body with

484 THE INDIAN MEDICAL GAZETTE [Aug., 1954

special reference to ascites in hepatic cirrhosis is reviewed. This drug is said to be compara-

tively safe even on repeated administration in

cirrhotic cases.

Out of a total of 35 cases of hepatic cirrhosis with ascites treated with mercurial diuretic in

the hospital, there was one fatality within 24 hours of the single injection of mersalyl, appa- rently from acute uraemia. Another case

showed signs of allergy to mercury but

recovered.

The occurrence of severe pain and tenderness at the site of injection in these cases is recorded.

Acknowledgement

My thanks are due to Dr. N. Gupta, M.B., D.T.M., & D.P.H., M.R.C.P., Professor-in-chargf? of the ward for his valuable encouragement anr to Dr. H. C. Barua, Superintendent, Assam

Medical College Hospitals, for permission tc

report the cases.

REFERENCES

Atkinson, M., Paton, Lancet, i, 128.

A., and Sherlock, Sheila (1954).

Blakemore, A. H. (1947). Nero York State J. M ed., 47, 479.

Blond, K., and Haler, The Liver. John Wright <fc

D. (1950). Sons Ltd., Bristol.

Eisenmenger, W. J. Ann. Intern. Med., 37, 261.

(1952).

Gerbode. F., and Holman, Amer. J. Surg., 82, 58. E. (1951).

Goodman L., and The Pharmacological Basis of Gilman, R. (1940). Therapeutics. Macmillan

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Hadfield, G. (1953) .. Recent Advances in Patho-

logy. J. & A. Churchill

Ltd., London.

Hayward, G. W. (1954). Practitioner, 172, 202.

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Karamchandani, P. V. Indian Med. J., 45, 257.

U951).

Linton, R. R., Hardy, Surg. Gyn. and Obstet., 87i

I. B., and Volaviler, 129.

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Therapeutics. J. & A-

Churchill Ltd., London.

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