EVENING COLIC IN INFANTS

1119 EVENING COLIC IN INFANTS A DOUBLE-BLIND TRIAL OF DICYCLOMINE HYDROCHLORIDE

substance better than the inert one, the total difference being 20. Typical remarks were as follows: " The second bottle didn’t have the

R. S. ILLINGWORTH M.D. Leeds, F.R.C.P., D.P.H., D.C.H.

(First " "

PROFESSOR OF CHILD

HEALTH, UNIVERSITY

OF SHEFFIELD

was

colic, also termed " three months’ colic ", is annoying condition in healthy thriving babies in the first three months of their life; and not one of innumerable different methods of treatment recommended has proved

satisfactory. I reviewed elsewhere -published reports concerning evening colic (Illingworth 1954). A blind trial of methyl scopolamine nitrate (’ Skopyl ’) (Illingworth 1955) indicated that this drug was useless in the dosage employed, the control inert substance giving just as much or more relief than the active drug. It seemed possible that an anticholinergic drug might be useful, and accordingly I decided to conduct a double-blind trial of dicyclomine hydrochloride (’ Merbentyl ’, diethylaminocarbethoxybicyclohexyl hydrochloride). This acts as a parasympathetic depressor, and has very few side-effects. Pakula (1952) tried this drug in infantile colic, and was

Nevertheless both bottles,

EVENING

effect

The first bottle was better." (First active.) The first bottle was no use. He improved greatly

(Second active.)

an

same

as

the first."

active.)

" The first bottle didn’t

help.

on

the second."

The second worked wonders."

(Second active.) " The first made no difference. The second bottle colic." (Second active.)

stopped the

single mother spoke in glowing terms of saying that " it was like magic ", and had

a

SCORES ALLOTTED IN DICYCLOMINE STUDY

convinced of its value. Method of Study carried out in the well-baby clinic at the study The diagnosis was based on Sheffield. Jessop Hospital, rhythmical attacks of screaming in the evenings in well, thriving babies who were gaining not less than 7 oz. per week during the period of observation. An important condition for admission to the study was the mother’s statement that the screaming continued unabated when the baby was picked up. All the babies were seen by me. All babies were less than 8 weeks old when treatment was instituted. When I was satisfied with the diagnosis I prescribed dicyclomine; and the pharmacist then dispensed either dicyclomine or an inert substance by random sampling. I saw the child a week later and recorded the mother’s words about the colic. The medicine was prescribed again, and the pharmacist then gave the opposite of that which she had given beforee.g., the active drug if the control material had been given on the first occasion. I saw the child again a week later. Only the pharmacist knew which material the child received. Only when I had tabulated all my results was I given the code which indicated the treatment given on each occasion. The results were graded from -to + 3. +1 signified that the child was slightly better, +that he was definitely better but still had some discomfort, +that he was very greatly improved and free from symptoms. -11 meant that he was slightly worse. A total of 20 patients were studied, but unfortunately 4 did not have the inert substance and 1 did not have the active drug. The dosage used was half a teaspoonful (approximately 5 mg.) before the 6 P.M. feed. The

was

Results

Of 16 patients receiving the inert substance 8 were unaffected, and the remaining 8 were given a total score of +-19, 4 patients receiving + 3 each. The mean score was +1-18 (see table). Of 20 patients receiving the active drug, 1 was unaffected, the remaining 19 patients being given a total score of +47. 12 patients were given +3 each. The mean score was +2-35. No patient in either group was worse with the treatment, unlike patients in the methylscopolamine-nitrate study referred to above. 3 mothers found the inert substance more effective than the active drug, 2 of these differing by one point: the total difference was +5. 9 mothers found the active

Italic

figures

are scores

obtained’on the active drug.

" done him the world of good ". A mother of a baby who received the active drug alone said that he was " much, much better. I’m so much relieved. The improvement was immediate". Discussion

Evening colic is a self-limiting condition, curing itself by the age of 2 months in mild forms, and by 3-4 months in severe forms. In a trial of a drug for such a condition, the double-blind method is very satisfactory; for, each patient being his own control, the factor of the increasing age of the child should be eliminated. The table shows that the factor of the increasing age of the child has not affected the results. Mothers are great believers in the magic of medicine, and the double-blind method effectively disposes of this factor in the assessment of results.

Several mothers were strikingly dogmatic about the difference in the effect of one bottle from that of the other; and in 7 out of 8 of such cases the mother’s opinion that one of the two bottles was ineffective corresponded to the fact that the offending bottle contained an inert substance. In the methyl-scopolamine-nitrate trial (Illingworth 1955) random sampling was used, but not the double-blind method. In that study 20 control babies received the inert substance, and 20 received the active drug. 14 in the " active group " were helped by the drug, and 5 were made worse: 16 were helped by the inert substance, but none were made worse. A further striking fact has emerged from the present

study-the decline in the number of babies suffering from evening colic. I cannot explain this. The feeding habits of the babies in the past two years do not appear to be any different from those in previous years. The clinical picture is so striking that there cannot have been any error of diagnosis in either group. Whereas five to ten years ago I frequently saw severe cases of evening colic, I rarely see such cases now.

1120

Summary A double-blind study of the effect of dicyclomine hydrochloride (’ Merbentyl’) on evening colic in infants (" three months’ colic ") has proved that the drug is of considerable value. No other drug has been proved to

be of value in the

treatment

of this condition.

I wish to thank Riker Laboratories Ltd., Loughborough, for supplying the dicyclomine and the inert material as control; and Miss C. Wood, chief pharmacist at the Jessop Hospital, Sheffield, for her cooperation. Dicyclomine is now marketed by Merrell National (Laboratories) Limited. REFERENCES

Illingworth, R. S. (1954) Arch. Dis. Childh. 29, (1955) Acta pœdiat., Uppsala, 44, 203. Pakula, S. F. (1952) Postgrad. Med. 11, 123.

165.

—

PREDNISONE IN THE RELIEF OF ACROPARÆSTHESIÆ F. LEES M.B. Sheff., M.R.C.P. SENIOR

REGISTRAR, MANCHESTER

ROYAL INFIRMARY

L. A. LIVERSEDGE B.A., M.B., B.Sc. Manc., M.D. Duke, M.R.C.P. LECTURER IN

NEUROLOGY,

when carrying a shopping-bag or when gripping. The index and middle fingers were affected mainly, and the trouble lasted about 15-20 minutes, usually being relieved by arm movement. From time to time she complained also of in her neck, and of aching in the finger-joints, wrists, pains and ankles. In June, in the Department of Surgery, cervical spondylosis was diagnosed because radiographs of the cervical spine showed narrowing and osteophyte formation at the c5/6 disc space. In September, when she was seen in the Department of Neurology, her symptoms were unchanged but she had swelling of the interphalangeal joints, wrists, and right ankle. The erythrocyte-sedimentation rate was 32 mm. in the lst hour (Wintrobe), and radiographs of the wrists showed some

occasionally

UNIVERSITY OF MANCHESTER

IN a recent review of 150 cases of acroparxsthesix, the results of which are to be published later, we came to the conclusion, previously reached by others (Brain et al. 1947, Kremer et al. 1953, Garland et al. 1957, Heathfield 1957), that carpal-tunnel decompression almost always cures this condition. On the whole, medical treatment has been disappointing, and we have failed with tolazoline (’Priscol ’), nicotinic acid, and various other putative vasodilator drugs. But if a suitable medical remedy could be evolved it would have definite advantages in certain circumstances-e.g., if there was any doubt about the diagnosis; as a temporary form of treatment whilst awaiting operation; if operation was contraindicated or if the patient (as often happens) expressed a wish not to have an operation; and in certain patients with associated diseases, particularly rheumatoid arthritis affecting the hands. During this investigation we observed with interest that arthropathy might be present in patients who complained of typical acroparxsthesix. The association is shown in the following examples.

Case-reports Case 1.-In February, 1958, a woman of 52 complained of pins and needles in both hands. This awakened her in the early hours of the morning, and she had similar sensations

juxta-articular porosis. Acroparassthesise with associated arthropathy was diagnosed, and although carpal-tunnel decompression was contemplated we decided to try giving her prednisone 5 mg. t.d.s., to see whether the pain in the wrists could be relieved and whether the acroparaesthesise would be affected. A month later she pronounced the tablets " absolutely wonderful "; all the joint swelling had gone, and she had had no further attack of parsesthesiae. She remained very well on this dosage, and when last seen in April, 1959, she had resumed work. Case 2.-In mid-December, 1958, a woman of 26 developed acroparsesthesiae in both hands (the right being affected more than the left), which woke her four or five times nightly. She had some tingling in the day time too, and occasionally she had pains in her back and metacarpophalangeal joints. Because the metacarpophalangeal joints were swollen, we thought there might be an associated arthropathy. We again decided to try the effect of prednisone 5 mg. t.d.s. Her symptoms had improved considerably after a week, and this improvement has been maintained. In April, 1959, prednisone was discontinued and the trouble recurred. When prednisone was given again the acroparxsthesiae disappeared, though she still complains of a little pain in the metacarpophalangeal joints.

Because of the symptomatic success in these 2 cases we decided to extend the use of prednisone to others in which no arthropathy could be demonstrated. 2 other patients with arthropathy have been so treated with improvement in both the paraesthesise and arthropathy, but we have also treated 13 patients with acroparaesthesiae but without arthropathy. All the results are summarised in the table.

provides another characteristic history. In October, of 51 began to get typical acroparsesthesise in 1958, both hands, which usually woke her in the early hours of the morning, sometimes two or three times, and came on occasionally during the day when she rested and when knitting. The interphalangeal joints showed slight spindling, but neurologically there were no abnormal findings. We decided to try the effect Case 3

a woman

SUMMARY OF CASES OF ACROPARaeSTHESIae TREATED WITH PREDNISONE

(ALL

WERE

FEMALE)