VENTRICULO-SUBDURAL DRAINAGE IN INFANTILE HYDROCEPHALUS

827 cardiac arrhythmias by the intravenous infusion of L-nor-adrenaline into healthy male volunteers. The mortality-rate in cases of shock with acute myocardial infarction is said to be 70-80% (Friedberg 1956). Our own experience supports this view, and suggests that the use of L-noradrenaline does not significantly affect the outcome of the illness (table 11). Calenda et al. (1953) expressed the describing a series of thirteen patients

opinion in noradrenaline

same on

We believe that the irritative effect of L-noradrenaline on the myocardium, which we have observed both clinically and in laboratory animals, is not sufficiently widely appreciated in clinical practice and is a factor which should certainly be taken into account in considering the use of this powerful drug in the treatment of myocardial infarction. In interpreting these results it should be pointed out that the dosage used in laboratory animals to produce cardiac arrhythmias was about eight to ten times the amount normally used under clinical conditions. The range of dosage needed in myocardial infarction to produce a pressor effect is about 0-1-1-6 tig. per kg. of body-weight per minute. Nevertheless, in view of the definite danger of producing serious cardiac arrhythmias with noradrenaline, we believe that if this drug is to be used at all it should only be used in myocardial infarction under direct electrocardiographic supervision. It seems probable that a rational approach to the treatment of shock in myocardial infarction can only be achieved when our knowledge of the basic mechanism involved in this process is better understood.

Summary At present noradrenaline is considered by many to be the drug of choice in the treatment of shock following myocardial infarction. The view is widespread that its value is enhanced by the absence of any central effect on the myocardium. Experimental and clinical studies demonstrating the tendency of noradrenaline to produce cardiac arrhythmias

presented. suggested that, in view of the dangers of producing arrhythmias, electrocardiographic supervision should be adopted if this drug is to be used in the treatment of cardiogenic shock. are

It is

Our thanks are due to our senior colleagues, Dr. E. N. Chamberlain and Dr. E. Wyn Jones, for permission to include certain of their patients in this series ; to Professor Maegraith not only for suggesting this study but also for the generous provision of laboratory facilities at the Liverpool School of

Tropical Medicine, where the experimental work was done ; to the Liverpool Medical Research Committee for a grant to and to Dr. cover the expenses of the experimental work ; Kanyika Devakul for her invaluable cooperation. REFERENCES

jun., Marcus, S., Mugler, F. jun., Strange, D., Agress, C. M. (1955) Amer. J. Med. 18, 622. Brigden, W. W. (1956) In Hunter, D. Price’s Textbook of the Practice of Medicine. 9th ed., London ; p. 846. Brooks, C. M., Hoffman, B. F., Suckling, E. E., Orias, O. (1955) The Excitability of the Heart. New York ; p. 219. Burn, J. H. (1956) Functions of Autonomic Transmitters. London ; A.

p. 99.

Calenda, D. G., Uricchio, J. F., Friedman, L.

M. (1953) Amer. J. med. Sci. 226, 399. Davies, D. D. (1957) Brit. med. J. i, 261. Friedberg, C. K. (1956) Diseases of the Heart. 2nd ed., Philadelphia and London ; p. 564. Gazes, P. C., Goldberg, L. I., Darby, T. D. (1953) Circulation, 8, 883. Goldenberg, M., Pines, K. L., Baldwin, E. F., Greene, D. G., Ron, C. E. (1948) Amer. J. Med. 5, 792. — Apgar, V., Deterling, R. A. jun., Pines, K. L. (1949) J. Amer. med. Ass. 140, 776. Goodman, L. S., Gilman, A. (1955) The Pharmacological Basis of Therapeutics. 2nd ed., New York and London ; p. 494. Kurland, G. S., Malach, M. (1952) New Engl. J. Med. 247, 383. Miller, A. J., Cheng, T. O., Freedman, M. (1955) Amer. Heart J. 567. Shifrin, A., Kaplan, B. M., Gold, H., Billings, A., Katz., L. N. (1953) J. Amer. med. Ass. 152, 1198. J. H., Skelton, J. M., Mills, L. C. (1953) Amer. J. Med. 15, 330. Sampson, J. J., Zipser, A. (1954) Circulation, 9, 38. Smith, K. S., Guz, A. (1953) Brit. med. J. ii, 1341. Von Euler, U. S. (1955) Lancet, ii, 151.

50,

-

Moyer,

SELECTION

OF PATIENTS BY SUBDURAL EXCRETION TEST

DYE

D. M. FORREST M.B. N.Z., F.R.C.S.

therapy.

Binder, M. J., Ryan, J.

VENTRICULO-SUBDURAL DRAINAGE IN INFANTILE HYDROCEPHALUS

SURGICAL

THE

REGISTRAR,

GREAT ORMOND

HOSPITAL

FOR

SICK

CHILDREN,

STREET, LONDON, W.C.1

K. M. LAURENCE Cantab., M.B. Lpool

M.A.

HYDROCEPHALUS RESEARCH FELLOW, THE HOSPITAL FOR SICK CHILDREN

G. H. MACNAB Edin., F.R.C.S.

M.B.

CONSULTANT SURGEON, THE HOSPITAL FOR SICK CHILDREN AND THE WESTMINSTER CHILDREN’S HOSPITAL

A METHOD of treatment for infantile hydrocephalus by drainage of cerebrospinal fluid into the subdural space was recently described (Forrest et al. 1957). Its success on the of of the the depends capacity lining space to absorb fluid in reasonable quantities. Certain pathological processes render the lining non-absorptive, but we have observed that C.S.F. rapidly disappears from the intact subdural space. To select patients for the opera-

tion it is therefore necessary to have a reliable test of the absorptive power of the subdural lining, and such a test we now describe. Method

The principle of the test is the injection of a measured quantity of dye into the subdural space and its quantitative estimation after recovery from the urine. Phenolsulphonphthalein (phenol-red) was used by Dandy and Blackfan (1913, 1914) to investigate the circulation of the c.s.F., and other workers have shown it to be a suitable indicator of the absorption of c.s.F. (Sweet et al. 1954) ; so we chose this dye for the present test. Our preliminary experiments with the dye showed that there was no significant difference in the rate of absorption whether it was diluted in physiological saline solution or in the patient’s own c.s.F. ; so we now use physiological saline solution as a diluent.

Injection The only difficulty in the test is in the accurate introduction of the dye into the subdural space, which, of We have course, is normally a potential space only. found it best to make a formal approach in the following way : Under general anaesthesia an incision 2 cm. long is made at the lateral angle of the anterior fontanelle ; or, if this is too small, a temporal burr-hole is used. Before the dura is opened, a short fine lumbar-puncture needle is passed into the opposite lateral ventricle, and fluid is withdrawn until the dura becomes indrawn. The latter is then punctured, and the cortex falls away, leaving an air-filled subdural space, which should be inspected for fluid and adhesions. A fine rubber catheter is passed into the space for a distance of about 5 cm., care being taken to avoid laceration of the cortex and its vessels. The dura is closed round the tube with a fine purse-string suture, About 5 cm. of and the wound is closed in layers. tubing is left outside the wound, and the end is spigoted.

Twenty-four hours after insertion of the catheter, when the wound may be assumed to have sealed itself round the tube, and the patient has recovered from the anaesthetic and is drinking well and passing an adequate volume of urine, the spigot is removed, and 3 mg. of dye is injected, followed by 5 ml. of saline solution to wash all the dye into the subdural space. The tube is then resealed. If some technical error renders the test inaccurate, a further injection of dye may be made as soon as dye ceases to colour the urine (usually about twenty-four hours after the first injection). When all the urine has been collected, the subdural tube is gently withdrawn.

828

IMPROVED TREATMENT FOR of dye.-The phenolsulphonphthalein is Preparation * in 6 of 1 in ml. ampoules containing mg. supplied dye ALLERGIC RHINITIS of alkali. Immediately before use the contents of the M. J. MAXWELL ampoule are neutralised by 1 Illl. of hydrochloric acid a 1 ml. of the resulting M.B. Leeds, D.L.O., F.R.C.S.E. (supplied in separate ampoule). mixture (containing 3 mg. of dye) is made up to 5 ml. CONSULTANT OTOLARYNGOLOGIST, NORTH AND WEST GROUPS, with pyrogen free physiological saline solution and is MANCHESTER REGIONAL HOSPITAL BOARD then ready for injection. MOST sufferers from allergic rhinitis derive some relief from anti-histamine therapy. There are many anti. Collection of urine.-All urine is collected for twentyhistamine drugs on the market, and treatment becomes a four hours after injection. As it is essential to avoid any matter of finding the one which produces the maximal loss of urine, we have found it safest to leave an indwelling benefit to the individual with minimal side-effects. This catheter in girls and to fix a length of Paul’s drainage tubing on to the penis in boys. The collection bottle is trial-and-error procedure is time-consuming and often changed after one, two, four, six, nine, twelve, eighteen, discouraging to both doctor and patient. Even the best treatment which can be found may not be entirely satis. and twenty-four hours, and the specimens are kept factory. It is difficult to control the symptoms of allergic separate. rhinitis throughout the night, and many patients complain Estimation.-The whole of each specimen of urine is that these are worst in the early morning. Increasing the rendered alkaline and centrifuged. The quantity of dye dose of anti-histamine usually produces side. night-time present in the supernatant fluid is estimated colori- effects on the of drug, but most often depending metrically with an Ilford filter no. 604, centrifuged drowsiness, from excessive type sedation, or dizziness. alkaline urine being used as a blank, and phenol-red as a The duration of effect of a drug may be extended by The biochemical details are described by standard. it in the form of ’Spansule’ capsules which preparing Laurence j(1957). have the added advantage of eliminating sharp peaks in A graph of the excretion figures at the above-menthe blood-level of the drug, thereby reducing side-effects. tioned intervals of time should form a smooth curve. A powerful but short-acting anti-histamine lends itself to Irregularities indicate a fault in technique or in the the application of this principle, and a compound of this child’s urinary flow. Experience has shown that, where type has been used in the present series of investigations. smooth

is obtained, a reliable index of the absorptive power of the subdural space is obtained by taking the total dye excreted in the first six hours and expressing it as a percentage of the total dye injected. a

curve

The test has been

satisfactorily performed

on

63

hydro-

The total excretion in the first six

hours varied from a trace up to 85% of the injected dye. All the patients who had a subdural haematoma gave extremely low figures, whereas those in whom there was a collection of clear fluid gave slightly higher (5-30%) but still low results. 33 patients underwent ventriculo-subdural drainage with a Forrest disc (Forrest et al. 1957) after a dye test. Of these, 16 excreted 50% or more in six hours, and in 10 of these 16 operation was successful. In none of the remaining 17 patients, having excretion figures of less than 50%, has the hydrocephalus been arrested. Thus, in the whole group, there has been a successful operation in only 30%, but in those excreting 50% or more, the success-rate is 62%. We feel, therefore, that, if ventriculo-subdural drainage is to be attempted, a preliminary dye test should be done, and only those patients who excrete 50% or more of the dye in the first six hours should be operated

Summary A

dye-excretion test to be used in selecting cases of hydrocephalus for the Forrest disc operation of ventriculosubdural drainage is described. There is clear evidence that a high excretion-rate of the dye from the subdural space (50% or more within six hours of injection) indicates that the operation should be successful. We wish to thank our colleagues at the Westminster Children’s Hospital and the Hospital for Sick Children for their assistance. One of us (K. M. L.) acknowledges the support of the research committee of the Hospital for Sick Children. REFERENCES

Dandy, W. E., Blackfan, K. D. (1913) J. Amer. med. Ass. 61, 2216. (1914) Amer. J. Dis. Child. 8, 406. Forrest, D. M., Laurence, K. M., Macnab, G. H. (1957) Lancet, i, 1274. Laurence, K. M. (1957) Arch. Dis. Childh. 32, 413. Sweet, W. H., Brownell, G. L., Scholl, J. A., Bowsher, D. R., Benda, P., Stickley, E. E. (1954) Publ. Res. Ass. nerv. ment. Dis. 34, 101. *

observed.

Preliminary Investigation A clinical trial of diphenylpyraline Swartz (1954) on 100 hay-fever patients.

was

made

by

The results did not show the drug to be an outstanding clinical success. 89 patients obtained symptomatic relief, but the duration of effect was very variable-in some instances as short as thirty minutes. In consequence, there was a corres. ponding variation in the frequency of dosage : some patients could manage on three doses daily, but others had to take a dose every two hours. The amount given at each dose varied from 1 to 4 mg. There was, however, a low incidence of sideeffects (12 %), and these were all of a minor character. In no case was it necessary to discontinue treatment.

The available evidence, therefore, shows that diphenylis an active anti-histamine with few side-effects, but of limited clinical application owing to the difficulty of estimating amount and frequency of dosage. This disadvantage now seems to have been overcome by the new form of presentation.

pyraline

on.

-

compound used is diphenylpyraline (1-methyl. piperidyl-4-benzhydryl ether). This has a potent antihistamine action. 0-5 mg. per kg., injected intraperi. toneally, gave complete protection to guineapigs exposed fifteen minutes later to a 2-5% histamine spray for ten minutes. The toxicity is low the oral L.D’50 for guinea. pigs being 215 mg. per kg. When guineapigs were exposed to a 10% diphenylpyraline spray daily for four months, growth-rate was not affected and no other changes were *

Results

cephalic patients.

Pharmacology The

-

Specially prepared for the purpose by Messrs. Savory & 143, New Bond Street, London, W.I.

Moore,

Most physicians are familiar with the principle of spansule capsules. Briefly, each capsule contains several hundred tiny pellets which carry the drug with a variable thickness of coating. Some of the drug is released as soon as the capsule dissolves : the rest becomes gradually available as the pellets

disintegrate at different times. The result peutic effect lasting for about twelve hours. A preliminary investigation with chronic allergic rhinitis.

was

is

made

an even

on

25

thera-

patients

There were 12 males and 13 females ; their ages ranged from 9 to 60 years, and 14 were over 30 years of age. Patients with complications, such as nasal polyps or secondary infections, were excluded. The symptorns were classed as severe in 4 cases, moderate in ] fI, and mild in 6. All had been treated previously with a variety of anti-histamines, with limited

improvement.