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a remarkable shift to reflexivity in cognitive style account for theseeming decline in IQ scores. This becomes evident if speed tests formeasuring IQs are used; such changes cannot be confirmed if IQpower tests are used instead. We found functional scores decreasedin all tests with a time limit, but this applied to neuropsychologicaltests as well as to cognitive and IQ tests.We found a slow deterioration up to the end of therapy, which was

up-to 24 months in the children we studied. After cessation of long-term combination chemotherapy, IQ (speed tests) and otherneuropsychological functions that had been altered during long-term treatment, improved remarkably except in children under 4years of age at diagnosis and start of therapy.Meadows et al. do not specify how many of their children were

still under treatment and how many were off therapy at the time ofthe third test, which they did at least at 3 years after diagnosis.Treatment lasted 3-5 years, and their children were diagnosedbetween January, 1975, and May, 1977. Thus we assume thatsome patients were tested while still on long-term chemotherapy.We feel that Meadows’ data should be looked at again to allow forpossible improvements in children coming to the end of treatment.We question the relevance of one of Meadows’ control groups.

The 6 ALL controls with no cranial irradiation were childrendiagnosed 7-13 years earlier. That these fare better than the ALLgroup with cranial irradiation can be attributed to the differenttimes between diagnosis and testing. This is supported by ourobservation of improvement in neuropsychological function aftercessation of therapy in children irradiated during treatment forALL.Another factor which Meadows et al. did not allow for is the long-

term influence of social environment (enrichment or deprivation)on the late performance of ALL children. This may considerablydiffer in children with ALL and children with other childhood

malignancies, such as Wilms’ tumours. Our data show that theseinfluences must be carefully evaluated, especially if very smallcontrol groups are to be the basis for statistical statements.Meadows’ study does not justify the conclusion that radiation

therapy for ALL with doses of 2400 rad to the brain is to blame fordeclines in IQ tests and cognitive function recognised early in thecourse of the disease in children still under therapy. Werecommend-because of other possible late adverse, especiallyphysical, effects of radiation treatment to the brain in ALLchildren-doses not above 1800 rad within modern treatment

protocols. This reduced dose, in our experience over the past 4years, does not adversely affect survival rates in ALL children.Whether the incidence of certain late sequelae such as

carcinogenesis is diminished by this approach remains to be seen.Divisions of Haematology/Oncologyand Neuropaediatrics,Department of Paediatrics,University of Mainz,6500 Mainz, West Germany

PETER GUTJAHRBIRGIT WALTHER

CONTINUOUS SUBCUTANEOUS ANALGESICS ANDANTIEMETICS IN DOMICILIARY TERMINAL CARE

SIR,-Pain and vomiting in patients with terminal malignancy aresometimes difficult to manage and control of vomiting often needsregular 4-hourly intramuscular injections. This is a great burden forgeneral practitioners and their community nurses and often thepatient ends up in hospital. We have used continuous subcutaneousinjections of opiate/antiemetic combinations for twenty-threepatients amongst those cared for by the Tunbridge Wells Hospice atHome team during the past eight months.A Graseby Dynamics digital electronic syringe driver is

programmed to give the total dose over 24-25 h. Haloperidol 5 mgand the entire daily dose of diamorphine are drawn into a syringeand the volume is made up to 10 ml with normal saline or water forinjection. Diamorphine is preferred to morphine because of itsmuch greater solubility. A 25 G Vygon butterfly needle is insertedsubcutaneously, either in the abdominal wall or in the

suprascapular region. 60-100 mm of tubing connects the needlewith the syringe driver which is worn in a small polyester shoulderholster.

Twelve patients had intractable vomiting, usually associated withobstruction; seven were unable to take oral medication in the last24-72 h of life; and in four patients oral analgesia seemed ineffectivedue to unknown factors or because of non-compliance withprescribed medication. Pain was a problem in sixteen patients.Nausea was eliminated in all patients, vomiting was relieved in all

but one case, and all patients were much more comfortable andappeared more alert.The 24 h dose of diamorphine ranged from 15 mg to 900 mg, with

a median dose of 90 mg. This gave excellent analgesia withoutsedation except in two patients whose pain was only partly relieved.If vomiting persisted despite haloperidol, metoclopramide 30-50mg and/or cyclizine 100-150 mg was added. If extra sedation wasrequired, hyoscine 1-2-2 mg in 24 h or methotrimeprazine 50-150mg in 24 h was added. Orphenadrine 20-80 mg in 24 h had to beadded to control drug-induced parkinsonism in three cases. If the 24h volume was greater than 10 ml, a 20 ml syringe was used and thetotal volume was made up to 16 - 5 ml. All these drugs are chemicallycompatible with each other but not with steroids, which are oftenrequired by these patients. Nine patients were able to continuetaking their steroids orally, and only three required intramuscularhydrocortisone.Complications were few and minor in nature. Some localised skin

reactions observed in the first few patients were thought to be due tothe use of prochlorperazine. Haloperidol was substituted. When acombination of antiemetics was used the butterfly needle usuallyhad to be resisted every 4-5 days. The catheter blocked on threeoccasions and the infusion ceased, and the butterfly needle waspulled out inadvertently in three cases; in both situations the needlewas easily resited by the local nursing staff.We feel that this technique has revolutionised the symptomatic

management of terminally ill patients, providing a higher standardof symptom control and enabling many patients to remain at homebecause of the greatly reduced demands on medical and nursingtime. The method is highly acceptable to patients, and families arereassured by the knowledge that the drugs are being administeredcontinuously, ensuring a constant level of symptom control.

Hospice at Home,Michael Tetley Hall,Sandhurst Road,Tunbridge Wells, Kent TN2 3JS

HAMISH T. HUTCHINSONGWENDA D. LEEDHAMANGELA M. KNIGHT

PINDOLOL IN POSTURAL HYPOTENSION

SiR.—Dr Davies and his colleagues (Oct. 31, p. 982) report thefailure of pindolol to improve postural hypotension in five patientswith chronic autonomic failure. We have found pindolol to beeffective in three patients with orthostatic hypotension due tochronic autonomic failure.’ 1 Postural hypotension due to

sympathetic degeneration is not a uniform clinical entity.2 2Although the distinction betwen a preganglionic or postganglionicefferent sympathetic lesion is difficult, it is relevant, because the siteof the lesion determines the degree of denervation supersensitivity,and thus the response to adrenoceptor stimulants.2 Patients withidiopathic orthostatic hypotension (IOH) due to a peripheralsympathetic lesion have lower levels of noradrenaline in plasmathan do patients with preganglionic lesions and central nervoussystem involvement, as in multiple system atrophy.3-5 In additionthe degree of denervation supersensitivity is less pronounced inpatients with multiple system atropy than in patients with IOR.3,4

4

Furthermore the responses of blood pressure and plasmanoradrenaline to tyramine are different in these two types of efferentsympathetic failure. 3-5

1. Man in ’t Veld AJ, Schalekamp MADH. Pindolol acts as beta-adrenoceptor agonist inorthostatic hypotension: Therapeutic implications. Br Med J 1981; 282: 929-31.

2. Bannister R. Chronic autonomic failure with postural hypotension, Lancet 1979; ii:404-06.

3. Bannister R, Davies B, Holly E, Rosenthal T, Sever P. Defective cardiovascularreflexes and supersensitivity to sympathomimetic drugs in autonomic failure. Brain1979; 102: 163-76.

4. Polinski RJ, Kopin IJ, Ebert MH, Weise V. Pharmacological distinction of differentorthostatic hypotension syndromes. Neurology 1981; 31: 1-7.

5. Ziegler G. Choosing therapy for postural hypotension. Drug Ther 1981 (October).97-114.