THE OTHER SIDE OF FLUPHENAZINE

1193 BRIEF ANAESTHESIA AND RECOVERY DAY-CASE surgery divides itself into two compart-

Major operations such as herniotomy are so painful that the patient afterwards must be transported home to bed, or at least to a chair. Other proceduresnotably, dental operations-are relatively trivial, and many patients elect to drive themselves home afterwards. Unfortunately nearly all the anaesthetic agents in common use are to some extent lipid-soluble and tend to find their way into body fat. With halothane the quantity retained is not sufficient to produce any narcotic effect, though the patient may smell it in the back of his nose for a day or two. A small dose of thiopentone or methohexitone loses its effect quickly, because of redistribution initially to the watery tissues of the body and secondarily to the fat. The drug is finally eliminated by a process of hepatic breakdown which can last for many hours and during which there is a measurable effect on central-nervoussystem function. In an investigation just reported’ the performance of volunteers in a driving simulator was impaired for at least eight hours after administration of these agents. So perhaps patients who have received a single anaesthetic dose of either thiopentone or methohexitone should be discouraged from driving a car or operating machinery until 24 hours afterwards. This ties in with the observation that electroencephalographic sleep patterns may appear up to twelve hours after a dose of methohexitone.The more rapid recovery which seems to follow methohexitone-to the point at which the patient opens his eyes, sits up, and can stand steadily-does not indicate complete rearousal. Indeed, with more sensitive tests the time to complete recovery with equianaesthetic doses of thiopentone and methohexitone is about the same.3 With two newer drugs, elimination depends on more active processes. Propanidid is rapidly broken down by an enzyme, possibly plasma-cholinesterase, and none of the drug is detectable in serum one to two hours after ments.

injection.4 Electroencephalographic sleep patterns are not found beyond 30 minutes after injection of 500-1000 mg of the drug; nor is there any deterioration of motor performance beyond 60 minutes.2S The driving simulator revealed similar recovery-times’ and a patient can probably drive safely within 2 hours of propanidid. Unfortunately this drug has precipitated cardiovascular collapse in a small proportion of patients,6 and its safety is in doubt. ’Althesin’ (alphadolone/alphaxalone) is the most recently developed intravenous aneesthetic agent. Elimination depends on active biliary excretion, probably after conjugation in the liver. Some investigations-notably, electroencephalography in laboratory animals7-indicate rapid recovery. Though the interval between administration and awakening seems about the same as with thiopentone, recovery from althesin is more complete.8 When pateints were tested

on

the simulator 2-4 hours after althesin

they did

1.

Korttila, K., Linnoila, M., Ertama, P., Hakkinen, S. Anesthesiology, 1975, 43, 291. 2. Doenicke, A., Kugler, J., Laub, M. Can. Anœsth. Soc. J. 1967, 14, 567. 3. Howells, T. H. Br. J. Anæth. 1968, 40, 182. 4. Doenicke, E., Kiumey, I., Kugler, J. ibid. p. 415. 5. Schienle, C., Med. Diss. Erlangen-Nurnberg, 1966. 6. Jarvis, C. A. N. Br. J. Anæsth. 1972, 44, 989. 7. Kavan, E. M., Julien, R. M., Elliot, H. W. Can. Anœsth. Soc. J. 1973, 20, 528. 8. Swerdlow, M. ibid. p. 186.

better than patients who had had other anaesthetics. However, there was a secondary impairment of alertness six hours after the drug.’ Possibly this was due to reabsorption, via an enterohepatic circulation, of either the parent substance or an active metabolite which had been excreted into the bowel. The same solubilising agent, ’Cremophor EL’, is present in both althesin and propanidid, and this agent is apparently responsible for the hypotensive episodes associated with propanidid. It is therefore not surprising that hypotension has also complicated anaesthesia with althesin. Althesin does, however, contain smaller amounts of cremophor EL; and perhaps hypotension will prove less of a hazard. Apparently, rapid recovery after brief intravenous anmsthesia cannot yet be achieved safely. For all its discomforts, could straight-forward halothane anaesthesia with nitrous oxide and oxygen be preferable? THE OTHER SIDE OF FLUPHENAZINE

neuroleptics are chiefly used for mainof schizophrenic patients who, for one reason or another, do not take oral medication and relapse. These drugs have enabled many patients to return to and be maintained in the community, have made a big difference to rehabilitation, and constitute an economy of time and resources.’ Patients on such drugs can be supervised by general practitioners or by suitably trained nurses attached to psychiatric outpatient clinics. How long should intramuscular maintenance therapy be continued? The placebo-controlled double-blind trial conducted by Hirsch and his colleagues2 suggested that some patients might need the treatment indefinitely, yet a third of the comparable population in this trial remained out of hospital while receiving placebo alone. It may be justifiable to withhold long-term treatment from patients with acute onset of illness, a clinical state which includes symptoms of "endogenous" depression, and a good premorbid personality.3 A number of investigators have reported a striking decrease in the number of admissions and the number of days in hospital after institution of maintenance treatment,4but Shepherd and Watt6 lately observed that, while fewer discharged schizophrenic patients so treated are readmitted to hospital, this advantage accrues only to those patients whose prognosis, irrespective of specific treatment, is more favourable as judged by length of stay in hospital. Nor is the transfer of care from the hospital service to the relatives and community services-intrinsic to maintenance-treatment programmes-an unqualified boon. LONG-ACTING

tenance treatment

A number of workers have dwelt

on the burden shouldered by relatives of schizophrenic patients who have returned from hospital,67 an important factor being that many patients who lose the symptoms exhibited in 1.

Villeneuve, A. in The Future of Pharmacotherapy: New Drug Delivery Systems (edited by F. J. Ayd, Jr); p. 61. International Drug Therapy Newsletter, Baltimore, Md., 1973. 2. Hirsch, S. R., Gaind, R., Rohde, P. D., Stevens, B. C., Wing, J. K. Br. med. J. 1973, i, 633. 3. Leff, J. Br. J. Hosp. Med. 1972, 8, 377. 4. Johnson, D., Freeman, H. Practitioner, 1972, 208, 395. 5. Denham, J., Adamson, J. Acta psychiat. scand. 1971, 7, 20. 6. Shepherd, M., Watt, D. C. Excerpta med. int. Congr Ser. no. 359, p. 379, 1974.

Goldberg, E. M. in Portfolio for Health (edited by G. McLachlan); p. 99. London, 1974. 8. Stevens, B. C. Psychol. Med. 1972, 2, 17. 9. Creer, C., Wing, J. K. Schizophrenia at Home. National Schizophrenia Fellowship, Surrey, 1974.

7.

1194 show other symptoms when at home, esa passivity and absence of initiative which render their lives rigid and uniform. Clearly more is required in the way of occupational rehabilitation, sheltered workshops, and access to direct psychiatric services if the social functioning of many patients on long-acting neuroleptics is to be improved. The process of discharge and maintenance on these drugs often exacts a price in terms of money, health, working capacity, and the general quality of life of all concerned which may require intensive social rather than clinical investigation. As Shepherd and Watt are careful to point out, all these factors, and not merely the achievement of hospital discharge or an improvement in the patient’s mental state, must be taken into account if the effectiveness of these drugs is to be realistically assessed.

hospital pecially

can

RENIN IN INTERNATIONAL UNITS

To ensure that an assay gives accurate and comparable results, two steps are essential. One is to assess objectively the validity, accuracy, and precision of the assay methods-perhaps best done collaboratively, by several experienced laboratories. The other is early provision of a reference standard, which should be stable,

carefully ampouled, well-characterised, readily available, and widely used. The report of an international collaborative study of renin assayl is useful in both respects. A series of coded plasma-samples containing variously low, normal, and high concentrations of renin and its substrate were assayed in 17 leading laboratories in nine countries. There was good agreement on the ranking of the renin content of the plasma and detailed information emerged on the precision obtainable with different assay techniques. The investigation showed that results of renin assays in which a common reference preparation of human renin was included could be expressed in terms of international units of renin defined by that reference preparation, and this has led to the establishment by the World Health Organisation of an International Reference Preparation of Human Renin,2-a long-felt need. The study also revealed many ways in which assay methods can be technically improved, such as control of pH throughout incubation, demonstration of the linearity of reaction velocity, and measurement of recovery of renin and its substrate through extraction procedures. The 26th report of the World Health Organisation Expert Committee on Biological Standardisationzopens further prospects of improvement, with its far-reaching recommendations on quality control of in-vitro diagnostic materials (notably kits and reagents for immunoassay). Although these recommendations are primarily intended as advice to Governments, the report goes into detail on standardisation in immuno-chemical and cytochemical assay methodology. Workers who are developing or using such methodology should heed the advice on validation of assay results and their proper reporting: the recommendations, if followed, should lead to great

improvement in the accuracy and precision of hormone assays. Then (and perhaps, only then) it may be possible to make a final judgment on the value and place of renin assays in medicine. 1. Bangham, D. R., Robertson, I., Robertson, J. I. S., Robertson, C. J., Tree, M. Clin. Sci. mol. Med. 1975, 48, suppl. 2, p. 135. 2. Tech. Rep. Ser. Wld. Hlth Org. p. 565, 1975.

MUCH IN JEOPARDY

ANYTHING we write for this issue on the conflict between the Government and the medical profession will be overtaken by events before the journal is published. The latest news we have of the unrest at the Government’s determination to separate private from N.H.S. practice in hospitals is that urgent consultations were said by Downing Street on Dec. 5 to be taking place. But, on the same day, Dr Derek Stevenson, Secretary of the B.M.A., added that there had been no meetings between the Government and the medical and dental professions since they met the Prime Minister on Dec. 3. Last Monday, Dec. 8, newspapers reported weekend meetings at B.M.A. House to discuss, it was conjectured, compromises which Mr Wilson might have suggested for the geographical distribution and timing of the phasing-out of pay-beds from N.H.S. hospitals (see p. 1199). There were even hints that part of the operation might be referred to the Royal Commission on the N.H.S. A concession such as that might give the consultants an opportunity to stand down from their battle

stations. The industrial action’ by some junior hospital doctors, who are dissatisfied by the new terms offered for

extra-duty allowances, was continuing to cause disruption. Some casualty departments were closed; and the treatment of emergencies in some areas seemed very unsatisfactory. Claims that all was being done to ensure no serious harm to patients carried less and less conviction. The way out seemed to lie in a compromise over the total sum available for overtime payments within the Government’s economic policy. Some estimates, put forward by the juniors and based on samples of extra-duty payments paid this year, differ by as much as a factor of three from the ceiling of i12 million a year on which the Government has hitherto insisted in defence of its policy. A new audit to interpret the latest retrospective overtime payments must now be speedily undertaken; and, while that is being done, the junior doctors should return to normal work. They have made their point and further striking will damage their cause and may bring dishonour on their name. On the consultants’ side, if their representatives can see some satisfactory shift in the Government’s attitude to the legislation forecast in the Queen’s Speech,2 they must take that cue to call off their sanctions, and threats of resignation, so that deliberations may continue in a more peaceful environment. Finally, the National Union of Public Employees must also respond to the need for calm by taking no retaliatory action against occupants of pay-beds. The atmosphere is overcharged with enmity (and the Secretary of State for Social Services has not been the best lightning conductor in some of her recent public remarks). As the Presidents and Deans of the Royal Colleges and Faculties have rightly proclaimed, concern for patients must override all other considerations. If the way out of both the destructive disputes is not on the horizon by the time these words appear, that means that the Government and the profession’s representatives have failed to achieve the necessary coming together and that patients and the country’s Health Service are in mounting jeo-

pardy. 1. See Lancet, Dec. 6, 2. ibid. Nov. 29, 1975,

1975, p. 1134. p. 1081.