BRAIN DEATH AND THE EEG

1085 serum enzymes. He is now on 30 mg prednisolone daily and leads a normal life without gastrointestinal symptoms or oedema. Both CDand MCGN3have been reported in association with CAH. The three conditions have not, however, been reported together in a single patient. This association seems unlikely to be due to chance alone. Immune complex formation could be the common

BRAIN DEATH AND THE EEG

factor. 3-5

V’e thank Dr Michael Hamilton for permission to report this case and the Joint Research Board of St Bartholomew’s Hospital, the National Fund for Research into Crippling Diseases, and the Wellcome Trust for financial

support.

Departments of Gastroenterology, Nephrology and Histopathology, St Bartholomew’s Hospital, London EC1A 7BE

E. T. SWARBRICK P. D. FAIRCLOUGH P. J. CAMPBELL D. A. LEVISON R. H. GREENWOOD L. R. I. BAKER

THE DEXAMETHASONE TEST AND DEPRESSION

SIR,-Underrecognised and poorly treated depressive illness has6 been referred to as one of the world’s major public health Hence most physicians would welcome a nosology of depressive illness and a guide to treatment, underpinned by firm biochemical, neuroendocrine, or other biological markers. Although results with the dexamethasone suppression test provide a promising strategy in this direction, your editorial of Oct. 4 (p. 730) omits some recent well-controlled negative findings. Klein et al.have reported on 100 unselected newly admitted depressive patients examined by the dexamethasone suppression test on admission to hospital and six weeks thereafter. The depressive symptoms were rigidly categorised by the research diagnostic criteria of Spitzer and Endicott, by the International Classification of Disease, and by the Newcastle rating scale. Raters stayed blind to the results of the dexamethasone suppression test. In this study, no relationship was found between the results of the dexamethasone suppression test and the categorical entities of the depressive disorders. In a smaller but similarly blind series of 24 patients in hospital with primary depression, we likewise have been unable to discriminate between depressive subcategories by abnormalities on the dexamethasone suppression test? Like others we found that abnormal suppression correlated significantly (p<0-01) with high baseline plasma cortisol levels. Unexpectedly the highest morning and afternoon cortisol baseline levels were found in our nonendogenous depressive subgroup (p<0’01), some of whom had a good outcome with psychotherapy alone. These findings were disappointing since the thrust of our investigation had been the evaluation of the dexamethasone suppression test as a guide to the

problems.

diagnosis of endogenous depression. a test which is abnormal in at most 50% of patients with depressive illness, it would be premature to conclude that a laboratory diagnosis of endogenous depression may now be at hand. Until the behavioural correlates and practical significance of abnormal dexamethasone suppression are further clarified, the recognition and treatment of depressive illness will remain a clinical task.

With

severe

Department of Psychiatry, Faculty of Medicine, University of British Columbia, Vancouver, B.C., Canada 2. Pollock

RALPH SHULMAN

The liver

in coeliac disease. Histopathology 1977; 1: 421-30. Griffel B, Naveh D. Membrano-proliferative glomerulonephritis associated with persistent viral hepatitis. Am J Clin Path 1973, 59: 222-28. 4 Thomas HC, De Villiers D, Potter B. Immune complexes in acute and chronic liver disease. Clin Exp Immunol 1978; 31: 150-57. 5 Doe WF, Booth CC, Brown DL. Evidence for complement-binding immune complexes in adult coeliac disease, Crohn’s disease and ulcerative colitis. Lancet

3

DJ.

Myers BD,

1973, 402-03. 6 7.

8

Ayd FJ, Taylor IJ, eds Mood disorders. The world’s major public health problem. Baltimore Ayd Medical Communications, 1978. Klein HE, Bender W, Benkert O, Holsboer F, Niederschweiberer A, Schmaub M Diagnostic differentiation of depressive syndromes by the dexamethasonesuppression test. Paper presented at the XI International Congress of the International Society ofPsychoneuro-endocrinology, Florence, June, 1980. Shulman R, Diewold P. A two-dose dexamethasone suppression test in patients with psychiatric illness. Can Psychiatr Assoc J 1977; 22: 417-22.

decade ago Beecher questioned whether physicians had "as yet achieved enough emotional and sociological maturity" to handle the whole question of brain death boldly, compassionately and with intelligence.’ Judging from some of the recent correspondence on the subject there is still considerable resistance to drawing logical conclusions from now widely observed facts. Dr Pampiglione’s questioning (Nov. 8, p. 1022) of terms such as "brain death", "cerebral death", and "brainstem death" and his support of the EEG need to be put in perspective. Those who have argued against the concept of brain death on philosophical or religious grounds2 must be given proper consideration. The proposition is, however, generally accepted. There is nothing wrong with the terms themselves although confusion has been generated by their inappropriate use (as in the equating of brain death with brainstem death). The utter dependence of a viable and conscious human being on a functioning brainstem is not difficult to grasp. It is common experience that individuals may remain responsive despite the destruction of a major part of one or both cerebral hemispheres-or indeed, in the case of anencephaly or severe hydrocephalus, with virtually no hemisphere function at all. By contrast lesions of strategic areas in the brainstem result in permanent coma, even if the hemispheres are intact. The brainstem also subserves the vital functions. All this is part of the physiology taught to every medical student and is surely common ground. No technological substitute for the functions of the brainstem is currently in sight. Should this ever come about our criteria-which deal explicitly with the clinical assessment of brain stem function-will need radical revision. It is in the light of these facts that the whole argument about the relevance (or irrelevance) of the EEG in the diagnosis of death needs to be looked at. It would be regrettable if to the special pleadings of television pro.ducers (out to be controversial rather than informative) were now to be added those of EEG departments. Dr Pampiglione is wrong, in our opinion, in believing that the 1971-73 American Collaborative Study3 "provided additional support for the use of the EEG in the assessment of brain death". This study, the design of which has been criticised from within the U.S.A.,4should be seen as the last attempt to defend an increasingly untenable position. Over the last decade the trend of informed opinion in the U.S.A. has been away from the EEG. In 1968 the Harvard Ad Hoc Committeespoke of the "flat or isoelectric EEG" being "of great confirmatory value" and recommended that two EEGs be performed 24 h apart. But within a year the same group "was unanimous in its belief that an electroencephalogram was not essential to a diagnosis of irreversible coma". In 1971 the purely clinical "Minnesota criteria" were published.This classic report described the value of the EEG (in the context of a known cause of coma and of clearly defined signs of brainstem death) as "extremely questionable". In 1975 one of the participants in the 1971-73 Collaborative Study presented data on some 200 patients. 98 had fulfilled the purely clinical Minnesota criteria, the remainder had had an EEG examination in addition. All had been kept on ventilators. None of these carefully followed cases had survived. This led Prof. F. Plum, who was present at the meeting, to query "whether it was necessary, or even desirable, to put the constraints of laboratory technique on what I believe can be or should be an accurate clinical diagnosis of cerebral death". The British Code of Practice7 endorses precisely this view. Many neurologists and neurosurgeons throughout the world used the Minnesota criteria for several years, keeping their patients on ventilators and invariably seeing cardiac function fail within a few

SiR,-Over

-

a

1. Beecher HK. After the "definition of irreversible coma" N Engl J Med 1969; 281: 1070-71 2. Byrne PA, O’Reilly S, Quay PM. Brain death: an opposing viewpoint. JAMA 1979; 242: 1985-90. 3. An appraisal of the criteria of cerebral death. JAMA 1977; 237: 982-86. 4 Walker AE, Molinari GF. Criteria of cerebral death. Trans Am Neurol Assoc 1975; 100: 29-35. 5.

Ad Hoc Committee of the Harvard Medical School A definition of death. JAMA 1968; 205: 85-88.

A, Chou SN. Brain death: 1971; 25: 211-18.

6. Mohandas

7. The removal of cadaveric organs for

HMSO,

1979.

a

clinical and

pathological study. J Neurosurg

transplantation,

a

code of practice. London:

1086

days.8-1O There were no reported exceptions. We have been through this distressing ritual ourselves in over 50 cases. Only fragments of this vast experience have been reported, probably because in this country we are relucant to publish when we have little new to contribute. Patients fulfilling the British criteria of brainstem death-which are even stricter than the American ones in relation to the definition of apnoea II-cannot logically be expected to have a more favourable prognosis. In 1978 the American Neurological Association downgraded the role of the EEG (in the determination of brain death) from a "requirement"3 to a "valuable confirmatory indicator".12 The EEG was still recommended but it was not specified whether the recommendation was neurologically or legally motivated. Last year Prof. Earl Walker, project coordinator of the earlier Collaborative Study, even admitted that "in a hospital which has no sophisticated diagnostic equipment the pronouncement of cerebral death may be made with certainty after 3 days of absence of all clinical evidences of brain function". 13 Ancillary techniques were only thought necessary for apnoeic comas of shorter duration. The trend away from the EEG probably reflects the recognition that it has nothing fundamental to say about the status of the brainstem in these particular patients, despite the fact that in practice there is a high correlation between isoelectric EEGs and loss of brainstem function. The EEG represents the activity of cortical neurones which-although modulated by brainstem and other deep central structures-may act independently in the absence of such modulation. The status of the cerebral hemispheres (and the EEG) is irrelevant to the identification of irreversible loss of brainstem function, which is the prime concern of the British Code of Practice. The EEG, in this context, is as depasse as some of the comas it is seeking to monitor. 14 Those who believe that the EEG "may be of some use" should be more explicit. What precisely can it tell us, that is relevant, when clinical examination reveals a non-functioning brainstem? The move away from the EEG has also gained momentum for more practical reasons (which flow from these cònsiderations)-namely, the unacceptably high proportion of false positive and false negative information it provides in clinical practice. Let us forget patients under the influence of drugs, hypothermia, or metabolic upsets, in whom the detection of isoelectric EEGs may lead to disastrous sequelae in the hands of the uninitiated. Repeatedly isoelectric EEGs have been recorded among patients surviving cerebral anoxia,IS-19 trauma,2° streptococcal meningitis,19 and herpes simplex encephalitis. 19 Hughes’ excellent and highly critical review of this whole area21 mentions a large number of other alleged. cases. Many can be dismissed because of poor documentation or obvious technical errors. Hughes rightly concludes, however, by admitting the possibility of reversible electrocerebral silence without drug intoxication or hypothermia. Such patients may have dead cerebral hemispheres-but brainstem still capable of some function. They should never be considered dead. They may live for days, weeks, or months. Specialists in electroencephalography often argue that some of Jennett B. Personal communication, 1980. 9. Gleave JRW. Transplants dilemma. Times, Oct. 27, 1980. 10. Ayim EN, Clark GPM. Brain death: Experience in an intensive care unit. E Afr Med J 1979; 56: 571-76. 11. Pallis C. Brain death and the BBC. Lancet 1980; ii. 911.

these cases did not "really" have isoelectric EEGs and that many of the provisions concerning adequate recording in this sort of situawere not adequately complied with. But in so doing they unwittingly devalue the claims of the EEG. The clinical signs of brainstem function have sharp, reproducible, unambiguous endpoints. After a few demonstrations any reasonably trained doctor could elicit them. The same cannot be said about the EEG. "The Intensive Care Unit is not a friendly environment for the electroencephalographer or EEG recordist". 24 Cerebral signals recorded at high gains have to compete with others generated from

tion 2,23

respirator, dialysis machine, heart-beat, ballistocardiogram, lfi. travenous drips, people walking in the ward, blood trickling into a bucket24-and even from technicians wearing nylon underwear. "Dissociations" also occur in the opposite direction. Residual activity in the EEG may be recorded in many patients in whom a careful examination had confirmed a total loss of brainstem function. Under these circumstances it is the clinical signs that are prognostically the more relevant. All such patients have died. 25.30 This is hardly surprising. The physical signs, after all, related to what was relevant-namely, the brainstem. EEGs are nevertheless still widely resorted to in the U. S.A., in the diagnosis of brain death. Few people are prepared honestly to discuss the cultural (rather than neurological) dimensions of this addiction. Our American colleagues practise in a litigious atmosphere in which "a climate of general public unease about brain death exists, partly engendered by sensational fiction". 31 For good or ill, instrumental medicine has taken giant steps forward-often evicting good clinical practice in its wake (it is not unusual, in certain parts of the U.S.A., for patients to be referred to a neurologist with a diagnosis of "CAT-negative headache"). Many American jurors have a touchingly na’ive faith in the supremacy of machines such as the EEG, do not realise that there is at least a 3% variance in the reading of such records3and are blissfully unaware of all the problems involved in obtaining artifact-free traces at high amplification. While maintaining our view that the EEG is irrelevant to the diagnosis of brainstem death, we would not seek to underplay its prognostic importance in the management of brain-damaged and seriously ill patients. It would be tragic, however, if an increasingly outmoded American practice (already discarded in Finland32 if not in Norway) were allowed to influence policy over here and to compel "the D.H.S.S., the Medical Research Council, the Royal College of Physicians, and other bodies" again to tread this well-worn ground. The B.B.C. Panorama television programme did untold harm in undermining public confidence by its tendentious presentation of an area of legitimate public concern. In the words of Charles Hadden Spurgeon "a lie is twice round the world before Truth has put on her beots". Cannot we proceed without our boots being weighted with the residues of controversies long settled? Department of Neurology, Royal Postgraduate Medical School, London W12

C. PALLIS

Royal Free Hospital, London NW3, and National Hospital, London WC1

B. MACGILLIVRAY

8.

12.

Report of the

Committee on Irreversible Coma and Brain Death Trans Am Neurol 103: 320-21. 13. Walker AE. Advances in the determination of cerebral death. Adv Neurol 1979, 22:

Assoc 1978; 167-77.

14. Mollaret P, Goulon M. Le coma dépassé. Revue Neurol 1959, 101: 3-15. 15. Bennet DM, Nord NM, Roberts TS, Mavor H. Prolonged "survival" with flat EEG following cardiac arrest. Electroenceph Clin Neurophysiol 1971; 30: 94. 16. Brierley JB et al. Neocortical death after cardiac arrest. Lancet 1971; ii: 560-65. 7. Crow HJ, Winter A. Serial electrophysiological studies in a case of 3 months survival

18. 19.

20. 21.

with flat EEG following cardiac arrest. Electroenceph Clin Neurophysiol 1969; 27: 332. Levin P, Kinnell J. Successful cardiac resuscitation despite prolonged silence of EEG. Arch Intern Med 1966; 117: 557-60. Pollack MA, Kellaway P Cortical death with preservation of brainstem function: Correlation of clinical, electrophysiologic and CT scan findings in 3 infants and 2 adults with prolonged survival. Trans Am Neurol Assoc 1978; 103: 36-38 Bricolo A, Benati A, Mazza C, Bricolo AP. Prolonged isoelectric EEG in a case of posttraumatic coma. Electroenceph Clin Neurophysiol 1971; 31: 174. Hughes JR Limitations of the EEG in coma and brain death. Ann NY Acad Sci 1978; 315: 121-36.

MG, Schwab RS, Masland RL. Cerebral death and the electroencephalogram. JAMA 1969, 209: 1505-10 23. Jorgenson EO. Technical contribution Requirements for recording the EEG at high sensitivity in suspected brain death. Electroenceph Clin Neurophysiol 1974. 36:

22. Silverman D, Saunders

65-69. 24. Bennett DR,

Hughes JR, Korein J, et al. Atlas of electroencephalography in coma and cerebral death. New York. Raven Press, 1976 25. Ashwal S, Schneider S. Failure of electroencephalography to diagnose brain deathin comatose children. Ann Neurol 1979; 6: 512-17. 26. Powner DJ, Fromm GH. The electroencephalogram in the determination of brain death. N EnglJ Med 1979, 300: 502. 27. Deliyannakis E, Ioannou F, Davaroukas A. Brainstem death with persistence of bioelectric activity of the cerebral hemispheres Clin Electroenceph 1975; 6: 7 5-79. 28. Korein J, Maccario M. On the diagnosis of cerebral death a prospective study of 55 patients to define irreversible coma. Clin Eleclroenceph 1971, 2: 178-99 29. Levy-Alvocer M, Babinet P. Etude des réactions chronologiques entre l’installation du tableau clinique de coma dépassé et la persistance d’une minime activité EEG a propos de 9 cas. Revue Neurol 1970; 122: 411-15 30. Jorgensen PB, Jorgensen EO, Rosenklint A. Brain death Pathogenesis and diagnosis. Acta Neurol Scand 1973; 49: 355-67. 31. Sweet WH. Brain death. N EnglJ Med 1978; 299: 410-11 32. Kaste M, Hillbom M, Palo J. Diagnosis and management of brain death Br Med J 1979, i: 525-27.

1087

SIR,-Now that we have reassured ourselves at length, that the British medical profession is right, unfailing, and superior, we only need to prove this to the rest of the world. Department of Haematology, St. George’s Hospital, London SW17 0QT

EDZARD ERNST

EPIDEMIOLOGY AND THE CLINICIAN lines in your own columns’ the suspicion of they advocate expropriation the lawful proprietors are legitimately moved to protest. Epidemiology is that branch of medical science that is concerned to understand the health of human communities and is central to community medicine which is that branch of medical practice that is concerned to promote the health of human communities. Clinicians deal with individuals, and although communities contain individuals they are not simply the aggregate of those individuals but of the transactions that occur among them. Epidemiological findings have relevance to the maintenance and promotion of the health of communities but not necessarily (and not often) to the health of individuals. Findings that result from the application of statistical methods to clinical problems are not epidemiological findings and much that goes under the name of "clinical epidemiology" reflects the confusion that such a selfcontradictory characterisation displays. The history of epidemiology illustrates clearly that its tributary themes-both methodological and theoretical-are ecological, demographic, and sociopolitical to a much greater extent than they are clinical, and the solutions which have arisen from epidemiological inquiry have rarely been usefully applicable either by clinicians or at the level of the individual. Epidemiological studies of the present major health problems-arteriosclerotic and neoplastic disease-exemplify the necessity for a political rather than a clinical approach to their solution. It is not practicable for individuals to choose a prudent diet and life style or to avoid environmental carcinogens in the face of prevailing social and economic policies. No one would wish to deter clinicians from the use of social or statistical methods in their clinical research. Most public health doctors are glad that clinicians are at last beginning to base their practice on scientific findings. But epidemiology is much older than clinical science and has a substantially more impressive record of successful implementation ofits findings as witnessed by nearly two centuries of community medicine practice. Your editorial and the paper by Orchard3 border on the impudence of the parvenu.

SIR,-Editorials

on

similar

and in those of your conspiracy, and when

partisan

contemporary2raise

Department of Epidemiology and Social Research, University of Manchester and University Hospital of South Manchester, Manchester M20 9QL

AEWYN SMITH

MIMS UNDER SCRUTINY

SIR,-May I comment on some of the points in your note (Nov. 1, p. 987) on Social Audit’s report Drug Disinformation: What British and multi-national drug companies tell doctors about their products at home and abroad ? You criticised the title of the report on the grounds that "abroad means Ireland". You did not mention that in 40 of the 200 comparisons made, the prescribing information supplied in the U.K. and Ireland was compared with the information given for identical products in Australia and the U.S. The report also emphasised the relevance of our research to the provision of prescribing information in developing countries. We listed all differences in prescribing information found between entries in MIMS U.K. and MIMS Ireland, reasoning that

information in one MIMS might usefully be included in the other-unless of course the information was superfluous, in which case it would be better if it did not appear at all. We did not suggest that all disparities were of great significance, let alone "earth shattering". We invited companies to comment on the significance and we stressed to them-as we did in the report itself-that the significance of the disparities would vary greatly. You seem (to a layman) curiously sanguine about the omission of information on contraindications and special precautions-found in well over half of the 200 entries examined. Is it, for example, really unexceptional that doctors in Ireland are effectively recommended to treat children with drugs for which "no adequate studies on young patients" have been performed? And would it also be unexceptional if the same thing happened in the U.K.? If not, then the dual standards in prescribing information you refer to in relation to developing countries in fact also apply much closer to home. Social Audit Ltd, 9 Poland

CHARLES MEDAWAR

MOTHERS ON THE WARD

SiR,-In their letter on "French beds" for mothers sleeping next their children, in a ward not originally designed for children, Dr Baum and his colleagues (Oct. 11, p. 807) refer to a Ministry of Health hospital building note of April, 1964, which the planners seem not to have consulted, perhaps because they were adapting a hospital area rather than designing a children’s ward from scratch. Without knowing the circumstances the planners were faced with it is impossible to say what might have been done to give mothers more sleeping room and amenities. All the same a result of this adaptation at the John Radcliffe Hospital was to make it difficult for the ward to meet one of the needs of children in hospital-namely, that parents should be able to stay with young ones, if possible. The building note states that, whereas in adult wards the proportion of single rooms should be not less than 20% of the total beds, "in children’s wards this proportion should be increased to 40 per cent to allow a sufficient number of bedrooms to be available for mother and child rooms, for unaccompanied children under 2 and for some new admissions etc". It goes on to say that, on a 20 bed ward, 12 beds should be in multi-bed rooms and 8 beds in single rooms and that "at least 4 of these single rooms to be sufficiently large to allow for an additional bed for a mother". An area of 140 sq ft (13 m2) or more would be adequate for the purpose. Baum et al. cite our paper of 1962’-in which we describe experience at Amersham Hospital with 1000 mothers rooming in with their sick children. On the strength of this experience we asserted that the ordinary care of her child by the mother in a general paediatric ward was not only perfectly practicable, given the sympathetic cooperation of the hospital staff, but also beneficial to the child under five and, what is often ignored, to the mother herself. The single rooms at Amersham Hospital were 140 sq ft in area and there were 8 of them (33%) in this well designed, just post-war, 24-bed ward. Could it have been done with smaller cubicles and fewer? We thought so-but there are limits, and some hospitals still have children’s wards that are very difficult to adapt, being designed in a period when mothers were allowed there only for breast-feeding or if their child’s life was threatened. The Nuffield Foundation architectural division, in a book2 which shaped the building note, listed 72 hospitals in 1961 providing accommodation for mothers. The provision ranged from one bed for mothers (in the nurses’ home) for 136 children’s beds, to "ample" (the Babies Hospital, Newcastle upon Tyne), 30% (Amersham Hospital, later 50% for the under-fives), and "cubicles used as required" at Pembury Hospital, 1.

Epidemiology and the clinician Lancet 1980, ii: 957. 2. Editorial. A plea for clinical epidemiology. Br Med J 1980, 281: 1163. 3 Orchard TJ Epidemiology in the 1980’s: Need for a change. Lancet 1980; 1. Editorial.

Street,

London W1V 3DG

MacCarthy D, Lindsay M, Morris I. Children in hospital with mothers. i:

2. Nuffield Foundation Division of Architectural Studies. Studies ii- 845.

in

Lancet

1962;

603-08.

hospital.

London- Oxford

University Press,

1963.

in

planning:

Children