284

UPPER AIRWAYS OBSTRUCTION AND HYPOXAEMIA IN PATIENTS

WITH SICKLE CELL ANAEMIA OR SICKLE CELL HAEMOGLOBIN C

DISEASE

I I I

polymerises the sickle haemoglobin molecules, impairingdeformability before the development of morphologically apparentsickle cells.6 The critical p02 level for unfractionated SS red bloodcells ranges between 7-6 and 18-4 kPa while it is between 11-2 and22kPa for the 20% of cells that are dense--representing theirreversibly sickled cells.6 The degree of hypoxaemia encounteredin these children, therefore, is sufficient to impair red cell

deformability and may result in increased vaso-occlusive pathology.An association between snoring and cerebral infarction has been

shown in adult male FinnS.7 In our 45 SS patients 5 have had acerebrovascular accident; 3 of whom had UAO with hypoxaemia.

Arterial hypoxaemia due to UAO from hypertrophy of the tonsilsand adenoids may be a major risk factor for the development ofcerebrovascular accident in patients with SS. There should,therefore, be a low threshold for identifying and treating UAO inthese patients.

Department of Haematology,Central Middlesex Hospital,London NW10 7NS;and Department of Paediatrics,

Brompton Hospital

SALLY C. DAVIESV. A. STEBBENSM. P. SAMUELSD. P. SOUTHALL

1. Sarnaik SA, Lusher JM. Neurological complications of sickle cell anaemia. Am JPaediatr Haematol Oncol 1982; 4: 386-94.

2. Powars D, Wilson B, Imbus C, Pegelow C, Allen J. The natural history of stroke insickle cell disease. Am J Med 1978; 65: 461-71

3. Southall DP, Croft CB, Stebbens VA, et al. Detection of sleep associated dysfunctionalpharyngeal obstruction m infants. Eur J Pediatr 1989; 148: 353-59.

4. Southall DP, Stebbens VA, Mirza R, Lang MH, Croft CB, Shinebourne EA. Upperairways obstruction with hypoxaemia and sleep disruption in Down syndrome. DevMed Child Neurol 1987; 29: 734-42.

5. Serjeant GR. Sickle cell disease. Oxford: Oxford University Press, 1985; 112, 302.6. Keidan AJ, Noguchi CT, Player M, Chalder SM, Stuart J. Erythrocyte heterogeneity

in sickle cell disease: effect of deoxygenation on intracellular polymer formation andrheology of sub-populations. Br J Haematol 1989; 72: 254-59.

7. Partinen M, Palomäki H. Snoring and cerebral infarction. Lancet 1985; ii: 1325-26.

ERYTHROPOIETIN AND AUTOLOGOUS BLOODDONATION

SiR,—In Japan, 10% or more of patients given homologousblood contract acute hepatitis. Since 5 million units are transfusedannually, at an average use of 5 per patient, 100 000 or so patientsbecome infected with non-A, non-B hepatitis (NANBH), and somewill proceed to chronic hepatitis and even cirrhosis and hepatoma.Autologous blood is a safe alternative but pre-deposited autologousblood has been underused for elective surgery.’ The time requiredand low yield have been cited as contributing factors for thisunderuse. Recombinant human erythropoietin (EPO) increaseserythropoiesis in renal failure2,3 and has been evaluated in a baboonmodel of intensive autologous donation.4We have used EPO (’EPOCH’, Chugai Pharmaceutical, Tokyo)

in a pilot study of autologous blood donation before orthopaedicsurgery. Donations followed American Association Blood Banks’

standards; 400 ml blood was donated 17, 10, and 3 days beforesurgery. Haemoglobin levels were measured at each donation andremained above 11-0 g/dl. Seven patients donated blood withoutEPO and were given two tablets of ferrous sulphate (210 mg iron)orally every day from 2 weeks before the first donation.

Haemoglobin levels in these patients before and after the first,second, and third donations were 13-8 (SE 1-1), 12-3 (1-0), 11-9(1-2), and 10-7 (0-6) g/dl, respectively. Two patients requiredhomologous blood (1 and 2 units) after their operations.

Five patients donated the same three units of autologous bloodbut received 6000 IU EPO three times a week, starting a weekbefore the first donation, supplemented with 40 mg saccharated

0 7 14 17 7

Days

Mean (and SE) haemoglobin levels in patients with or without EPObefore and after three 400 ml autologous blood donations.

ferric oxide intravenously at each donation. Haemoglobin levelsbefore and after the first, second, and third donations were 13.6 6(0-4), 13-7 (06), 12-5 (0-7), and 127 (0-5) g/dl, respectively (figure).The haemoglobin of EPO-treated patients after the third donation(ie, just before the operation) was significantly higher than that ofthe patients not given EPO (p < 0-001). None of five patients givenEPO required homologous blood transfusion.Thus EPO seems to lessen the anaemia induced by predonation

of autologous blood and may prevent exposure to homologousblood during elective surgery. Autologous transfusions coupledwith EPO has the potential to lower morbidity, mortality, andhealth care costs.

Blood Transfusion Service,and Departments of Urologyand Orthopaedic Surgery,

Saitama Medical Center,Saitama Medical School,Kawagoe, Saitama 350, Japan

HIROO MAEDAYUKO HITOMIRANKO HIRATAHIROSHI TOHYAMA

JUNJI SUWATANOBUYUKI TSUZUKIHIROYUKI SHINDO

1. Toy PT, Strauss RG, Stehling LC, et al. Predeposited autologous blood for electivesurgery: a national multicenter study. N Engl J Med 1987; 316: 517-20.

2. Winearls CE, Oliver DO, Pippard MJ, Reid C, Downing MR, Cotes PM. Effect ofhuman erythropoietin derived from recombinant DNA on the anaemia of patientsmaintained by chronic hemodialysis. Lancet 1986; ii: 1775-78.

3. Escbach JW, Egrie JC, Downing MR, Browne JK, Adamson JW. Correction of theanemia of end-stage renal disease with recombinant human erythropoietin. N EnglJ Med 1987; 316: 73-78.

4. Levine EA, Rosen AL, Gould SA, et al Recombinant human erythropoietin andautologous blood donation. Surgery 1988; 104: 365-69.

MATERNAL PYREXIA AND THE FETUS

SIR,-Mr Fusi and colleagues (June 3, p 1250) show thatmaternal pyrexia is associated with the use of epidural analgesia inlabour. They speculate that this may result in fetal compromise byproducing a fetal tachycardia with consequent depletion ofcatecholamines, resulting in a reduced ability to adapt to the stress oflabour. However, a simpler explanation may be that the fetus,becoming pyrexial, increases its metabolic rate and oxygenrequirements, resulting in fetal compromise if these requirementsare not met.

Several studies have established that fetal temperature is higherthan maternal temperature by about 0’5&deg;C, with the fetus

continually losing heat to the mother along this temperaturegradient.1,2 Furthermore, the temperature gradient between fetusand mother may increase with maternal pyrexia. Maternal pyrexiain the pregnant ewe was associated with increasing fetal temperature,which was linked to a fall in fetal blood pressure, tachycardia,hypoxia, acidosis, and eventually fetal death.

285

Mammalian temperature homoeostasis involves the

counterbalancing of heat loss with heat production, resulting in thethermoneutral environment so essential for survival. The extent towhich the various thermoregulatory mechanisms are made to workdepends on several factors including metabolic rate, ambient

temperature, and the ability to dissipate heat by evaporative waterloss, conduction, convection, and radiation. The fetus cannot loseheat by many usual routes and is thus vulnerable to overheating inthe event of maternal pyrexia. The consequent rise in bodytemperature would lead to an increased metabolic rate and oxygendemand which an impaired placenta (what effect doeschorioamnionitis have?) and a pyrexial labouring mother may notbe able to supply. A secondary consequence of fetal pyrexia andincreased metabolism would be an increase in fetal heat production,which if not dissipated by the placenta would result in a further risein fetal temperature and oxygen requirements.

Conferences

WHAT MUST WOMEN BE TOLD ABOUT THEPILL?

IN June, an emeritus professor of medicine from Harvardtold me of a new US self-help group founded by academics,Travellers Anonymous. Its aim is to talk potentialconference participants out of attending unnecessaryconferences, especially when these are scheduled to last formore than a day and to take place abroad. On July 16-21, theUniversity of London’s Logan Hall hosted the AmericanSociety of Law and Medicine’s second conference onHealth, Law, and Ethics, which attracted some 600

registrations. (The next meeting will be in Hawaii, Jan 2-6,1990.) For their C300 registration fee, participants wereprovided with the opportunity to hear, and perhaps to meet,well-known academics, lawyers, doctors, ethicists, and othercolleagues from all over the world. Daily plenary sessionswere followed by a variety of smaller meetings. Thecavernous subterranean auditorium, capacity about 1000,was never more than one-half to one-third full. The thread

running through the conference was how far the law shouldand could intervene to regulate issues that may arise frombirth to death.The conference began with the many medicolegal aspects of the

acquired immunodeficiency syndrome. This was followed, after"lunch on your own" (every day), by medical malpractice andinformed consent. Then came rationing (with ration pronounced asin station by the US contingent) of health care. Then we movedfrom the euthanasia debate to the mental competence/conceptioncontroversy, and rounded off with coercion, medicine, and the state.The organisers-Alexander Capron and Larry Gostin, of theAmerican Society of Law and Medicine, and Dr John Havard,formerly chief executive of the British Medical Association-provided a full programme and a large panel of experts. As withevery massive gathering there was a loss of the intimacy, thespontaneous and uninhibited discussion, and the bonding of thewhole group that develop naturally with smaller numbers.One measure of a successful meeting is the level and quality of

audience participation. Here insufficient emphasis was given todiscussion, there were too many prepared presentations in a tightprogramme. Prolixity was seldom tackled head on, although onesessional chairman twice strode across the huge stage to tell speakersto keep to time-but he himself not only introduced the topics butalso commented on every talk and then asked the session’s speakersto comment on each other’s papers. Few minutes remained fordiscussion.Meanwhile (July 17-19) the Royal Society of Medicine (RSM)

meeting on Oral Contraceptives and Breast Cancer and the Issue ofInformed Consent, organised by Dr Ronald Mann, took place in

This mechanism may explain some of the sudden fetal deathsassociated with maternal pyrexia and clinical chorioamnionitissecondary to prolonged rupture of the amniotic membranes. Thesedeaths are usually ascribed to fetal infection and the mother istreated with antibiotics. We agree with Fusi and colleagues that amore careful appraisal of the role of maternal temperature is calledfor in this and similar situations and that the role of antipyreticagents should be evaluated.

Department of Paediatrics and Obstetrics,Rotunda Hospital,Dublin, Ireland

T. G. MATTHEWSB. GAUGHAN

1. Smith LEW. Effects of temperature on the development of the chicken embryo. ArchPathol 1939; 28: 422-25.

2. Adamson K, Towell ME. Thermal homeostasis of the fetus and newborn.

Anesthesiology 1965; 26: 531-35.

the luxury of the the Society’s premises in London. Oral

contraceptives provide lucrative profits: world wide over 60 millionwomen are currently on the "pill". The conflicting flow of data fromstudies (the latest being the UK National Case Control Study) onwhether or not the pill increases the risk of breast cancer, especiallyamong younger women, have caused great anxiety amongmanufacturers, patients, and epidemiologists (some of whomsniped disagreeably at one another for much of the three days, inboth public and private). The RSM meeting was heavily subsidised(registration fee 100), and in the audience of some 200 there was asubstantial (but largely publicly silent) contingent from drugcompanies. This time there was no shortage of audience

participation; nor did we have to face the paper cups, plastic spoons,and "lunch on your own" arrangements of the Logan Hall. Therefreshment sessions thus added to the serious discussion of thematerial presented, and participants regrouped for further debate.The aim of the meeting was to gather together key investigators andset them before an expert and representative audience with a view toprobing the question of whether and if so, how far, combined oralcontraceptives cause an increase in breast cancer, and to try toreconcile the mass of conflicting data and the interpretations.The RSM meeting accepted that little or nothing was known

about the causes of breast cancer, and that any increased incidenceof breast cancer was statistically slight (relative risk 15-1-7),though, as stressed by clinicians and consumer representatives, itsmaterialisation in the individual was a tragedy for that woman. Inhis Jephcott Lecture, Prof Martin Vessey said that even on theassumption of a 1 5&mdash;1 increased incidence of risk in some youngerwomen who had been long-term users, the pill should be regardedpositively. It was far more efficient than other forms of

contraception (apart from sterilisation) and offered unexpectedbenefits to women with menstrual problems, iron-deficiencyanaemia, and benign breast disease, and offered some protectionagainst ovarian and endometrial cancer. On the adverse side itincreased the risk of chlamydial pelvic inflammatory disease,thromboembolism, stroke, and acute myocardial infarction.

Smoking was the biggest contraindication. Also, the pill providedno barrier against the human immunodeficiency virus and othersexually transmitted diseases. Vessey concluded that the risks wereless for modem pill users and that it was, on the evidence available,reasonable to continue oral contraception.As the second day proceeded, one doctor, expressing the view of

many, said glumly that he was increasingly perplexed by the mass ofconflicting data. Dr Malcolm Pike said that in the context of breastcancer a woman should either be pregnant or lactating, a prospectwhich did not commend itself to anybody.By the last day it was clear that many factors could influence the

incidence of breast cancer in pre-menopausal women (feeding, dateof menarche, and interval between that and first confinement,duration of use of the pill before a term delivery, suppression oflactation, and ability to ovulate). There had also been changes insocial norms (eg, with regard to breast feeding and timing of familiesby working women) and behaviours, not to mention changes in theconstitution of oral contraceptives. It was clear that not all these