SLEEP APNŒA SYNDROMES

218 in article 29 that everyone has duties to the community, and W.H.O. could have named a healthy lifestyle as one of these.

T. C. BEARD

SIR,- The Declaration of Alma-Ata is a marvellous sight to behold in The Lancet of Nov. 11, 1978. It further defines human rights in a specific manner and clearly defines health as a human right. Despite the "naysayers" and "doubting Thomases", I believe that we in the health professions owe a debt of gratitude to the framers of the declaration. The specific objectives are attainable, and I would draw attention to the tenth paragraph which says that a substantial reduction in armaments via peace, detente, and disarmament should release resources for health care. The reallocation of the vast funds utilised for war could be a mighty force for improving health conditions throughout the globe. I, for one, urge the U.S. Government to take the necessary practical steps to bring this idea to fruition. Rockland

County Department of Health,

Pomona, N.Y. 10970, U.S.A.

STEPHEN R.

REDMOND,

Commissioner of Health

ALDOSTERONE IN MYXŒDEMA

SIR,-Dr Marks and his colleagues found, in patients with

’

a relation between increments in thyroxine treatand both urinary aldosterone excretion and plasmaaldosterone concentration. The well-known disturbances of sodium and water metabolism in myxoedemasuggested a preliminary study of the aldosterone response to A.c.T.H. stimulation. In four untreated patients with myxoedema, four with hyperthyroidism, and four controls A.c.T.H. was administered as single injections (125 g + 62.5 fLg ’Synacthen’).3 Plasmaaldosterone was measured by the method of Vetter et al.4

myxoedema, ment

’

SIR9 The paper by Dr Douglas and colleagues (Jan. 6, p.l) same issue indicate the influence of in cardiorespiratory disease and also point to the lack of normal data on regulatory mechanisms during sleep. While the findings reported offer important clinical discriminants Douglas et al. do not fully consider what is currently known of the changes in the regulation of breathing that occur with sleep. This probably stems from the fact that their studies, like those of others recently, were carried out in abnormal man first and then in a few normals. While there is little doubt of the severity of the sleep-related hypoxaemia in the "bluebloaters", the ontogeny of the disesase process is essential for real progress in prevention. Is it a primary respiratory disorder complicated by normal changes in sleep-or disordered sleep regulation compromising respiratory disease? In other words could the blue-bloater be predicted much earlier in life? In Douglas’s study the healthy subjects were not controls, being much younger than the patients. Older people have a higher P aco2 and a lower P a02 during sleep,’ and maleness is associated with a higher and earlier incidence of upper-airway obstruction in the form of snoring.2 Sleep-induced apnoea syndrome has been associated with almost complete loss of non-R.E.M. (rapid eye movement) sleep3 whereas chronic hypoxaemia in kittens reduced the amount of R.E.M. sleep with respiratory failure occurring in non-R.E.M. sleep.4 Whether sleep is normal in either situation is unknown. It follows from this that defining the point, (i.e., sleep state), at which respiratory failure occurs is imprecise by present criteria. Thus the actual defect in regulation remains uncertain. Recent work in laboratory animals and human infants suggests that non-R.E.M. sleep is an "automatic" state, very dependent on peripheral sensory input for respiratory rhythm and drive whereas R.E.M. sleep is substantially unaffected by such input. A ventilatory response to hypoxaemia is present in both sleep states but is absent to hypercapnia in R.E.M. sleep. Per-

and your editorial in the

34 Gilmore Crescent,

Garran, Canberra, A.C.T. 2605, Australia

SLEEP APNŒA SYNDROMES

PLASMA-ALDOSTERONE BEFORE AND AFTER A.C.T.H. STIMULATION

sleep

state

haps more important, significantly greater hypoxasmia and hypercapnia develop before arousal occurs in R.E.M. This arousal usually occurs within safe limits.5 Thus respiratory failure in different ways depending on sleep state. If the blue-bloater already has a decreased response to CO2 when awake then non-R.E.M.sleep may well represent a vulnerable state to him. A word on methods is necessary here. Minute ventilation is still widely used as a measure of respiratory drive. In compromised respiratory disease or in sleep, where the regulation of breathing is different but not defective, this is an inappro-priate measure. The relationship between alveolar ventilation and respiratory effort would seem a better indication of the efcan occur

basal unstimulated aldosterone levels were the in the three groups, and no relationship was found between plasma-aldosterone and the plasma concentrations of thyroxine and triiodthyronine. In all patients plasma-aldosterone increased during A.C.T.H. stimulation. However, the increase in the myxoedema group (275%) was smaller than that seen in hyperthyroid patients and controls (about 400%). Thus our preliminary results support those of Marks et al. and indicate some type of disturbance of aldosterone metabolism in myxoedema. The most important feature of myxoedema, in this context, is probably a reduced ability to respond with increased aldosterone secretion. However, we do not know whether this contributes to the impaired salt and water metabolism.

The

same

mean

(and normal)

Medical

Department E,

Fredenksberg Hospital, Copenhagen, Denmark 1. 2.

K. ØLGAARD KARIN BORUP

Marks, P., Anderson, J., Vincent, R. Lancet, 1978, ii, 1277. Aikawa, J. K. Ann. intern. Med. 1956, 44, 30. 3. Ølgaard, K., Madsen, S. Acta med. scand. 1977, 201, 77. 4. Vetter, W., Vetter, H., Siegenthaler, W. Acta endocr. 1973, 74, 558.

fectiveness of breathing. Breathing is predominantly diaphragmatic in R.E.M. sleep’ with loss of phasic activity of the accessory muscles of respiration and expiratory upper-airway resistance.7 This is probably important to the newborn with a compliant chest wall but it may also be relevant to the adult with compromised respiratory reserve. Normal profiles of

respiratory control and sleep state throughout development are essential for a practical preventive and therapeutic rationale to respiratory failure-whether acute (e.g., apnoea and sudden death) or chronic. Tracheotomy, although dramatically effective in some instances of sleep-induced apnoea, is hardly a testimony to a clear under1. 2.

Webb, P. J. appl. Physiol. 1974, 37, 899. Lugaresi, E., Coccagna, G., Ciriguotta, F. in Sleep Apnea Syndromes (edited by C. Giulleminault and W. C. Demont); p. 13. New York, 1978. 3. Tilkian, A. G., Guilleminault, C., Schroeder, J. S. and others. Am. J. Med. 1977, 63, 348. 4. Baker, T. L., McGinty, D. J. Science, 1977, 198, 419. 5. Phillipson, E. A. Am. Rev. resp. Dis. 1977, 115, suppl., 217. 6. Duron, B. Bull. Physiopathol. respir. 1972, 8, 1031. 7. Harding, R., Johnson, P., McClelland, M. E. J. Physiol. 1977, 272, 14 P.

219

standing of the regulation of breathing or successful preventive medicine. Nuffield Institute for Medical Research,

University of Oxford, Headington, Oxford OX3 9DS

P. JOHNSON

SIR,-Dr Douglas and colleagues and you describe the of

due

un-

obstructive with chronic

expected frequency hypoxaemic episodes or central apnoea during sleep in adult patients respiratory diseases. The significant decreases in oxygenation were detectable only because of the use of a continuous technique to monitor the patient’s oxygen saturation. Apnoea in newborn infants, particularly in the premature, is quite common and a major problem for neonatologists. The incidence of apnceic spells is significantly related to sleep.1-3 However, in infants, as in Douglas’s study in adults, only the availability of methods for the continuous monitoring of arterial oxygenation, such as the transcutaneous Paz technique,4 has to

lity and monosynaptic inhibition during sleep. Continuous monitoring of partial pressure of carbon dioxide with a transcutaneous electrode has recorded increases of 30 mm Hg or 7 more during sleep in some infants.’ We feel these findings confirm those reported by Douglas et al.-namely, intermittent hypoxacmia and hypertension are fairly common in sleep-related apnoea-and that this pattern be considered in all age-groups. We agree with you that methods for continuous monitoring of Po2 or S02 and, when available, PC02 should be routinely used in studies of disturbances in respiratory regulation in adults, children, and infants for more accurate diagnosis. must

1. P. is

a

Humboldt fellow.

Departments of Obstetrics and Gynæcology, University of Marburg, 3550 Marburg an der Lahn, West Germany, and University of Zürich, Switzerland

JOYCE PEABODY RENATE HUCH ALBERT HUCH

CEREBRAL INFARCTION AND ALCOHOL

SIR,-I would like to add to the list Dr Hillbom and Dr Kastel provide of possible explanations for brain infarction in young adults with previous alcoholic intoxication. Extracranial vessel compression from unusual posturing during alcoholic stupor was not considered. There are pointers to such a mechanism .2 Similarly, neck trauma-minor or, perhaps, forgotten-could be contributory in such cases.45 1 Over the past year our neurology service has seen at least three cases where the only plausible connection to be had from the history in a young adult with a stroke was alcohol intoxication preceding the ictus. Two of these patients had neck discomfort which, in retrospect, could have been a form of carotodynia. Department of Neurology, Bowman-Gray School of Medicine, Winston-Salem, North Carolina 27103, U.S.A.

J. L. PRENDES

PIPERACILLIN AND HÆMORRHAGIC CYSTITIS

Polygraphic tracing

for infant with

diagnoses

of near-miss

S.I.D.S. assessment of the frequency and significance of the decreases in Po2 during apnoeic phases. In our studies of 45 infants,5 thoracic impedance failed to detect 63% of apnceic episodes resulting in Pal less than 40 mm Hg. A common cause of this failure was a pattern of disorganised breathing recorded by thoracic impedance and accompanied by intermittent absence of nasal air flow and rapid falls in Pal, The figure shows part of the polygraphic record for an infant admitted with a diagnosis of "near-miss sudden-infant-death syndrome". Neither thoracic impedance nor heart-rate monitoring could detect this prolonged episode of hypoxsemia. As in Douglas’s study, blood-pressure, reflected in "blood flow under the electrode"6 increased, as did intracranial pressure. The implication of these increases for the risk of intracranial haemorrhage in apnoeic infants must be cpnsidered. All spontaneous episodes occurred during sleep, most often rapid-eye-movement or transitional sleep. The xtiology is felt to be airways obstruction or paradoxical breathing due to chest-wall instabi-

permitted

SIR,-In his letter on hx-morrhagic cystitis ascribed to carbencillin given intravenously as treatment of chronic pulmonary Pseudomonas aeruginosa infections in cystic fibrosis Dr Moller6 mentions one patient who had haematuria after treatment with the related compound piperacillin and cited our clinical investigator’s brochure. The "patient" referred to was a "normal" 23-year-old male volunteer participating in a pharmacokinetic study of intramuscular piperacillin sodium with lignocaine, at a dose of 1 - 0 g three times a day on three successive days, and one week later was given piperacillin sodium without lignocaine, at an i.m. dose of 1 g three times a day for three successive days. During the initial screening interview, this volunteer gave a history of passing a kidney stone some 4 months before the study. The clinical investigator felt that the 100 red blood-cells per high-power field which appeared in this man’s urine, 1 day after the last dose of piperacillin, was possibly due to "a small stone nicking the ureter". A urinalysis 3 weeks later was normal. The man had no symptoms during the study or at follow-up. Department of Clinical Research, Lederle Laboratories, American Cyanamid Company, Pearl River, New York 10965, U.S.A.

Hathorn, M. K. S. Foetal and Neonatal Physiology: proceedings of the Sir Joseph Barcroft symposium. Cambridge, 1973. 2. Finer, N., Abroms, I., Taeusch, H., Jr. Pediat. Res. 1975, 9, 365. 3. Gabnel, M., Albani, M., Schulte, F. J. Pediatrics, 1976, 57, 142. 4. Huch, R., Huch, A., Lübbers, D. W. J. perinat. Med. 1973, 1, 183. 5. Peabody, J., Gregory, G., Willis, M., Lucey, J., Tooley, W. Pediat. Res. 1977, 11, 539. 6. Peabody, J. L., Willis, M. M., Gregory, G. A., Severinghaus, J. W. Birth

Defects orig. Art. Ser. (m the press).

JOY

J., Gregory, G. A., Willis, M. M., Tooley, W. H., Phillip, A. G. S., Lucey, J. F. ibid. (in the press). 1. Hillbom, M., Kaste, M. Lancet, 1978, ii, 1181. 2. Alajouanine, T., Castaigne, P., Cambier, J., Lianantonakis, E. Bull. Soc. Méd. Hôp. Paris, 1958, 74, 21. 3. Janeway, R., Toole, J., Leinbach, L., Miller, H. Archs Neurol. 1966, 15, 7. Peabody,

1

VINCENT A.

211. 4. Jernigan, W., Gardner, W. J. Trauma, 1971, 11, 429. 5. Towne, J., Neis, D., Smith, J. Archs Surg. 1972, 104, 565. 6. Møller, N. E. Lancet, 1978, ii, 946.