- Email: [email protected]
Hyperbaric oxygen
336
effects of each variable on renin concentration; but it does seem (though BROWN et al. do not say so) that the very much higher levels of renin in the first case before treatment might be connected with the lower renal blood-flow, as suggested by the raised blood-urea concentration. Other indices of sodium and water metabolism were not much different in the two cases.
It is not clear why hypotension should persist with such raised renin levels; moreover, angiotensin infusion resulted in a negligible pressor response in these patients. By contrast, patients with primary hyperaldosteronism and low renin-angiotensin levels are invariably hypertensive. Possibly changes in sodium balance alter the sensitivity of blood-vessel walls to angiotensin, either directly or by changes in intravascular volume. However, hypertension can be present in primary aldosteronism in the presence of an unequivocally normal total-exchangeable-sodium value and serum-sodium concentration. The possibility arises that the sensitivity of the blood-vessel wall to angiotensin and other pressor agents is altered by the intracellular sodium level or by the distribution of the ion across the cell wall. Aldosterone affects this distribution in all cells, and so it will be abnormal in both hyper and hypo aldosteronism. FRIEDMAN and FRIEDMAN 10 have shown that the pressor effect of angiotensin infusion is accompanied by shifts of sodium and potassium across aortic cell walls. If these shifts were mediated by adosterone they would not take place in the absence of the adrenal glands; and if the pressor response depended on this ionic shift the blood-pressure would not rise. On the other hand, if aldosterone levels were consistently high the hypertensive response might appear at low renin-angiotensin levels, as in primary aldosteronism. BROWN et awl. demonstrated movement of water and sodium from intracellular to extracellular fluid during steroid therapy in one of their patients. it is not yet certain which of the many related factors is the final one in controlling renin secretion-or even whether there is more than onethe classical experiments of GOLDBLATT2 suggest that renal blood-flow is possibly the most important. The other influences could all act through this final common pathway. If so, a hypothetical scheme could be postulated to explain the chain of events following, for instance, sodium depletion. In the first place, plasmasodium concentration, and therefore osmolality, would fall, and antidiuretic-hormone secretion would cease. Water would be lost through the kidneys, thus ensuring that plasma osmolality and the osmotic gradient across cell membranes were maintained. This gain would be achieved at the expense of blood-volume and bloodpressure. But the reduced plasma-volume, by decreasing renal blood-flow, would stimulate renin secretion and angiotensin production, with two advantages : blood-pressure, as well as osmolality, would be maintained in the short term, and aldosterone secretion would be increased, so that any available sodium was retained
Although
10.
Friedman, S. M., Friedman, C. L. Can. med. Ass. J. 1964, 90, 167.
the renal tubules, thus minimising further sodium loss and ensuring that the deficit was corrected as rapidly as possible. If, in addition, aldosterone, by affecting the distribution of sodium between extracellular and intracellular fluid, increases the sensitivity of the blood-vessels to the pressor effect of angiotensin, then the advantage of the close connection between control of sodium, water, and blood-pressure for the maintenance of homoeostasis is clear. We have been concerned only with the systemic effects of renin. On p. 329 Dr. BRITTON proposes an interesting hypothesis which suggests that renin also acts locally to regulate renal blood-flow. According to this view a low renal blood-flow is associated not only with release of renin into the general circulation, thus raising the systemic blood-pressure, but also with decrease of a local renin-angiotensin effect on the afferent arteriole, thus increasing renal blood-flow selectively. Similarly, decreased systemic renin release is associated with increased local action. If so, this reciprocal local effect could be added to the scheme we have outlined, thus indicating that maximum protection is provided for the kidney.
by
Hyperbaric Oxygen (O.H.P.) cannot yet claim the therapeutic respectability of oxygen at normal pressure, in spite of evidence attesting to its value in certain conditions. Perhaps one explanation is that evaluation HYPERBARIC oxygen
of the clinical effects of O.H.P. has been restricted to a small number of centres, of which less than a handful have the means to document the progress of extensive clinical trials. In this country high-pressure oxygen is administered, with few exceptions, by single-unit pressure vessels in which the compressing gas is oxygen. Because of the fire hazard, monitoring of patients during the compression is reduced to a minimum. Extensive monitoring of patients exposed to hyperbaric oxygen is really possible only with a compressed-air chamber large enough to house both staff and equipment. The fire hazard is much less in high-pressure air, but the cost of such large installations is prohibitive. As with other methods of giving oxygen, the ultimate aim of O.H.P. is to increase the amount of oxygen available to the tissues, the limiting factor being the toxicity of the gas when given in excess. Thus O.H.P. has been used in the management of congenital cyanotic heart-disease, neonatal asphyxia, and coal-gas poisoning in an attempt to overcome the associated generalised hypoxia. The severity of cyanosis in infants with right-to-left cardiovascular shunting may be relieved by O.H.P., although large increases in pressure (4 atmospheres absolute, for example) may be required to achieve a measurable improvement in oxygenation. The surgical treatment of these infants in a hyperbaric environment2 has reduced the number of operative 1. 2.
Denison, D. M., Ernsting, J., Tonkins, W. J., Cresswell, A. W. Nature, Lond. 1968, 218, 1110. Bernhard, W. F., Filler, R. M. Am. J. Surg. 1968, 115, 661.
337
failures; and the
of otherwise troublesome arrhythmias causes less concern, since their correction is simpler in the absence of serious hxmoglobin desaturation. The treatment of hypoxia in the asphyxiated newborn infant by O.H.P. has been a subject for controversy. A controlled clinical trial showed that the number of survivors after this therapy did not differ significantly from the number of survivors after tracheal intubation combined with manual ventilation,3 though its supporters emphasise the simplicity of the highpressure-oxygen method. O.H.P. is the most efficient form of gaseous resuscitation in coal-gas poisoning.4 The duration of hypoxia is diminished, which may account for the absence of neurological and cardiovascular sequelse in one series.5 In centres where mortality among patients poisoned by coal-gas is already low, however, the provision of a static pressure vessel is unlikely to reduce the mortality-rate further.s onset
at increased pressure has been applied in the of many forms of regional ischsemia, interest being concentrated on ischsemia of the limbs, of the brain, and of the heart. In spite of reports of relief of rest pain and rapid healing of ischsemic ulcers, the published results of O.H.P. treatment of degenerative vascular disorders are generally disappointing.7 Brief and infrequent exposure of these patients to O.H.P. may explain some of the poor results; and it has also been shown that peripheral vasoconstriction is evoked by O.H.P. in the limbs of patients with ischaemic vascular disease. It remains to be seen whether a combination of more intensive hyperbaric oxygenation with regional vasodilator drugs, as recently suggested,9 will speed the healing of ischsemic ulcers and limit the progress of pre-gangrenous changes. In traumatic ischxmia and ischsemia in skin grafts, the value of O.H.P. is more definite.6 Here it can offer temporary relief of tissue hypoxia, the final result in each patient depending on how quickly a collateral blood-supply develops. Hyperbaric oxygen has also been examined as a treatment for ischsemia of the brain, and, in one study of 22 patients with acute cerebrovascular occlusions,1O almost half showed some clinical recovery during brief periods of pressurisation at 2-3 atmospheres. In 2 of the patients the improvement persisted after decompression. In patients with cerebral oederna secondary to head injury or to circulatory arrest SUKOFF et al.11 reported reduction of cerebrospinal-fluid pressure and relief of
Oxygen
treatment
Hutchison, J. H., Kerr, M. M., Inall, J. A., Shanks, R. A. Lancet, 1966, i, 935. 4. Douglas, T. A., Lawson, D. D., Ledingham, I. McA., Norman, J. N., Sharp, G. R., Smith, G. ibid. 1962, i, 68. 5. Smith, G., Ledingham, I. McA., Sharp, G. R., Norman, J. N., Bates, 3.
E. H. ibid. p. 816. 6.
7.
8.
9. 10. 11.
Ledingham, I. McA. in Modern Trends in Pharmacology and Therapeutics (edited by W. F. M. Fulton); p. 96. London, 1967. Slack, W. K., Thomas, D. A., De Jode, L. R. J. in Proceedings of the Third International Conference on Hyperbaric Medicine (edited by I. W. Brown and B. G. Cox); p. 621. Washington, 1966. Pollock, J. G., Bell, G., Ledingham, I. McA. in Blood Flow through Organs and Tissues (edited by W. H. Bain and A. M. Harper); p. 408. Edinburgh, 1968. Schraibman, I. G., Ledingham, I. McA. Br. J. Surg. 1968, 55, 384. Heyman, A., Saltzman, H. A., Whalen, R. E. Circulation, 1966, 33, suppl. 2, 20. Sukoff, M. H., Hollin, S. A., Jacobson, J. H. Surgery, St. Louis, 1967, 62, 40.
neurological deficits during exposure to O.H.P. Much experimental evidence supports the value of O.H.P. in the treatment of acute myocardial infarctionin spite of disappointing results in one investigation which failed to demonstrate any significant immediate or later protection from oxygen at 2 atmospheres absolute compared with oxygen at normal pressure.12 More recently, it has been shown that the low initial arterial oxygen tension in some patients with myocardial infarction is more readily and effectively corrected by O.H.P. than by oxygen at normal pressure.13 Not surprisingly, therefore, hyperbaric-oxygen therapy is being considered particularly in the management of patients with serious arrhythmias, cardiogenic shock, and severe left heart-failure, although no convincing indication of its value has yet emerged. Hyperbaric oxygen is being evaluated in three other situations associated with regional ischxmia-operations on major vessels, malignant disease, and organ preservation. During certain vascular operations (for example, on the aorta or on the extracranial carotid vessels) the blood-supply to distal tissues may be critically reduced. Some evidence exists that o.H.P. may go some way to lessen the risk of hypoxic damage,14 but the possibilities are only beginning to be explored. Probably the earliest clinical application of O.H.P. was in association with radiotherapy for malignant disease. Preliminary data from some of the controlled trials suggest worthwhile improvement with hyperbaric oxygen,15 16 though others 17 were less encouraging. In one inquiry,17 the clinical impression that the growth of metastases might be hastened in patients treated with O.H.P. has not been confirmed either in experimental animals or in other groups of patients.18 19 In conjunction with hypothermia O.H.P. has been widely used to prolong the viability of stored non-perfused organs.2° There are, however, two facts which cast considerable doubt upon the primary role of oxygen increased pressure when used in this way. For one thing, the oxygen tension in the tissues falls within minutes of an organ being separated from its bloodsupply even in an environment of hyperbaric oxygen.21 at
Furthermore, it has been shown that an environment of nitrogen, or even helium, at increased pressure may be as efficacious as oxygen in preserving tissue viability.22 12.
Cameron, A. J. V., Gibb, B. H., Ledingham, I. McA., McGuiness, J. B. in Hyperbaric Oxygenation (edited by I. McA. Ledingham); p. 277. Edinburgh, 1965. 13. Cameron, A. J. V., Hutton, I., Kenmure, A. C. F., Murdoch, W. R. Lancet, 1966, ii, 833. 14. Jacobson, J. H., II, Wang, M. C. H., Freedman, P., Reich, T., Chezar, J., Rendell-Baker, L. in Proceedings of the Third International Conference on Hyperbaric Medicine (edited by I. W. Brown and B. G. Cox); p. 463. Washington, 1966. 15. Churchill-Davidson, I., Foster, C. A., Wiernik, G., Collins, C. D., Pizey, N. C. D., Skeggs, B. B. L., Purser, B. R. Br. J. Radiol. 1966, 39, 321. 16. Van den Brenk, H. A. S., Madigan, J. P., Kerr, R. C. Clin. Radiol. 1967, 18, 54. 17. Cade, I. S., McEwan, J. B. Cancer, N.Y. 1967, 20, 817. 18. Johnson, R. E., Kagan, A. R., Bryant, T. L. Radiology, 1967, 88, 775. 19. Plenk, H. P., Card, R. Y. Am. J. Roentg. 1967, 99, 900. 20. Rudolf, L. E., Mandel, S. Transplantation, 1967, 5, 1159. 21. Matloff, D. B., Mobley, T. L., Schwartz, S. I. Archs Surg., Chicago, 1966, 92, 83. 22. Lyons, G. W., Dietzman, R. H., Lillehei, R. C. J. Am. med. Ass. 1966, 196, 584.
338
The claim that O.H.P. enhances the undoubted merits of artificial perfusion at normal atmospheric pressure needs further examination. The state of shock has almost as many forms of treatment as it has causes. O:H.P. will increase oxygen consumption in the brain during shock 23 and diminish the oxygen debt24 and mortality 25 of long periods of haemorrhagic shock. The evidence for the value of O.H.P. in shock associated with septicaemia or endotoxaemia is much less certain. Hyperbaric oxygen also seems a logical measure in the treatment of airembolism, gaseous distension of the gut, and the various acute forms of decompression sickness, and in the first two conditions clinical successes have been reported.26 27 The use of pressurised oxygen instead of air in the treatment of decompression sickness reduces the total barometric pressure required. 28 The risks to attendants within the pressure vessel are thereby reduced and the efficiency of the treatment may be little
altered.
susceptibility of aerobic and anaerobic microorganisms to oxygen poisoning has been closely studied.29 There is no doubt that the in-vitro growth of most organisms is inhibited in an environment of raised oxygen pressure. Animal experiments have shown, however, that, unless an inhibitory pressure of the gas is brought into intimate contact with the organisms, infection may proceed unabated. Encouraging results have been reported in the treatment of longstanding suppurative osteomyelitis 30 and in the prevention of infection of surface burns. Not surprisingly the treatment of anaerobic infection has received much attention, particularly infection by Clostridium welchii. O.H.P. inhibits production of the Cl. welchii exotoxin. Intermittent exposure of patients with gas-gangrene to oxygen at 3 atmospheres absolute has brought dramatic benefit in the first forty-eight hours of therapy.31 While O.H.P. now replaces traditional surgical treatment in some centres, others have judged it wiser to combine O.H.P. with conservative measures of proved value, such The
as incision of infected tissue and administration of antibiotics. The real value of O.H.P. in the treatment of gas-gangrene is hard to assess, since the effect of conventional therapy in this condition, apart from military experience, is (with one or two notable exceptions 32) poorly documented. 23.
Harper, A. M., Ledingham, I. McA., McDowall, D. G. in Hyperbaric Oxygenation (edited by I. McA. Ledingham); p. 342. Edinburgh,
24.
Clark, R. G. in Wound Healing (edited by C. F. W. Illingworth); p. 215. London, 1966. Attar, S., Scanlan, E., Cowley, R. A. in Proceedings of the Third International Conference on Hyperbaric Medicine (edited by I. W. Brown, B. G. Cox); p. 417. Washington, 1966. Stewart, J. S. S., Keddie, N. C., Middleton, M. D., Hopkinson, W. I., Williams, K. G. Lancet, 1964, i, 669. Takita, H., Olszewski, W., Schimert, G., Lanphier, E. H. J. thorac. cardiovasc. Surg. 1968, 55, 682. Goodman, M. W. Aerospace Med. 1964, 35, 1204. Irvin, T. T., Smith, G. Surgery, St. Louis, 1968, 63, 363. Perrins, D. J. D., Slack, W. K., Thomas, D. A., Maudsley, R. H., Colwill, M. R. in Proceedings of the Third International Conference on Hyperbaric Medicine (edited by I. W. Brown and B. G. Cox); p. 578. Washington, 1966. Brummelkamp, W. H. Ann. N.Y. Acad. Sci. 1965, 117, 688. Altemeier, W.A. in Proceedings of the Third International Conference on Hyperbaric Medicine (edited by I. W. Brown and B. G. Cox); p. 481. Washington, 1966.
1965.
25.
26. 27. 28. 29. 30.
31. 32.
Humanæ Vitæ THE impact on the world’s richer communities of the sad and long-pondered encyclical which came out of the Vatican last week will not necessarily be great, but it will surely increase the difficulties of those who are striving in many countries, notably in Latin America, to raise economic standards by introducing measures for population control. The official positions of Latin American nations have long been a barrier to such action; but at least one observernow speaks hopefully of " truly remarkable shifts in the climate of discussion and in the opinion of Latin American intellectualschanges which only began to be apparent in the early 1960’s ". A substantial increase in attention to population problems, the accumulation of startling new census data, medical concern over abortion-rates (the rate in Chile was reported to be half the birth-rate), and the provision of funds and technical assistance from North America all contributed to this awakening. And the hope (now confounded) of a relaxation in the rigorous teaching of Rome must have been another influence. The remarkable speed of the change was reflected in 1965 in the words of President CAMARGO of Colombia, often judged to be one of the most religiously conservative Catholic nations in the world: " For us, the human solution, the Christian solution, the economically and politically sound solution is birth control." To the many who share that view, the Pope’s new utterance of old advice must come as a chill shock. Not all demographers, however, accept that Catholic teaching always has much effect on birth-rates. DAY2 concludes that " the problem seems not to be one of Catholic teaching in predominantly Catholic countries. The frequently voiced hope that the Church will change its position on family planning ... appears largely irrelevant." Catholic teaching, DAY maintains, " will be a factor leading to higher fertility among Catholics only when (a) there exists a high level of economic development, and (b) Catholics constitute a numerically and politically important, but not dominant, minority of the population ". MIR63 declares that " the doctrinaire position of the Catholic Church does not constitute an obstacle for family planning. The persistence of a very high birth rate in Latin America cannot be attributed to the predominantly Catholic conditions of the population, but to the social and economic backwardness in which they live ". The fertility promoted by wretched conditions of life, for biological rather than religious reasons, will remain the chief cause of overpopulation. The feeding, the education, the basic care of large families is seldom easy in Colombia (or, for that matter, in Clapham) and, now that knowledge of birth-control methods is spreading more easily in almost every land, awareness of the benefit they confer on day-to-day family economics Mayone Stycos, J. Human Fertility in Latin America; p. 301. Ithaca, New York, 1968. 2. Day, L. H. Catholic Teaching and Catholic Fertility. Paper 202, Proceedings of 1965 World Population Conference. New York, 1.
1967. 3. Miró, C. Caracteristicas Demográficas de América Latina, Santiago, 1963. Cited by Mayone Stycos, J. Human Fertility in Latin America; p. 182. Ithaca, New York, 1968.
effects of each variable on renin concentration; but it does seem (though BROWN et al. do not say so) that the very much higher levels of renin in the first case before treatment might be connected with the lower renal blood-flow, as suggested by the raised blood-urea concentration. Other indices of sodium and water metabolism were not much different in the two cases.
It is not clear why hypotension should persist with such raised renin levels; moreover, angiotensin infusion resulted in a negligible pressor response in these patients. By contrast, patients with primary hyperaldosteronism and low renin-angiotensin levels are invariably hypertensive. Possibly changes in sodium balance alter the sensitivity of blood-vessel walls to angiotensin, either directly or by changes in intravascular volume. However, hypertension can be present in primary aldosteronism in the presence of an unequivocally normal total-exchangeable-sodium value and serum-sodium concentration. The possibility arises that the sensitivity of the blood-vessel wall to angiotensin and other pressor agents is altered by the intracellular sodium level or by the distribution of the ion across the cell wall. Aldosterone affects this distribution in all cells, and so it will be abnormal in both hyper and hypo aldosteronism. FRIEDMAN and FRIEDMAN 10 have shown that the pressor effect of angiotensin infusion is accompanied by shifts of sodium and potassium across aortic cell walls. If these shifts were mediated by adosterone they would not take place in the absence of the adrenal glands; and if the pressor response depended on this ionic shift the blood-pressure would not rise. On the other hand, if aldosterone levels were consistently high the hypertensive response might appear at low renin-angiotensin levels, as in primary aldosteronism. BROWN et awl. demonstrated movement of water and sodium from intracellular to extracellular fluid during steroid therapy in one of their patients. it is not yet certain which of the many related factors is the final one in controlling renin secretion-or even whether there is more than onethe classical experiments of GOLDBLATT2 suggest that renal blood-flow is possibly the most important. The other influences could all act through this final common pathway. If so, a hypothetical scheme could be postulated to explain the chain of events following, for instance, sodium depletion. In the first place, plasmasodium concentration, and therefore osmolality, would fall, and antidiuretic-hormone secretion would cease. Water would be lost through the kidneys, thus ensuring that plasma osmolality and the osmotic gradient across cell membranes were maintained. This gain would be achieved at the expense of blood-volume and bloodpressure. But the reduced plasma-volume, by decreasing renal blood-flow, would stimulate renin secretion and angiotensin production, with two advantages : blood-pressure, as well as osmolality, would be maintained in the short term, and aldosterone secretion would be increased, so that any available sodium was retained
Although
10.
Friedman, S. M., Friedman, C. L. Can. med. Ass. J. 1964, 90, 167.
the renal tubules, thus minimising further sodium loss and ensuring that the deficit was corrected as rapidly as possible. If, in addition, aldosterone, by affecting the distribution of sodium between extracellular and intracellular fluid, increases the sensitivity of the blood-vessels to the pressor effect of angiotensin, then the advantage of the close connection between control of sodium, water, and blood-pressure for the maintenance of homoeostasis is clear. We have been concerned only with the systemic effects of renin. On p. 329 Dr. BRITTON proposes an interesting hypothesis which suggests that renin also acts locally to regulate renal blood-flow. According to this view a low renal blood-flow is associated not only with release of renin into the general circulation, thus raising the systemic blood-pressure, but also with decrease of a local renin-angiotensin effect on the afferent arteriole, thus increasing renal blood-flow selectively. Similarly, decreased systemic renin release is associated with increased local action. If so, this reciprocal local effect could be added to the scheme we have outlined, thus indicating that maximum protection is provided for the kidney.
by
Hyperbaric Oxygen (O.H.P.) cannot yet claim the therapeutic respectability of oxygen at normal pressure, in spite of evidence attesting to its value in certain conditions. Perhaps one explanation is that evaluation HYPERBARIC oxygen
of the clinical effects of O.H.P. has been restricted to a small number of centres, of which less than a handful have the means to document the progress of extensive clinical trials. In this country high-pressure oxygen is administered, with few exceptions, by single-unit pressure vessels in which the compressing gas is oxygen. Because of the fire hazard, monitoring of patients during the compression is reduced to a minimum. Extensive monitoring of patients exposed to hyperbaric oxygen is really possible only with a compressed-air chamber large enough to house both staff and equipment. The fire hazard is much less in high-pressure air, but the cost of such large installations is prohibitive. As with other methods of giving oxygen, the ultimate aim of O.H.P. is to increase the amount of oxygen available to the tissues, the limiting factor being the toxicity of the gas when given in excess. Thus O.H.P. has been used in the management of congenital cyanotic heart-disease, neonatal asphyxia, and coal-gas poisoning in an attempt to overcome the associated generalised hypoxia. The severity of cyanosis in infants with right-to-left cardiovascular shunting may be relieved by O.H.P., although large increases in pressure (4 atmospheres absolute, for example) may be required to achieve a measurable improvement in oxygenation. The surgical treatment of these infants in a hyperbaric environment2 has reduced the number of operative 1. 2.
Denison, D. M., Ernsting, J., Tonkins, W. J., Cresswell, A. W. Nature, Lond. 1968, 218, 1110. Bernhard, W. F., Filler, R. M. Am. J. Surg. 1968, 115, 661.
337
failures; and the
of otherwise troublesome arrhythmias causes less concern, since their correction is simpler in the absence of serious hxmoglobin desaturation. The treatment of hypoxia in the asphyxiated newborn infant by O.H.P. has been a subject for controversy. A controlled clinical trial showed that the number of survivors after this therapy did not differ significantly from the number of survivors after tracheal intubation combined with manual ventilation,3 though its supporters emphasise the simplicity of the highpressure-oxygen method. O.H.P. is the most efficient form of gaseous resuscitation in coal-gas poisoning.4 The duration of hypoxia is diminished, which may account for the absence of neurological and cardiovascular sequelse in one series.5 In centres where mortality among patients poisoned by coal-gas is already low, however, the provision of a static pressure vessel is unlikely to reduce the mortality-rate further.s onset
at increased pressure has been applied in the of many forms of regional ischsemia, interest being concentrated on ischsemia of the limbs, of the brain, and of the heart. In spite of reports of relief of rest pain and rapid healing of ischsemic ulcers, the published results of O.H.P. treatment of degenerative vascular disorders are generally disappointing.7 Brief and infrequent exposure of these patients to O.H.P. may explain some of the poor results; and it has also been shown that peripheral vasoconstriction is evoked by O.H.P. in the limbs of patients with ischaemic vascular disease. It remains to be seen whether a combination of more intensive hyperbaric oxygenation with regional vasodilator drugs, as recently suggested,9 will speed the healing of ischsemic ulcers and limit the progress of pre-gangrenous changes. In traumatic ischxmia and ischsemia in skin grafts, the value of O.H.P. is more definite.6 Here it can offer temporary relief of tissue hypoxia, the final result in each patient depending on how quickly a collateral blood-supply develops. Hyperbaric oxygen has also been examined as a treatment for ischsemia of the brain, and, in one study of 22 patients with acute cerebrovascular occlusions,1O almost half showed some clinical recovery during brief periods of pressurisation at 2-3 atmospheres. In 2 of the patients the improvement persisted after decompression. In patients with cerebral oederna secondary to head injury or to circulatory arrest SUKOFF et al.11 reported reduction of cerebrospinal-fluid pressure and relief of
Oxygen
treatment
Hutchison, J. H., Kerr, M. M., Inall, J. A., Shanks, R. A. Lancet, 1966, i, 935. 4. Douglas, T. A., Lawson, D. D., Ledingham, I. McA., Norman, J. N., Sharp, G. R., Smith, G. ibid. 1962, i, 68. 5. Smith, G., Ledingham, I. McA., Sharp, G. R., Norman, J. N., Bates, 3.
E. H. ibid. p. 816. 6.
7.
8.
9. 10. 11.
Ledingham, I. McA. in Modern Trends in Pharmacology and Therapeutics (edited by W. F. M. Fulton); p. 96. London, 1967. Slack, W. K., Thomas, D. A., De Jode, L. R. J. in Proceedings of the Third International Conference on Hyperbaric Medicine (edited by I. W. Brown and B. G. Cox); p. 621. Washington, 1966. Pollock, J. G., Bell, G., Ledingham, I. McA. in Blood Flow through Organs and Tissues (edited by W. H. Bain and A. M. Harper); p. 408. Edinburgh, 1968. Schraibman, I. G., Ledingham, I. McA. Br. J. Surg. 1968, 55, 384. Heyman, A., Saltzman, H. A., Whalen, R. E. Circulation, 1966, 33, suppl. 2, 20. Sukoff, M. H., Hollin, S. A., Jacobson, J. H. Surgery, St. Louis, 1967, 62, 40.
neurological deficits during exposure to O.H.P. Much experimental evidence supports the value of O.H.P. in the treatment of acute myocardial infarctionin spite of disappointing results in one investigation which failed to demonstrate any significant immediate or later protection from oxygen at 2 atmospheres absolute compared with oxygen at normal pressure.12 More recently, it has been shown that the low initial arterial oxygen tension in some patients with myocardial infarction is more readily and effectively corrected by O.H.P. than by oxygen at normal pressure.13 Not surprisingly, therefore, hyperbaric-oxygen therapy is being considered particularly in the management of patients with serious arrhythmias, cardiogenic shock, and severe left heart-failure, although no convincing indication of its value has yet emerged. Hyperbaric oxygen is being evaluated in three other situations associated with regional ischxmia-operations on major vessels, malignant disease, and organ preservation. During certain vascular operations (for example, on the aorta or on the extracranial carotid vessels) the blood-supply to distal tissues may be critically reduced. Some evidence exists that o.H.P. may go some way to lessen the risk of hypoxic damage,14 but the possibilities are only beginning to be explored. Probably the earliest clinical application of O.H.P. was in association with radiotherapy for malignant disease. Preliminary data from some of the controlled trials suggest worthwhile improvement with hyperbaric oxygen,15 16 though others 17 were less encouraging. In one inquiry,17 the clinical impression that the growth of metastases might be hastened in patients treated with O.H.P. has not been confirmed either in experimental animals or in other groups of patients.18 19 In conjunction with hypothermia O.H.P. has been widely used to prolong the viability of stored non-perfused organs.2° There are, however, two facts which cast considerable doubt upon the primary role of oxygen increased pressure when used in this way. For one thing, the oxygen tension in the tissues falls within minutes of an organ being separated from its bloodsupply even in an environment of hyperbaric oxygen.21 at
Furthermore, it has been shown that an environment of nitrogen, or even helium, at increased pressure may be as efficacious as oxygen in preserving tissue viability.22 12.
Cameron, A. J. V., Gibb, B. H., Ledingham, I. McA., McGuiness, J. B. in Hyperbaric Oxygenation (edited by I. McA. Ledingham); p. 277. Edinburgh, 1965. 13. Cameron, A. J. V., Hutton, I., Kenmure, A. C. F., Murdoch, W. R. Lancet, 1966, ii, 833. 14. Jacobson, J. H., II, Wang, M. C. H., Freedman, P., Reich, T., Chezar, J., Rendell-Baker, L. in Proceedings of the Third International Conference on Hyperbaric Medicine (edited by I. W. Brown and B. G. Cox); p. 463. Washington, 1966. 15. Churchill-Davidson, I., Foster, C. A., Wiernik, G., Collins, C. D., Pizey, N. C. D., Skeggs, B. B. L., Purser, B. R. Br. J. Radiol. 1966, 39, 321. 16. Van den Brenk, H. A. S., Madigan, J. P., Kerr, R. C. Clin. Radiol. 1967, 18, 54. 17. Cade, I. S., McEwan, J. B. Cancer, N.Y. 1967, 20, 817. 18. Johnson, R. E., Kagan, A. R., Bryant, T. L. Radiology, 1967, 88, 775. 19. Plenk, H. P., Card, R. Y. Am. J. Roentg. 1967, 99, 900. 20. Rudolf, L. E., Mandel, S. Transplantation, 1967, 5, 1159. 21. Matloff, D. B., Mobley, T. L., Schwartz, S. I. Archs Surg., Chicago, 1966, 92, 83. 22. Lyons, G. W., Dietzman, R. H., Lillehei, R. C. J. Am. med. Ass. 1966, 196, 584.
338
The claim that O.H.P. enhances the undoubted merits of artificial perfusion at normal atmospheric pressure needs further examination. The state of shock has almost as many forms of treatment as it has causes. O:H.P. will increase oxygen consumption in the brain during shock 23 and diminish the oxygen debt24 and mortality 25 of long periods of haemorrhagic shock. The evidence for the value of O.H.P. in shock associated with septicaemia or endotoxaemia is much less certain. Hyperbaric oxygen also seems a logical measure in the treatment of airembolism, gaseous distension of the gut, and the various acute forms of decompression sickness, and in the first two conditions clinical successes have been reported.26 27 The use of pressurised oxygen instead of air in the treatment of decompression sickness reduces the total barometric pressure required. 28 The risks to attendants within the pressure vessel are thereby reduced and the efficiency of the treatment may be little
altered.
susceptibility of aerobic and anaerobic microorganisms to oxygen poisoning has been closely studied.29 There is no doubt that the in-vitro growth of most organisms is inhibited in an environment of raised oxygen pressure. Animal experiments have shown, however, that, unless an inhibitory pressure of the gas is brought into intimate contact with the organisms, infection may proceed unabated. Encouraging results have been reported in the treatment of longstanding suppurative osteomyelitis 30 and in the prevention of infection of surface burns. Not surprisingly the treatment of anaerobic infection has received much attention, particularly infection by Clostridium welchii. O.H.P. inhibits production of the Cl. welchii exotoxin. Intermittent exposure of patients with gas-gangrene to oxygen at 3 atmospheres absolute has brought dramatic benefit in the first forty-eight hours of therapy.31 While O.H.P. now replaces traditional surgical treatment in some centres, others have judged it wiser to combine O.H.P. with conservative measures of proved value, such The
as incision of infected tissue and administration of antibiotics. The real value of O.H.P. in the treatment of gas-gangrene is hard to assess, since the effect of conventional therapy in this condition, apart from military experience, is (with one or two notable exceptions 32) poorly documented. 23.
Harper, A. M., Ledingham, I. McA., McDowall, D. G. in Hyperbaric Oxygenation (edited by I. McA. Ledingham); p. 342. Edinburgh,
24.
Clark, R. G. in Wound Healing (edited by C. F. W. Illingworth); p. 215. London, 1966. Attar, S., Scanlan, E., Cowley, R. A. in Proceedings of the Third International Conference on Hyperbaric Medicine (edited by I. W. Brown, B. G. Cox); p. 417. Washington, 1966. Stewart, J. S. S., Keddie, N. C., Middleton, M. D., Hopkinson, W. I., Williams, K. G. Lancet, 1964, i, 669. Takita, H., Olszewski, W., Schimert, G., Lanphier, E. H. J. thorac. cardiovasc. Surg. 1968, 55, 682. Goodman, M. W. Aerospace Med. 1964, 35, 1204. Irvin, T. T., Smith, G. Surgery, St. Louis, 1968, 63, 363. Perrins, D. J. D., Slack, W. K., Thomas, D. A., Maudsley, R. H., Colwill, M. R. in Proceedings of the Third International Conference on Hyperbaric Medicine (edited by I. W. Brown and B. G. Cox); p. 578. Washington, 1966. Brummelkamp, W. H. Ann. N.Y. Acad. Sci. 1965, 117, 688. Altemeier, W.A. in Proceedings of the Third International Conference on Hyperbaric Medicine (edited by I. W. Brown and B. G. Cox); p. 481. Washington, 1966.
1965.
25.
26. 27. 28. 29. 30.
31. 32.
Humanæ Vitæ THE impact on the world’s richer communities of the sad and long-pondered encyclical which came out of the Vatican last week will not necessarily be great, but it will surely increase the difficulties of those who are striving in many countries, notably in Latin America, to raise economic standards by introducing measures for population control. The official positions of Latin American nations have long been a barrier to such action; but at least one observernow speaks hopefully of " truly remarkable shifts in the climate of discussion and in the opinion of Latin American intellectualschanges which only began to be apparent in the early 1960’s ". A substantial increase in attention to population problems, the accumulation of startling new census data, medical concern over abortion-rates (the rate in Chile was reported to be half the birth-rate), and the provision of funds and technical assistance from North America all contributed to this awakening. And the hope (now confounded) of a relaxation in the rigorous teaching of Rome must have been another influence. The remarkable speed of the change was reflected in 1965 in the words of President CAMARGO of Colombia, often judged to be one of the most religiously conservative Catholic nations in the world: " For us, the human solution, the Christian solution, the economically and politically sound solution is birth control." To the many who share that view, the Pope’s new utterance of old advice must come as a chill shock. Not all demographers, however, accept that Catholic teaching always has much effect on birth-rates. DAY2 concludes that " the problem seems not to be one of Catholic teaching in predominantly Catholic countries. The frequently voiced hope that the Church will change its position on family planning ... appears largely irrelevant." Catholic teaching, DAY maintains, " will be a factor leading to higher fertility among Catholics only when (a) there exists a high level of economic development, and (b) Catholics constitute a numerically and politically important, but not dominant, minority of the population ". MIR63 declares that " the doctrinaire position of the Catholic Church does not constitute an obstacle for family planning. The persistence of a very high birth rate in Latin America cannot be attributed to the predominantly Catholic conditions of the population, but to the social and economic backwardness in which they live ". The fertility promoted by wretched conditions of life, for biological rather than religious reasons, will remain the chief cause of overpopulation. The feeding, the education, the basic care of large families is seldom easy in Colombia (or, for that matter, in Clapham) and, now that knowledge of birth-control methods is spreading more easily in almost every land, awareness of the benefit they confer on day-to-day family economics Mayone Stycos, J. Human Fertility in Latin America; p. 301. Ithaca, New York, 1968. 2. Day, L. H. Catholic Teaching and Catholic Fertility. Paper 202, Proceedings of 1965 World Population Conference. New York, 1.
1967. 3. Miró, C. Caracteristicas Demográficas de América Latina, Santiago, 1963. Cited by Mayone Stycos, J. Human Fertility in Latin America; p. 182. Ithaca, New York, 1968.