Postgrad Med J: first published as 10.1136/pgmj.42.488.378 on 1 June 1966. Downloaded from POSTGRAD. MED. J., (1966), 42, 378
INERT GAS NARCOSIS -AN INTRODUCTION
1. P. UNSWORTH, B.M., B.Ch., L.R.C.P., Walton Hospital, Liverpool
INERT gas narcosis is the physical and mental peculiar charm and in some persons, symptoms disturbance, both sulbjective and objective, that of intoxication are present". It was not until occurs when breathing gas mixtures containing 1861 that a professional diver described his certain members of the inert gases under pres- own signs and sym,ptoms, and suggested a pre- sure. These include krypton, argon, xenon, nitro- cautionary measure. J. B. Green, an American, gen and possilbly neon. The phenomenon of reported that on his deep dives of 150 feet or narcosis associated with nitrogen has been more, 'he noticed a feeling of excitement fol- alternatively termed "nitrogen intoxication" lowd by drowsiness, and he considered it im- though "narcosis" is the generally accepted portant that at this stage, the diver should be name. (Unsworth, 1960; Miles, 1962.) brought u'p. From Green's full description it It is more than a hundred years since the is clear that he noted hallucinatory changes first report in print of the problem that has been and impairment of a diver's judgement. Paul facing divers ever since their descents went Bert (1878) remarked upon the objective signs deeper than 100 feet or the ambient pressure when nitrogen is 'breathed under pressure but at by copyright. increased above 4 atmosiphere-nitrogen nar- that time did not pursue their cause though he cosis. For many years, it was only helmeted established that dissolved nitrogen was the divers and caisson workers who were 'sulbject aetiological factor in decompression sickness or to this condition, but With the introduction dur- the "bends". ing the last three decades of self-contalined The next report of nitrogen narcosis came underwater 'breathing apparatus, free divers are from Damant (1930) d-uring the British Ad- even more liable to the serious and fatal side miralty IDeep Sea diving trials to 320 feet. effects of nitrogen narcosis. Damant described the findings of 'Hill and Selby,
The signiificance of inert gas narcosis has a that although the dlivers were all 'picked men http://pmj.bmj.com/ bearing not only on naval diving in warfare but who had 'been put through a specially searching also undersea salvage and exploration. With medical examination, some of them became the introduction of ihigh pressure chambers into abnormal mentally or emotionally. The effect the field of anaesthesia and surgery, the in- was attributed at first to the high ambient air herent properties of nitrogen narcosis may have pressure and oxygen poisoning, or to ilmpurities wider implications, as, 'for example, the pos- such as carbon dioxide or monoxide. But care- si'ble use of nitrogen or other inert gas, under ful work ruled these out, and though
oxygen on September 26, 2021 by guest. Protected pressure as an anaesthetic agent, or as a side- and carbon diox'ide were no 'longer held res- effect when 'high pressures of compressed air ponsilble, no incrimination of nitrogen was made. are used. The first definiitive theory that nitrogen was t-he aetiological factor in mental changes while Historical under air pressure was put forward in 1935 In 1826 Colladon, a French physician, descriib- by Behnke, Thompson and Motley. They stated ing a prolonged descent in a dliving bell, re- that air at, and higher than, 3 atmospheres, pres- marked u'pon !his "state of excitement as if I sure exerted a narcotic effect on man, with had drunk some alcoholic liquor". It is doubt- euphoria, mental retardation and loss of neuro- ful if, 'in fact, Colladon did suffer from narcosis muscular control, with coma intervening at as the bell only descended to 20 metres although higher 'pressures. his comparison with alcohol would suggest it. Since the end of the 'war, research on substi- Another Frenchman, Junod, in 1835, noted that tution diluents continued and in 1948 the oxy- under pressure "the functions of the brain are hydrogen mix,ture was introduced (Zetterstrom: activated, imagination is lively, thoughts have a Burjstedt and Severin). Ten years earlier, how- Postgrad Med J: first published as 10.1136/pgmj.42.488.378 on 1 June 1966. Downloaded from June, 1966 UNSWORTH: Inert Gas Narcosis 379 ever, Behnke and Yaribrough, and End (1938) becomes dtifficult and 'the recollcstion of ideas had used helium as diluent in gas mixtures. This requires great effort. Other symptoms noticed eliminated nitrogen narcosis from deep dives 'include perilpherall numbness, lip 'trebling not though both hydrogen and helium had difficult undlike that of oxygen poisoning, and hallucin-a- features, the former being explosive with a tions. Occasionally ithis iiniltial ph,ase of nibrogen higher oxygen concentration that 4 per cent, stimulation may be passed very rapidly and and the latter posing problems of decompres- almost ,unnldiced, ,the diverithen being affected sion, voice distortion and thermal conductivity. very profoundly by the phase of exitreme Considerable experimental work has been lethargy and drowsiness. carried out on the qualitative and quantitative The signs of nitrogen narcosis are most con- measurement of mental disaibility of nitrogen veniently observed in a pressure chamber. These under pressure, with that of Bennett and his include delayed responses to sensory stimuli co-workers outstanding. They used both electro- particularly visual, aud'itory and tactile. Mis- encephalographic changes and flicker-fusion takes are made in mental arithmetic that would frequencies in estimating time of onset of nar- not normally 'be made on the surface. A loss cosis. ('Bennett and Glass, 1957; Bennett, 1958, of fine neuro-muscular contrcl and co-ordina- Bennett and Cross, 1960.) tion renders a delicate manipulation impossible. Other workers attempted to ;relate changes Although all individuals are narcotised to some in performance efficiency to pressure of inert extent under pressure, an emotionally stable gases. (S'hilling and Wil'lgrube, 1937; Kiessling person reacts to the stress by increased effort and Maag, 1960; Frankenhaeuser, Graff-Lon- and may carry out his task quite well until nevig and Hesser, 1963; Poulton, Catton and consciousness is 'lost. The unstaJble individual Carpenter, 1964.) These latter workers, in their is incapable of any further purposeful effort. initial experiments, found evidence of perform- As the pressure is increased, the signs and ance impairment in su'bjects at only 2 atmos- symptoms 'become more severe, there is loss pheres absolute but more recent work has not of memory that may last for many 'hours, and by copyright. revealed any abnormality lbelow 4 atmospheres between 10 and 13 atmospheres loss of con- absolute. sciousness occurs. With a helmet diver, this is not so dangerous as wit-h a free diver in Clinical Features 'whom the loss of the mouthpiece would result The signs and symptoms of inert gas narcosis in death 'by drowning. are varialble in 'tiime 'of onset, aind in regard The similarity between the presenting features to the pressure at which it appears, individuals of nitrogen narcosis and acute alcoholic poison- show some effedt 'soon after reaching 4 'atmos- ing is very close and hence the first descrip- pheres absoluite. Sensitivity differs among divers tion of Junod is so apt and observant. The http://pmj.bmj.com/ and some may have demonstralble signs at Jess French name for the condition, "l'Ivresse", is pressure while 'others m'ay inot be affected fti,l that used for -the vice of drunkenness. Another the pressure reaches 5 or 6 atmospheres. Many interesting parallel between nitrogen narcosis factors influence the pressure at which the onset and alcoholic poisoning is the variability and of symp:oms may occur and ;the severilty of individual susceptibility that exist. Resistance the at,ack. Exertion, prevlious faibigue, alcoholic to nitrogen narcosis (and alcohol) can be built excess prior to 'a dive, even apprehension, may and up 'by practice experience, and adaptation on September 26, 2021 by guest. Protected both advance 'onset and increase severilty. It also does occur. appears thait carbon difoxide retention, through either ilneffecltive apparatus or an increased pro- Theories portion of carbon dioxide in ;bhe respired gas, Many theories have'been proposed to explain ailso speeds 'the onset of narcosis. inert gas narcosis. The first, put forward in The symptoms which generaitly, though not 1835 by Junod and later in 1881 by Moxon, i'nevxKJalbly, appear first are lightheadedness, suggested increased pressure alone as the factor dizziness, euphoria, aind apparent mental stimu- involved. J'unod considered that "the increased laltion associaited with great self-confidence. The density of the air lessened the calibre of the completion of a difficult underwater task will venous vessels, resulting in greater blood flow seem easy ..ald straightforward, and safety pre- in the arterial system and towards principal cautior, usualily metlicul'ou'sly observed, appear nerve centres especially the brain, protected 'by to 'become superfluous. The subject shows a its bony case from direct pressure". He thought grea)t itendency to become jovial and 'alkative, that this increased blood 'flow stimulated the a,nd easily amused. Later, mental concentrattion nerve centres and resulted in narcosis. Moxon, Postgrad Med J: first published as 10.1136/pgmj.42.488.378 on 1 June 1966. Downloaded from 380 POSTGRADUATE MEDICAL JOURNAL June, 1966 on the other hand, regarded the increased pres- pressure were not due to oxygen. Recently the sure as driving the blood from the surface of interest in h'igh partial pressures of oxygen as the body into parts not accessible to respiratory a cause of narcosis has been re-aroused by exchange and that this devitalised blood caused Fenn (1965). 'His hypothesis stems from some emotional changes. These theories iare patently interesting work done on the fruit fly, Droso- incorrect. If pressure did affect superficial blood phila, in atmospheres of oxygen and nitrogen flow, cutaneous 'blanching would Tbe obvious under pressure. From his experiments he but this does not occur. The physical properties demonstrated that a correlation exists between of the body are such that it may be regarded the proportions of oxygen and nitrogen, and as incompressitble, with pressure being equalised the survival rates of the flies while under pres- throughout the body bulk. A further argument sure. Though he states that his results are not against pressure alone being responsible for directly applicable to human diving, he does inert gas narcosis is the later demonstration suggest that it may be possiible by keeping the that ibreathing gas mixtures of different con- oxygen tension low or normal to avoid the nar- stituents at the same pressures induced different cotic effects of nitrogen at depth. This would levels of mental and physical change. certainly substantiate the claims of Albert Buhl- The psychological aspect of deep diving was man and Hans Keller (1962) that nitrogen once blamed as the cause of narcosis (Hill and narcosis does not exist, even with 90 per cent Greenwood, 1906). When psyehological tests nitrogen, at 600 feet. But, although Fenn sug- were carried out on divers who had failed to gests a lowering of -the oxygen partial pressure, complete tasks under pressure, Plhillips (1931) this has been strongly criticised by many showed that many of these subjects were of the workers as dangerously incorrect. The effect suppressed nervous type who habitually exer- of decreasing t'he Po2 without substituting a cised control and that they suffered from latent third gas, would 'be to increase the inert gas suppressed claustrophobia. Phillips had little tension, and thereby markedly potentiate nar- hesitation in ascribing the objective mental cosis. by copyright. changes of his deep diivers to mental instability. Narcosis experienced under compressed air However, if divers, or subjects in a pressure was attributed to nitrogen by Behnke, Thomp- chamber, are supplied with different gas mix- son and Motley (1935). The manner in which tures at the same 'pressure, the severity of signs nitrogen acted was considered to be due to its and symptoms may be altered. It is unl'ikely oil/water solubility ratio, acting in the same that claustrophobia or other psychological manner as the diphasic anaesthetic agents. The deviation contrilbute directly to inert gas nar- correlation between solubility of anaesthetic cosis although they may provide a background agents in water and lipid and its depressant of instability against which early changes of action had been described much earlier by http://pmj.bmj.com/ narcosis become more apparent. Meyer (1899). Behnke and his co-workers found Breathing oxygen at atmospheric pressure that if nitrogen is replaced in a gas mixture by causes sutbjective and objective reactions in helium, the narcotic effect is lessened or some individuals and Birch (1859), reporting abolished. Conversely if argon is sutbstituted, these, maintained that they were not of psycho- the narcosis is more profound and with earlier logical origin. Thus the stimulating effect of onset. Such gases as krypton and xenon have increased oxygen tension in compressed air was also been used in mixtures at atmospheric pres- on September 26, 2021 by guest. Protected postulated as a cause of the "compressed air" sure and have produced definite central nervous syndrome. In 1878 Bert made this assumption system depression and anaesthesia in both that high oxygen tensions produced such effects, animals and man. ('Lawrence, Loomis, Tobias and he utilised ,high air pressures in his experi- and Turpin, 1946; Cullen and Gross, 1951; Car- ments into oxygen toxicity. Other workers since penter, 1953). The ease with which a gas pro- then (have been olf the same opinion (Binger, motes narcosis under pressure is directly Faulkner and Moore, 1927; Smith, Heim, proportional to its fat soluibility and oil/water Thomson and Drinker, 1932). distribution coeflicient (Table 1), and this led Not until Donald (1947) did anyone clearly early workers to use hydrogen or helium as define the salient features of oxygen poisoning diluent in gas mixtures to be used under pres- and when compared with those of nitrogen sure, as narcosis only occurs with these two under pressure, there should 'be no doubt that under extremely high pressures. there exist two separate conditions. Damant A further agent once thought to 'be the cause (1930) was convinced that the subjective and of the narcosis associated w'ith inert gases is objective changes associated with air under carbon dioxide. The narcotic and anaesthetic Postgrad Med J: first published as 10.1136/pgmj.42.488.378 on 1 June 1966. Downloaded from June, 1966 UNSWORTH: Inert Gas Narcosis 381 TABLE 1 GAS SOLUBILITIES
Solubilities in mg./ml. solvent at 370C.
Gas Water Fat Distribution coefficient Argon 0.027 0.140 5.2 Nitrogen 0.013 0.067 5.1 Hydrogen 0.017 0.036 2.1 Heliam 0.009 0.015 1.66
TABLE 2 GAS DENSITIES Hydrogen- Helium- Nitrogen- Argon- oxygen oxygen oxygen (air) oxygen Viscosity relative to air 0.35 0.66 1 1.13 Wt. in lbs. of 1 cu. ft. at 1 atmo. 0.022 0.026 0.081 0.193 effects of this gas were noted by many early sure. It is true that a large excess of CO2 workers i(Bert, 1878; Hill and Flack, 1908). may diminish rather than augment ventilation,by copyright. Case and Haldane (1941) found that carbon and that an increased partial pressure of oxygen dioxide added to compressed air en'hanced the may modify the response to carbon dioxide narcotic effect, and noted the increase in res- (Dripps and Dumke, 1943) bu't the Pco2 increase piration associated with a rise in partial pres- may not be large (Rashbass, 1955) or alterna- sure of CO2 in compressed air. Bean (1945; tively the Po2 may not ibe greatly raised. It is 1950) has put forward the most detailed theory possible that compression using nitrogen causes and he considers CO2 an important contrilbutor a desensitisation to carbon dioxide, and there- to, if not chief cause of, those reactions attri- fore CO2 retention with no hyperventilation. buted to nitrogen. Bean postulates that com- The increased density and viscosity of air, and http://pmj.bmj.com/ pression increases the partial pressure of carbon other gas mixtures i(Table 2), contribute to the dioxide by interfering with t'he dynamics of air diminution of effective pulmonary ventilation. flow within the respiratory tree, and leads to When carbon dioxide is added to the inspired hypercapnia. As pressure increases, air density mixture, this has an additive effect on nitrogen rises and ventilatory efficiency is reduced. As or inert gas narcosis. It 'has been suggested that Miles (1957) has shown, if air is breathed at 200 the vasodilatation of increased partial pressures
feet, the maximum breathing capacity is re- of carbon dioxide, particularly on the cerebral on September 26, 2021 by guest. Protected duced by 50 per cent, and at 600 feet, the circulation, allows the effects of high oxygen reduction is 75 per cent. partial pressure to become apparent and that A study by Bean '(1950) on the rapid com- the picture under these circumstances is a com- pression of anaesthetised dogs showed a pro- bination of nitrogen narcosis and oxygen nounced increase in alveolar Pco2. The experi- toxicity. Work of Hesser and his colleagues mental data'put forward, though limited, were (1963) has shown that oxygen excess has a considered to provide evidence that changes in potentiating effect on nitrogen narcosis, and alveolar CO2, and alterations of blood and that performance efficiency decreased with in- tissue CO2 caused, or contributed to, nitrogen creasing oxygen pressure. It was suggested that narcosis. However, one point made by Bean this increase in narcotic effect was possijbly due to explain t'he lack of hyperventilation in res- to interference with carbon dioxide elimination ponse to high blood Pco2 was that the response from the tissues, one of the factors involved to a given C02 increase in compressed air may in simple oxygen toxicity. Thus raised partial not be the same as the response at normal pres- pressures of oxygen increases that of carbon Postgrad Med J: first published as 10.1136/pgmj.42.488.378 on 1 June 1966. Downloaded from 382 382 POSTGRADUATE MEDICAL JOURNAL June, 1966 dioxide and nitrogen and carbon dioxide have symptoms of narcosis would be alleviated at a synergistic narcotic action. the same time. Bii'hlman (1963) be!lieved he could explain An alternative method of determining the on- the sensations and difficulties attributed to set of changes in cortical activity in subjects nitrogen narcosis by altered respiratory physio- under pressure has been used by Bennett and logy, mainly CO,2 retention due to hypoven- Cross (1960). They showed that using fusion tilation. His protege Hans Keller has dived to frequency of a flickering neon light and electro- 600 feet using '90 per 'cent nitrogen without encephalography, the time to abolition of alpha- apparent signs of narcosis. However, several of blocking and maintained fusion of flicker are Biuhlman's divers other than Keliler, comiplained the same. This method of flicker fusion may be of abnormal sensations under high pressures of used in those individuals who do not show nitrogen and argon. Biuhlman suggested that, alpha-blocking even at atmospheric pressure. under pressure, some specific and reversible gas configuration formed in the brain, dependent, Site of Action not on the nature, ibut on the density of the The site of action where inert gases under gas, a view not incompatible with the nitrogen pressure induce narcotic change is still not hypothesis. entirely clear. It seems probable that the cortex Of the several agents proposed to explain is not affected directly 'but via some part of pressure narcosis, nitrogen, or other inert gas, the brain stem. One site that has been suggested has been most widely accepted. Carbon dioxide is the reticular formation of the mid-brain and retention will contribute to the severity of signs hypothalamus, a neuronal system connected and symptoms initiated by an inert gas but it with consciousness (Magoun, 1952; French, Ver- is doubted if it alone produces the clinical zeano, Magoun, 1953). Magoun showed that picture. stimulation of t'his activating system roused an animal from sleep, converting the EEG pat-
tern from slow sleep waves to more rapid lower by copyright. Electrical Studies voltage waves of activity. He also demonstrated In an attempt to discover upon which part that the electrocorticogram was blocked upon of the nervous system nitrogen and the inert stimulation of the reticular formation. It is gases acted, Bennett and his co-workers (1957; thought that the action of high pressure nitro- 1960) investigated t'he EEG patterns of human gen and other inert gases is upon the reticular subjects under pressure. Earlier experiments formation, and the time to abolish alpha-block- (Marshall, 1951; Jullien, Roger and Chatrian, ing may be due to gaseous diffusion throughout 1953) had shown that EEG waves were altered the brain stem and thalamus. by increased air pressure. The main and most On a cellular level, it is less easy to define the http://pmj.bmj.com/ important finding by Bennett and Glass was site of action of inert gases as narcotic agents. the abolition of alpha-wave blocking. This The reticular formation is an extremely complex occurrence of alpha-blocking is found in 50 per system of neurones, short nerve fibres and cent of normal subjects at atmospheric pressure synapses, and inert gas molecules under pres- when the subject concentrates on mental arith- sure may affect any one or all of these con- metic or similar problem. It was found that if stituents. the subject was exposed to a high enough pres- Marshall (1951), using nitrogen and argon up sure for a long enough ti'me, the alpha-blocking to 96 atmospheres, could not show any effect on September 26, 2021 by guest. Protected was abolished. The time from beginning of on 'isolated frog sciatic nerve, and no effect exposure to pressure till abolition was found on frog nerve-muscle preparations with nitro- to be inversely proportional to the square of gen at 82 atmospheres. But she did find that the pressure. The relationship between time to spinal synapses and therefore reflexes were sen- the abolition of desynchronisation of alpha sitive to inert gas pressures. More recently, rhythm and pressure has suggested a nitrogen Gottlieb and Weatherley (1965) confirmed that or inert gas diffusion gradient into some part high pressures of helium, neon, nitrogen and of the central nervous system (Hempleman, argon up to 15 atmospheres had no effect on 1952) producing impairment of m e n t a 1 transmission across neuromuscular junctions or efficiency. If after abolishing alpha-blocking, an along nerve fibres, in frog sciatic nerve- oxy-helium mixture is substituted for the nitro- gastrocnem'ius muscle preparations. Work of gen-oxygen mixture, alpha-blocking will re- French and others (1953), points to the synapses appear. This would suggest nitrogen as the of the reticular formation as possible sites of agent responsible, as any concurrent signs and interference with normal conduction, and has Postgrad Med J: first published as 10.1136/pgmj.42.488.378 on 1 June 1966. Downloaded from lune, 1966 UNSWORTH: Inert Gas Narcosis 383 shown that synaptic transmission in the central showed that the glia provides a maintenance nervous system is more susceptible to the effects system for the neurone and acts as the blood/ of narcotics than the conduction process in brain barrier, the two forming a close unit, nerve fibres, and some memlbers of the inert anatomically, histologically and metabolically. gases may be included among the narcotics. When he suibjected preparations to atmospheres Bennett (1964) using auditory provoked stimuli of low oxygen tension, the glial cell converted recorded from the cortex of cats, has suggested from aerobic to anaerobic production of energy that the most likely sites for blockage are the resulting in a drop of efficiency from 55 per central synapses, and that the level of narcosis cent to only 3 per cent. This permitted the is related to a critical concentration of inert neurone to utilise all available oxygen. Hyden gas molecules at t'hese sites. pointed out that the glial cell was composed A further theoretical site of action of nitro- of 70 per cent lipoid material while the neurone gen is within the neurone itself or within the was only 5 per cent. Thus the glial cell might neurone/glial unit which has been demonstrated be expected to atbsorb more nitrogen than the so well by Hyden (1962). He describes how the neurone and be more affected by any deranging glial supporting cell entirely covers the neurone influence. Should this occur, oxygen consump- and acts as the barrier between the neurone and tion of the glia will drop as will its efficiency. the capillary, and the two constitute a bio- This depletion of energy may cause delay in chemical and functional unit. Even the prota- ionic potassium and sodium exchange with the gonists of the theory that the neurone is affected neurone, to delay in suibstrate transfer and ulti- by nitrogen, are divided as to the exact mechan- mately to cessation of adequate function of ism. There are those who support the lipid neurone and glia. This would support the his- theory originated iby H. H. iMeyer in 1899 and totoxic hypoxia and lipid theories as proposed modified by Clements and Wilson (1962) to by Clements and Wilson, and other workers. A state that nitrogen under pressure acts at lipid similar theory of decreased membrane perme- interfacial films within living cells. The an- albility was proposed by Mullins (1954) althoughby copyright. tagonists of the lipid theory (Pauling, 1961; he argued that it was inert gas molecules accu- Miller, 1961) claim there is a protein-binding mulating in the membrane pores that hindered action with formation of microcrystals within permeability of ionic material. It may be that the cytoplasm. the point at which aerobic respiration within Clements and Wilson believe that inert gases the glia gives way to anaerobic glycosis coin- can interact significantly with the interfacial cides with the abolition of alpha-blocking on lipoprotein of living cells altering both perme- the EEG. ability and enzyme relationships, and thus inter- The argument that the brain consists largely fering with oxidative p1hosphorylation and of water and is, therefore, unlikely to be influ- http://pmj.bmj.com/ electron 'transport whlich probably are enced by highly fat-soluble compounds is put associated with the llipoproteins of the forward by antagonists of the 'lipid theory of mitochonidria. They suggest an histotoxic narcosis and anaesthesia, mainly Pauling (1961). anoxia, a view supported by Russek He offers, as alternative, a theory of micro- (1962), Miles (1962), Bennett (1963), and crystal formation within cell cytoplasm quite earlier work of Ebert, Hornsey and Howard independent of lipid cell membranes or other (1958) on the effect of irradiation on growth structures. Pauling suggests that nitrogen and of bean shoots in inert gases. It was suggested other inert gases such as xenon, take part in the on September 26, 2021 by guest. Protected by Ebert and his colleagues that oxygen was formation of clathrates, in which the gas atoms responsible for radiosensitivity, and displace- occupy chambers in a framework of molecules. ment of oxygen from sites within the cell by These molecules interact with one another nitrogen reduced this sensitivity. Using an anti- through hydrogen bonding to give nitrogen or psychotic agent Frenquel, Bennett (1963) xenon hydrate. The clathrates to be present at showed a protective action in rats not only body temperature must be stalbilised by cyto- against inert gas narcosis but also oxygen plasmic proteins, hence this theory is sometimes poisoning. Bennett suggests that nitrogen nar- referred to as "protein binding". Pauling pos- cosis is an histotoxic hypoxia, increasing the tulates that these microcrystals act in two ways metabolic work of the central nervous system by trapping electrically charged ions asso- in the production of central inhibition. ciated with impulse conduction and damping Hyden describes the biochermical and func- down electrical circuits, and 'by preventing close tional interrelationship ibetween the neurone enough contact of enzyme/suibstrate configura- and its supporting element, the glial cell. He tions and thus decreasing the rate of chemical Postgrad Med J: first published as 10.1136/pgmj.42.488.378 on 1 June 1966. Downloaded from 384 POSTGRADUATE MEDICAL JOURNAL June, 1966 reactions and, therefore, metabolic rate of cells. BENNETT, P. B. (1958): Flicker Fusion Frequency A somewhat similar theory has been and Nitrogen Narcosis. A comparison with E.E.G. proposed Changes and the Narcotic Effect of Argon Mix- by Miller (1961) but Which does not involve tures, M.R.C. (RNPiRC) Report U.P.S. 176. the formation of clathrates. Featherstone and BENNETT, P. B., and CRoss, A. V. E(1960): Alterations Schoen'born (1964) have reviewed the bio- in the Fusion Frequency of Flicker Correlated physical aspects of both lipid- and with Electroencephalograph Changes at Increased protein- Partial Pressures of Nitrogen, J. Physiol. (Lond.), binding theories proposed and they conclude 151, 28P. that there is no clear evidence that either pre- BENNETT, P. B. ((1963): Prevention in Rats of Nar- ponderates but that probably a mutual relation- cosis Produced by Inert Gases at High Pressures, Thip exists. Amer. J. Physiol., 205, 1013. BENNETT, P. B. (1964): The Effects of High Pressures of Inert Gases on Auditory Evoked Potentials in Conclusions Cat Cortex and Reticular Formation, Electroenceph. Although the narcosis from inert gases under clin. Neurophysiol., 17, 388. BERT, P. (1878): La Pression Barometrique. Paris: pressure may be avoided by the use of sub- Masson. stitution mixtures, the academic investigation BINGER, C. A. L., FAULKNER, J. M., and MOORE, as to the exact cause of this phenomenon con- R. L. (1927): Oxygen Poisoning in Mammals, J. tinues. The use of hydrogen, helium and pos- exp. Med., 45, 849. sibly neon, as diluents, and of anti-narcotic BIRCH, S. B. (1859): On Oxygen as a Therapeutic Agent, Brit. med. J., ii, 1033. drugs, as yet theoretical, have been investigated BUHLMAN, A. (1963): "Deep Diving", p. 52, Proc. and help to reduce the incidence of narcosis. Second Congress Underwater Activites London. The elucidation of inert gas narcosis being his- BURJSTEDT, H., and SEVERIN, G. (1948): The Preven- totoxic anoxia remains as the latest of much tion of Decompression Sickness and Nitrogen Nar- cosis by Use of Hydrogen as a Nitrogen Substitute, work to be done on problems associated with Milit. Surg., 103, 107. nitrogen and other inert gases under pressure. CARPENTER, F. G. (1953): Depressant Action of Inert Gases on the Central Nervous System in Mice,
Summary Amer. J. Physiol., 172, 471. by copyright. Inert CASE, E. M., and HALDANE, J. B. S. i(1941): Human gas narcosis is a condition affecting Pihysiology under High Pressure, J. Hyg. (Lond.), the physical and mental state of subjects breath- 41, 225. ing air or mixtures containing certain of the CLEMENTS, J. A., and WILSON, K. M. (1962): The inert gases at pressures greater than 4 atmos- Affinity of Narcotic Agents for Interfacial Films, pheres. The signs and symptoms are Proc. nat. Acad. Sci. (Wash.), 48, 1008. described COLLADON, M. (1826): Relation d'une Descqnte en and possible theories advanced, from Which the Mer dans la Cloche du Plongeur. Paris. most tenable are nitrogen, or other inert gas, COUSTEAU, J. Y. (1954): The Silent World. London: and carbon dioxide retention. The protein and Hamish Hamilton. CULLEN, S. C., and GROSS, E. G. (1951): The Anes- lipid http://pmj.bmj.com/ binding properties of inert gases under thetic Properties of Xenon in Animals and Human pressure are mentioned. Finally, several sites Beings with Additional Observations on Krypton, of action are suggested, among which are the Science, 113, 580. centre synapses and the neuroglial cell. DAMANT, G. C. C. (1930): Physiological Effects of Work in Compressed Air, Nature (Lond.), 126, 606. The author wishes to thank Professor T. C. Gray, DONALD, K. W. (1947): Oxygen Poisoning in Man Surgeon-Calptain S. Miles, R.N., and especially Dr. Brit. med. 1., i, 172. P. B. Bennett, for their advice and help. DRIPPS, R. D., and DUMKE, P. R. (1943): Effects of Narcotics on Balance between Central and Chemo- REFERENCES receptor Control of Respiration, J. Pharmacol. exp. on September 26, 2021 by guest. Protected Ther., 77, 290. BEAN, J. W. (1945): Effects of Oxygen at Increased EBERT, M., HORNSEY, S., and HOWARD, A. (1958): Pressure, Physiol. Rev., 21, 1. Effects on Radiosensitivity of Inert Gases, Nature BEAN, J. W. (1950): Tensional Changes of Alveolar (Lond.), 181, 613. Gas in Reactions to Rapid Compression and De- END, E. (1938): Use of New Equipment and Helium compression and Question of Nitrogen Narcosis, Gas in World Record Dive, J. Indust. Hyg., 20, 51 1. Amer. J. Physiol., 161, 417. FEATHERSTONE, R. M., and SCHOENBORN, B. P. (1964): BEHNKE, A. R., THoMPSON, R. M., MOTLEY, E. P. Protein and Lipid Binding of Volatile Anaesthetics, (1935): Psychological Effects from Breathing Air at Brit. J. Anaesth., 36, 105. Four Atmospheres Pressure, Amer. J. Physiol., FENN, W. 0. (1965): Inert Gas Narcosis, Ann. N.Y. 112, 554. Acad. Sci., 117, 760. BEHNKE, A. R., and YARBROUGH, 0. D. (1938): FRANKENHAEUSER, M., GRAFF-LONNEVIG, V., and Physiologic Studies of Helium, U.S. nav. med. Bull., HESSER, C. M. (1963): Effects on Psychomotor 36, 542. Functions of different Nitrogen-oxygen Gas Mix- BENNETT, P. B., and GLASS, A. ((1957): High Partial tures at Increased Ambient Pressures, Acta. physiol. Pressures of Nitrogen and Abolition of Blocking Scand., 59, 400. of the Occipital Alpha Rhythm, J. Physiol., 13S8, FRENCH, J. D., VERZEANO, M., and MAGOUN, H. W. 18P. ;(1953): Neural Basis of the Anesthetic State, Arch. Postgrad Med J: first published as 10.1136/pgmj.42.488.378 on 1 June 1966. Downloaded from Junte, 1966 UNSWORTH: Inert Gas Narcosis 385
Neurol. Psychiat. (Chic.), 69, 519. MARSHALL, J. M. (1951): Nitrogen Narcosis in Frogs GOTrLIEB, S. F., and WEATHERLY, J. M. (1965): and Mice, Amer. J. Physiol., 166, 699. PIhysiological Effects of the Noble Gases on Frog MEYER, H. H. (1899): Zur Theorie der Alkoholnar- Sciatic Nerve and Gastrocnemius Muscle, Amer. kose, Arch. exp. Path. Pharmak., 42, 109. J. Physiol., 208, 407. MILES, S. (1957): The Effect of Changes in Baro- GREEN, J. B. (1861): Diving With and Without metric Pressures on Maximum Breathing Capacity, Armour. Buffalo: Leavitt. J. Physiol. (Lond.), 137, 85P. MILES, S. (1962): Underwater Medicine. London: HEMPLEMAN, H. V. (1952): A New Theoretical Basis Staples Press. for the Calculation *of Decompression Tables, MILLER, S. L. (1961): A Theory of Gaseous Anes- M.R.C. (RNPRC) Report U.P.S., 131, A. thetics, Proc. nat. Acad. Sci. '(Wash.), 47, 1515. HILL, L., and FLACK, M. (1908): The Effect of Ex- MoxoN, W. (1881): Croonian Lectures on the Influ- cess of Carbon Dioxide and of Want of Oxygen ence of the Circulation on the Nervous System, upon the Resipiration and the Circulation, J. Lancet, i, 565. Physiol. (Lond.), 37, 77. MULLINS, L. J. (1954): Some Physical Mechanisms HILL, L., and GREENWOOD, M. (1906): The Influence in Narcosis, Chem. Rev., 54, 289. of Increased Barometric Pressure on Man, Proc. PAULING, L. (1961): A Molecular Theory of General roy. Soc., B., 77, 442. Anesthesia, Science, 134, 15. HYDEN, H. (1962): The Neurone and its Glia-a PHILLIPS, A. E. (1931): Recent Research Work in Biochemical and Functional Unit, Endeavour, 20, Deep Sea Diving, Proc. roy. Soc. Med., 25, 693. 144. POULTON, E. C., CARPENTER, A., and CATIN, K. J. JULLIEN, G., ROGER, A., and CHATRIAN, G. E. (1953): (1963): Mild Nitrogen Narcosis?, Brit. med. J., Preliminary Report on Variations of the E.E.G. ii, 1450. of the Cat at Various Air Pressures, Riv. Neurol., POULTON, E. C., CATroN, M. J., and CARPENTER, A. 23, 357. (1964): Efficiency at Sorting Cards in Compressed JUNOD, T. (1835): Recherches sur les Effets Pihysiolo- Air, Brit. J. Industr. Mcd., 21, 242. giques et Therapeutiques de la Compression et de RASHBASS, C. (1955): The Unimportance of Carbon la Rarefaction de I'air, taut sur le Corps que les Dioxide as a Cause of Nitrogen Narcosis, M.R.C. Membres Isoles, Ann. gen. de Med., 2nd Series, 9, (RNPRC) Report U.P.S., 153. 157. RUSSEK, M. (1962): International Congress. Series 47, p.l87, London: Excerpta Medca Founda:tion.
KIESSLING, R. J., and MAAG, C. H. (1960): Per- by copyright. formance Impairment as a Function of Nitrogen SHILLING, C. W., and WILLGRUBE, W. W. (1937): Narcosis, U.S. Navy Experimental Diving Unit Quantitative Study of Mental and Neuromuscular Research Reactions as Influenced by Increased Air Pressure, Report, 3-60, 1. U.S. nav. med. Bull., 35, 373. LAWRENCE, J. H., LOOMIS, W. F., TOBIAS, C. A., and SMITH, F. J. C., HEIM, J. W., THOMPSON, R. M., and TURPIN, F. H. (1946): Narcotic Effect of Xenon. DRINKER, C. K. (1932): 'Bodily Changes and Devel- Preliminary Observations on the Narcotic Effect of opment of Pulmonary Resistance in Rats Living Xenon with a Review of Values for Solubilities of under Compressed Air Conditions, J. exp. Med., Gases in Water and Oil, J. Physiol (Lond.), 105, 56, 63. 197. UNSWORTH, I. P. (1960): Nitrogen Narcosis, Some MAGOUN, H. W. (1952): The Ascending Reticular Aspects, St. Mary's Hosp. Gazette, 66, 272.
Activating System, Res. Publ. Ass. nerv. ment. Dis., ZETrERSTROM, A. (1948): Deep Sea Diving with Syn- http://pmj.bmj.com/ 30, 480. thetic Gas Mixtures, Milit. Surg., 103, 104. on September 26, 2021 by guest. Protected