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Breath Alcohol Analysis and the Blood : Breath Ratio B . M . W R I G H T , MA, MB
^
u.„n^
Clinical Research Centre. Watford Road. Harrow
T. P.JONES, PhD, A R i c
k'ii'rti'^^lfclZstry.
University of Wales Institute of Science and Technology. King Edward VII Avenue. Cardiff
SUMMARY T h e history of b r e a t h alcohol analysis a n d of t h e c o n c e p t of a blood : b r e a t h r a t i o is briefly reviewed a n d it is suggested t h a t t h e r a t i o is always lower a n d more variable than predicted by accepted theory. U s i n g gas liquid c h r o m a t o g r a p h y for b o t h b r e a t h a n t l blood it h a s been s h o w n t h a t t h e blood : b r e a t h r a t i o falls d u r i n g expiration a n d only reaches its presently a c c e p t e d value of 2100 : 1, p r e d i c t e d from in vitro studies, after p r o l o n g e d r e b r e a t h i n g . I t is suggested t h a t this is d u e to alcohol b e i n g a b s o r b e d from t h e b r e a t h d u r i n g e x p i r a t i o n b y t h e m u c o s a of t h e u p p e r r e s p i r a t o r y t r a c t , t o r e p l a c e t h a t lost d u r i n g inspiration. Proposals a r e m a d e for further studies a n d for modifications in present b r e a t h s a m p l i n g p r o c e d u r e s w h i c h c o u l d m a k e b r e a t h analysis a n a c c e p t a b l e substitute for blood analysis in all except m a r g i n a l cases.
INTRODUCTION The determination of the blood alcohol concentration by means of breath analysis has now been practised for nearly 50 years (Bogen, 1927) but the success of legislation in many countries in reducing road accidents by enacting an alcohol limit has recently re newed interest in the subject and led to improved methods for breath analysis based on physical devices such as fuel cells. Practically all designers of these devices, however, have assumed that there is a fixed known ratio between the breath and blood levels, which is valid for all people at all times, so that the precision and accuracy of the determination of the blood level are believed to be limited only by the precision and accuracy of the breath analysis. The belief in a fixed blood : breath ratio is usually traced back to Liljestrand and Linde (1930)
who put forward the concept that complete equilibration takes place in the alveoli but that re-equilibration occurs at the lower temperature of the upper respiratory tract during expiration, so that the alcohol level in expired alveolar air is controlled by the breath temperature. In fact, however, the belief is mainly attributable to Harger and his colleagues who, in a long series of studies from 1930 to 1950, determined the air : water and air : blood partition ratios at various temperatures (Harger et al., 1950). They assumed a mean expired alveolar air tempera ture of 34°C and therefore concluded that the mean blood : breath alcohol ratio was 2100 : 1, the blood : air partition ratio in vitro at this temperature. Because of conflicting evidence produced by other workers (Haggard and Greenburgh, 1934) over the same period, the United States National Safety Council (1953) issued an agreed statement, signed by all the leading workers in the field, which referred to 'the constant (our italics) ratio existing between the concentration of alcohol in the alveolar air and the blood'. This led to a belief amongst legal and police authorities that the ratio was not only constant, but absolutely and unquestionably correct, and this belief has persisted to the present time,
THE BREATHALYZER The 'Breathalyzer'* (Borkenstein and Smith, 1962), the first and, until quite recently, the only available instrument for reasonably * N o t t o b e confused w i t h ' b r e a t h a l y s e r s ' , a generic t e r m used in this c o u n t r y for screening devices.
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precise breath analysis in the field was designed to read directly in blood alcohol units, using the 2100 : 1 ratio, and the volume of the sample and the quantities of chemicals were calculated accordingly. Almost from its inception, however, the 'Breathalyzer' was observed to give rather low readings (Harger, 1965) and greater variability in the blood : breath ratio than could be accounted for by analytical errors in the two measurements. Nevertheless, the 'Breathalyzer' came into such general use throughout the world that it has given its name as a generic term to all breath alcohol analysers, and has made a great contribution to the control of road traffic accidents involving alcohol (Borkenstein et al., 1964) and to psychological studies of the eflfects of alcohol (Drew et al, 1959). Innumerable breath : blood correlation studies have been made with the 'Breathalyzer', nearly all of which agree in showing that the instrument under-reads 10-15 per cent, giving a blood : breath ratio of about 2300 : 1 (Begg et al, 1964) and is a relatively poor predictor of blood alcohol.
GAS CHROMATOGRAPHY In 1970, therefore, it was decided to start a fresh investigation of the factors governing the blood : breath ratio using gas chroma tography, which had then become available for both blood and breath, and which gave results of a precision formerly unobtainable. Full details of the authors' methods will be published but the following is a brief account of the experiments and results. Blood analysis was carried out by the gas chromatographic method of Curry et al., (1966) with the blood diluted 10 times with an aqueous propanol internal standard. For breath analysis the Gas Chromatograph Intoximeter (GCI) (Penton and Forrester, 1969) was used. This instrument takes a 0·25 ml sample from the breath while the subject is blowing through it into a bag fitted with a whistle which blows when the bag is full, so that the operator can ensure that a certain minimum volume of air has been discarded before he presses the sampling button.
Using the instrument in this way, with a minimum discard volume of 21, it was possible to confirm that the 2100 : 1 ratio led to an underestimate of the blood alcohol and that the correct ratio was about 2300 : 1. The precision of the estimate of blood alcohol concentration was also lower (s.d. = about 5 mg per 100 ml) than that to be expected from the known precision of the breath and blood analyses (combined s.d. = 3 mg per 100 ml). Repetition of Harger's experiments on the blood : air ratio in vitro gave results agreeing very closely with his, so that the discrepancy could not be explained by an error in the determination of the blood : breath ratio in vitro. It was therefore decided to make a detailed study of the breath alcohol level during expiration, in relation to both volume and temperature. Volume was meas ured with a Wright Respirometer (Wright, 1955) fitted to the outlet of the GCI and temperature with a thermistor inserted in the mouthpiece, connected to a recorder. Preliminary studies showed that the breath alcohol level rose continually and did not reach a steady level even at the end of a full expiration. Moreover, the alcohol level was less than that expected from the temperature at the moment of sampling, as predicted from the blood alcohol concentration of a sample taken at the same time. It was there fore decided to adopt a modified version of Harger's technique of rebreathing, using equipment kindly loaned by him. The rebreathing bag was maintained at 40°C all the time so as to prevent condensation, and, instead of the sample being taken from the bag as was done by Harger, the subject delivered his last expiration directly into the GCI. The volume of air expired during rebreathing was measured with a second respirometer inside the bag, and this volume was added to the volume of the final expira tion into the GCI. In other words, rebreath ing was regarded as effectively a form of prolonged expiration. At the end of 4 or 5 rebreathings, the breath alcohol reached a steady level which was very close to the alcohol level in a sample of air equilibrated with the subject's blood at the same temperature in vitro. By taking
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Wright et a i . : Breath Alcohol Analysis
this level as 100 per cent it was possible to plot curves of breath alcohol level versus volume of expiration, which may be called 'alcohol expirograms', on the same scale for subjects with different blood alcohol concen trations. Similarly, the problem of the steady metabolic fall in blood alcohol concentration was overcome by taking a 5-rebreathing sample immediately before or after each sample taken after less than 5 rebreathings, and expressing the result of the latter as a percentage of the former.
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Alcohol expirograms, prepared in this way for 6 subjects, are shown in Fig. 7, in which breath temperature and alcohol level are plotted against expired volume at the moment of sampling. The lower points on the graph show the rise in breath temperature during expiration and it can be seen that it usually reached a peak just before the end of a full expiration, but rises further during rebreathing. It never quite reaches 36°C even though the rebreathing bag was held at 40°C. There is considerable intersubject
S 1" •
90
—
Breath alcohol concentration A • o as % of rebreathed alr level «• ·
U
80
Breath alcohol concentration corrected for temperature Α
·
36
• a 35
i 1
A
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331
32
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A. 4
6
8
'EXPIRED-'VOLUME
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Pig. 1: Alcohol expirogram on 6 subjects showing the relation of predicted and actual breath alcohol concen trations to breath temperature and expired volume.
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variation, some of which may have been due to variations in ambient temperature and humidity, but Harger's assumption of a mean temperature of 34°C after a 1 litre discard is seen to be reasonable. The two upper curves show the theoretical and actual changes in breath alcohol level during expiration. The single dots show the expected results if the level were simply dependent on temperature, obtained by correcting the 100 per cent reading after 5 rebreathings for the temperature at the moment of sampling. The differentiated points show the actual levels and it can be seen that, at the beginning of expiration, they are well below the expected levels, and do not reach them until after 2 or 3 rebreath ings. Thus no single-breath sampling tech nique could possibly give a correct estimate of the blood alcohol level using the 2100 : 1 ratio. In addition, substantial inter- and intrasubject variations in breath : blood rela tionship can be seen to occur, especially at the beginning of expiration, which cannot be attributed solely to temperature effects.
DISCUSSION These observations account for the deficiency of alcohol in the expired air, and for its variability in relation to the blood alcohol concentration but do not explain them. Variability could be explained to some extent by expired air temperature variations resulting from incomplete temperature equili bration, but the latter cannot explain the deficiency of alcohol, because it would lead not to a lower but to a higher alcohol level in the breath because the breath temperature is falling during expiration. A possible explanation, however, is that both the deficiency and the variability of breath alcohol level are due to the extremely high solubility of alcohol in water and the fact that the upper respiratory tract ( U R T ) is covered with a thin, aqueous layer of mucus. Thus, although the volume of the anatomical dead space in the U R T is only about 200 ml (Weibel, 1963) for relatively insoluble gases and vapours, its volume for alcohol is effectively enormously increased by the mucus layer. This layer is about 5 microns
thick and the surface area of the dead space is about 6000 cm* (Weibel, 1963), giving a volume of about 3 ml of mucus which, with a partition rate of about 2000 : 1 at equilibrium could absorb more than half the alcohol from a full vital capacity expiration. During inspiration this layer will lose some of its alcohol to the inspired air, as well as water vapour and heat, but this will not increase the alcohol concentration in the expired air because re-equilibration at a higher tempera ture has taken place in the lungs. Conse quently, during expiration the mucus layer could extract more alcohol from the breath than would be removed by simple tempera ture equilibration. For this to occur, however, two conditions must be satisfied. More alcohol than water must be extracted during inspira tion so that the surface alcohol concentration is lowered, and the alcohol must not be significantly replaced from the bloodstream between inspiration and expiration. The first condition is easily satisfied because it can be shown that, at equilibrium at 34°C, the alcohol : water ratio in the gas phase is about 8 times that in the liquid phase (Enticknap and Wright, 1965). The second cannot be dealt with quite so easily. One answer is that the cavity of the U R T is known as the 'dead space' because it takes no appreciable part in ordinary physiological gas exchange, but it has already been seen that the extreme solubility of alcohol puts it into a special category. However, whereas the alveolar walls are only about 1 micron thick, the distance from the surface of the mucus in the upper respiratory tract to the nearest capillary is about 40 microns (Weibel, 1963). The blood supply to the alveoli is also enormous, so that each breath is equili brated with about half its own volume of blood, while the mucosa of the U R T has only the normal blood supply of about 40 ml per minute per 100 g of tissue (Keele and Neil, 1971) so that, even if diffusion rates allowed, it would be impossible to replace all the missing alcohol in the time available. Since the maxi mum alcohol deficiency observed is only about 20 per cent at the beginning of expiration it seems reasonable to suppose that it could be accounted for by the mechanism suggested.
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Wright et a l . : Breath Alcohol Analysis
PRACTICAL CONSIDERATIONS If this theory is correct any further studies of the blood : breath relationship must concen trate on the condition of the U R T , and studies of the blood : breath ratio in vitro or in the lungs are largely irrelevant. Such factors as ambient temperature and humidity, whether the subject was talking or had his mouth shut just before giving the sample (Wright, 1962), and any pathological condi tions such as bronchitis that may affect the U R T are likely to be far more relevant to the blood : breath ratio in vivo. Some preliminary studies have been made along these lines which the authors propose to continue, but meanwhile it may be useful to consider the effect of this theory on the practical problem of determining the blood alcohol concentration by breath analysis, and this can best be shown by a further consideration of Fig. 1. It is obvious that there is an increase in accuracy and precision of the estimate of blood alcohol concentration with increase of expired volume, and that these are further increased by rebreathing. The improvement produced by rebreathing is, however, small and probably not worth the extra trouble involved. The deficiency of alcohol in the breath is related to expired volume, and the rate of change of deficiency with volume is also related to volume, thus indicating that it is desirable to obtain as large an expired volume as possible. This can easily be done with physical methods because they can use a very small sample aspirated from the breath, so the subject is only required to blow past the sampling port, and the resistance to breathing can be made negligible. Even so, it is likely to be impossible to obtain a discard volume of more than 2 1 in many cases, at which point the blood : breath ratio is still changing rapidly, so for precise work it may be necessary to measure the expired volume and adjust to the ratio accordingly. A further improvement could be made by measuring and adjusting for breath tempera ture, and it is possible to conceive of a portable analyser that would incorporate both these features and yet be much less complex and expensive than, for example, a
209
gas Chromatograph for blood analysis. Meanwhile, however, by adopting a mean ratio of 2300 : I it is possible to eliminate the systematic error in the blood : breath ratio and with, for example, a fuel cell analyser with very low resistance to breathing, to reduce the s.d. of the blood alcohol concentra tion estimate to less than 7 m g per 100 ml under laboratory conditions. The error under field conditions would undoubtedly be sub stantially greater because of the effect of ambient conditions on the blood : breath ratio but, with a suitably designed instrument, a police station or even a police car might approach laboratory conditions. Although it is clear that breath analysis as a method of determining the blood alcohol concentration can never match the accuracy and precision of direct blood analysis on a single sample, the fact that it can be repeated over a period of time means that it can probably now give a more reliable estimate of a subject's tissue alcohol level than can be obtained with a single sample of blood. Finally, the problem of alcohol analysis needs to be considered more broadly. The present practice in the United Kingdom is to set a limit of 80 mg per 100 ml, which is fairly high, and enforce it to the limit of the precision and accuracy of blood analysis. However, only a minority of offenders have blood levels so close to the limit as to be affected by the precision of the analysis so that if a less precbe method, such as breath analysis, were used instead with a somewhat lower limit, exactly the same results could be achieved at very much less expense. Breath analysis lends itself to such a policy because its results are known immediately, so that the police could use their discretion in marginal cases as they do, for example, over speed limits. Blood analysis would be retained for cases who do not wish to accept the result of breath analysis and the decision of the police to prosecute, but the experience in Northern Ireland, where this policy is in force, suggests that such cases would be few (Howard and Morgan, 1969). NOTES T h e investigations described in this p a p e r w e r e c a r r i e d out b y A . W . J , as p a r t of his work for a P h D
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thesis s u p p o r t e d b y a s t u d e n t s h i p from t h e Science R e s e a r c h C o u n c i l a n d will b e described in detail in a later p u b l i c a t i o n . B . M . W . a t t e n d e d a m e e t i n g of t h e O r g a n i z a t i o n for E c o n o m i c C o - o p e r a t i o n a n d D e v e l o p m e n t R e s e a r c h G r o u p o n t h e 'Eflfects of Alcohol o n D r i v e r B e h a v i o u r ' in Paris in J u n e 1972, a n d a n I n t e r n a t i o n a l Conference o n ' R e s e a r c h M e t h o d o l o g y for R o a d s i d e Surveys of D r i n k i n g - D r i v i n g ' o r g a n i ^ e d b y t h e N a t i o n a l Safety Council in Paris in M a y , 1974. M u c h of t h e b a c k g r o u n d information a b o u t t h e design a n d p e r f o r m a n c e of b r e a t h alcohol devices was o b t a i n e d a t these m e e t i n g s . ACKNOWLEDGEMENTS T h e a u t h o r s a r e i n d e b t e d to m a n y of their colleagues for v a l u a b l e discussions a n d i n f o r m a t i o n , especially D r M . J . H a l s e y a n d D r J . G . J o n e s of t h e Clinical R e s e a r c h C e n t r e a n d D r J . S. P a r k of t h e U n i v e r s i t y of W a l e s Institute of Science a n d T e c h n o l o g y . Fig. 1 was d r a w n by M r P a u l D a r t o n of t h e Clinical R e s e a r c h C e n t r e ' s D e p a r t m e n t of M e d i c a l Illustration. Finally, the a u t h o r s w o u l d like to t h a n k Professor R . N . H a r g e r for l e n d i n g his r e b r e a t h i n g e q u i p m e n t , a n d for m u c h v a l u a b l e advice a n d information. REFERENCES Begg T . B . , H i l l I . D . a n d Nickolls L . C . (1964) B r e a t h a l y z e r a n d K i t a g a w a - W r i g h t m e t h o d s of m e a s u r i n g b r e a t h a l c o h o l . Br. Med. J. 1, 9 - 1 5 . Bogen Ε . (1927) D r u n k e n n e s s ; q u a n t i t a t i v e s t u d y of a c u t e alcoholic i n t o x i c a t i o n . J.A.M.A. 98, 15081511. Borkenstein R . F . , C r o w t h e r R . F . , S h u m a t e R . P . , Zeil W . B . a n d Z y l m a n R . (1964) The Role of the Drinking Driver in Τηφ€ Accidents. B l o o m i n g t o n , I n d . , I n d i a n a University. Borkenstein R . F . a n d S m i t h H . W . (1962) T h e B r e a t h a l y z e r a n d its a p p l i c a t i o n s . Med. Sei. Law 2, 13-22. C u r r y A . S., W a l k e r G . W . a n d S i m p s o n G . S. (1966) D e t e r m i n a t i o n of e t h a n o l in b l o o d b y gas c h r o m a t o g r a p h y . Analyst 9 1 , 7 4 2 - 7 4 3 . D r e w G . C , C o l q u h o u n W . P . a n d L o n g H . A . (1959) Medical Research Council Memorandum No. 38. L o n d o n , HMSO,
E n t i c k n a p J . E . a n d W r i g h t B . M . (1965) In-vivo d e t e r m i n a t i o n of t h e b r e a t h : b l o o d alcohol r a t i o . I n Proceedings of the Fourth International Conference on Alcohol and Traffic Safety. B l o o m i n g t o n , I n d . , I n d i a n a University, p p . 161-169. H a g g a r d H . W . a n d G r e e n b e r g L . A. (1934) Studies in t h e a b s o r p t i o n a n d e l i m i n a t i o n of ethyl-alcohol I I . T h e excretion of a l c o h o l in u r i n e a n d expired a i r ; a n d t h e d i s t r i b u t i o n of a l c o h o l b e t w e e n air a n d w a t e r , b l o o d a n d u r i n e . J . Pharmacol. Exp. Ther. 5 2 , 150-166. H a r g e r R . N . (1965) p e r s o n a l c o m m u n i c a t i o n . H a r g e r R . N . , F o r n e y R . B . a n d Barnes H . B . (1950) E s t i m a t i o n of level of b l o o d a l c o h o l from analysis of b r e a t h . J. Clin. Med. 3 6 , 3 0 6 - 3 1 8 . H o w a r d A . J . a n d M o r g a n W . H . D . (1969) N e w legislation t o c o n t r o l d r i n k i n g a n d d r i v i n g in N o r t h e r n I r e l a n d . I n : Proceedings of the Fifth Inter national Conference on Alcohol and Traffic Safety, Frei burg, Germany. S c h u l z V e r l a g ( I I ) , p p . 5 3 - 5 9 . K e e l e C . A. a n d Neil E. (1971) I n : Samson Wright's Applied Physiology. L o n d o n , O x f o r d U n i v e r s i t y Press, p. 62. Liljestrand G . a n d L i n d e P . (1930) Uber die Ausscheid ung des Alkohols mit der Exspirationsluft. Skand. Arch. Physiol. 6 0 , 2 7 5 - 2 9 8 . P e n t o n J . R . a n d Forrester M . R . (1969) A gas c h r o m a t o g r a p h i c b r e a t h analysis system w i t h p r o visions for storage a n d d e l a y e d analysis of samples. I n : Proceedings of the Fifth International Conference on Alcohol and Traffic Safety, Freiburg, Germany. S c h u l z V e r l a g ( I I ) , p p . 79-87." U n i t e d States N a t i o n a l Safety C o u n c i l (1953) Com mittee on Tests for Intoxication. Evaluating chemical tests for intoxication. C h i c a g o . W e i b e l E . R . (1963) Morphometry of the Human Lungs. Berlin, S p r i n g e r V e r l a g . W r i g h t B. M . (1955) A r e s p i r a t o r y a n e m o m e t e r . J . Physiol. 127, 2 5 . W r i g h t B . M . (1962) Proceedings of Third International Conference on Alcohol and Traffic Safety. L o n d o n , British Medical Association.J. D . J . H a v a r d (ed.), p p . 2 5 1 257. W r i g h t B. M . (1964) Alcohol a n d traffic safety. Med. J. 1, 182.
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Br.
205
Breath Alcohol Analysis and the Blood : Breath Ratio B . M . W R I G H T , MA, MB
^
u.„n^
Clinical Research Centre. Watford Road. Harrow
T. P.JONES, PhD, A R i c
k'ii'rti'^^lfclZstry.
University of Wales Institute of Science and Technology. King Edward VII Avenue. Cardiff
SUMMARY T h e history of b r e a t h alcohol analysis a n d of t h e c o n c e p t of a blood : b r e a t h r a t i o is briefly reviewed a n d it is suggested t h a t t h e r a t i o is always lower a n d more variable than predicted by accepted theory. U s i n g gas liquid c h r o m a t o g r a p h y for b o t h b r e a t h a n t l blood it h a s been s h o w n t h a t t h e blood : b r e a t h r a t i o falls d u r i n g expiration a n d only reaches its presently a c c e p t e d value of 2100 : 1, p r e d i c t e d from in vitro studies, after p r o l o n g e d r e b r e a t h i n g . I t is suggested t h a t this is d u e to alcohol b e i n g a b s o r b e d from t h e b r e a t h d u r i n g e x p i r a t i o n b y t h e m u c o s a of t h e u p p e r r e s p i r a t o r y t r a c t , t o r e p l a c e t h a t lost d u r i n g inspiration. Proposals a r e m a d e for further studies a n d for modifications in present b r e a t h s a m p l i n g p r o c e d u r e s w h i c h c o u l d m a k e b r e a t h analysis a n a c c e p t a b l e substitute for blood analysis in all except m a r g i n a l cases.
INTRODUCTION The determination of the blood alcohol concentration by means of breath analysis has now been practised for nearly 50 years (Bogen, 1927) but the success of legislation in many countries in reducing road accidents by enacting an alcohol limit has recently re newed interest in the subject and led to improved methods for breath analysis based on physical devices such as fuel cells. Practically all designers of these devices, however, have assumed that there is a fixed known ratio between the breath and blood levels, which is valid for all people at all times, so that the precision and accuracy of the determination of the blood level are believed to be limited only by the precision and accuracy of the breath analysis. The belief in a fixed blood : breath ratio is usually traced back to Liljestrand and Linde (1930)
who put forward the concept that complete equilibration takes place in the alveoli but that re-equilibration occurs at the lower temperature of the upper respiratory tract during expiration, so that the alcohol level in expired alveolar air is controlled by the breath temperature. In fact, however, the belief is mainly attributable to Harger and his colleagues who, in a long series of studies from 1930 to 1950, determined the air : water and air : blood partition ratios at various temperatures (Harger et al., 1950). They assumed a mean expired alveolar air tempera ture of 34°C and therefore concluded that the mean blood : breath alcohol ratio was 2100 : 1, the blood : air partition ratio in vitro at this temperature. Because of conflicting evidence produced by other workers (Haggard and Greenburgh, 1934) over the same period, the United States National Safety Council (1953) issued an agreed statement, signed by all the leading workers in the field, which referred to 'the constant (our italics) ratio existing between the concentration of alcohol in the alveolar air and the blood'. This led to a belief amongst legal and police authorities that the ratio was not only constant, but absolutely and unquestionably correct, and this belief has persisted to the present time,
THE BREATHALYZER The 'Breathalyzer'* (Borkenstein and Smith, 1962), the first and, until quite recently, the only available instrument for reasonably * N o t t o b e confused w i t h ' b r e a t h a l y s e r s ' , a generic t e r m used in this c o u n t r y for screening devices.
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precise breath analysis in the field was designed to read directly in blood alcohol units, using the 2100 : 1 ratio, and the volume of the sample and the quantities of chemicals were calculated accordingly. Almost from its inception, however, the 'Breathalyzer' was observed to give rather low readings (Harger, 1965) and greater variability in the blood : breath ratio than could be accounted for by analytical errors in the two measurements. Nevertheless, the 'Breathalyzer' came into such general use throughout the world that it has given its name as a generic term to all breath alcohol analysers, and has made a great contribution to the control of road traffic accidents involving alcohol (Borkenstein et al., 1964) and to psychological studies of the eflfects of alcohol (Drew et al, 1959). Innumerable breath : blood correlation studies have been made with the 'Breathalyzer', nearly all of which agree in showing that the instrument under-reads 10-15 per cent, giving a blood : breath ratio of about 2300 : 1 (Begg et al, 1964) and is a relatively poor predictor of blood alcohol.
GAS CHROMATOGRAPHY In 1970, therefore, it was decided to start a fresh investigation of the factors governing the blood : breath ratio using gas chroma tography, which had then become available for both blood and breath, and which gave results of a precision formerly unobtainable. Full details of the authors' methods will be published but the following is a brief account of the experiments and results. Blood analysis was carried out by the gas chromatographic method of Curry et al., (1966) with the blood diluted 10 times with an aqueous propanol internal standard. For breath analysis the Gas Chromatograph Intoximeter (GCI) (Penton and Forrester, 1969) was used. This instrument takes a 0·25 ml sample from the breath while the subject is blowing through it into a bag fitted with a whistle which blows when the bag is full, so that the operator can ensure that a certain minimum volume of air has been discarded before he presses the sampling button.
Using the instrument in this way, with a minimum discard volume of 21, it was possible to confirm that the 2100 : 1 ratio led to an underestimate of the blood alcohol and that the correct ratio was about 2300 : 1. The precision of the estimate of blood alcohol concentration was also lower (s.d. = about 5 mg per 100 ml) than that to be expected from the known precision of the breath and blood analyses (combined s.d. = 3 mg per 100 ml). Repetition of Harger's experiments on the blood : air ratio in vitro gave results agreeing very closely with his, so that the discrepancy could not be explained by an error in the determination of the blood : breath ratio in vitro. It was therefore decided to make a detailed study of the breath alcohol level during expiration, in relation to both volume and temperature. Volume was meas ured with a Wright Respirometer (Wright, 1955) fitted to the outlet of the GCI and temperature with a thermistor inserted in the mouthpiece, connected to a recorder. Preliminary studies showed that the breath alcohol level rose continually and did not reach a steady level even at the end of a full expiration. Moreover, the alcohol level was less than that expected from the temperature at the moment of sampling, as predicted from the blood alcohol concentration of a sample taken at the same time. It was there fore decided to adopt a modified version of Harger's technique of rebreathing, using equipment kindly loaned by him. The rebreathing bag was maintained at 40°C all the time so as to prevent condensation, and, instead of the sample being taken from the bag as was done by Harger, the subject delivered his last expiration directly into the GCI. The volume of air expired during rebreathing was measured with a second respirometer inside the bag, and this volume was added to the volume of the final expira tion into the GCI. In other words, rebreath ing was regarded as effectively a form of prolonged expiration. At the end of 4 or 5 rebreathings, the breath alcohol reached a steady level which was very close to the alcohol level in a sample of air equilibrated with the subject's blood at the same temperature in vitro. By taking
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Wright et a i . : Breath Alcohol Analysis
this level as 100 per cent it was possible to plot curves of breath alcohol level versus volume of expiration, which may be called 'alcohol expirograms', on the same scale for subjects with different blood alcohol concen trations. Similarly, the problem of the steady metabolic fall in blood alcohol concentration was overcome by taking a 5-rebreathing sample immediately before or after each sample taken after less than 5 rebreathings, and expressing the result of the latter as a percentage of the former.
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Alcohol expirograms, prepared in this way for 6 subjects, are shown in Fig. 7, in which breath temperature and alcohol level are plotted against expired volume at the moment of sampling. The lower points on the graph show the rise in breath temperature during expiration and it can be seen that it usually reached a peak just before the end of a full expiration, but rises further during rebreathing. It never quite reaches 36°C even though the rebreathing bag was held at 40°C. There is considerable intersubject
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Pig. 1: Alcohol expirogram on 6 subjects showing the relation of predicted and actual breath alcohol concen trations to breath temperature and expired volume.
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variation, some of which may have been due to variations in ambient temperature and humidity, but Harger's assumption of a mean temperature of 34°C after a 1 litre discard is seen to be reasonable. The two upper curves show the theoretical and actual changes in breath alcohol level during expiration. The single dots show the expected results if the level were simply dependent on temperature, obtained by correcting the 100 per cent reading after 5 rebreathings for the temperature at the moment of sampling. The differentiated points show the actual levels and it can be seen that, at the beginning of expiration, they are well below the expected levels, and do not reach them until after 2 or 3 rebreath ings. Thus no single-breath sampling tech nique could possibly give a correct estimate of the blood alcohol level using the 2100 : 1 ratio. In addition, substantial inter- and intrasubject variations in breath : blood rela tionship can be seen to occur, especially at the beginning of expiration, which cannot be attributed solely to temperature effects.
DISCUSSION These observations account for the deficiency of alcohol in the expired air, and for its variability in relation to the blood alcohol concentration but do not explain them. Variability could be explained to some extent by expired air temperature variations resulting from incomplete temperature equili bration, but the latter cannot explain the deficiency of alcohol, because it would lead not to a lower but to a higher alcohol level in the breath because the breath temperature is falling during expiration. A possible explanation, however, is that both the deficiency and the variability of breath alcohol level are due to the extremely high solubility of alcohol in water and the fact that the upper respiratory tract ( U R T ) is covered with a thin, aqueous layer of mucus. Thus, although the volume of the anatomical dead space in the U R T is only about 200 ml (Weibel, 1963) for relatively insoluble gases and vapours, its volume for alcohol is effectively enormously increased by the mucus layer. This layer is about 5 microns
thick and the surface area of the dead space is about 6000 cm* (Weibel, 1963), giving a volume of about 3 ml of mucus which, with a partition rate of about 2000 : 1 at equilibrium could absorb more than half the alcohol from a full vital capacity expiration. During inspiration this layer will lose some of its alcohol to the inspired air, as well as water vapour and heat, but this will not increase the alcohol concentration in the expired air because re-equilibration at a higher tempera ture has taken place in the lungs. Conse quently, during expiration the mucus layer could extract more alcohol from the breath than would be removed by simple tempera ture equilibration. For this to occur, however, two conditions must be satisfied. More alcohol than water must be extracted during inspira tion so that the surface alcohol concentration is lowered, and the alcohol must not be significantly replaced from the bloodstream between inspiration and expiration. The first condition is easily satisfied because it can be shown that, at equilibrium at 34°C, the alcohol : water ratio in the gas phase is about 8 times that in the liquid phase (Enticknap and Wright, 1965). The second cannot be dealt with quite so easily. One answer is that the cavity of the U R T is known as the 'dead space' because it takes no appreciable part in ordinary physiological gas exchange, but it has already been seen that the extreme solubility of alcohol puts it into a special category. However, whereas the alveolar walls are only about 1 micron thick, the distance from the surface of the mucus in the upper respiratory tract to the nearest capillary is about 40 microns (Weibel, 1963). The blood supply to the alveoli is also enormous, so that each breath is equili brated with about half its own volume of blood, while the mucosa of the U R T has only the normal blood supply of about 40 ml per minute per 100 g of tissue (Keele and Neil, 1971) so that, even if diffusion rates allowed, it would be impossible to replace all the missing alcohol in the time available. Since the maxi mum alcohol deficiency observed is only about 20 per cent at the beginning of expiration it seems reasonable to suppose that it could be accounted for by the mechanism suggested.
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Wright et a l . : Breath Alcohol Analysis
PRACTICAL CONSIDERATIONS If this theory is correct any further studies of the blood : breath relationship must concen trate on the condition of the U R T , and studies of the blood : breath ratio in vitro or in the lungs are largely irrelevant. Such factors as ambient temperature and humidity, whether the subject was talking or had his mouth shut just before giving the sample (Wright, 1962), and any pathological condi tions such as bronchitis that may affect the U R T are likely to be far more relevant to the blood : breath ratio in vivo. Some preliminary studies have been made along these lines which the authors propose to continue, but meanwhile it may be useful to consider the effect of this theory on the practical problem of determining the blood alcohol concentration by breath analysis, and this can best be shown by a further consideration of Fig. 1. It is obvious that there is an increase in accuracy and precision of the estimate of blood alcohol concentration with increase of expired volume, and that these are further increased by rebreathing. The improvement produced by rebreathing is, however, small and probably not worth the extra trouble involved. The deficiency of alcohol in the breath is related to expired volume, and the rate of change of deficiency with volume is also related to volume, thus indicating that it is desirable to obtain as large an expired volume as possible. This can easily be done with physical methods because they can use a very small sample aspirated from the breath, so the subject is only required to blow past the sampling port, and the resistance to breathing can be made negligible. Even so, it is likely to be impossible to obtain a discard volume of more than 2 1 in many cases, at which point the blood : breath ratio is still changing rapidly, so for precise work it may be necessary to measure the expired volume and adjust to the ratio accordingly. A further improvement could be made by measuring and adjusting for breath tempera ture, and it is possible to conceive of a portable analyser that would incorporate both these features and yet be much less complex and expensive than, for example, a
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gas Chromatograph for blood analysis. Meanwhile, however, by adopting a mean ratio of 2300 : I it is possible to eliminate the systematic error in the blood : breath ratio and with, for example, a fuel cell analyser with very low resistance to breathing, to reduce the s.d. of the blood alcohol concentra tion estimate to less than 7 m g per 100 ml under laboratory conditions. The error under field conditions would undoubtedly be sub stantially greater because of the effect of ambient conditions on the blood : breath ratio but, with a suitably designed instrument, a police station or even a police car might approach laboratory conditions. Although it is clear that breath analysis as a method of determining the blood alcohol concentration can never match the accuracy and precision of direct blood analysis on a single sample, the fact that it can be repeated over a period of time means that it can probably now give a more reliable estimate of a subject's tissue alcohol level than can be obtained with a single sample of blood. Finally, the problem of alcohol analysis needs to be considered more broadly. The present practice in the United Kingdom is to set a limit of 80 mg per 100 ml, which is fairly high, and enforce it to the limit of the precision and accuracy of blood analysis. However, only a minority of offenders have blood levels so close to the limit as to be affected by the precision of the analysis so that if a less precbe method, such as breath analysis, were used instead with a somewhat lower limit, exactly the same results could be achieved at very much less expense. Breath analysis lends itself to such a policy because its results are known immediately, so that the police could use their discretion in marginal cases as they do, for example, over speed limits. Blood analysis would be retained for cases who do not wish to accept the result of breath analysis and the decision of the police to prosecute, but the experience in Northern Ireland, where this policy is in force, suggests that such cases would be few (Howard and Morgan, 1969). NOTES T h e investigations described in this p a p e r w e r e c a r r i e d out b y A . W . J , as p a r t of his work for a P h D
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thesis s u p p o r t e d b y a s t u d e n t s h i p from t h e Science R e s e a r c h C o u n c i l a n d will b e described in detail in a later p u b l i c a t i o n . B . M . W . a t t e n d e d a m e e t i n g of t h e O r g a n i z a t i o n for E c o n o m i c C o - o p e r a t i o n a n d D e v e l o p m e n t R e s e a r c h G r o u p o n t h e 'Eflfects of Alcohol o n D r i v e r B e h a v i o u r ' in Paris in J u n e 1972, a n d a n I n t e r n a t i o n a l Conference o n ' R e s e a r c h M e t h o d o l o g y for R o a d s i d e Surveys of D r i n k i n g - D r i v i n g ' o r g a n i ^ e d b y t h e N a t i o n a l Safety Council in Paris in M a y , 1974. M u c h of t h e b a c k g r o u n d information a b o u t t h e design a n d p e r f o r m a n c e of b r e a t h alcohol devices was o b t a i n e d a t these m e e t i n g s . ACKNOWLEDGEMENTS T h e a u t h o r s a r e i n d e b t e d to m a n y of their colleagues for v a l u a b l e discussions a n d i n f o r m a t i o n , especially D r M . J . H a l s e y a n d D r J . G . J o n e s of t h e Clinical R e s e a r c h C e n t r e a n d D r J . S. P a r k of t h e U n i v e r s i t y of W a l e s Institute of Science a n d T e c h n o l o g y . Fig. 1 was d r a w n by M r P a u l D a r t o n of t h e Clinical R e s e a r c h C e n t r e ' s D e p a r t m e n t of M e d i c a l Illustration. Finally, the a u t h o r s w o u l d like to t h a n k Professor R . N . H a r g e r for l e n d i n g his r e b r e a t h i n g e q u i p m e n t , a n d for m u c h v a l u a b l e advice a n d information. REFERENCES Begg T . B . , H i l l I . D . a n d Nickolls L . C . (1964) B r e a t h a l y z e r a n d K i t a g a w a - W r i g h t m e t h o d s of m e a s u r i n g b r e a t h a l c o h o l . Br. Med. J. 1, 9 - 1 5 . Bogen Ε . (1927) D r u n k e n n e s s ; q u a n t i t a t i v e s t u d y of a c u t e alcoholic i n t o x i c a t i o n . J.A.M.A. 98, 15081511. Borkenstein R . F . , C r o w t h e r R . F . , S h u m a t e R . P . , Zeil W . B . a n d Z y l m a n R . (1964) The Role of the Drinking Driver in Τηφ€ Accidents. B l o o m i n g t o n , I n d . , I n d i a n a University. Borkenstein R . F . a n d S m i t h H . W . (1962) T h e B r e a t h a l y z e r a n d its a p p l i c a t i o n s . Med. Sei. Law 2, 13-22. C u r r y A . S., W a l k e r G . W . a n d S i m p s o n G . S. (1966) D e t e r m i n a t i o n of e t h a n o l in b l o o d b y gas c h r o m a t o g r a p h y . Analyst 9 1 , 7 4 2 - 7 4 3 . D r e w G . C , C o l q u h o u n W . P . a n d L o n g H . A . (1959) Medical Research Council Memorandum No. 38. L o n d o n , HMSO,
E n t i c k n a p J . E . a n d W r i g h t B . M . (1965) In-vivo d e t e r m i n a t i o n of t h e b r e a t h : b l o o d alcohol r a t i o . I n Proceedings of the Fourth International Conference on Alcohol and Traffic Safety. B l o o m i n g t o n , I n d . , I n d i a n a University, p p . 161-169. H a g g a r d H . W . a n d G r e e n b e r g L . A. (1934) Studies in t h e a b s o r p t i o n a n d e l i m i n a t i o n of ethyl-alcohol I I . T h e excretion of a l c o h o l in u r i n e a n d expired a i r ; a n d t h e d i s t r i b u t i o n of a l c o h o l b e t w e e n air a n d w a t e r , b l o o d a n d u r i n e . J . Pharmacol. Exp. Ther. 5 2 , 150-166. H a r g e r R . N . (1965) p e r s o n a l c o m m u n i c a t i o n . H a r g e r R . N . , F o r n e y R . B . a n d Barnes H . B . (1950) E s t i m a t i o n of level of b l o o d a l c o h o l from analysis of b r e a t h . J. Clin. Med. 3 6 , 3 0 6 - 3 1 8 . H o w a r d A . J . a n d M o r g a n W . H . D . (1969) N e w legislation t o c o n t r o l d r i n k i n g a n d d r i v i n g in N o r t h e r n I r e l a n d . I n : Proceedings of the Fifth Inter national Conference on Alcohol and Traffic Safety, Frei burg, Germany. S c h u l z V e r l a g ( I I ) , p p . 5 3 - 5 9 . K e e l e C . A. a n d Neil E. (1971) I n : Samson Wright's Applied Physiology. L o n d o n , O x f o r d U n i v e r s i t y Press, p. 62. Liljestrand G . a n d L i n d e P . (1930) Uber die Ausscheid ung des Alkohols mit der Exspirationsluft. Skand. Arch. Physiol. 6 0 , 2 7 5 - 2 9 8 . P e n t o n J . R . a n d Forrester M . R . (1969) A gas c h r o m a t o g r a p h i c b r e a t h analysis system w i t h p r o visions for storage a n d d e l a y e d analysis of samples. I n : Proceedings of the Fifth International Conference on Alcohol and Traffic Safety, Freiburg, Germany. S c h u l z V e r l a g ( I I ) , p p . 79-87." U n i t e d States N a t i o n a l Safety C o u n c i l (1953) Com mittee on Tests for Intoxication. Evaluating chemical tests for intoxication. C h i c a g o . W e i b e l E . R . (1963) Morphometry of the Human Lungs. Berlin, S p r i n g e r V e r l a g . W r i g h t B. M . (1955) A r e s p i r a t o r y a n e m o m e t e r . J . Physiol. 127, 2 5 . W r i g h t B . M . (1962) Proceedings of Third International Conference on Alcohol and Traffic Safety. L o n d o n , British Medical Association.J. D . J . H a v a r d (ed.), p p . 2 5 1 257. W r i g h t B. M . (1964) Alcohol a n d traffic safety. Med. J. 1, 182.
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Br.
