DETECTION AND DETERMINATION OF HIGHER OXIDES OF NITROGEN

Brit. J. Anaesth. (1967), 39, 425

DETECTION AND DETERMINATION OF HIGHER OXIDES OF NITROGEN BY

M. L. KAIN,* B. T. COMMINS, G. DKON-LEWIS AND J. F. NUNN

From the Department of Anaesthesia, University of Leeds, the Department of General Fuel Science, Houldsworth School of Applied Science, Leeds, and the MJLC. Air Pollution Research Unit, St. Bartholomew's Hospital Medical College, London SUMMARY

Methods for the detection and determination of nitric oxide (NO) and nitrogen dioxide (NOj) or tetroxide (NaO4) as contaminants of nitrous oxide are discussed. Most methods depend on detection of the nitrite ion formed from NO 2 , and the importance of first oxidizing NO to NO 2 is stressed. For retrospective detection of gross contamination in a clinical situation starch iodide paper appears satisfactory, and has a sensitivity of at least 300 p.pjn. for NO allowed to react with oxygen in a syringe. The possible desirability of testing cylinders of nitrous oxide before connecting to hospital pipelines is mentioned; gas-testing kits employing reagents adsorbed on silica gel columns may be suitable for this. Finally, the extremely sensitive and accurate colorimetric method of Saltzman, involving diazotization by nitrite ion of sulphanilic acid and alpha naphthylethylenediamine, is described. It appears that, in the past, contamination of nitrous oxide cylinders with higher oxides of nitrogen has been a rare though disastrous occurrence (Smith, 1967). It is an event which is unlikely to be seen by an anaesthetist more than once in his lifetime and it is improbable that diagnosis can be based on previous experience. It thus appears important that the anaesthetist should have some simple means of testing gas remaining in a cylinder in order to confirm or disprove suspicion that contamination has occurred. For such a method to be of any practical value it must be simple, since it would be impractical for all hospitals to maintain a complex analytical technique in readiness for an event which, it is hoped, will be of the utmost rarity. In this paper we have explored the reliability and applicability of really simple techniques which appear to be suitable for the anaesthetist in a clinical situation. It is not the usual practice for drugs (other than bromethol) to be tested for the presence of contaminants within a hospital. It is, however, conceivable that in the future it may be thought * Supported by U.S.PJLS. Fellowship No. 1-F3-GM31, 742-01, National Institute of General Medical Sciences.

advisable to carry out an analysis of gases which are to be widely distributed through a pipeline system since such a system carries the possibility of simultaneous disaster to a large number of patients. We have, therefore, included discussion of fairly quantitative techniques for detection of oxides of nitrogen which would be applicable to cylinder analysis if this should be deemed necessary. We also describe the more complex analytical methods which have very great sensitivity and specificity and are more appropriate to quality control on the part of the manufacturers and to the study of atmospheric pollution. SENSITIVITY REQUIREMENTS

The two oxides of nitrogen which may contaminate cylinders of nitrous oxide are nitric oxide (NO) and nitrogen dioxide (NO2) with its dimer NjO4, also known as nitrogen tetroxide or peroxide. Of the less stable higher oxides, nitrogen trioxide (N3O3) has not been reported as a contaminant but could be present in small quantities, while nitrogen pentoxide (N2O5) is unlikely to be present (Sidgwick, 1950). It would be desirable to be able to state the degree of danger to which the patient is exposed

426

BRITISH JOURNAL OF ANAESTHESIA

by various concentrations of oxides of nitrogen. filler's disease) and concentrations which cause Unfortunately, this is not precisely known and the well-known picture of pulmonary oedema and the information available is often conflicting death occurring 12 to 24 hours after a single (Gray, 1959). Studies on animals have shown wide exposure. The exact exposure ranges to produce species differences in susceptibility, making their these clinical effects in man are not known, but applicability to man doubtful. The complex it has been stated that a concentration of 100 chemistry of the compounds, described by Austin p.p.m. of higher oxides of nitrogen inhaled for (1967), often makes it difficult to be certain to 1 hour produces severe toxic effects in man (see which compound the animals have been exposed. Powell, 1961, p. 174). Although methods of detecting a few hundred Reports of human exposure consist largely of industrial accidents or exposure of farmers to parts per million may be adequate for indicating ''nitrous fumes" from silage, and here again there that disastrous contamination of nitrous oxide has is usually uncertainty about the details of ex- occurred, much more stringent methods are posure. needed for production quality control and for In the present state of knowledge we can do study of air pollution. We may, therefore, dislittle more than state our impressions of the tinguish three levels of discrimination in analytical hazards to the anaesthetized patient based on in- methods, although admittedly the boundaries are formation available in the literature and on the to a certain extent arbitrary: studies on dogs reported by Greenbaum and his colleagues (1967). In addition to the concentra- (1) A simple though relatively insensitive method which will enable an anaesthetist to detertion of the toxic gas, it is evident that duration mine retrospectively whether gross conand temporal pattern of exposure are also tamination of nitrous oxide has been important In the anaesthetic situation one is responsible for an unexpected acute deteriorusually dealing with a single exposure lasting ation in a patient's condition occurring between a few minutes and a few hours. during an anaesthetic or soon afterwards. Although the distinction between nitric oxide Such a method could materially assist the and nitrogen dioxide is important for analytical anaesthetist in reaching the correct diagnosis methods, evidence for a differential toxicity of the as quickly as possible, and we believe that a two gases is not very convincing and, as a hazard sensitivity of 500 p.pjn. (0.05 per cent) is of anaesthesia, they may be considered together. sufficient for this purpose. There is a vast difference in concentration between the acceptable limit of oxides of nitrogen (2) There may be a place for a somewhat more elaborate method which will detect 10-100 for chronic exposure of industrial personnel and p.p.m. which might be suitable for prosthat which is needed to cause symptoms during or immediately after a single acute exposure. pective screening of atmospheres intended Good industrial practice, assuming exposure lastfor inhalation. ing 8 hours a day for indefinite periods, aims at (3) The most sensitive methods will detect less a concentration of less than 10 parts per million than 1 p.pjn. although the price is paid in (p.pjn.) of total higher oxides. However, experiincreased complexity. Such methods are ments on animals suggest that even this may be appropriate for production quality control too high (see Powell, 1961), and 5 p.p.m. has been and for studies of atmospheric pollution. advanced as a more appropriate upper limit for long exposures (Wagner et al., 1965). At the other DETECTION BY THE UNAIDED SENSES extreme, it is probable that it would require several hundred parts per million, perhaps even Two of the human senses are directly relevant to 1,000 p.p.m. (0.1 per cent), to produce signs that the detection of nitrogen dioxide. NO 3 has a would alert an anaesthetist during an anaesthetic. distinct reddish-brown colour, with a threshold of Within this hundredfold range of concentrations visibility falling between 1,000 and 10,000 p.pjn. lie amounts which have caused delayed, life- depending on circumstances. NjO is colourless 4 threatening bronchiolitis fibrosa obliterans (silo- but, in dilute concentrations at room temperature,

DETECTION AND DETERMINATION OF fflGHER OXIDES OF NITROGEN it is largely dissociated into NO 3 . In our studies brown fumes of NO 3 have been clearly visible at temperatures as low as 0°C. The characteristically pungent and nauseating odour of NO, is said to be detectable in concentrations as low as 1 p.pjn. However, accommodation to the odour undoubtedly occurs, and odour is considered a very unreliable guide to toxic hazard. It is of interest that some anaesthetists in the past were in the habit of smelling nitrous oxide from new cylinders to judge its fitness for inhalation (Blomfield, 1926). THE PROBLEM OF NITRIC OXIDE

Nitric oxide is odourless and colourless. Its recognition has proved to be a major difficulty in the detection of contamination of nitrous oxide. Although it is oxidized to NO a by oxygen or air even at room temperature, the kinetics of the reaction are peculiar (Austin, 1967). High concentrations are converted rapidly even in air, while small but still dangerous concentrations take longer. For example, the time required for half conversion of NO at an original concentration of 100,000 p.pjn. (10 per cent) is 3.6 seconds, while at 100 p.p.m. 60 minutes are required for half of the NO to be oxidized to NO a . Most chemical methods detect NO2 or nitrite ion, which makes it imperative that NO be oxidized before these methods are applied. The oxidation can be accomplished either by allowing sufficient time for the reaction with gaseous oxygen, or by employing an oxidizing agent, such as potassium permanganate. The decolorization of permanganate has been used for the detection of NO, but the sensitivity of the method is not great. Austin (1967) has described the fractionation of N 2 0 / N 0 and N,O/NOj mixtures in a cylinder. The concentration of nitric oxide in a cylinder of nitrous oxide will decrease very rapidly during use. Therefore, the concentration to which a patient has been exposed will always be greater than that which is found on retrospective testing. If the contaminant is nitrogen dioxide, its concentration will rise during use of the cylinder since nitrogen dioxide is less volatile fhpn nitrous oxide. However, if a cylinder has chilled during use, the vapour pressure of nitrogen dioxide may be so low that its concen-

427

tration in the effluent gas falls even though a considerable quantity remains in the cylinder. Cylinders should, therefore, be warmed to room temperature before retrospective testing, and any testing procedure which aims at completeness should include sampling from both gas and liquid phases. CHEMICAL METHODS

Starch and Iodide. In clinical practice, a method is needed which is rapid and requires no elaborate training. The materials for the test must be easily obtainable and reasonably stable. These considerations rule out most of the standard quantitative methods. The material which appeared to us best suited for the purpose was starch iodide paper. It was suggested in the 1930s as a detector for oxides of nitrogen in industrial atmospheres (Chemical Detectors, 1964). It appears to be better than litmus paper for the purpose (Cholak and McNary, 1943). Both the British and United States Pharmacopoeias include the use of starch and iodide solutions for the detection of oxidizing substances in nitrous oxide. Every schoolboy will have seen the striking blue colour produced when starch and iodine are brought together. If one has filter paper impregnated with starch and an iodide salt, oxidizing agents will oxidize the iodide to iodine, and the paper will turn a colour ranging from faint purple through bright blue to almost black, depending on the amount of oxidizing agent present. The effect of higher oxides of nitrogen on starch iodide paper can easily be appreciated by holding a piece of the test paper, moistened with water, over fuming nitric acid. Nitrogen dioxide combines with water to form nitric and nitrous acids, and the oxidation of iodide is most easily expressed as the action of nitrous ion: 2NO, - + 21- + 4H+ >I2 + 2H 3 O+2NO. The two practical problems which arise with this method are the necessity for converting NO to NO 2 , and the question of sensitivity of starch iodide paper to nitrogen dioxide. The first problem may be met by allowing sufficient time for at least some of the nitric oxide present to react with oxygen. The second question has been answered by laboratory experiment,

428

BRITISH JOURNAL OF ANAESTHESIA TABLE I

Sensitivity of starch iodide Cone, of NO in gas stream

Vol. of gas sample (ml)

%

p.p.m.

0.2 0.1 0.05

2,000 1,000 500

5 5 5

500 300 500 125

15 15 5 15

Vol. of air or O, added (ml)

paper.

Cone, of NO in syringe (p.p.mO

Time for first colour change (min)

500 250 125

1.25 4.0 40.0

375 225 125 94

1.75 4.0 11.0 No change after 30

(A) MIXED WITH AIR

15 15 15 (B) MIXED WITH o,

0.05 0.03 0.05 C.0125

using a sampling technique appropriate to a clinical situation. Experimental studies. Pure nitric oxide from a cylinder* was passed through a calibrated Rotameter, and mixed with a stream of pure argon in various proportions, to obtain concentrations of NO between 125 and 2,000 p.p.m. (0.0125 to 0.2 per cent). Samples were drawn from the flowing gas stream into ordinary disposable 20-ml syringes through disposable hypodermic needles. Before sampling, a small piece of starch iodide paper,f moistened with distilled water, was placed in each syringe. Another piece of moist starch iodide paper served as a control for colour comparison. A sample of 5 or 15 ml was drawn from the gas stream and the remaining volume of the 20-ml syringe was filled with air or oxygen. The time of first appearance of a purple tinge in the paper was noted. The results are summarized in table I. With lower concentrations of NO, there is a considerable advantage in rapidity gained by using Oa instead of air in the syringe. We conclude that the practical threshold of sensitivity of starch iodide paper for nitric oxide, when a 5-ml sample of test gas is mixed with 15 ml of oxygen, is 300 p.p.m. (0.03 per cent) for a colour change within 5 minutes. This degree of sensitivity in a clinical spot test appears sufficient for identification of a disaster due to the * Air Products Co. 99+ per cent pure. t "Starch and Iodine Paper", BDH Lab., Chemicals Division, Poole, England.

5 5 15 5

presence of higher oxides of nitrogen. However, it should be remembered that the colour change indicates the presence of an oxidizing substance, and is not specific for NO 2 . Suggested routine. In clinical practice, the simplest method of checking a suspect cylinder which is still attached to an anaesthetic troliey would be as follows. Turn on N3O and O3 Rotameters in a ratio of about 3:1. Just before sampling, place a small piece of moistened starch iodide paper into a 20-ml transparent syringe and push the plunger most of the way in. Keep a second piece of moistened starch iodide paper as a colour control. Sample gas into the syringe from a point in the circuit before the p s has passed through a soda-Lime canister (or through the patient 1). After drawing the sample into the syringe, cap it and observe the paper. A negative test does not exclude the presence of higher oxides of nitrogen, but allows one to conclude that they are not present in such amounts as to account for acute clinical signs appearing a short time after the beginning of exposure to the suspect gas. If serious suspicion of gross contamination exists, it is advisable to perform the test in a wellventilated area away from other personnel, and to vent the gas to the outside. It is unlikely that simple methods of analysis will reveal the presence of nitrogen dioxide in the expired air of a patient inspiring less than 1 per cent (10,000 p.p.m.). Because of its chemical reaction with water, NO. is taken up by the body to a much greater extent than is the case for

DETECTION AND DETERMINATION OF fflGHER OXIDES OF NITROGEN

429

ship (Saltzman, 1954; Thomas et al., 1956), the method is not entirely satisfactory. It is the only method presently available which will determine all three oxides separately. The most reliable method available at present for the determination of NO, (or N a O 4 ) is the Silica Gel Test Kits. colorimetic method developed by Saltzman As stated earlier, it might be thought desirable (1954). This method has also been adapted for to check large cylinders of nitrous oxide for con- the measurement of NO after first oxidizing it tamination before connecting to hospital pipeline to NO a (Thomas et al., 1956; Ellis, 1964; Ripley, supplies. It would be desirable to have a detector dingenpeel and Burn, 1964). The method about ten times as sensitive as starch iodide paper, depends on the determination of the nitrous acid but here again relative ease of use and satisfactory formed when the NO 2 dissolves, diazotizing shelf life are essential. After a survey of field sulphanilic acid which then couples with a methods for industrial use (Chemical Detectors, naphthyl ethylene diamine to give a magenta 1964), it appears that test kits employing silica colour. The details of this method for determining gel columns would prove satisfactory. In general low concentrations of NO and NO 2 in nitrous these depend on a colour reaction, with the length oxide are as follows. The gas from the nitrous of colour change along the column giving an oxide cylinder is fed at 0.4 l./min into a train indication of the approximate concentration of of bubblers containing absorbing reagent and an NO 2 in a standard volume of gas tested. Tubes oxidant for converting NO to NO 3 ; a pressure of are also available with a permanganate oxidizing about 100 mm Hg above atmospheric is needed. stage for the conversion of NO to NO 2 . An The first two 125-ml fritted bubblers in the train example of such a device is the Multi Gas Detec- (Gallenkamp gas washing bottles, 66 X1) contain tor Model 21/31 manufactured by Dragerwerk, 40 ml of absorbing reagent (Saltzman, 1954); Lubeck. With measuring tube "10/a nitrous gas", these bubblers absorb only the NO 3 and are the calibration is from 10 to 100 p.pjn. of higher followed by two non-fritted 125-ml bubblers oxides for a gas sample of 500 ml. containing 50 ml of acid permanganate or a tube packed with pieces of glass fibre filter Most Sensitive Method—the Diazo Reaction. impregnated with acid permanganate (Ellis, 1964; Though the clinician may have to content him- Ripley, Clingenpeel and Burn, 1964) which conself with simple methods for the detection of vert any NO to NO;, which is then absorbed in higher oxides of nitrogen, the chemist has at his two further fritted bubblers. The acid perdisposal means for the accurate determination of manganate has to be prepared carefully to prevent the individual oxides of nitrogen in very small the formation of permanganic acid; this is quantities. Perhaps the most exacting application avoided by dissolving 2.5 g of potassium perof these methods is in the field of atmospheric manganate in about 10 ml of cooled 2.5 per cent pollution control. We now describe methods w/w sulphuric add. However, this oxidizing which are appropriate to this discipline, but the solution is not wholly reliable since some NO 3 methods are applicable wherever the apparatus formed by the oxidation of NO can dissolve in the reagent and some may remain unoxidized and chemical skills are available. The measurement of the separate oxides of (Ripley, Clingenpeel and Burn, 1964). The nitrogen in admixture is very difficult. Rabson, efficiency of oxidation by glass fibre filters Quilliam and Goldblatt (1960) have claimed to impregnated with acid permanganate or dichrobe able to differentiate between NO, NO, and mate has been tested and these would appear to N 3 O, and have determined the concentrations of be better oxidants for NO (Ellis, 1964; Ripley, each in mixtures. However, their method depends Clingenpeel and Burn, 1964). on assuming that NO, in solution gives rise to For high concentrations of NO or NO 3 the gas equimolar quantities of nitrite and nitrate, and must first be diluted with a gas which contains because there is some doubt about this relation- negligible quantities of the two gases and no

anaesthetic agents, whose uptake depends simple physical solution alone. It is extremely likely that NOj would be detected at all in expired gas of a patient after exposure to the had terminated.

on unthe gas

430 oxygen (to prevent oxidation of any NO). Nitrogen, helium or argon are suitable; the diluting gas should first be tested as described above using a train of bubblers. If the diluting gas is suspected of containing small amounts of higher oxides of nitrogen, these can be removed with a tube fitted with soda-lime after first passing the gas through an efficient oxidation stage as previously described. The diluting gas should be connected to a short piece of p.v.c. and then to a thick-walled glass vessel of about 1 litre capacity, whose outlet is joined to the previously described train of bubblers; the flow rate of gas through the bubblers should not be greater than 0.4 l./min. After the diluting gas has been passed through the system for a few minutes to displace any oxygen, a sample of the nitrous oxide being tested is introduced; this is done by filling a 100-ml syringe and needle with the test gas, piercing the short section of p.v.c. tubing upstream of the dilution vessel and allowing the nitrous oxide to mix over a period of 2 minutes with the diluting gas. If the absorbing reagent becomes supersaturated, then 10 ml or even 1 ml of test gas should be used. The scrubbing efficiency of the pair of fritted bubblers at 0.4 l./min flow rate is high, and negligible quantities of NO a pass on from the second fritted bubbler. The nitric oxide passes on and is rapidly oxidized by the oxidation stage to NO 2 , the latter being absorbed in the final pair of fritted bubblers. After about 10 minutes the gases should be completely absorbed and the intensity of the colours in the bubblers can be measured spectrophotometrically at 550 m^ after waiting a further 15 minutes for full colour development. The calibration of the reagent is made by adding known amounts of sodium nitrite solution. Assuming the empirically determined relationship that 1 mole of NO2 gives the same colour as 0.72 moles of sodium nitrite (Saltzman, 1954), the concentration of N 0 2 can be determined if the volume of the test gas is known. Stratmann and Buck (1966), however, have recently found that 1 mole of NO 2 gives the same colour as 1 mole of nitrite and thus, at the time of writing this paper, there is some doubt about the true factor for calibrating the Saltzman reagent. However, despite the doubt about calibration, the method described above represents the most reliable one

BRITISH JOURNAL OF ANAESTHESIA available at present. It is furthermore the most sensitive, and concentrations of less than 1 p.p.m. can be determined. PHYSICAL METHODS

The discussion of physical methods of analysis of higher oxides of nitrogen has been left until last because in general they are not useful for determining very low concentrations. The mass spectrometer is an exception, but even in expert hands the problem of calculating the original quantities of higher oxides of nitrogen present from the data emerging from the instrument is not an easy one. Both NO and NO 2 (though not N.O,,) are paramagnetic because they contain an unpaired electron. NO has a magnetic susceptibility about half as great as the most strongly paramagnetic of all common gases, oxygen. The magnetic susceptibility of NO 2 is about one-tenth that of oxygen. Thus even traces of oxygen would invalidate determinations of higher oxides by the paramagnetic method, and it can be ruled out as a practical method in the present context. Absorption spectrometry has been successfully applied to relatively high concentrations. In the visible range, the optical density of NO 3 varies with temperature as well as concentration, and at room temperature the sensitivity of the method is low (0.1 to 1 per cent, depending on path length). Infra-red analysis is considerably more sensitive but has not found wide application. It should be remembered that the corrosive and destructive properties of higher oxides of nitrogen are a threat to analytic instruments and special precautions are necessary to prevent damage to the mechanism. CONCLUSION

We have described a crude but simple test (starch iodide paper), a sensitive field test requiring a small amount of special equipment (gas sampling pump with silica gel column), and a very sensitive chemical method (the Saltzman reaction). These methods have been selected from the vast number of chemical methods which have at one time or another been applied for detection or determination of higher oxides of nitrogen. Discussion of all possible methods was deemed inappropriate,

DETECTION AND DETERMINATION OF HIGHER OXIDES OF NITROGEN and instead we nave selected ihe above methods as examples of detection or determination at different orders of sensitivity, specificity and complexity. The interested reader is referred to systematic texts for thorough treatment of the subject (Kolthoff and Elving, 1961). It is, of course, to be hoped that testing of nitrous oxide by the consumer will never be required, although the extensive and disturbing history of the subject, reviewed by Smith (1967), must inject a note of caution. REFERENCES

Austin, A. T. (1967). The chemistry of the higher oxides of nitrogen as related to the manufacture, storage and administration of nitrous oxide. Brit. J. Anaesth., 39, 345. Blomfield, J. (1926). Recent investigations concerning nitrous oxide, and the ignition points of some anaesthetic vapours. Proc. roy. Soc. Med., 19, 39. Chemical Detectors (1964). Document TID-4500 (26th ed.), p. 219. Washington: Office of Technical Services, U.S. DepL of Commerce. Cholak, J., and McNary, R. (1943). Determination of the oxides of nitrogen in air. J. industr. Hyg. Toxicol, 25, 354. Ellis, C. F. (1964). A suggested procedure for converting NO in low concentrations to NO,. Ah Wat. Pollut., 8, 297. Gray, E. LeB. (1959). Oxides of nitrogen: their occurrence, toxicity, hazard; brief review. A.MA. Archs. bid. Hlth., 19, 479. Greenbaum, R., Bay, J., Hargreaves, M. D., Kain, M. L., Kelman, G. R., Nunn, J. F., Prys-Roberts, C , and Siebold, K. (1967). Effects of higher oxides of nitrogen on the anaesthetized dog. Brit. J. Anaesth., 39, 393. Kolthoff, I. M., and Elving, P. J. (1961). Treatise on Analytical Chemistry, Pan II, Vol. 5, p. 233. New York: Interscience. Powell, M. (1961). Toxic fumes from shotfiring in coal mines. Ann. occup. Hyg., 3, 162. Rabson, S. R., Quilliam, J. H., and Goldblatt, E. (1960). The elimination of nitrous fumes from blasting gases. J. S. Afr. Inst. Min. Metall., 61, 152. Ripley, D. L., Clingenpeel, J. M., and Burn, R. W. (1964). Continuous determination of nitrogen oxides in air and exhaust gases. Air Wat. Pollut., 8, 455. Saltzman, B. E. (1954). Colorimetric microdetermination of nitrogen dioxide in the atmosphere. Analyt. Chem., U, 1949. Sidgwick, N. V. (1950). The Chemical Elements and their Compounds, VoL 1, p. 691. Oxford: University Press. Smith, W. D. A. (1967). A history of nitrous oxide and oxygen anaesthesia. Part X: The early manufacture, storage and purity of nitrous oxide. Brit. J. Anaesth., 39, 351. Stratmann, H., and Buck, M. (1966). Messung von Stickstoffdioxid in der Atmosphare. Air Wat. PoUut., 10, 313.

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Thomas, M. D., MacLeod, J. A., Robbins, R. C , Goettelman, R. C , Eldridge, R. W., and Rogerts, L. H. (1956). Automatic apparatus for determination of nitric oxide and nitrogen dioxide in the atmosphere. Analyt. Chem., 28, 1810. Wagner, W. D., Duncan, B. R., Wright, P. G., and Stokinger, H. E. (1965). Experimental study of threshold limit of NO,. Arch, environm. Hlth.. 10, 455.

DETECTION ET DETERMINATION DES OXYDES NITRIQUES FORTS SOMMAIRE

On discute des precedes de detection et de determination de l'oxyde azotique (NO) et du peroxyde d'azote (NO,) ou du tetroxyde (N,OJ en tant que substances contaminant le protoxyde d'azote. La plupart des proc6d6s sont basis sur la detection de l'ion nitrite formi a partir de NOj et l'importance qu'il y a d'oxyder d'abord NO en NO, est soulignfe. En vue de la detection retrospective d'une contamination grossiere dans des circonstances propres a la clinique, l'emploi de papiers r^actifs a l'iodure d'amidon semble donner satisfaction et prfaente une sensibility d'au moins 300 parties pour mille pour l'oxyde azotique autorise' a entrer en reaction avec l'oxygene dans une seringue. On indique qu'il est possible et recommande' de recourir i l'emploi de cylindres de contr61e du protoxyde d'azote avant le branchement sur les canalisations de I'h6pital. A cet effet, des nicessaires destines au controle des gaz et employant des r&ctifs adsorbed sur des colonnes de gel de silice peuvent tres bien convenir. Enfin, on decrit la mithode colorimitrique de Saltzman, mithode extrfimement sensible et precise, mettant en oeuvre une diazotisation de Pacide sulfanilique et de l'alpha-naphtyl-e'thylene-diamine par l'ion nitrite.

FESTSTELLUNG UND BESTIMMUNG HOHERER STICKSTOFFOXYDE ZUSAMMENFASSUNG

Es werden die Methoden zur Feststellung und Bestimmung von Stickoxyd (NO) und Stickstoffdioxyd (NO,) oder -tetroxyd (N,OJ als Verunreinigungen von Stickoxydul (Lachgas) erortert. Die meisten Verfahren stutzen sich auf den Nachweis des aus NO, gebildeten Nitrit-Ions; es wird betont, wie wichtig es ist, zunSchst NO zu NO, zu oxydieren. Zur nachtraglichen Feststellung grober Verunreinigungen erscheint im klinischen Betrieb die Verwendung von Jodstarkepapier ausreichend, das eine Empfindlichkeit von wenigstens 300 p.p.m. (Partikel pro Million) gegeniiber NO hat, welches rnnn in einer Spritze mit Sauerstoff reagieren lafit. Es wird ausgefiihrt, dafl es moglicherweise wiinschenswert ware, die Lachgasflaschen zu prflfen, bevor sie an das Zuleitungssystem des Krankenhauses. angeschlossen werden; hierfur konnten Gasprflfausriistungen mit Reagenzien, die in Quarzgelsaulen adsorbiert sind, geeignet sein. Schliefihch wird das. aufierst empfindliche und genaue kolorimetrische Verfahren von Saltzman beschrieben, das sich der Diazotisierung von Sulfanilsaure und Alpha-NaphthylHthylendiamin durch Nitrit-Ionen bedient