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HIGHER OXIDES OF NITROGEN IN ANAESTHETIC GAS CIRCUITS
Brit. J. Anaesth. (1967), 39, 382
HIGHER OXIDES OF NITROGEN IN ANAESTHETIC GAS CIRCUITS BY
M. L. KAIN*
Department of Anaesthesia, University of Leeds, England SUMMARY
Few anaesthetists can claim experience of the interaction between higher oxides of nitrogen and anaesthetic gas circuits. Indeed, recent perusal of the literature has yielded only a single paper on the subject (Hamelberg, Mahaffey and Bond, 1961). Yet the highly toxic nature of the contaminants in question requires that all factors relating to their possible accidental administration to patients be considered. The problem may be divided into two parts: firstly the influence of gas circuit factors on the composition of gases reaching the patient and theatre personnel, and secondly the effects of these reactive substances on the material of the gas circuit, and perhaps on other anaesthetic substances. EFFECTS OF CIRCUITS ON GASES
Residence Time in the Circuit. With the relatively inert gases and vapours in general use for anaesthesia, the residence time of gases in the circuit is of no special interest, except perhaps with regard to time of contact between expired gas and soda-lime (Adriani, 1962). Residence time is, however, of great interest in the case of nitric oxide, which reacts with oxygen to form nitrogen dioxide. The unusual kinetics of this reaction have been discussed elsewhere in this number (Austin, 1967). The rate of conversion of nitric oxide to nitrogen dioxide depends not only on the amount of oxygen present, * Supported by USPHS Fellowship No. 1-F3-GM-31, 742-01, National Institute of General Medical Sciences.
but also on the square of the concentration of nitric oxide. Thus for high concentrations of nitric oxide, oxidation is fairly rapid, as described in elementary chemistry texts, but at low concentrations the reaction is far slower. The result is that the proportion of nitric oxide and nitrogen dioxide from a cylinder of nitrous oxide contaminated with nitric oxide actually reaching the patient will depend on the residence time of the gases in the circuit as well as on the proportion of oxygen being provided. Nitric oxide emerging from a contaminated nitrous oxide cylinder connected to an anaesthetic trolley will first come in contact with oxygen at the manifold above the flowmeter bank. Thus the transit time between cylinder reducing valve and flowmeter can be ignored. Following the flowmeter manifold, most modern anaesthetic machines have provision for one or more vaporizers, which either accept part or all of the main gas stream or have a parallel oxygen supply which then joins the main stream. All gases are collected at some common point, to which patient breathing circuits are connected. In the Boyle's machine in common use in this country, one can either attach a bag mount and corrugated tubing as is done with the Magill and non-rebreathing systems, or else the gases are led from the common point via thick-walled tubing to a circle absorber head. Alternatively gases may be led from the common point directly to the patient for insufflation, or to a to-and-fro arrangement with Waters canister. The time taken by gas flowing at a constant
Downloaded from http://bja.oxfordjournals.org/ at Georgetown University on May 28, 2015
Gas circuit factors such as volume, material composition, placement of leaks and presence of soda-lime may influence the pattern of exposure to higher oxides of nitrogen of anaesthetized patients and theatre staff. Soda-lime is temporarily effective as an absorbent for the higher oxides. Presence of higher oxides may be expected to hasten deterioration of circuit components, particularly certain metals, rubber and nylon.
HIGHER OXIDES OF NITROGEN IN ANAESTHETIC GAS CIRCUITS rate to traverse a length of tubing is given by the formula time (sec) = 0 . 0 1 5 X ^
383
where d = diameter of the lumen (cm), L = length of tube (cm), V=gas flow rate (l./min), and 0.015 is a constant to adjust the units. It might appear that simply applying this equation to a circuit of known dimensions would yield the residence time in the circuit of any particular molecule. However, difficulties arise because of streaming, turbulence and perhaps incomplete mixing of gases. Furthermore, in the TABLE I clinical situation, flow pattern may be influenced Appearance times of carbon dioxide in transit from by the patient's respiration and the presence of flowmeter to patient. recesses such as the reservoir bag and in-circuit Respirator vaporizers. Fresh AppearIn order to determine the approximate resi- Tidal Frequency gas ance vol. (strokes/ Min. vol flow time* dence time of gases in actual anaesthetic circuits, G./min) (l./min) (sec) simple experiments were performed using carbon ao min) (A) SEMI-CLOSED CIRCLE SYSTEM dioxide as a tracer gas, with a Beaver ventilator 0.5 20 4.1 simulating a spontaneously-breathing patient. A 10 3 0.5 20 10 3.5 5 Hartmann and Braun rapid infra-red carbon di2.3 0.5 20 10 7 oxide analyzer served as the detector and its out0.5 20 10 10 1.7 1.0 10 10 5 3.6 put was recorded on a Mingograph recorder with 5.3 0.5 10 5 5 rapid paper speed. The time lag of the detection 4.5 20 5 0.25 5 system was 0.45 seconds. A Boyle anaesthetic trolley was studied with (B) MAGILL CIRCUIT either a circle-absorber system or a Magill circuit 2.7 10 3 0.5 20 connected. The former consisted of a conven0.5 20 10 5 3.9 10 7 4.1 0.5 20 tional absorber head comprising a pair of uni10 1.3 10 20 0.5 directional valves and a canister. Fresh gas 1.0 10 10 5 3.1 entered the system immediately upstream of the 5 5 3.2 10 0.5 20 5 5 3.5 0.25 inspiratory valve. The canister was filled with exhausted soda-lime to prevent interference. The * Corricted for sampling lag of 0.45 sec. bag-mounting site on the absorber head was conThe results are summarized in table I. Fresh nected to the 2-litre bag by a 1 metre length of corrugated tubing. The ventilator (representing a gas flow rate appears to be the most important patient) was connected to the absorber head by variable and, with the circle system, a direct the usual pair of 1-metre corrugated tubes meet- relation was found between fresh gas flow rate ing at a conventional Y-piece. The spring-loaded and rapid appearance of carbon dioxide. The relief valve on the Y-piece served as the only leak results are less consistent with the Magill circuit. from the system. Sampling for carbon dioxide In examining the records it was observed that detection was from the junction of the Y-piece some of the variation in appearance times was and ventilator. probably caused by testing in different phases The Magill circuit consisted of a T-piece bag of the respirator cycle. Although this factor makes mount with a 2-litre bag. A 1-metre corrugated the data in table I more difficult to interpret, it tube led from the bag to the spring-loaded relief also illustrates the complexity of these seemingly valve, which was connected directly to the venti- simple measurements.
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lator. Sampling was again at the junction of gas circuit and ventilator. Oxygen was delivered from the oxygen flowmeter at predetermined rates (hereafter referred to as fresh gas flow). The ventilator was connected and the circuit allowed to stabilize. Then carbon dioxide was turned on at the flowmeter bank as suddenly as possible and the record simultaneously marked. The time of first appearance of carbon dioxide at the sampling point was determined by measuring the records and subtracting the instrumental lag.
BRITISH JOURNAL OF ANAESTHESIA
384
TABLE II
Per cent conversion of nitric oxide to nitrogen dioxide in 3.5 sec at ambient temperature and pressure. [nitial concentration of nitric oxide
p.p.m.
100
1,000
10,000
%
0.01
0.1
1.0
Initial concentration of oxygen (%)
25
0.12
1.2
12.3
50
0.24
2.4
24.6
These results would be of great practical significance if the differential toxicity of nitric oxide and nitrogen dioxide were precisely known. Unfortunately this is not the case, although quantity of nitrogen dioxide present is important when detection is at issue (Kain et al., 1967). It might be objected that after the first breadi, concentration of oxides of nitrogen in a semiclosed anaesthetic circuit would rise because of conservation of the patient's exhaled gas. In fact, with customary flow rates of fresh gases there is little conservation of expired gas with the Magill circuit (Kain and Nunn, 1967) and, furthermore, experiments on dogs reported elsewhere in this number (Greenbaum et al., 1967) suggest that, in the concentrations studied, very little contaminant is exhaled, presumably because of reaction with water in the lungs and respiratory tract. In a circle system, soda-lime may be an effective filter (see below). Effect of Leaks. Nearly all anaesthetic systems in which nitrous oxide is administered require provision of leaks to allow excess gas to escape. They are usually in
the form of spring-loaded relief valves. In the present context, their position in the circuit is of importance in two ways. First, their placement can influence the pattern of gas flow and therefore the residence time of gases in the circuit. Secondly, they may be placed in the circuit either before or after fresh gas has passed into the patient, or through a soda-lime canister. This is of importance if the anaesthetist is to be alerted because of abnormal odour or colour of escaping gas. Either the patient or the soda-lime canister may act as a filter, so that gas emerging from relief valves distal to them may have been "scrubbed". This feature of the circuit may also determine the degree of exposure to higher oxides of the anaesthetist and other theatre personnel. In case of gross contamination the toxic hazard to staff must be considered. Solubility of Gases in Circuit Components. Another factor which would alter the concentration of higher oxides of nitrogen reaching a patient is solubility in or reactivity with components of the gas circuit. This problem is discussed below under "Effects of gases on circuits". Soda-lime. The ability of strong alkalis to absorb acid gases is well known. It was demonstrated 150 years ago that barium oxide (the anhydride of barium hydroxide) would absorb nitrogen dioxide (the anhydride of an equimolecular mixture of nitric and nitrous acids) (DuLong, 1816). Exactly 100 years later, Guareschi (1916) showed that sodalime and potash-lime were capable of absorbing nitrogen dioxide at ordinary temperatures. The reaction with sodium hydroxide is probably as follows (Gmelin, 1936): 2NaOH+2NO 3 ->NaNO,+NaNO, + H 2 O. If nitric oxide is present as well, the following additional reaction has been described (Wilson and Wilson, 1959): 2NO + N,O 4 + 4NaOH->4NaNO, + 2H2O. In fact, absorption in strong alkali solution, followed by determination of nitrate and nitrite ions, may be used for the determination of nitrogen dioxide (Chariot and Bezier, 1957). It appears that in a system free of oxygen and water,
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The purpose of the measurements was to determine the order of magnitude of residence time under clinical circumstances. It may be concluded that the range of times is probably of the order of 1.3 to 5.3 seconds, and that for purposes of calculation a figure of 3.5 seconds might be chosen as an average to cover a variety of combinations of fresh gas flow and minute volume. Using the figure of 3.5 seconds given above as an estimate of average residence time of a molecule of gas in an anaesthetic machine, from flowmeter to patient, the quantities of nitric oxide which would be converted to nitrogen dioxide can be calculated for various initial concentrations of nitric oxide and of oxygen (table II).
HIGHER OXIDES OF NITROGEN IN ANAESTHETIC GAS CIRCUITS sodium and calcium hydroxides fail to absorb nitric oxide. This point is only of academic interest in anaesthesia as modem anaesthetic sodalime is hydrated, and oxygen is likely to be abundant in the gas mixture. Thus a rather complex system exists in which the reactions illustrated above take place.
about 8 minutes. Calculated another way, each gram of soda-lime is able to absorb about 1.1 ml of actual higher oxides. (2) The colour indicator was rapidly affected, going from its usual green colour very quickly through a violet hue to the tan colour characteristic of exhausted soda-lime. The tan colour corresponded to a condition in which higher oxides were passing freely through the absorbent. In the 30-g U-tube with gas flows as stated above, the change to violet colour was noticed within 1-2 seconds, with many of the granules appearing tan within 1 minute, and complete conversion to the tan colour in 3 minutes, by which time the absorption of oxides of nitrogen had ceased. (3) Unlike the reaction of carbon dioxide absorption, the reaction of soda-lime with higher oxides of nitrogen produced no heat. In fact, the temperature of the Waters canister fell about 1°C during passage of gas mixtures, but this probably represents a cooling effect of the rapidly flowing gas. (4) Soda-lime which was exhausted with regard to oxides of nitrogen still showed ability to absorb carbon dioxide. A 30-g sample of lime appeared completely tan after passage of 2 per cent nitric oxide in air for 5 minutes and had ceased to absorb oxides of nitrogen. 5.6 per cent carbon dioxide in oxygen was then passed through and the effluent monitored with an infra-red analyzer. The effluent initially contained 0.8 per cent carbon dioxide, and this rose gradually to 3.8 per cent over 20 minutes. Heat and water vapour were evolved, but less than usual. DISCUSSION
It is unfortunate that soda-lime is only able to afford transient protection against higher oxides. It appears that a surface reaction is responsible for absorption and the surface may become rapidly coated with nitrates and nitrites. The colour indicator, sodium manganate in this case, is essentially a pH indicator. Although I have not determined its threshold of sensitivity for colour change in the presence of the higher oxides, my impression is that it is probably less sensitive than the relatively crude indicator starch iodide paper described elsewhere (Kain et al., 1967), as well as being even less specific. Thus it appears that soda-
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Experimental observations. In order to observe the absorption of higher oxides of nitrogen by soda-lime of the type used in anaesthesia, the following experiments were performed. Pure nitric oxide from a cylinder was led through a calibrated flowmeter and mixed with measured flows of air, oxygen or oxygen-free nitrogen to obtain concentrations of 1-2 per cent of higher oxides. Sofnol B.P. 5-10 mesh soda-lime was placed either in a Waters canister (450 g of absorbent) or a transparent glass U-tube (30 g of absorbent). Early in the experimental work it was observed that the colour indicator in the sodalime (sodium manganate in this case) began changing colour almost immediately when exposed to concentrations of 1-2 per cent of higher oxides of nitrogen at total flow rates of 5-10 l./min even when nitric oxide was passed in the absence of oxygen. (It is unlikely that the system was entirely airfree.) In later experiments, the glass U-tube containing 30 g of soda-lime was placed beyond the Waters canister as a crude indicator of leakage of higher oxides through the latter. Other methods of detection distal to the canister included collection of gas in polyethylene bags for visual inspection for brown fumes of nitrogen dioxide, after admixture of oxygen. Gas was also sampled into evacuated flasks for subsequent spectrophotometric analysis using the diazo reaction of Saltzman (1954), following absorption of the gas into sodium hydroxide and serial dilutions to bring the solution within range for this very sensitive method. The results of a number of varied observations may be summarized as follows: (1) For a short period soda-lime absorbs higher oxides of nitrogen from a flowing gas stream. At concentrations of 1-2 per cent in a total flow of 5-10 l./min, the "scrubbing" ability is exhausted rather rapidly. The duration of efficiency was of the order of 1 second per gram of soda-lime. A freshly filled Waters canister was effective for
385
386
BRITISH JOURNAL OF ANAESTHESIA
lime cannot be recommended either as a filter to protect against higher oxides of nitrogen or as a detector for these contaminants. EFFECTS OF GASES ON CIRCUITS
ACKNOWLEDGEMENT
The author wishes to thank Dr. G. Dixon-Lcwis of the Houldsworth School of Applied Science, University of Leeds, for material and conceptual assistance. REFERENCES
Adriani, J. (1962). The Chemistry and Physics ot Anesthesia, 2nd ed. Springfield, Illinois: Thomas. 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. Chariot, G., and Bezier, D. (1957). Quantitative Inorganic Analysis. London: Methuen. DuLong, P. L. (1816), cited by Mellor, J. W. (1928). A Comprehensive Treatise on Inorganic and Theoretical Chemistry, Vol. VIII, p. 545. London: Longmans, Green. Eger, E. I. n, and Brandstater, B. (1963). Solubility of methoxyflurane in rubber. Anesthesiology, 24, 679. Larson, C. P., and Severinghaus, J. W. (1962). The solubility of halothane in rubber, soda lime and various plastics. Anesthesiology, 23, 356. Gmelins Handbuch der Anorganischen Chemie (1936), 8th ed., Vol. 4. Berlin: Deutsche Chemische Gesellschaft. Gray, P., and Yoffe, A. D. (1955). The reactivity and structure of nitrogen dioxide. Chem. Rev., 55, 1069. Greenbaum, R., Bay, J., Hargreaves, M. D., Kain, M. L., Kelman, G. R., Nunn, J. F., Prys-Roberu, C , and Siebold, K. (1967). Effects of higher oxides of nitrogen on the anaesthetized dog. Brit. J. Anaesth., 39, 393. Guareschi, I. (1916), cited by Mellor (1928); see undei DuLong. Hamelberg, W., Mahaffey, J. S., and Bond, W. E. (1961)! Nitrous oxide impurities: a case report. Anesth. Analg. Curr. Res., 40, 408.
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Introduction of halogenated vapours into anaesthetic practice led to observations of damage to components of anaesthetic circuits (Proceedings of the Symposium of Methoxyflurane, 1963). This occurred despite the relative inertness of the vapours. A very reactive compound such as nitrogen dioxide might be expected to damage anaesthetic circuit components. Rubber is attacked by any of the higher oxides of nitrogen, with addition of a molecule of nitrogen dioxide or nitrous anhydride (N a O,) per C 5 -C 10 unit of the rubber molecule and consequent denaturation (Naunton, 1961). In addition to chemical attack on rubber, the higher oxides are also soluble in it (Gmelin, 1936). This fact complicates the question of residence times of the gases in the circuits, as well as questions of time course of changes in concentration. Eger, Larson and Severinghaus (1962) showed for halothane and Eger and Brandstater (1963) for methoxyflurane that solubility of these vapours in rubber appreciably altered the time course of build-up of concentration of the vapours in anaesthetic circuits. They also pointed out the possibility of subsequent emergence of the vapours from solution and inadvertent administration after the vaporizer was turned off. The same effect will occur with higher oxides of nitrogen, and contaminated rubber or plastic components should be destroyed. Many synthetic polymer materials are also attacked by the higher oxides. Polyvinylchloride, however, is relatively resistant, and is therefore useful in the handling of the higher oxides, although nitrogen dioxide appears to dissolve in it rather freely. On the other hand, nylon is rapidly attacked. The report of Hamelberg, Mahaffey and Bond (1961) described deterioration of a nylon diaphragm in a nitrous oxide reducing valve. The cylinder of nitrous oxide was analyzed and found to be contaminated with higher oxides of nitrogen, but the exact identity and quantity of contaminants present were not successfully determined.
Metals vary in their susceptibility to attack. In the metal parts of the anaesthetic circuit near to the patient or soda-lime canister, where moisture is abundant, the effects are likely to be of the sort caused by small quantities of rather concentrated nitric acid. Aluminium, stainless steel and chromium coating are quite resistant (Uhlig, 1958), while copper and brass are very susceptible to attack. Glass is resistant to almost all corrosive agents except hydrogen fluoride. Considering the free radical properties of nitrogen dioxide (Gray and Yoffe, 1955), reaction with anaesthetic gases or vapours would appear possible. I have been unable to find reference to the existence of such reactions under conditions obtaining in an anaesthetic circuit, although it is known that nitrogen dioxide will induce peroxide formation in liquid diethyl ether.
HIGHER OXIDES OF NITROGEN IN ANAESTHETIC GAS CIRCUITS
OXYDES AZOTIQUES FORTS PRESENTS DANS LES CIRCUITS DESTINES AUX GAZ ANESTHESIQUES SOMMAIRE
Des facteurs tels que le volume, la composition des mate'riaux, la position des ouvertures et la presence de chaux sodee, intervenant dans les canalisations de gaz
peuvent jouer un r61e sur la nature de l'exposition aux oxydes azotiques forts a laquelle sont soumis les malades ancsthesies et le personnel de la salle d'opexations. La chaux sodee est temporairement effkace en tant que substance capable d'absorber les oxydes forts. On peut s'attendre a ce que la presence de ces derniers accilere la deterioration des constituants des canalisations, en particulier de certains mitaux, du caoutchouc et du nlyon.
H5HERE STICKSTOFFOXYDE IN INHALATIONSNARKOSE-SYSTEMEN ZUSAMMENFASSUNG
Gasstromungsfaktoren wie Volumen, stoffliche Zusammensetzung, Anordnung von Austrittsstellen und Vorhandensein von Natronkalk konnen einen Einflufi ausiiben auf das allgemeine Erscheinungsbild der Einatmung von hoheren Stickstoffoxyden durch anasthesierte Patienten und Operationssaal-Personal. Natronkalk ist als Absorber fur die hoheren Oxvde zeitweilig wirksam. Es ist zu erwarten, dafi bei Vorhandensein von hoheren Oxyden die Zersetzung von Bestandteilen der Narkoseapparatur, insbesondere von bestimmten Metallen, Gummi und Nylon, btschleunigt wird.
BOOK REVIEW Year Book of Anesthesia (1966-1967). Edited by Stuart C. Cullen, MJ). Year Book Medical Publishers (Chicago); Lloyd-Luke (London). Pp. 397; illustrated. Price 64s. This latest edition follows very closely in its form the previous volumes in this series, almost even to the number of pages devoted to the various aspects of anaesthesia presented. There is, however, some bias in favour of obstetrical anaesthesia which occupies almost double its previous spacs, and so reflects the increasing interest and knowledge in this subject. The summaries of the many papers prepared by the editor are a great tribute to his tenacious coverage of the work reported in the last year, and if most of this has been of a research and scientific nature, rather than clinical, the latter is not overlooked especially in the post-anaesthetic period. Throughout, however, he recognizes again that technical management of anaesthesia is becoming almost foolproof, and that advances are to be sought in the avoidance, or correction if need be, of physiological trespass or deviation. It would be reasonable to indicate some items which have been chosen for inclusion: e.g., acid-base states, especially in relation to infants and newborns; the relation of the pH of gastric contents to the production of untoward effects when inhaled;complications of intubation and tracheostomy—a sound reminder in these
days when such manoeuvres are so often lightly undertaken. Extracts on pages 199 and 203 act as reminders that some attention should clearly be given to arterial oxygen tensions during nitrous oxide/oxygen anaesthesia. The editor endears himself to many once more by his happy knack of introducing a wholesome breath of common sense in debunking the occasional pedantic conclusion. This feature appears in some of his wellrecognized comments or by his choice of excerpt. A couple of the latter point out that capillary sampling from a histaminized or wanned ear gives results as adequate for clinical use as those from arterial puncture. His comments remind the reader that control of blood loss in radical mastoidectomy is quite possible without controlled hypotension. He is always happy to recall that the use of vasopressors is far from being the only correct treatment for collapse of the blood pressure; while, on the other hand, his comment on psychiatric complications in an Intensive Care Unit is a little harsh. There is an odd unimportant misprint, but the end of a paragraph is missing on page 93. The volume is printed, illustrated and bound in the manner to which we are accustomed and contains a subject and author index. It can be truly said that it has something for every anaesthetist. H. H. Pmkerton
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Kain, M. L., Commins, B. T., Dixon-Lewis, G., and Nunn, J. F. (1967). Detection and determination of higher oxides of nitrogen. Brit. J. Anaesth., 39, 425. Nunn, J. F. (1967). Fresh gas flow and rebreathing in the Magill circuit with spontaneous respiration. Proc. roy. Soc. Med. (in press). Naunton, W. J. S. (ed.) (1961). The Applied Science of Rubber, p. 135. London: Arnold. Proceedings of the Symposium on Methoxyflurane (1963). Discussion, p. 95. Queensborough, Kent: Abbott Laboratories. Saltzman, B. E. (1954). Colorimetric microdetennination of nitrogen dioxide in the atmosphere. Analyt. Chem., 26, 1949. Uhlig, H. H. (ed.) (1958). The Corrosion Handbook, pp. 45, 148, 354. New York: Wiley. Wilson, C. L., and Wilson, D. W. (1959). Comprehensive Analytical Chemistry, p. 315. Amsterdam: Elsevier.
387
HIGHER OXIDES OF NITROGEN IN ANAESTHETIC GAS CIRCUITS BY
M. L. KAIN*
Department of Anaesthesia, University of Leeds, England SUMMARY
Few anaesthetists can claim experience of the interaction between higher oxides of nitrogen and anaesthetic gas circuits. Indeed, recent perusal of the literature has yielded only a single paper on the subject (Hamelberg, Mahaffey and Bond, 1961). Yet the highly toxic nature of the contaminants in question requires that all factors relating to their possible accidental administration to patients be considered. The problem may be divided into two parts: firstly the influence of gas circuit factors on the composition of gases reaching the patient and theatre personnel, and secondly the effects of these reactive substances on the material of the gas circuit, and perhaps on other anaesthetic substances. EFFECTS OF CIRCUITS ON GASES
Residence Time in the Circuit. With the relatively inert gases and vapours in general use for anaesthesia, the residence time of gases in the circuit is of no special interest, except perhaps with regard to time of contact between expired gas and soda-lime (Adriani, 1962). Residence time is, however, of great interest in the case of nitric oxide, which reacts with oxygen to form nitrogen dioxide. The unusual kinetics of this reaction have been discussed elsewhere in this number (Austin, 1967). The rate of conversion of nitric oxide to nitrogen dioxide depends not only on the amount of oxygen present, * Supported by USPHS Fellowship No. 1-F3-GM-31, 742-01, National Institute of General Medical Sciences.
but also on the square of the concentration of nitric oxide. Thus for high concentrations of nitric oxide, oxidation is fairly rapid, as described in elementary chemistry texts, but at low concentrations the reaction is far slower. The result is that the proportion of nitric oxide and nitrogen dioxide from a cylinder of nitrous oxide contaminated with nitric oxide actually reaching the patient will depend on the residence time of the gases in the circuit as well as on the proportion of oxygen being provided. Nitric oxide emerging from a contaminated nitrous oxide cylinder connected to an anaesthetic trolley will first come in contact with oxygen at the manifold above the flowmeter bank. Thus the transit time between cylinder reducing valve and flowmeter can be ignored. Following the flowmeter manifold, most modern anaesthetic machines have provision for one or more vaporizers, which either accept part or all of the main gas stream or have a parallel oxygen supply which then joins the main stream. All gases are collected at some common point, to which patient breathing circuits are connected. In the Boyle's machine in common use in this country, one can either attach a bag mount and corrugated tubing as is done with the Magill and non-rebreathing systems, or else the gases are led from the common point via thick-walled tubing to a circle absorber head. Alternatively gases may be led from the common point directly to the patient for insufflation, or to a to-and-fro arrangement with Waters canister. The time taken by gas flowing at a constant
Downloaded from http://bja.oxfordjournals.org/ at Georgetown University on May 28, 2015
Gas circuit factors such as volume, material composition, placement of leaks and presence of soda-lime may influence the pattern of exposure to higher oxides of nitrogen of anaesthetized patients and theatre staff. Soda-lime is temporarily effective as an absorbent for the higher oxides. Presence of higher oxides may be expected to hasten deterioration of circuit components, particularly certain metals, rubber and nylon.
HIGHER OXIDES OF NITROGEN IN ANAESTHETIC GAS CIRCUITS rate to traverse a length of tubing is given by the formula time (sec) = 0 . 0 1 5 X ^
383
where d = diameter of the lumen (cm), L = length of tube (cm), V=gas flow rate (l./min), and 0.015 is a constant to adjust the units. It might appear that simply applying this equation to a circuit of known dimensions would yield the residence time in the circuit of any particular molecule. However, difficulties arise because of streaming, turbulence and perhaps incomplete mixing of gases. Furthermore, in the TABLE I clinical situation, flow pattern may be influenced Appearance times of carbon dioxide in transit from by the patient's respiration and the presence of flowmeter to patient. recesses such as the reservoir bag and in-circuit Respirator vaporizers. Fresh AppearIn order to determine the approximate resi- Tidal Frequency gas ance vol. (strokes/ Min. vol flow time* dence time of gases in actual anaesthetic circuits, G./min) (l./min) (sec) simple experiments were performed using carbon ao min) (A) SEMI-CLOSED CIRCLE SYSTEM dioxide as a tracer gas, with a Beaver ventilator 0.5 20 4.1 simulating a spontaneously-breathing patient. A 10 3 0.5 20 10 3.5 5 Hartmann and Braun rapid infra-red carbon di2.3 0.5 20 10 7 oxide analyzer served as the detector and its out0.5 20 10 10 1.7 1.0 10 10 5 3.6 put was recorded on a Mingograph recorder with 5.3 0.5 10 5 5 rapid paper speed. The time lag of the detection 4.5 20 5 0.25 5 system was 0.45 seconds. A Boyle anaesthetic trolley was studied with (B) MAGILL CIRCUIT either a circle-absorber system or a Magill circuit 2.7 10 3 0.5 20 connected. The former consisted of a conven0.5 20 10 5 3.9 10 7 4.1 0.5 20 tional absorber head comprising a pair of uni10 1.3 10 20 0.5 directional valves and a canister. Fresh gas 1.0 10 10 5 3.1 entered the system immediately upstream of the 5 5 3.2 10 0.5 20 5 5 3.5 0.25 inspiratory valve. The canister was filled with exhausted soda-lime to prevent interference. The * Corricted for sampling lag of 0.45 sec. bag-mounting site on the absorber head was conThe results are summarized in table I. Fresh nected to the 2-litre bag by a 1 metre length of corrugated tubing. The ventilator (representing a gas flow rate appears to be the most important patient) was connected to the absorber head by variable and, with the circle system, a direct the usual pair of 1-metre corrugated tubes meet- relation was found between fresh gas flow rate ing at a conventional Y-piece. The spring-loaded and rapid appearance of carbon dioxide. The relief valve on the Y-piece served as the only leak results are less consistent with the Magill circuit. from the system. Sampling for carbon dioxide In examining the records it was observed that detection was from the junction of the Y-piece some of the variation in appearance times was and ventilator. probably caused by testing in different phases The Magill circuit consisted of a T-piece bag of the respirator cycle. Although this factor makes mount with a 2-litre bag. A 1-metre corrugated the data in table I more difficult to interpret, it tube led from the bag to the spring-loaded relief also illustrates the complexity of these seemingly valve, which was connected directly to the venti- simple measurements.
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lator. Sampling was again at the junction of gas circuit and ventilator. Oxygen was delivered from the oxygen flowmeter at predetermined rates (hereafter referred to as fresh gas flow). The ventilator was connected and the circuit allowed to stabilize. Then carbon dioxide was turned on at the flowmeter bank as suddenly as possible and the record simultaneously marked. The time of first appearance of carbon dioxide at the sampling point was determined by measuring the records and subtracting the instrumental lag.
BRITISH JOURNAL OF ANAESTHESIA
384
TABLE II
Per cent conversion of nitric oxide to nitrogen dioxide in 3.5 sec at ambient temperature and pressure. [nitial concentration of nitric oxide
p.p.m.
100
1,000
10,000
%
0.01
0.1
1.0
Initial concentration of oxygen (%)
25
0.12
1.2
12.3
50
0.24
2.4
24.6
These results would be of great practical significance if the differential toxicity of nitric oxide and nitrogen dioxide were precisely known. Unfortunately this is not the case, although quantity of nitrogen dioxide present is important when detection is at issue (Kain et al., 1967). It might be objected that after the first breadi, concentration of oxides of nitrogen in a semiclosed anaesthetic circuit would rise because of conservation of the patient's exhaled gas. In fact, with customary flow rates of fresh gases there is little conservation of expired gas with the Magill circuit (Kain and Nunn, 1967) and, furthermore, experiments on dogs reported elsewhere in this number (Greenbaum et al., 1967) suggest that, in the concentrations studied, very little contaminant is exhaled, presumably because of reaction with water in the lungs and respiratory tract. In a circle system, soda-lime may be an effective filter (see below). Effect of Leaks. Nearly all anaesthetic systems in which nitrous oxide is administered require provision of leaks to allow excess gas to escape. They are usually in
the form of spring-loaded relief valves. In the present context, their position in the circuit is of importance in two ways. First, their placement can influence the pattern of gas flow and therefore the residence time of gases in the circuit. Secondly, they may be placed in the circuit either before or after fresh gas has passed into the patient, or through a soda-lime canister. This is of importance if the anaesthetist is to be alerted because of abnormal odour or colour of escaping gas. Either the patient or the soda-lime canister may act as a filter, so that gas emerging from relief valves distal to them may have been "scrubbed". This feature of the circuit may also determine the degree of exposure to higher oxides of the anaesthetist and other theatre personnel. In case of gross contamination the toxic hazard to staff must be considered. Solubility of Gases in Circuit Components. Another factor which would alter the concentration of higher oxides of nitrogen reaching a patient is solubility in or reactivity with components of the gas circuit. This problem is discussed below under "Effects of gases on circuits". Soda-lime. The ability of strong alkalis to absorb acid gases is well known. It was demonstrated 150 years ago that barium oxide (the anhydride of barium hydroxide) would absorb nitrogen dioxide (the anhydride of an equimolecular mixture of nitric and nitrous acids) (DuLong, 1816). Exactly 100 years later, Guareschi (1916) showed that sodalime and potash-lime were capable of absorbing nitrogen dioxide at ordinary temperatures. The reaction with sodium hydroxide is probably as follows (Gmelin, 1936): 2NaOH+2NO 3 ->NaNO,+NaNO, + H 2 O. If nitric oxide is present as well, the following additional reaction has been described (Wilson and Wilson, 1959): 2NO + N,O 4 + 4NaOH->4NaNO, + 2H2O. In fact, absorption in strong alkali solution, followed by determination of nitrate and nitrite ions, may be used for the determination of nitrogen dioxide (Chariot and Bezier, 1957). It appears that in a system free of oxygen and water,
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The purpose of the measurements was to determine the order of magnitude of residence time under clinical circumstances. It may be concluded that the range of times is probably of the order of 1.3 to 5.3 seconds, and that for purposes of calculation a figure of 3.5 seconds might be chosen as an average to cover a variety of combinations of fresh gas flow and minute volume. Using the figure of 3.5 seconds given above as an estimate of average residence time of a molecule of gas in an anaesthetic machine, from flowmeter to patient, the quantities of nitric oxide which would be converted to nitrogen dioxide can be calculated for various initial concentrations of nitric oxide and of oxygen (table II).
HIGHER OXIDES OF NITROGEN IN ANAESTHETIC GAS CIRCUITS sodium and calcium hydroxides fail to absorb nitric oxide. This point is only of academic interest in anaesthesia as modem anaesthetic sodalime is hydrated, and oxygen is likely to be abundant in the gas mixture. Thus a rather complex system exists in which the reactions illustrated above take place.
about 8 minutes. Calculated another way, each gram of soda-lime is able to absorb about 1.1 ml of actual higher oxides. (2) The colour indicator was rapidly affected, going from its usual green colour very quickly through a violet hue to the tan colour characteristic of exhausted soda-lime. The tan colour corresponded to a condition in which higher oxides were passing freely through the absorbent. In the 30-g U-tube with gas flows as stated above, the change to violet colour was noticed within 1-2 seconds, with many of the granules appearing tan within 1 minute, and complete conversion to the tan colour in 3 minutes, by which time the absorption of oxides of nitrogen had ceased. (3) Unlike the reaction of carbon dioxide absorption, the reaction of soda-lime with higher oxides of nitrogen produced no heat. In fact, the temperature of the Waters canister fell about 1°C during passage of gas mixtures, but this probably represents a cooling effect of the rapidly flowing gas. (4) Soda-lime which was exhausted with regard to oxides of nitrogen still showed ability to absorb carbon dioxide. A 30-g sample of lime appeared completely tan after passage of 2 per cent nitric oxide in air for 5 minutes and had ceased to absorb oxides of nitrogen. 5.6 per cent carbon dioxide in oxygen was then passed through and the effluent monitored with an infra-red analyzer. The effluent initially contained 0.8 per cent carbon dioxide, and this rose gradually to 3.8 per cent over 20 minutes. Heat and water vapour were evolved, but less than usual. DISCUSSION
It is unfortunate that soda-lime is only able to afford transient protection against higher oxides. It appears that a surface reaction is responsible for absorption and the surface may become rapidly coated with nitrates and nitrites. The colour indicator, sodium manganate in this case, is essentially a pH indicator. Although I have not determined its threshold of sensitivity for colour change in the presence of the higher oxides, my impression is that it is probably less sensitive than the relatively crude indicator starch iodide paper described elsewhere (Kain et al., 1967), as well as being even less specific. Thus it appears that soda-
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Experimental observations. In order to observe the absorption of higher oxides of nitrogen by soda-lime of the type used in anaesthesia, the following experiments were performed. Pure nitric oxide from a cylinder was led through a calibrated flowmeter and mixed with measured flows of air, oxygen or oxygen-free nitrogen to obtain concentrations of 1-2 per cent of higher oxides. Sofnol B.P. 5-10 mesh soda-lime was placed either in a Waters canister (450 g of absorbent) or a transparent glass U-tube (30 g of absorbent). Early in the experimental work it was observed that the colour indicator in the sodalime (sodium manganate in this case) began changing colour almost immediately when exposed to concentrations of 1-2 per cent of higher oxides of nitrogen at total flow rates of 5-10 l./min even when nitric oxide was passed in the absence of oxygen. (It is unlikely that the system was entirely airfree.) In later experiments, the glass U-tube containing 30 g of soda-lime was placed beyond the Waters canister as a crude indicator of leakage of higher oxides through the latter. Other methods of detection distal to the canister included collection of gas in polyethylene bags for visual inspection for brown fumes of nitrogen dioxide, after admixture of oxygen. Gas was also sampled into evacuated flasks for subsequent spectrophotometric analysis using the diazo reaction of Saltzman (1954), following absorption of the gas into sodium hydroxide and serial dilutions to bring the solution within range for this very sensitive method. The results of a number of varied observations may be summarized as follows: (1) For a short period soda-lime absorbs higher oxides of nitrogen from a flowing gas stream. At concentrations of 1-2 per cent in a total flow of 5-10 l./min, the "scrubbing" ability is exhausted rather rapidly. The duration of efficiency was of the order of 1 second per gram of soda-lime. A freshly filled Waters canister was effective for
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lime cannot be recommended either as a filter to protect against higher oxides of nitrogen or as a detector for these contaminants. EFFECTS OF GASES ON CIRCUITS
ACKNOWLEDGEMENT
The author wishes to thank Dr. G. Dixon-Lcwis of the Houldsworth School of Applied Science, University of Leeds, for material and conceptual assistance. REFERENCES
Adriani, J. (1962). The Chemistry and Physics ot Anesthesia, 2nd ed. Springfield, Illinois: Thomas. 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. Chariot, G., and Bezier, D. (1957). Quantitative Inorganic Analysis. London: Methuen. DuLong, P. L. (1816), cited by Mellor, J. W. (1928). A Comprehensive Treatise on Inorganic and Theoretical Chemistry, Vol. VIII, p. 545. London: Longmans, Green. Eger, E. I. n, and Brandstater, B. (1963). Solubility of methoxyflurane in rubber. Anesthesiology, 24, 679. Larson, C. P., and Severinghaus, J. W. (1962). The solubility of halothane in rubber, soda lime and various plastics. Anesthesiology, 23, 356. Gmelins Handbuch der Anorganischen Chemie (1936), 8th ed., Vol. 4. Berlin: Deutsche Chemische Gesellschaft. Gray, P., and Yoffe, A. D. (1955). The reactivity and structure of nitrogen dioxide. Chem. Rev., 55, 1069. Greenbaum, R., Bay, J., Hargreaves, M. D., Kain, M. L., Kelman, G. R., Nunn, J. F., Prys-Roberu, C , and Siebold, K. (1967). Effects of higher oxides of nitrogen on the anaesthetized dog. Brit. J. Anaesth., 39, 393. Guareschi, I. (1916), cited by Mellor (1928); see undei DuLong. Hamelberg, W., Mahaffey, J. S., and Bond, W. E. (1961)! Nitrous oxide impurities: a case report. Anesth. Analg. Curr. Res., 40, 408.
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Introduction of halogenated vapours into anaesthetic practice led to observations of damage to components of anaesthetic circuits (Proceedings of the Symposium of Methoxyflurane, 1963). This occurred despite the relative inertness of the vapours. A very reactive compound such as nitrogen dioxide might be expected to damage anaesthetic circuit components. Rubber is attacked by any of the higher oxides of nitrogen, with addition of a molecule of nitrogen dioxide or nitrous anhydride (N a O,) per C 5 -C 10 unit of the rubber molecule and consequent denaturation (Naunton, 1961). In addition to chemical attack on rubber, the higher oxides are also soluble in it (Gmelin, 1936). This fact complicates the question of residence times of the gases in the circuits, as well as questions of time course of changes in concentration. Eger, Larson and Severinghaus (1962) showed for halothane and Eger and Brandstater (1963) for methoxyflurane that solubility of these vapours in rubber appreciably altered the time course of build-up of concentration of the vapours in anaesthetic circuits. They also pointed out the possibility of subsequent emergence of the vapours from solution and inadvertent administration after the vaporizer was turned off. The same effect will occur with higher oxides of nitrogen, and contaminated rubber or plastic components should be destroyed. Many synthetic polymer materials are also attacked by the higher oxides. Polyvinylchloride, however, is relatively resistant, and is therefore useful in the handling of the higher oxides, although nitrogen dioxide appears to dissolve in it rather freely. On the other hand, nylon is rapidly attacked. The report of Hamelberg, Mahaffey and Bond (1961) described deterioration of a nylon diaphragm in a nitrous oxide reducing valve. The cylinder of nitrous oxide was analyzed and found to be contaminated with higher oxides of nitrogen, but the exact identity and quantity of contaminants present were not successfully determined.
Metals vary in their susceptibility to attack. In the metal parts of the anaesthetic circuit near to the patient or soda-lime canister, where moisture is abundant, the effects are likely to be of the sort caused by small quantities of rather concentrated nitric acid. Aluminium, stainless steel and chromium coating are quite resistant (Uhlig, 1958), while copper and brass are very susceptible to attack. Glass is resistant to almost all corrosive agents except hydrogen fluoride. Considering the free radical properties of nitrogen dioxide (Gray and Yoffe, 1955), reaction with anaesthetic gases or vapours would appear possible. I have been unable to find reference to the existence of such reactions under conditions obtaining in an anaesthetic circuit, although it is known that nitrogen dioxide will induce peroxide formation in liquid diethyl ether.
HIGHER OXIDES OF NITROGEN IN ANAESTHETIC GAS CIRCUITS
OXYDES AZOTIQUES FORTS PRESENTS DANS LES CIRCUITS DESTINES AUX GAZ ANESTHESIQUES SOMMAIRE
Des facteurs tels que le volume, la composition des mate'riaux, la position des ouvertures et la presence de chaux sodee, intervenant dans les canalisations de gaz
peuvent jouer un r61e sur la nature de l'exposition aux oxydes azotiques forts a laquelle sont soumis les malades ancsthesies et le personnel de la salle d'opexations. La chaux sodee est temporairement effkace en tant que substance capable d'absorber les oxydes forts. On peut s'attendre a ce que la presence de ces derniers accilere la deterioration des constituants des canalisations, en particulier de certains mitaux, du caoutchouc et du nlyon.
H5HERE STICKSTOFFOXYDE IN INHALATIONSNARKOSE-SYSTEMEN ZUSAMMENFASSUNG
Gasstromungsfaktoren wie Volumen, stoffliche Zusammensetzung, Anordnung von Austrittsstellen und Vorhandensein von Natronkalk konnen einen Einflufi ausiiben auf das allgemeine Erscheinungsbild der Einatmung von hoheren Stickstoffoxyden durch anasthesierte Patienten und Operationssaal-Personal. Natronkalk ist als Absorber fur die hoheren Oxvde zeitweilig wirksam. Es ist zu erwarten, dafi bei Vorhandensein von hoheren Oxyden die Zersetzung von Bestandteilen der Narkoseapparatur, insbesondere von bestimmten Metallen, Gummi und Nylon, btschleunigt wird.
BOOK REVIEW Year Book of Anesthesia (1966-1967). Edited by Stuart C. Cullen, MJ). Year Book Medical Publishers (Chicago); Lloyd-Luke (London). Pp. 397; illustrated. Price 64s. This latest edition follows very closely in its form the previous volumes in this series, almost even to the number of pages devoted to the various aspects of anaesthesia presented. There is, however, some bias in favour of obstetrical anaesthesia which occupies almost double its previous spacs, and so reflects the increasing interest and knowledge in this subject. The summaries of the many papers prepared by the editor are a great tribute to his tenacious coverage of the work reported in the last year, and if most of this has been of a research and scientific nature, rather than clinical, the latter is not overlooked especially in the post-anaesthetic period. Throughout, however, he recognizes again that technical management of anaesthesia is becoming almost foolproof, and that advances are to be sought in the avoidance, or correction if need be, of physiological trespass or deviation. It would be reasonable to indicate some items which have been chosen for inclusion: e.g., acid-base states, especially in relation to infants and newborns; the relation of the pH of gastric contents to the production of untoward effects when inhaled;complications of intubation and tracheostomy—a sound reminder in these
days when such manoeuvres are so often lightly undertaken. Extracts on pages 199 and 203 act as reminders that some attention should clearly be given to arterial oxygen tensions during nitrous oxide/oxygen anaesthesia. The editor endears himself to many once more by his happy knack of introducing a wholesome breath of common sense in debunking the occasional pedantic conclusion. This feature appears in some of his wellrecognized comments or by his choice of excerpt. A couple of the latter point out that capillary sampling from a histaminized or wanned ear gives results as adequate for clinical use as those from arterial puncture. His comments remind the reader that control of blood loss in radical mastoidectomy is quite possible without controlled hypotension. He is always happy to recall that the use of vasopressors is far from being the only correct treatment for collapse of the blood pressure; while, on the other hand, his comment on psychiatric complications in an Intensive Care Unit is a little harsh. There is an odd unimportant misprint, but the end of a paragraph is missing on page 93. The volume is printed, illustrated and bound in the manner to which we are accustomed and contains a subject and author index. It can be truly said that it has something for every anaesthetist. H. H. Pmkerton
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Kain, M. L., Commins, B. T., Dixon-Lewis, G., and Nunn, J. F. (1967). Detection and determination of higher oxides of nitrogen. Brit. J. Anaesth., 39, 425. Nunn, J. F. (1967). Fresh gas flow and rebreathing in the Magill circuit with spontaneous respiration. Proc. roy. Soc. Med. (in press). Naunton, W. J. S. (ed.) (1961). The Applied Science of Rubber, p. 135. London: Arnold. Proceedings of the Symposium on Methoxyflurane (1963). Discussion, p. 95. Queensborough, Kent: Abbott Laboratories. Saltzman, B. E. (1954). Colorimetric microdetennination of nitrogen dioxide in the atmosphere. Analyt. Chem., 26, 1949. Uhlig, H. H. (ed.) (1958). The Corrosion Handbook, pp. 45, 148, 354. New York: Wiley. Wilson, C. L., and Wilson, D. W. (1959). Comprehensive Analytical Chemistry, p. 315. Amsterdam: Elsevier.
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