Nitrous oxide and oxygen from a single cylinder

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1 VOL 19 NO 1 ANBSTHESIA JANUARY 1964 Nitrous oxide and oxygen from a single cylinder P.V. COLE, FFARCS Tutor in Anaesthetics St Bartholomew s Hospital, ECl The search for the perfect form of demand analgesia for women in normal labour has not yet ended. There are two methods in common use. Trichlorethylenelair mixtures have an effect which is slow to develop, but cumulative; nitrous oxide/air mixtures contain less than the ideal inspired oxygen concentration 1 and are often given from unreliable machines. No other mixture is at present approved by the Central Midwives Board for midwives working alone. Mixtures of nitrous oxide and oxygen are safe, potent and quickly eliminated. Doughty and McAneny2 suggest that 70% may be the best concentration of nitrous oxide to mix with oxygen; a further trial is now being carried out by the Medical Research Council. Two machines are currently available which produce, on demand, varying mixtures of the two gases. No machine is infallible. If a consistent mixture of nitrous oxide and oxygen could be delivered from a single cylinder this would be a convenient and fool proof means of providing analgesia in the labour ward or the home. However, the fact that nitrous oxide liquefies under pressure while oxygen does not creates technical difficulties. Barach and Rovenstine 3 first suggested mixing nitrous oxide and oxygen in a single cylinder; their total cylinder pressure (7OOpsig) was below the liquefaction pressure of nitrous oxide, but although this avoided technical difficulties it seriously limited the capacity of the cylinder. Tunstall4 made a preliminary announcement that gaseous mixtures of 50% and 60% nitrous oxide with oxygen had recently been produced by the British Oxygen Company at a total cylinder pressure of 2,OOOpsig without altering the composition of the mixture. Tunstall suggested that such cylinders might provide a safe and constant mixture for obstetrical use and the position seemed very promising. Before pre-mixed cylinders could be acceptable for use by midwives without supervision, it would be necessary to demonstrate that the 3

2 4 ANESTHESIA proportion of each gas delivered was the same as that intended by the manufacturer throughout the life of the cylinder under all conditions of clinical use. The present paper shows that in some circumstances the delivered concentration of nitrous oxide may become dangerously high. THEORETICAL CONSIDERATIONS Liquefaction of pure nitrous oxide is expected when its partial pressure exceeds the following values : at 20 C 7501b/in2 10 C 600lb/in2 0 C 470 lb/in2 -IOcC 370 Ib/in 2 In an ideal two-component system if a cylinder contains nitrous oxide at or below these pressures, it should be possible to add oxgyen without causing liquefaction of nitrous oxide; the total cylinder pressure will rise, but the partial pressure of nitrous oxide will not. Thus, a 50% nitrous oxide/oxygen mixture would have a total cylinder pressure of 15oOpsig; the nitrous oxide partial pressure would be 75Opsig and the mixture would remain entirely gaseous. Table 1 shows the pressure relationships that should prevail for various mixtures. TABLE 1 Maximum ilieoreiical cylinder pressures obtainable for varioiis mixtures of nitrous oxide and oxygen at 20 C PARTIAL PARTIAL PARTIAL RATIO PRESSURE RATIO PRESSURE RATIO PRESSURE Nitrous oxide 50 % 75Opsig 60% 75Opsig 70% 75Opsig Oxygen 50% 75Opsig 40% 5OOpsig 30% 32Opsig Total possible 15OOpsig 125Opsig 107Opsig pressure In practice, it is found that with a cylinder containing 60% nitrous oxide the total pressure can be as much as 3,OOOpsig without liquefaction occurring, despite the fact that this gives a theoretical nitrous oxide partial pressure of 18OOpsig. Clearly, the cylinder contents do not behave like an ideal two component system. When pressure is applied to the surface of a liquid, as by a compressed gas, the vapour pressure of the liquid rises without change in temperature. This is a general thermodynamic effect, unrelated to any specific attraction that the gas may have for the molecules of the liquid. In the case of liquid nitrous oxide exposed to a pressure of 7501b/in2 of oxygen at 20 C its vapour pressure would be expected to increase by at least 150lb/in2- to about 9001b/in2. This would permit

3 ANESTHESIA 5 the total possible pressure in a 50% nitrous oxide cylinder to be increased to 1 8OOpsig without liquefaction occurring. It is also possible that highly compressed oxygen may exert a specific attraction on the vapour molecules of nitrous oxide. Compressed gases can exert a high attraction on the molecules of solids in contact with them - a phenomenon described as the solubility of solids in highly compressed gases. There seems no reason why the same phenomenon should not occur in the case of a gas and the vapour above a liquid. EXPERIMENTAL METHODS Two mixtures were used, 60/40 and 50/50% nitrous oxide and oxygen in nominal 40 cu.ft. cylinders. A more potent mixture (70/30%) was originally promised, but the manufacturers later doubted the stability of this mixture. Small samples from the cylinders were analysed for their oxygen content by means of a Servomex-type 101 paramagnetic oxygen analyser. Analysis required not more than 10 litres of mixture, a loss which would not significantly affect the pressure within the cylinder. INVESTIGATIONS AND RESULTS Storage 60/40 and Sol50 % nitrous oxide/oxygen cylinders were stored both upright and horizontally for three months. There was no change in the oxygen concentration delivered TEMPERATURE OC FIGURE 1 The effects of cold on the oxygen concentration delivered by two cylinders

4 6 ANESTHESIA Einp tying The contents of one cylinder were completely discharged. No change could be detected in the delivered concentration throughout the life of the cylinder. Coolitig Upright cylinders were immersed to the neck in a bath of brine, whch was stirred by a stream of compressed air. The brine was cooled slowly; cylinder pressure and bath temperature were measured and, periodically, samples were analysed for oxygen content. Figure 1 shows the effect of cooling a nominal 60/40% nitrous oxide/oxygen cylinder. Pressure fell, but delivered oxygen concentration remained constant until the bath temperature was -1.5"C. Delivered oxygen concentration then began to rise. Cooling took about 3; hours and there was probably little temperature gradient across the cylinder wall since slower cooling did not affect the temperature at which delivered oxygen concentration began to change. On the other hand, when cooling was more rapid a lower bath temperature was reached before the issuing oxygen concentration rose. Figure 1 also depicts a similar experiment with a nominal 50/50% nitrous oxide oxygen cylinder. A lower bath temperature was reached before delivered oxygen concentration changed; the mean of five such experiments was -8 C. hi version while cold A nominal 60/40 % nitrous oxide/oxygen cylinder was inverted at -8 C. The delivered oxygen concentration fell to approximately 4%, and this proved a consistent finding. Pure nitrous oxide was never obtained. Rewarming Cylinders were cooled below the temperature at which it was known that the delivered oxygen concentration rose; they were then allowed to rewarm slowly, while still immersed in brine. The following is a typical result : A nominal 60/40 % nitrous oxide/oxygen cylinder, which had delivered 41.6 % oxygen at room temperature, delivered 55.3% at -7.5"C. Six hours later the brine temperature had risen to 11 "C. - a temperature which, during cooling, would not have changed the delivered oxygen concentration from 41.6% - and at this time the issuing mixture contained 54.9 % oxygen. Four hours later, when the cylinder was at room temperature, the delivered oxygen concentration was 53.4% - still 12% above the original concentration before cooling. The cylinder was left undisturbed, and daily samples were analysed. The delivered oxygen concentration did not return to its original level for four days. Repeated experiments showed that if a cylinder was cooled and

5 ANESTHESIA 7 allowed to rewarm undisturbed as much as seven days could elapse before the delivered oxygen concentration returned to its original value. If cylinders were inverted at least three times, or shaken vigorously, after rewarming, the return to normal composition was hastened. Inverting cold cylinders did not alter the delivered oxygen concentration as long as the cylinders were allowed to settle upright before sampling. Return to normal composition could also be hastened by rewarming cylinders in the horizontal position. The contents of all cylinders so treated were back to normal within twenty-four hours, though they seldom took less than eighteen hours. Emptying after cooling and rewarming Cylinders were cooled below the temperature at which it was known that the delivered oxygen concentration would rise. They were then CYLINDER PRESSURE p sig (Approx) 7dSC0 l3p" llf" "p"?po 5:O i Z 0 ' I- z40 Z W 9 '30-5 g y 20 2 z w u LL -,\. - \ \ I - l0- I I I FULL 3t4 1/2 '14 '-._- EMPT FIGURE 2 Oxygen concentration delivered after cooling and rewarming two cylinders when contents are run off at 5~/min. L O %, nitrous oxide/oxygen %, nitrous oxideloxygen

6 8 ANESTHESIA allowed to stand upright in a room for three hours, at the end of which their surfaces felt warm to the touch. Cylinder contents were then completely run off at 5 L/min; pressure and oxygen concentration were measured. Figure 2 depicts the result in a nominal 60% nitrous oxide cylinder. This cylinder, which originally delivered 43.7 % oxygen, gave 59.7 % oxygen at -8 C. This concentration had not changed after the cylinder had stood for three hours in a warm room, although rewarming had increased the pressure from 1300 to 152Opsig. As the contents were run off pressure fell progressively, as expected. Simultaneously, there was a progressive fall in delivered oxygen concentration ; when the cylinder was about half empty, the pressure gauge indicating approximately 700psig, the delivered oxygen concentration was about the same as before cooling (43.7%). When the cylinder was threequarters empty the delivered oxygen concentration suddenly fell from 30 % to 2.9 % in the course of a few minutes. When the contents were almost exhausted the delivered oxygen concentration was only 1.4%, i.e., 98.6 % nitrous oxide. A similar experiment was carried out on a nominal 50/50% nitrous oxide/oxygen cylinder which was cooled to -10 C. Figure 2 shows that the oxygen concentration delivered by the cylinder rose from 53% before cooling to 62.7 % after cooling and standing for three hours in a warm room in the upright position. As the contents were run off the oxygen Concentration again slowly fell and about one hour before the contents were exhausted the oxygen concentration dropped from 41 % to 8.2% during the course of ten minutes. Finally, the delivered oxygen concentration was only 5.8 %. DISCUSSION There seems little doubt that if premixed cylinders are kept at room temperature they will deliver a constant mixture of nitrous oxide and oxygen independent of emptying, position, or storage time. If they are cooled a temperature is reached, depending on the initial nitrous oxide concentration, at which the delivered oxygen concentration begins to rise. This is almost certainly due to liquefaction of nitrous oxide with the formation of an oxygen rich mixture above, The magnitude of this effect depends on the degree of cooling after liquefaction begins. When the cylinder is allowed to rewarm the nitrous oxide probably evaporates, but it remains in a concentrated layer at the bottom of the cylinder rather than mixing evenly with the oxygen. Thus, even when room temperature is regained, samples taken from an upright cylinder contain more than the original concentration of oxygen. If the cylind-

7 ANESTHESIA 9 er is not agitated, this effect can persist for a week. Return to original conditions can be accelerated by repeated inversion of the cylinder when it has rewarmed, or by vigorous shaking. If the cylinder is rewarmed in the horizontal position the contents return to normal within twentyfour hours, and this is probably the effect of a larger interface between oxygen and nitrous oxide. The effects of the separation brought about by cooling are well shown when the samples of a rewarmed cylinder are completely run off. An oxygen rich mixture is first delivered, leaving a nitrous oxide rich mixture which is expelled during the latter part of the life of the cylinder. At last, almost pure nitrous oxide is delivered, this effect being more marked with 60% nitrous oxide cylinder than a 50/50% mixture. The clinical significance of these findings is brought home by figure 3 and table 2. Figure 3 shows the maximum and minimum air temp- TABLE 2 Number of nights between September I 1962 and May , when temperature fell below -1 C and -7 C. (Measured as 'Ground Frost' and 'Grass Temperature', 4in above ground level.) PLACE BELOW -1 C BELOW -7 C Dyce Airfield (nr. Aberdeen) 108 nights 27 nights Shawbury (Shropshire) 101 nights 46 nights Boscombe Down (Wiltshire) 109 nights 32 nights Gatwick Airport (Surrey) 103 nights 39 nights Thorney Island (nr. Portsmouth, Hants) 86 nights 30 nights eratures in London, Manchester and Edinburgh during a ten week period last winter. Minimum temperatures were often below -1 "C and not uncommonly below -8 C. Minimum ground temperatures were considerably lower (Table 2). In most hospitals in this country cylinders are stored outside, with or without cover, or in unheated sheds. They are also transported in open lorries. It is quite possible for such cylinders to cool below the liquefaction temperature of nitrous oxide and then to be brought into the Maternity Ward for use soon after. In the present experiment, cylinders were emptied at the rate of Sr/min. The average requirement of a woman in labour, breathing from a Minnitt's apparatus, would roughly correspond to a continuous flow of 4~/min5. It is, therefore, no exaggeration to say that as the contents of a premixed cylinder became depleted a patient in labour could breathe a dangerously high concentration of nitrous oxide, with disastrous results. This effect would be more pronounced if a 60/40 % nitrous oxide/oxygen cylinder was in use.

8 ANESTHESIA OEC E M 8 E R 'b2 17 I C 31 I b Centigrade I I lb I7 I8 I b Centigrade 3 FEBRUARY '63 I b II I2 I3 14 I5 Ib I Maximum and minimum air temperatures recorded during a ten-week period last winter (by kind permission of The Guardian) FIGURE 3 CONCLUSION The oxygen concentrations delivered by cylinders filled with 60/40 % and 50/50% mixtures of nitrous oxide and oxygen at 2,oOOpsig were analysed after storage, cooling and rewarming. Cooling produced liquid nitrous oxide at the bottom of the upright cylinder, with persistence of a nitrous oxide rich mixture in this region after rewarming. An oxygen rich mixture was then delivered early in the life of the cylinder, with a nitrous oxide rich mixture towards the end which sometimes contained as little as 1.5% oxygen. This effect could persist for a week after rewarming unless the cylinder was agitated. The use of such cylinders for obstetrical analgesia is potentially dangerous, especially with 60/40 % nitrous oxide/oxygen mixtures. Unless complete mixing of the cylinder contents before use could be guaranteed, or it could be insured that the cylinders never get cold, it is unlikely that the Central Midwives Board would approve their use by unsupervised midwives. Ackno wlrdgeinents I would like to thank Dr H. G. Epstein for technical assistance and Dr J. Parkhouse for advice and criticism of this paper. The cylinders were supplied by the British Oxygen Company...,

9 References ANESTHESIA ICOLE, P.V. and NAINBY-LUXMOORE, R.C. (1962). Anmthesia, 17, 505 ~DOUGHTY, A. and MCANENY, T.M. (1963). Anmthesia (in press) 3BARACH, A.L., ROVENSTINE, E.A. (1945). Anesthesiology, 6,449 1UNSTALL, M.E. (1961). Luncet, ii, 964 SEPSTEIN, H. G. Personal communication Addenda (1) Since this paper was submitted for publication a preliminary communication by M. E. Tunstall has appeared in the British Medical Journal (Brit. med. J., 2, ). Dr Tunstall confirms many of the above findings but nevertheless contends that 50/50 % nitrous oxide/oxygen mixtures are suitable for clinical use on the grounds that: (a) previously cooled cylinders can be quickly rewarmed by immersing them in water at 42OC for five minutes; (b) their contents can then be returned to normal by inverting the cylinder three times. Whilst not denying that this is perfectly possible the author is still of the opinion that the unsupervised midwife could not reasonably be held responsible for this task. But the final decision should lie with the Central Midwives Board. (2) The British Oxygen Company have since abandoned 60140% nitrous oxide/ oxygen cylinders and have agreed only to produce 50% ones. They have also agreed to affix prominent notices to the cylinders warning against the effects of cold. Provided these precautions are strictly adhered to, and the cylinders are never stored outside in the winter, they should be perfectly safe for clinical use.

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