IMPLICATIONS OF PREMIXED GASES AND APPARATUS FOR THEIR ADMINISTRATION

Transcription

1 Brit. J. Anaesth. (1968), 40, 675 IMPLICATIONS OF PREMIXED GASES AND APPARATUS FOR THEIR ADMINISTRATION BY M. E. TUNSTALL Premixed gases signify mixtures of two or more different gases compressed together in one and the same storage cylinder. "Premixed gas" is a common-usage term for 50 per cent oxygen, 50 per cent nitrous oxide, v/v, stored in the same cylinder at a filling pressure of 1,980 pounds per square inch gauge (p.si.g.) (139 kg/sq.cm gauge) or 136 atmospheres absolute (arm). The raisons d'etre of premixed gases are safety, portability, simplicity, accuracy and economy. The major use of "premixed gas" is in British obstetrics. The major use of respirable premixed gases outside the medical sphere occurs in underwater work with an aqualung. Safety. The primary component of a respirable gas mixture is oxygen. Its supply must not cease before that of the other gas or gases in the mixture. Premixing ensures a supply of oxygen until all sources are empty. The need for ensuring the supply of oxygen is greatest when the administration of a respirable gas mixture is not under constant direct medical supervision. THE DEVELOPMENT OF PREMIXED MEDICAL GASES Clinical. In 1922 the Union Carbide and Carbon Company and the Linde Air Products Company provided all the premixed oxygen and carbon dioxide used for the treatment of experimental carbon monoxide poisoning in humans at Yale University. Steel cylinders were charged with oxygen and 5 per cent carbon dioxide to 126 arm. In the experiments Henderson and Haggard (1922) used a simple "on demand" inhalational apparatus for the provision of oxygen and carbon dioxide in the treatment of the poisoning. The "on demand" principle, namely the supply of gas to meet the demands of inspiration only, effected an economy in gas usage. The apparatus was simple because no mixing valve was necessary to mix the gases. Accuracy of concentration of the secondary component was important because of the unpleasant subjective effects of inhaling concentrations of carbon dioxide greater than 5 per cent. Premixing ensured accuracy and constancy of the mixture. The premixing of helium and oxygen used by Barach (1936) for the management of airway obstruction again offered the advantages of safety, simplicity, accuracy and economy. But safety was Barach's foremost requirement. In 1945 Barach and Rovenstine proposed that nitrous oxide should always be mixed with oxygen in the same storage cylinder. They were concerned at the mortality and morbidity of that time due to the deliberate use of hypoxia, in techniques of nitrous oxide and oxygen anaesthesia, for the purpose of aiding induction or producing more profound anaesthesia. They suggested, therefore, that nitrous oxide and oxygen anaesthesia should not be administered with an oxygen concentration below 20 per cent. They were convinced that this could not be assured unless such mixtures were prepared and delivered from a single cylinder. They stated that provided the cylinders were not filled to pressures above 700 p.sa.g. (48 atm) at room temperature, the mixture would come out uniformly from start to finish. The choice of 48 atm was based on the critical temperature and pressure of nitrous oxide; 36.5"C and 71.7 atm respectively. (At the critical temperature and pressure the liquid and vapour phases are identical, the temperature is the maximum at which the two phases can co-exist and the pressure is the maximum at which the two phases can co-exist.) Tunstall (1961) introduced a mixture of equal parts of nitrous oxide and oxygen compressed together in the same storage cylinder for the relief of pain in labour. The mixture was released by an aqualung demand regulator, it was self-administered and it was inhaled intermittently by the mother in time with uterine contractions. The cylinders were filled to a pressure of 136 atm.

2 676 BRITISH JOURNAL OF ANAESTHESIA Prior to 1961 it was not generally thought possible for such a mixture to "-main in a single phase at this pressure at room temperature. The economical filling pressures for medical gas cylinders is 136 atm for die "permanent gases" (gases with critical temperatures well below zero). Physics. The premising of oxygen and nitrous oxide, the former a "permanent gas", the latter a gas which on account of pranking is subjected to supercritical pressures and subcritical temperatures, is of special interest. Andrews (1869) wrote: "Carbonic acid at 35.5 "C, and under 108 atmospheres of pressure, stands nearly midway between the gas and the liquid; and we have no valid grounds for assigning it to the one form of matter any more than to the other." He also found that in a mixture of equal volumes of air and carbon dioxide, at a given temperature below the critical temperature of the latter, the pressure volume curve approximated more nearly to that of a curve for carbon dioxide alone at a higher temperature. In 1880 Hannay and Hogarth were able to show that a crystal of potassium iodide disappears and enters the gaseous phase when exposed to gaseous alcohol at 300 C Masson and Dolley (1923) demonstrated the deviations of compressed gaseous mixtures from Dalton's third hypothesis (Dalton, 1801). Kay (1936) in his work on the densities of petroleum mixtures under definite conditions of temperature and pressure showed that the critical point at which all the mixture vaporized varied according to the mixture. This point he referred to as the pseudocritical point The relevance of his observations to premixed nitrous oxide and oxygen is dear later from the following observations which he made (table I). It can be seen that propane has dissolved in compressed methane gas and that the temperatures at which propane separates out as a liquid is lower than the critical temperature of propane. The solubility of nitrous oxide in compressed oxygen gas is parallel. Substance Methane Propane Methane 90% + propane 10%, Methane 40% + propane 60%, v/v TABLE I Critical temperature CO (-82.5) ( ) Pseudocritical temperature CQ Critical pressure (atm) (43) Critical pressure (atm) v/v Figures in brackets obtained from Hodgman (1958). Diepen and Scheffer (1948) determined the saturation concentrations of naphthalene in ethylene at 12, 25 and 35"C, and at various pressures. They found that the concentrations of naphthalene were as much as 25,000 times as great as those predicted from its vapour pressure. It indicated a specific solubility effect. Webster (1952) discovered that the vapour pressure of solid carbon dioxide at 150 C is increased to more than a thousand times its normal value in the presence of air at 200 atm. In 1961 the author wrote to the British Oxygen Company Ltd., asking them "whether equal portions of nitrous oxide and oxygen would come off a cylinder containing equal parts of these two gases?". They "verified that the literature was completely silent on this point". Further inquiry initiated an investigation by the British Oxygen Company Ltd., and led to the discovery of "premixed gas", now sold under the trade name Entonox. THE PHYSICS OF "PREMKED GAS" (ENTONOX) The following data have been obtained from the British Oxygen Company Ltd. (table II). TABLE II Nitrous oxide 50% nitrous oxide in oxygen Property Oxygen Density at 1 atm at 15.56'C (g/l) Critical temperature * 7 ("Q Critical pressure (atm) Not experimentally verified. (pseudocritical)

3 PREMIXED GASES AND APPARATUS FOR THEIR ADMINISTRATION 677 The pseudocritical temperatures of varying mixtures of nitrous oxide and oxygen are as shown in table HI. Concentration of nitrous oxide in oxygen (per cent) TABLE III Condensation temperature (pseudocritical) CQ Figure 1 demonstrates the increasing compressibility of mixtures of nitrous oxide and oxygen with increasing nitrous oxide percentages. Figure 2 is a guide to the preparation of premixed nitrous oxide and oxygen. Premixed nitrous oxide and oxygen the problem of low temperatures. When a full cylinder of premixed nitrous oxide and oxygen is cooled to below 7 C some of the nitrous oxide separates and settles as a liquid in the dependent portion of the cylinder. The contents of the cylinder are then no longer in a single phase. On decanting the cylinder in the upright position an oxygen-rich mixture appears first and an oxygen-poor mixture appears later. Cole (1964) was the first to point out that rewarming a cylinder of premixed nitrous oxide and oxygen that had been exposed to cold below 7 C did not result in prompt reversion to a single-phase mixture. Tunstall (1963) confirmed this but discovered that the immediate return of the mixture to a single phase after rewarming could be achieved by the simple expedient of agitating the contents of the cylinder by inverting it three times. The single phase is then permanent if its temperature remains above -7 C Midwives responsible for using premixed nitrous oxide and oxygen at home confinements are asked to observe the following rules immediately prior to the administration of inhalational analgesia: (1) Ensure that the cylinder is at a safe temperature. This is achieved either if it has remained in the delivery room (assumed always to be more than 10 C) for at least 2 hours, or if it has been placed in warm water at body temperature for 5 minutes. (Hot water is not to be used and the valve is to be kept out of the water.) (2) Invert the cylinder completely three times after the safe temperature has been achieved. The midwives are also instructed to use the cylinders lying in the horizontal position. It is suggested that the simplest way of dealing with hospital-size cylinders (2,000 litre and 5,000 litre sizes), which possibly have been exposed to low temperatures during transportation from the manufacturers during winter, lies in a method of bonded storage. The cylinders should be stored lying in a horizontal position for 24 hours, in a room not below 10 C, before issue. Reversion in the absence of any agitation, to a single phase, takes place more rapidly with the cylinder in the horizontal position than in the vertical position. Local hospital delivery in winter involving outside journeys of more than 10 minutes duration should be undertaken using covered hospital transport. The responsibility in hospital for providing cylinders of premixed nitrous oxide and oxygen in a single phase should be that of the Hospital Authority. PORTABILITY The inquiry which led to the discovery of premixed nitrous oxide and oxygen was precipitated by the special needs of British domiciliary obstetrics. Nitrous oxide in air introduced by Minnitt (1934) has been in the hands of midwives acting on their own responsibility since Premixing nitrous oxide and oxygen offered greater safety but apparatus for home confinements would need to be portable. Four steel medical gas cylinders (of the size designated as 12 cubic feet oxygen) filled with premixed nitrous oxide and oxygen yield 2,000 litres of a mixture of 50 per cent nitrous oxide, 50 per cent oxygen, v/v. Four full cylinders of the same size, one of nitrous oxide containing 909 litres, and three of oxygen each containing litres will, used together, yield 1,818 litres of a mixture of 50 per cent nitrous oxide, 50 per cent oxygen, v/v.

4 0.8« O.M « ~ O.JS " 0.J«- O.M M - o.n - CM U o.u - 0.1« F1LUNO RATIO (OUNCES or CAS OUNCES WATER CAPACITY) OXYGEN NTTHOOS OXIDE J / J o.oe - o oe - 0.O / / % VOLUME NjO W DESIRED UOTTURE OXSDK, \ voumc a OXTGEH FIG. 1 Compression of nitrous oxide/oxygen mixtures at 19.8 C. (By courtesy of the British Oxygen Company Ltd.) K 40 FIG. 2 Weights of gases required to fill cylinders to 1980 Lb./sq.in. at 19.8 C. (By courtesy of the British Oxygen Company Ltd)

5 PREMIXED GASES AND APPARATUS FOR THEIR ADMINISTRATION 679 Therefore when the mixture is premised, there is slightly more of it available for the same weight of cylinders, only one cylinder need be used or carried at a time, no mixing device is needed, and there is no complication of cylinders of nitrous oxide and oxygen emptying out of phase with each other. With regard to British domiciliary obstetrics it has been variously deduced (Crawford and Tunstall, 1968) that a midwife, in order to cover the needs of most of her patients undergoing confinement at home, would require to carry two full 500 litre cylinders of premixed nitrous oxide and oxygen for multigravid patients and three for primigravid patients. It can be seen that if there were separate full cylinders of the same size of nitrous oxide and oxygen to be used it would mean one cylinder of nitrous oxide and two of oxygen for multigravid patients and one of nitrous oxide and three of oxygen for primigravid patients. That is, an extra cylinder per patient would have to be carried. Furthermore there would be the extra weight of the necessary mixing device. Portability is also of importance in itinerant private anaesthetic practice. The combination of premixed nitrous oxide and oxygen, a compensated vaporizer for volatile agents and a range of injectable drugs is able, with a minimum weight of equipment, to meet the whole range of requirements of modem general anaesthesia. APPLICATIONS OF PREMIXED GASES Diving. Each increase of depth in water of 10 metres adds a pressure of one atmosphere (1 atm) surrounding the diver. Nitrogen narcosis appears at partial pressures of atm. Oxygen produces signs of toxidty at partial pressures above 2 atm, and it is also toxic to the lungs when inhaled for prolonged periods at above 0.7 atm. Carbon dioxide causes difficulty at 0.03 atm, and it also potentiates nitrogen and oxygen toxicity. Added to these problems is the increased work of ventilation due to gases becoming denser at depth. It is therefore obvious why a diver working at, say, 90 metres breathes a mixture of 15 per cent oxygen, 15 per cent nitrogen and 70 per cent helium. He is then breadiing oxygen at 1.5 atm and nitrogen at 1.5 atm. The nitrogen and oxygen are below toxic pressures, the density of the mixture is reduced by helium so that there is less chance of carbon dioxide retention, and decompression stops during the ascent are less prolonged as there is less nitrogen to excrete. A diver at the same depth living in an underwater house would be able to live on 3 per cent oxygen in his breathing mixture. It should be noted that helium is eight times less narcotic than nitrogen (Miles, 1962). In the case of the diver working at 90 metres, who is swimming and non-helmeted, his demand regulator would be on his person. His breaming mixture whether in cylinders on his back or fed by a line from cylinders in his diving bell would be premixed. On changing to another mixture on change of depth his cylinders would be switched. Diving is undertaken with the "permanent gases", so the problem of phase separation due to cooling does not arise. Special therapy. The applications of oxygen-carbon dioxide and oxygen-helium mixtures are well known and have been mentioned earlier. Research. In a project where the subject is to inhale a mixture of constant composition, premixing the gases provides accuracy with simplicity. PREMIXED NITROUS OXIDE AND OXYGEN Obstetrics. Entonox is a trade mark of the British Oxygen Company Ltd., which is applied both to "premixed gas" (50 per cent nitrous oxide, 50 per cent oxygen, v/v) and to a demand regulator called the Entonox Analgesic Apparatus. In 1965 the Central Midwives Board approved the use of Entonox by midwives on their own responsibility. Relief of pain in labour is at die moment the major use of premixed nitrous oxide and oxygen. It is difficult for diose not familiar with British obstetric practice to understand how 50 per cent nitrous oxide has been so popular for so long. But it has been estimated that 80 per cent of the nation's mothers are delivered by unsupervised midwives. Therefore retention of maternal co-operation and unassisted delivery are dominant requirements. It is the absence of cumulative

6 680 BRITISH JOURNAL OF ANAESTHESIA effect of intermittently inhaled nitrous oxide, plus the fact that the majority of women obtain relief from use of the apparatus, which has enabled nitrous oxide to hold its place in obstetrics. The subject has been enlarged upon elsewhere (Tunstall, 1968). General anaesthesia. Nitrous oxide is a rapidly-eliminated potent analgesic agent. Incorporated in general anaesthetic techniques it reduces the necessary levels of the more potent and toxic agents, volatile (Saidman et al., 1966) or intravenous. If 50 per cent was to become the maximum concentration of nitrous oxide available its use in modern anaesthesia would remain unchanged. But with trained anaesthetists, modem equipment and the absence of the need for portability there appears at present no strong indication to introduce premixed gas into the normally equipped operating theatre. Nitrous oxide analgesia. The majority of clinical situations where pharmacological analgesia is indicated require a duration of therapy too long for continuous direct medical supervision. This means that the therapy must be in the hands of nurses a greater part of the time. But because of fear of accidental overdose or anoxia, respirable analgesic gas mixtures are rarely placed in the hands of unsupervised non-medical staff. Premixed nitrous oxide and oxygen offers, therefore, an answer to apparatus failure or to accident due to human error or inattention. Provided the face mask does not obstruct the airway when the supply of gas ceases the supply of oxygen never fails, as room air is then inhaled. Delivery systems for nitrous oxide analgesia in the postoperative period have been described by Parbrook (1967a). The potency of 50 per cent nitrous oxide is such that the majority of subjects in order to remain conscious and therefore co-operative can only inhale nitrous oxide continuously if the concentration is less than 50 per cent (Parbrook, 1967b). Reduced concentrations of premixed gas are simply achieved by dilution with room air. For nitrous-oxide-resistant subjects, and according to Hustead (1964) 10 per cent of a population are under-reactors, their threshold could be lowered by the concurrent administration of narcotic analgesics. In spite of the pioneer observations of Klikovich (1881) the use of nitrous oxide for the relief of pain remains largely unexploited. A cylinder of premixed nitrous oxide and oxygen, a flowmetcr and a simple face mask with an aperture which allows air dilution are all that is needed safely to administer varying concentrations of nitrous oxide up to 50 per cent Indications for nitrous oxide analgesia range from the treatment of coronary thrombosis on the journey from home to hospital, of shock, for postoperative pain relief and to facilitate physiotherapy, for the treatment of pain due to burns, medical procedures and dental work not warranting general anaesthesia. The whole subject has been admirably reviewed by Parbrook (1968) with many references. Sykes and Orr (1966) have suggested that premixed nitrous oxide and oxygen cylinders should be attached to resuscitation trolleys. The advantages of ventilation with premixed nitrous oxide and oxygen during cardiopulmonary resuscitation on a subject who becomes conscious are obvious. APPARATUS FOR THE ADMINISTRATION OF PREMTXED NITROUS OXIDE AND OXYGEN The design of the storage cylinder is basic. It is apparent from the considerable rise in pressure which accompanies rise in temperature (fig. 3) that this should fulfil the same construction specifications as that of oxygen cylinders. Premixed nitrous oxide and oxygen cylinders in Britain have non-interchangeable outlet connections and are colour coded. These are currently not specified but are under consideration for the revision of British Standard There are two methods of releasing premixed gases from a storage cylinder, "on demand" or "continuous" flow. Release on demand. The principles and certain details of the demand valve have remained unchanged since the invention and perfection of that for diving by Rouquayrol and Denayrouze in 1865 (Poulct and Barincou, 1964). The negative pressure in a breathing tube generated by the subject on inspiration causes movement of a diaphragm which actuates the mechanism for the release of gas stored under pressure. Modern demand regulators are designed to operate at minimum negative

7 PREMEXED GASES AND APPARATUS FOR THEIR ADMINISTRATION 681 pressures, produce self-perpetuating flows which can be arrested by minimum positive pressures, release gas at peak flows over 500 l./min and compensate for variations in atmospheric and/or underwater pressure. K I TO I 80 I VOLUME HjO M I X WC. X4S"C. FIG. 3 Effect of temperature on pressure of cylinders filled to 1980 Lb./sq.in. at 19.8 C. (By courtesy of the British Oxygen Company Ltd.) The design of demand valves is too large a subject to be dealt with in this paper. Aqualung valves vary greatly in their degree of sophistication. The valves are robust but their users are TO expected to dismantle, clean, and check them regularly. On the other hand, the Entonox apparatus for obstetric analgesia is a demand valve in whose design long periods without servicing are given priority as well as robustness. Entonox meets me specification British Standard 4272 (Part 2) In medicine the main indication for "on demand" apparatus is in obstetric analgesia. Continuous flow apparatus. All that is required for continuous flow release of gas from a cylinder is a needle valve and a flowmeter. A pressure-reducing valve is necessary if continual adjustment of the needle valve is to be avoided. In their comment on demand systems in dental anaesthetic machines, Latham and Parbrook (1967) state that high gas flows with portable apparatus are uneconomical when adjuvants such as methohexitone and halotbane are used. Latham (1968, personal communication) in his private dental practice always uses 50 per cent nitrous oxide in oxygen whether it be from his portable premixed nitrous oxide and oxygen machine or the dental surgeon's static apparatus. He achieved a reduction in expense on gases when using his portable premixed nitrous oxide and oxygen apparatus on account of being able to deliver the mixture accurately by continuous controlled flow into a reservoir bag (Latham and Parbrook, 1966). The existence of portable anaesthetic machines on the market testifies to a need, both in Great Britain and abroad, for portability. Some of these machines are based on calibrated vaporizers for the administration of the potent volatile agents. Examples have been described by Boulton (1966). The addition of premixed gas would in certain circumstances augment the usefulness of these machines. The scope of the simple closed circuit for halothane described by Bodman, Gerson and Smith (1967) would possibly be widened by the use of premixed nitrous oxide and oxygen from a 500 litre cylinder instead of the use of oxygen. A minimum maintenance flow rate of 2-4 l./min would be desirable (Crowley, Falconer and Lundy, 1948; Smith, 1966). A relatively high gas flow would be advisable in the first 10 minutes on account of the rapid initial uptake of nitrous

8 682 BRITISH JOURNAL OF ANAESTHESIA oxide (Eger, I960, 1963). The system and optimum technique would need to be investigated before recommendation. CONCLUSION Premised gases are used in domiciliary obstetrics and in underwater work by divers. The prime object of placing a respirable gas mixture in one and the same storage cylinder is safety. Safety is enhanced because the oxygen cannot run out before the other components of the mixture. Premixing eliminates the need for a mixing device and therefore facilitates a reduction in weight and complexity of the breathing apparatus. Furthermore only one cylinder need be in use at a time. REFERENCES Andrews, T. (1869). On the continuity of the gaseous and liquid states of matter. Phil. Trans, R. Soc. of London, 159, 575. Barach, A. L. (1936). The therapeutic use of helium. J. Amer. med. Ass., 107, Rovenstine, E. A. (1945). Hazard of anoxia in nitrous oxide anesthesia. Anesthesiology, 6, 449. Bodman, R. I., Gerson, G., and Smith, K. (1967). A simple closed circuit for halothane anaesthesia. Anaesthesia, 22, 476. Boulton, T. B. (1966). Anaesthesia in difficult situations. Anaesthesia, 21, 513. British Standards Institution (1968). Specification for anaesthetic and analgesic machines. British Standard 4272, Part 2. Cole, P. V. (1964). Nitrous oxide and oxygen from a single cylinder. Anaesthesia, 19, 3. Crawford, J. S., and Tunstall, M. E. (1968). Notes on respiratory performance during labour. Brit. J. Anaesth., 40, 612. Crowley, J. H., Falconer, A., and Lundy, J. S. (1948). Certain factors influ:ncing percentage of oxygen in mixtures of nitrous oxide and oxygen. Anesth. Analg., 27, 255. Dalton, J. (1801). New theory of the constitution of mixed aeriform fluids, and particularly the atmosphere. Nicholson's Philosophical Journal, 5, 241. Diepen, G. A. M., and Scheffer, F. E. C. (1948). The solubility of naphthalene in supircritical ethylene. J. Amer. chem. Soc., 70, Eger, E. I. (n) (I960). Factors affecting the rapidity of alteration of nitrous oxide concentration in a circle system. Anesthesiology, 21, 348. Eger, E. I. (u) (1963). Applications of a mathematical model of gas uptake. Uptake and distribution of Anaesthetic Agents (eds. Papper, E. M., and Kitz, R. J.), ch. 8. New York: McGraw-Hill. Hannay, J. B., and Hogarth, J. (1880). On the solubility of solids in gases. Proc. roy. Soc., 30, 178. Henderson, Y., and Haggard, H. W. (1922). The treatment of carbon monoxide asphyxia by means of oxygen plus carbon dioxide inhalation. J. Amer. med. Ass., 79, Hodgman, C. D. (editor-in-chief) (1958). Handbook of Chemistry and Physics, 39th ed., p Cleveland: Chemical Rubber Publishing Co. Hustead, R. F. (1964). Nitrous oxide in obstetrics. Clm. Anesth., 1, 97. Kay, W. B. (1936). Density of hydrocarbon gases and vapors at high temperature and pressure. Ind. Eng. Chem., 28, Klikovich, S. (1881). Nitrous Oxide and experiences with its therapeutic administration. St. Petersburg. Latham, J. W., and Parbrook, G. D. (1966). The use of premixed nitrous oxide and oxygen in dental anaesthesia. Anaesthesia, 21, 472. (1967). Premixed gas machine. Anaesthesia, 22,316. Masson, I., and Dolley, L. G. F. (1923). The pressure of gaseous mixtures. Proc. roy. Soc., 103, 525. Miles, S. (1962). Underwater Medicine, p London: Staples Press. Minnitt, R. J. (1934). A new technique for the selfadministration of gas-air analgesia in labour. Lancet, 1, Parbrook, G. D. (1967a). Techniques of inhalational analgesia in the postoperative period. Brit. J. Anaesth., 39, 730. (1967b). The levels of nitrous oxide analgesia. Brit. 7. Anaesth., 39, 974. (1968). Therapeutic uses of nitrous oxide. Brit. J. Anaesth. (publication pending). Poulet, G., and Barincou, R. (1964). Underwater Swimming, p. 52. London: Newnes. Saidman, L. J., Munson, S., Eger, E. I. (n), and Babad, A. (1966). Minimum alveolar concentrations of methoxyfhirane, halothane, fluroxene, cyclopropane and nitrous oxide in man. Anesthesiology, TJ, ITS. Smith, T. C. (1966). Nitrous oxide and low inflow circle systems. Anesthesiology, 27, 266. Sykes, M. K., and Orr, D. S. (1966). Cardio-pulmonary resuscitation. Anaesthesia, 21, 363. Tunstall, M. E. (1961). Obstetric analgesia. Lancet, 2, 964. (1963). Effect of cooling on premixed gas mixtures for obstetric analgesia. Brit. med. J., 2, 915. (1968). Analgesia and anaesthesia; chapter in Obstetrics and Gynaecology (ed. Baird, D.). Edinburgh: Livingstone. Webster, T. J. (1952). The influence of pressure on the equilibrium between carbon dioxide and air. Proc. roy. Soc., 214, 61.