|
|
|||||||||||||||||||||||||||||||
|
Part 1: The Application of the Gas Laws Part 2: The Confusing Stuff about Anaesthetic Vapours Part 1. The application of the Gas Laws. 2.1 Of all the agents we use, only Oxygen is stored in gaseous form at room temperature. This is because the critical temperature of Oxygen is -118 degrees Celsius. Consequently, cylinders containing Oxygen obey the gas laws, and as I mentioned in tutorial 1, the pressure gauge on the cylinder directly represents the amount of gas inside as PV. 2.2 The main supply of oxygen in a hospital usually comes for a liquid oxygen tank. Huge quantities of the gas can be stored in this way, with the result that it is very economical. The container is a giant sized thermos flask, insulated from the outside. In the liquid container the temperature is kept at -160 degrees Celsius, the vapour pressure at this temperature being 7 bar. The oxygen is heated using a coil, and as the liquid evaporates, that which is left behind is cooled. This is because heat is required for vaporisation, the phase shift from liquid and gas: this is known as latent heat, it is borrowed by the molecules which are evaporation, and donated by those left behind. Although the cooling of the liquid reduces its saturated vapour pressure, and this is a problem in anaesthetic vaporisers (we will discuss this later), it is an advantage in the liquid oxygen container: as long as there is continuous usage of the oxygen supply, the liquid cools itself, making its storage very energy efficient. 2.3 Nitrous Oxide has a boiling point of -88 0C and a critical temperature of +36 degrees Celsius. This means that, in room air (20 0Celsius), N20 is a gas, but because it is below it’s critical temperature, it can be stored under pressure as a liquid. Consequently, cylinders of Nitrous Oxide contain liquid and vapour. In the UK and Ireland, 65% of the N20 cylinder is filled with liquid, vapour fills the rest (the filling ratio is 0.65) - this allows for liquid expansion if the ambient temperature rises: if there is too much liquid in the cylinder, expansion could cause explosion. 2.4 The pressure gauge on a cylinder of Nitrous Oxide measures only the vapour pressure. As the liquid in the cylinder evaporates, it constantly replenishes the gas this is used up, and the vapour pressure remains the same until there is only a small amount of liquid left. So by looking at the gauge you have absolutely no idea how much Nitrous Oxide is in the cylinder. Classic exam question: How do you estimate how much is in a cylinder of N20? We apply what we learnt about Avogadro’s number in the thprevious tutorial: you need to know two things e empty. - the weight of cylinder now, and the weight when it is Subtract the N20 two and you have the weight of the liquid inside. We know that 1 mole of N20 occupies 22.4 litres at standard temperature and pressure. The molecular weight of N20 is 44. If the cylinder contains 2.5 kg (2500 g) of N20, then you can calculate the volume of gas by dividing the weight by the molecular weight and multiplying it by 22.4: 2500/44 x 22.4 = 1272 Litres. Adiabatic cooling 2.5 One other thing you should know about Nitrous Oxide is the concept of Adiabatic cooling. This word is harder to pronounce than understand. Whenever matter changes phase, an increase or decrease in the surrounding temperature occurs depending on whether it is becoming more solid or more gaseous. If a nitrous oxide cylinder is suddenly turned on "full blast", frost can actually form on the outlet due to adiabatic cooling.2.6 Nitrous Oxide and Oxygen are combined in a 50:50 ratio, called Entonox, in maternity units for analgesia. Gases in a mixture have a critical temperature at which the mixture will separate into its constituent individual gases: the Pseudo-critical temperature. For entonox this is -5.5 degrees Celsius. Below this the N20 liquefies, and the 02 remains as a gas. If one were to breath this in, one would inspire virtual 100% Oxygen until this is used up, and then 100% Nitrous Oxide. The outcome would be disastrous.PART 2: THE CONFUSING STUFF ABOUT ANAESTHETIC VAPOURS. People get confused about the physical properties of anaesthetic vapours, because each has a different relevance. This is a simple overview: Solubility and the Blood-Gas Partition Coefficient 2.7 The solubility of an inhalation anaesthetic determines how fast it works and how fast it wears off. The more insoluble a drug is, the quicker it works.Solubility Illustration 1. Imagine two cups of warm water: into one you put a spoon of sugar and into the other a spoon of sand. Which will be in higher concentration in the bottom of the cup? The sand is insoluble, the sugar dissolves, so very little reaches the bottom. For bottom of cup read brain. Solubility Illustration 2. If one breathes in a highly soluble anaesthetic vapour, such as Ether, as soon as it arrives in the alveoli it dissolves off into the bloodstream and ends up in muscle, fat, bone - everywhere, and so, as you can imagine, very little ether arrives where one wants it - in the brain. Consequently it takes "all day" to go to sleep and wake up. Desflurane, on the other hand, is extremely insoluble; it stays in the alveoli and only a small amount of agent passes, undissolved, in the blood; the tension thus becomes high in the brain (if the concentration of drug is high in the alveoli, it’s high in the brain!). Because Desflurane is so insoluble, its alveolar concentration (and consequently its brain concentration) rises and falls very quickly - and the patient goes asleep and wakes up very quickly. Solubility is related to, and described by: the Blood-Gas Partition Coefficient (BGPC):BGPC Illustration Imagine a container in which there is 1 litre of blood exposed to an atmosphere of Isoflurane. As you would expect a certain amount of Isoflurane will dissolve into the blood. When this equilibrates 1.14 litres of the Isoflurane has entered the blood. If the atmosphere were Nitrous Oxide then 0.47 litres would have dissolved, if it were Ether - 12 litres. The amount that dissolves is related to the Ostwald solubility coefficient for that substance, and, for blood it is known as the blood-gas partition coefficient.2.9 Gases move from areas in which they are in high concentration to where the concentration is lower (diffusion). In the body the speed that this occurs at depends upon the various partition coefficients. Even though Nitrous Oxide is highly insoluble in blood, as an anaesthetic agent, it is twenty times more soluble than Nitrogen. Nitrogen contributes 79% of what is in air, and consequently alveoli and all air containing spaces such as the bowel and middle ear. So, if one adds Nitrous Oxide into the alveoli, it diffuses out along the concentration gradient much faster than Nitrogen, and the gases left behind are concentrated into a smaller space ( the concentration effect). Moreover if there is another anaesthetic agent in the alveolus, its effective concentration increases (the second gas effect) and gets ever closer to inspired concentration. The quicker the alveolar (= brain) concentration reaches inspired concentration (of volatile agent), the quicker the patient goes asleep.There are two drawbacks to the second gas effect whereby N20 diffuses in and out of spaces quicker than Nitrogen. The first is that air filled spaces expand in the presence of N20 e.g. the bowel, this may make bowel surgery difficult, a pneumothorax may enlarge and cause cardiovascular compromise. The second problem is diffusion hypoxia: when one turns off the flow of Nitrous Oxide at the end of anaesthesia, then the concentration in the alveoli is lower than in the blood. Consequently N20 floods in from the blood, usurping the 02 and N2 in the process. This is the opposite of the concentration effect, whereby alveolar gases are diluted with N20 and the patient breathes in a hypoxic mixture. To overcome this, one should administer 100% oxygen to the patient until the Nitrous washes out. The concentration effect and the second gas effect are terms describing different aspects of the same phenomenon: the reduction in the size of the alveolus due to the marginally greater solubility of Nitrous Oxide over Nitrogen. Drug Potency and MAC
2.10 The Potency of the drug: potency is a pharmacological property - a pharmacodynamic effect. One drug is more potent than another if it takes a smaller amount of that drug than the other to achieve the same effect. Whiskey is more potent than beer, but they both get you drunk! Potency is described in inhalational anaesthetics by the term MAC = Minimal Alveolar Concentration. This is the equivalent of the ED5O in pharmacology.
The MAC is defined as the end tidal (expired not inspired) concentration of anaesthetic agent at which 50% of the population will not move in response to a surgical stimulus (skin incision). What people forget about the MAC is that MAC does not equal anaesthesia, as 50% of patients will move at this concentration. MAC follows a "normal distribution"; consequently other measures such as MAC/ED 95, MAC aware and MAC awake are used. Movement does not mean awareness, this occurs at 0.3MAC. Five Things you must know about MAC MAC is not static:
Reasons why we use Nitrous Oxide: 1. Vapour sparing effect: the amount of inhalational agent required is reduced (decreased MAC), this is more economical. 2. Reduced inspired concentration of inhalational agents: reduction in the cardiovascular and respiratory depressant effects of the volatile agents. N20 smoothens the anaesthetic. 3. Nitrous Oxide has mild analgesic properties.
The Oil-Gas Partition Coefficient 2.12 We don’t know how anaesthetic agents work. We do know that all volatile agents are highly lipophilic, and that there is a lot of lipid in cell membranes. Meyer and Overton hypothesised, at the beginning of the century that anaesthetic agents acted at the level of the lipid membrane and, consequently potency is related to lipophilicity. Halothane is highly lipid soluble, Isoflurane less so, and Nitrous Oxide is comparatively insoluble in fat. Lipid solubility is represented by the oil-gas partition coefficient (OGPC): again, the larger the number, the higher the solubility. The OGPC for Hal is 220, for Iso is 97 and for N20 s 1.4. The Minimal Alveolar Concentration (MAC) is mathematically related to the OGPC.How OGPC (MAC/ Potency) and BGPC interact. An ideal anaesthetic would act extremely quickly (be highly insoluble in blood: have a low blood gas partition coefficient), and achieve anaesthesia at very low concentrations (be very potent- highly soluble in fat [brain]: have a high oil gas partition coefficient. Desflurane is highly insoluble (BGPC of 0.42), but not potent (OGPC of 18.7, MAC of 6.0). Methoxyflurane is extremely potent (OGPC 950, MAC 0.2), but is also very soluble in blood (BGPC 13). If you find this difficult to grasp, consider Desflurane to be a 6.0 litre Porsche, which does 0 - 60 mph in 4 seconds, but guzzles fuel, and Methoxyflurane to be a 1.0 litre city car, does 60 miles per gallon, but takes all week to get from 0 to 60 mph. What determines how quickly an anaesthetic wears of? 2.13 The blood gas partition coefficient is important to a certain extent, as once the drug is in the blood, the lower the BGPC, the quicker the drug is excreted through the lungs. However, every tissue in the body has its own tissue-blood partition coefficient and as the tissues act as a reservoir for anaesthetic gas, the rate at which this diffuses back from the tissues ultimately determines how quickly the patient wakes up.
TISSUE BLOOD PARTITION COEFFICIENTS
The combination of the tissue-blood and blood-gas partition coefficients determines how quickly the patient wakes up. As you would imagine patients wake very quickly from Desflurane, and quite slowly from Halothane. Sevo is quicker than Iso because of its much lower BGPC. Finally, as you can see, volatile agents dissolve much better in fat than in any other tissue. The more fat, the longer the wash out time: obese patients wake up much more slowly! Top of Page
|
||||||||||||||||||||||||||||||