Ep 11 – MAC and the Partition Co-Efficients

Introduction and Podcast Overview

00:00-01:03

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Hi everyone, this is James at Gas Gas Gas. First off I want to apologise as I feel a bit high on paint fumes due to my exciting Sunday activities, but that is contextual because we’re going to talk about volatile anaesthetics and MAC. Just want to take a brief moment to say if you’re enjoying this podcast, please tell your friends about it. And I’m quite enjoying the exponential rate of growth that this podcast seems to be experiencing.

Anyway, without further ado, we’re going to talk about MAC.

Defining MAC (Minimum Alveolar Concentration)

01:03-01:56

This is minimum alveolar concentration, and this is a concept originally developed to guide anaesthetic depth, which is used today. It is said that a MAC of one, which is particular to the expired concentration of the anaesthetic agent you’re using, will yield a patient that fifty percent of the time won’t wriggle or move when a surgeon comes along and does a standard skin and steel incision.

Of note, this patient will not have been induced with propofol, they won’t have muscle relaxants on board, nor do they have any opiates on board with this MAC of one. An important factor with MAC is that it scales with age. Young people classically require more agent, older people less, and this changes by about six percent per decade.

There’s a ton of important definitions to get through when we’re talking about MAC.

Effect Site and Alveolar Concentration

01:56-02:58

First up, effect site: place in the body the anaesthetic agent acts. Particularly in an ideal world, it would be a delight if we could measure the concentration of our anaesthetic agent at that point. However, sticking probes in brains, probably not cricket. There are other effect sites, though, that are relevant to other aspects of the effects of these anaesthetic agents, like the myocardium or smooth muscle, because it influences blood pressure and myocardial contractility.

So we have to fudge surrogate markers of this concentration in the brain. And to get there we have to think about what concentration of anaesthetic agent is in the alveolus, the alveolar concentration. It’s important to note that you can imagine at the start of an anaesthetic, the alveolar concentration is going to swing around quite a lot as plasma hoovers up agent from the alveolus as blood goes past. However, this would settle over time as you creep towards that steady state equilibrium that we talked about in our previous Volatile Compartments podcast.

End-Tidal Concentration Measurement

02:58-04:03

How do we measure the alveolar concentration? Well, we can’t stick a probe down someone’s lungs to measure the concentration. Again, probably not cricket. So we’re stuck taking a further step back from the site we want to measure, because as we know, more invasive things are more accurate, and less invasive things are classically less accurate, but there’s an appropriate balance to strike when you’re putting probes in brains or in lungs. Not so good.

So we measure the end-tidal concentration of anaesthetic gas. This will generally fairly accurately reflect the alveolar concentration of anaesthetic agent when it’s met that equilibrium we’ve just mentioned. And it’s end-tidal, because if it were the start of the expiratory phase that you were measuring, you’re going to be measuring mostly dead space, which probably contains the concentration of anaesthetic gas in your anaesthetic circuit, and you would be quite the lemon to presume that that reflected the depth of anaesthesia your patient was in. So we don’t want to be a lemon.

And this measurement, end-tidal concentration, is where MAC comes in.

MAC Values for Different Agents

04:03-04:57

MAC minimum alveolar concentration is a bell curved research-based number that is particular to the anaesthetic agent in choice, i.e., sevoflurane, in a standard adult, a sort of thirty to forty year old. An end-tidal sevoflurane concentration of 2.2 yields a MAC of one, i.e., if you were to put a slice across their belly with nothing else on board, half the time they’d wriggle.

This is different with different drugs. Isoflurane has an end-tidal concentration that achieves MAC of 1.2, halothane 0.75, desflurane 6.6. You need quite a bit more desflurane in someone. There are other types of MAC, which we’re going to get on to later.

Wash-In Curves

04:57-05:59

Another thing that’s probably going to get bandied around as you study is this concept of wash-in curve. This is a delightful graph that you might need to learn. X-axis is your time in minutes of administration, and the Y-axis is the fraction in the alveolus (FA) over the fraction inhaled (FI).

You can imagine that the FA to FI ratio would only really get to 1 in a very, very equilibrated patient. If you weren’t losing gas to scavenging, if the patient wasn’t mopping up and cleaning up a bit of that sevoflurane, it would take a very long time to get to one. But you can get relatively close to one over time.

This graph is a good way of demonstrating the rate of uptake and the volume that you could possibly fill the patient with sevoflurane, or desflurane, or halothane. Think about that in a volume of distribution-y manner. Going to get onto that, don’t worry.

Partial Pressure

05:59-06:56

Another joyous set of definitions that are important concepts to understand and actually confuse the crap out of me to start with. Partial pressure. So this is the pressure within a system exerted by a component within it. It’s easiest just to think about the atmosphere here.

So, standard atmosphere at standard temperature: 101.325 kilopascals at 15 degrees Celsius. And we know that there’s about twenty-one percent oxygen in this atmosphere. So in this simple system, the partial pressure of oxygen is twenty-one kilopascals if the air is dry.

Now, if there’s water vapour lurking within this 101.325 kilopascals because the water vapour’s muscled on in and it’s not a dry system, then actually the partial pressure of oxygen will end up being less. This is a concept elaborated on in the alveolar gas equation, which is relevant to anaesthesia in intensive care medicine, but something I’m not going to cover yet. Too far. Too much.

Blood-Gas and Oil-Gas Coefficients

06:56-07:59

Blood-gas coefficient is a ratio of how readily soluble something is between its phase in gas and its phase in blood, i.e., how much can dissolve into it. Do remember that there’s lots of things floating around in plasma, for example, nitrogen, CO2 and oxygen. Oxygen and CO2 are somewhat bound and dissociated into red blood cells, but there’s a dissolved fraction in the plasma itself. That also bears out for dissolving anaesthetic agents into people’s plasma, so it can be transported off to their brain.

The last thing to define before we get into the meat of everything is the oil-gas coefficient. This is much like the blood-gas partition coefficient, but it instead balances between how soluble in a gas state versus how soluble this anaesthetic agent is in an oil. The oil actually used is olive oil, interestingly enough, and they just use that as a marker for how readily able this agent is dissolvable in someone.

Review of Definitions

07:59-08:27

So there’s a bucket of definitions there. We’ve talked effect sites, alveolar concentration, end-tidal concentration, MAC, and then elaborated a little bit on partition coefficients, particularly the concept of partial pressure and the oil-gas blood-gas coefficient, and I’ve waffled a bit about wash-in curves.

Going to talk in a little bit more detail about partial pressure, the blood-gas coefficient and the oil-gas coefficient, and then we’re going to get into the meat of things, which is what really is MAC? And you’re going to be blown away with how delightfully exciting that is.

Partial Pressure in Detail

08:27-10:27

So, just to get into partial pressure a little bit further, we’ve mentioned this concept that the partial pressure is the pressure exerted by one singular component within a system. In air, where you’ve got oxygen and nitrogen and a titchy bit of CO2 and some other noble gases floating around, if you were to take all those other gases out and just retain one, then the pressure that would exert on your system is reflected in the system overall.

So if you’ve got 21% oxygen and you took everything else out and then measured the pressure again in that system, the pressure would then be 21 kilopascals in a system that was originally 101 kilopascals.

So this concept bears out somewhat in the pressure exerted in a liquid and also the interface between a gas and a liquid. So we’re now going to imagine a system. We’ve got a 200ml container, and within that, there’s 100 millilitres of plasma, and above that is a mix of 100% oxygen with ten percent volatile. So really, it’s ninety percent oxygen, ten percent volatile.

If you leave that percolating around, eventually it will settle into an equilibrium, whereby some of that volatile will dissolve into the plasma, some of that oxygen will dissolve into the plasma, but also whatever’s lurking in the plasma as a gas would dissolve out, i.e., nitrogen would eke out of the plasma and into that gaseous space, as would the CO2 and anything else that’s lurking.

Partition Coefficients Explained

10:27-11:14

Now in a very simple world you could imagine that the ratio might be one to one. However, it’s not one to one, because some things prefer to be dissolved and other things prefer not to be dissolved. This ratio, this balance between the two states, is the partition coefficient. And that’s what we’re talking about when we think about the blood-gas coefficient and the oil-gas coefficient: the partition between these two states.

So what is blood-gas partition coefficient? It is how soluble in the blood your volatile of choice is. It’s important to bear in mind that just because you can dissolve a lot into the blood doesn’t necessarily mean that you get a load coming out of the blood and into the tissues that this blood is being pumped past. Equally, this is very different to the amount of anaesthetic gas you’ve managed to soak into the person over the course of an hour-long anaesthetic.

Blood-Gas Coefficient and Clinical Effects

11:14-12:00

In the exam, if they’re asking you about volatiles, they’re probably going to want to ask you about blood-gas coefficients or oil-gas coefficients and how they bear out the clinical thing in front of you.

So, blood-gas coefficient relates to the onset and offset time in your patient. I imagine this as if it’s not very soluble in blood, but your alveolus is chock full of gas and some of it’s got to go somewhere, it gets forced into the blood, but it immediately wants to hop back out into whatever organ or tissue the blood goes past, because it just doesn’t want to be in the blood, but it had to, because the alveolus was just full.

So things that are less soluble from a blood-gas coefficient perspective equals faster onset time. Therefore, this is one compartment that you have to fill with which to then exert a pressure into the compartment you’re aiming for.

So if something’s terribly soluble, then it’s a really big puddle you’ve got to fill up before some of it might think, “Oh, bloody hell, this plasma’s absolutely full. I need to go in the brain now, ‘cause I can’t get into the alveolus ‘cause that’s full.”

Oil-Gas Coefficient and Potency

12:00-13:40

In contrast, oil-gas doesn’t have any real particular influence on onset and offset time in quite as literal a manner. Generally, if something is highly lipid-soluble, then it quite joyfully will hop into fatty tissues. But if it’s terribly lipid-soluble, it means that pool the patient is very large, so you can pour lots and lots and lots of agent into them.

There is generally a correlation between lipid solubility and the potency of the anaesthetic agent. So things that are very soluble tend to have a more potent effect, meaning you need lower end-tidal concentrations to achieve MAC. Halothane: MAC of 0.75 end-tidal, which is really low. It’s very soluble, 220, versus sevoflurane’s solubility, which is 47 or a quarter of that.

Once upon a time, this lipid solubility was conflated with the anaesthetic agent’s working mechanism. That is, if enough dissolved into some fatty tissues, it would disrupt the fatty tissues and mess with the neuronal communication, leading to anaesthesia. This has been disproven. And actually, we know that these anaesthetic agents seem to work on GABA.

I think about this in that if something is super soluble in fat, there’s a really big space to fill the patient up. They’re probably going to take longer to wake up if they find themselves eeking out a little bit of this anaesthetic agent into the plasma, which then eeks off into the brain and keeps them anaesthetised. Covered this before, so I’m not going to go into more detail.

It was important to cover all that again because it’s a very core concept and something that is examined on really often.

What MAC Really Means

13:40-14:26

So going into MAC. What is really MAC? We’ve spoken that a MAC of one reflects that 50% of your standard population who just have volatile on board will not wriggle when you slice into them and generally by extension they’re not going to remember stuff. That’s quite critical. But what does that MAC of one really mean?

Well, that is your ED50. It’s smack bang in the middle of your bell curve of wriggly patients, and therefore you can presume that a MAC of 1.1, which is one standard deviation from the mean, will mean that sixty-eight percent of patients will not wriggle, and a MAC of 1.2 means that 95% of your patients will not wriggle.

Different Types of MAC

14:26-15:53

Are we really just obsessed with patients who wriggle? Well, whilst the surgeons seem to panic as soon as they say, “Oh, the patient’s moving,” we know that really the most important thing is that the patient doesn’t remember.

And there are, in fact, loads of research and studies that try and identify how much gas you need on board to make sure that someone doesn’t remember. This is called MAC amnesia, and it’s generally about 0.25 MAC. And this is a MAC of an anaesthetic agent that will suppress memory formation for a noxious stimulus.

Interestingly, and somewhat contrarily, you have something called MAC awake, and that is, fifty percent of patients won’t open their eyes if you kindly ask them to, and it’s about a third of standard MAC, so 0.3. And you’ve seen MAC awake a lot in that sometimes patients with a MAC of 0.3, when you’re trying to wake them up, will open their eyes and then close their eyes again, and some just don’t, and they’re flat as a pancake.

And then you’ve got MAC BAR, BAR standing for Block Adrenergic Response. This is about 1.7 MAC, and will obtund any response to your surgical stimulus, i.e., no heart rate increase, no blood pressure increase. It’s quite heavy-handed to have a MAC of 1.7 to achieve that.

There are also some suggestions, although it’s a bit more rule of thumb, that you need a MAC of at least 1.3 to intubate a kiddie, and a MAC of like 3 to intubate an adult. I’m sure if you’ve ever attempted either you realise that there’s coughing, there’s spluttering, there’s bucking, it’s generally very crap and doesn’t really bear out in reality.

Why Not Use Lower MAC?

15:53-17:03

So it sounds like making sure a patient doesn’t remember only requires a scant whiff of volatile anaesthetic relative to the heavy-handed approach we are currently throwing around. Why doesn’t everyone adjust beneath their tyres to a depth of two standard deviations above MAC awake? Waste less gas, have less side effects?

Good question. And that’s because you may find yourself stuck in Guedel’s stage two of anaesthesia, which is the excitatory phase, where you’ve got much higher odds of laryngospasm with your airway, your patient’s going to wriggle a lot more, and they’re going to get a bit tachycardic and hypertensive. It just looks a bit ugly, doesn’t it?

It’s also going to leave you with quite sparse room for error. And, as I’m sure you think and know, if you have an accidentally aware patient, it’s bad news for everyone involved, and particularly you and the patient.

So what could we do about this? Bearing in mind, these are measurements with no other agents on board.

Effect of Opioids on MAC

17:03-18:02

Cahalan et al. found that MAC and MAC BAR diminish rapidly with opiates on board. It’s important to note that MAC awake did not really change very much with or without their fentanyl infusions they were using. So it goes to show that that ability to be awake and form memories is less impacted than the obtunding of surgical stimulus and the reduction in patient wriggliness that comes about with using opiates. It kind of creates a bit of a hard floor that you don’t want to cross, doesn’t it?

It’s difficult to demonstrate whether or not exceptionally stimulating surgery also tips you closer towards consciousness and memory formation. You could say, “Well, they’ve got enough gas on board, they can’t make memories.” But also, you could think, “Well, if it’s really painful, if they’ve had a thoracotomy, for example,” then it might stimulate them to the point where they’re awake enough to form memories. It’s better safe than sued.

Research on Memory Formation

18:02-18:39

Some more academic anaesthetic boffins, Dwyer and colleagues, found that a MAC of 0.6 plus of isoflurane completely impaired memory formation, both implicit and explicit.

So there’s a number of different subcategories of MAC that might help you more nuancedly anaesthetise people and decide how much other opiate you want on board and how wriggly you’re going to accept the patient. If someone’s doing eye surgery, you don’t want them wriggling, but if they’re clobbering someone’s hip with a mallet and a chisel, then a bit of wriggling probably ain’t the end of the world.

Clinical Application and Personal Approach

18:39-19:31

How do I think about this overall? Well, sticking to MAC of one will keep the patient and your boss quiet, especially if that’s their perhaps rudimentary approach. No one’s going to tell you off for everything at MAC of one. The patient might take a while to wake up, but it’s not the end of the world. It might be that the boss is actually a lower MAC person.

I’ve recently been involved in a paediatric laparotomy where the end-tidal sevoflurane in about a 10-year-old was 1.1. They had had six mics per kilo of fentanyl. The MAC was about 0.5, and the patient was fine, didn’t make any memories, naturally, and weren’t wriggling too much because they had paralysis on board.

So, I think for me, having re-explored all this, I might be happier cruising at 0.8 MAC than I was before, especially in the knowledge that I’ve fed the patient paracetamol, non-steroidals, opiates, and then thought about the fun stuff like magnesium or clonidine or dexmedetomidine.

Important Caveats

19:31-20:09

An important counter note to this obtunding of MAC BAR and MAC comparative to MAC awake is that in those studies, they used fentanyl TCI at quite high doses compared to our measly one hundred mic fentanyl induction dose.

Importantly though, you’re naturally going to maintain a volatile concentration that is well in excess of MAC awake in order to stop them forming new memories. And if they’re hypertensive and tachycardic, then you know that you probably need to give them more opiate.

Conclusion

20:09-20:38

I’m going to do a separate episode comparing and contrasting volatile anaesthetics because it’s too much for one. I hope you enjoyed listening today. Please tell all your mates.

If you found it useful or awful, please like and subscribe and rate the show. Definitely check out the show notes for those diagrams and the detail of this content. It is a bucket of content to get to grips with. Keep working at it and you will get better, faster and stronger. It is vital to keep your interest alive for the science that we’re covering and not overcook yourself. You will be amazed by what you know come exam day. Don’t freak out, keep studying.