Ep 7 – Compartmentalised Volatiles and a brief jaunt with Sevoflurane

How Do Volatile Anesthetics Behave in the Body?

Volatile anesthetics distribute into various body compartments, affecting their onset and offset times. Factors like blood-gas partition coefficients and tissue solubility influence their pharmacokinetics and clinical effects.

This diagram describes anaesthetic circuits from a drug compartment perspective

Model answer and questions

What influences the onset time of a volatile anaesthetic agent

Physical (somewhat)

• Concentration delivered
• Alveolar Minute ventilation
• FRC size,
• Cardiac output
• Presence of second gas
• Circuit leaks / Circuit Size or primed /

Raise MAC requirement

• Young age
• Hyperthermia
• Hypernatraemia
• Elevated catecholamine state
• Chronic opioid use (and abstinent for surgery)
• Chronic alcohol use (and abstinent for surgery)

REDUCE MAC (old,cold,pregnant)

• Increasing age (old)
• Pregnancy
• Hypothermia
• Hyponatraemia
• Anaemia
• Hypotension

Drugs: Synergistic agents

• Acute alcohol intake (being drunk)
• Acute intake of CNS depressant drug: opioids, benzo, TCAs
• Lithium 
• Lidocaine
• Magnesium
• Clonidine / Dexmed

Anaesthetic Agent Specific

Partition coefficients

A low B:G coeff as the agent doesn’t really want to be in blood and as it cant escape back out into the highly concentrated lungs it squeaks out into the tissues. So onsets faster

All these factors influence the wash in curveof drug from 0 concentration in the human to equilibrated concentration.

This takes us into the core concept to understand and observe whilst using volatiles in your early anaesthetic years

The Anaesthetic Circuit!

This is a real hands on compartmental model which you can indirectly see, measure and fiddle with!

The 'Compartments' = The Circuit up to the airway device, the airway device, its deadspace + the patients dead space + the lungs + the blood + the brain/heart other organs + muscle + fat.

What do you see at the start of a case,  well early on the patient soaks up a bunch of volatile as you hose it in down a nice steep concentration gradient (lots in the circuit + not much in the patient) you are generally running a higher concentration and then at a point, you have to step down the dose going to the patient – you’ve filled up the easily filled bits of them (blood, brain, muscle (the more vascular bits) and then your cruise for a bit longer at this reduced rate , do your notes stare at the appendix being flopped about, and then you notice the concentration  is creeping up in the circuit, Now you’ve filled their fat so now you can eek down to a dose rate that matches the clearance in agent in the person (sevo = 3-5% hepatic deflourination unless they are enzyme induced – i.e smokers, booze, isoniazid cyp 2EI) + the losses in the circuit to the scavenging and CO2 Sampling  / any leaks there may be.

At this point you can (turn your flows all the way down, tighten up the alarms for fio2 and ET sevo  and sit smugly knowing you aren’t wasting a drop. In the uk we don’t worry very much at all about the  compounds that might appear due to soda lime (Compounds thoughtfully labelled ABCDE) and get the flows to 300-400ml/min of fresh gas. (or even less as long as you watch the bellows don't collapse)

Then you decide to turn the ship around and head for the light, so you want to achieve a significant negative concentration gradient turn the sevo off, ramp up the flows to clear the circuit, and if they are not breathing you may as well hyperventilate them.

An apnoeic patient will not wake any time soon as weve learnt that only 1/20^th of the sevo is mopped up by the liver. The lungs are the route of elimination here.

So we want to clear the circuit, and swap the gas out of the lungs plenty in order to maintain a negative gradient to speed things along.

And youll think youre the king of the world their mac has gone from 1.1 to .6 with speed and down you go! But then, despite continuing to do what you do you get to 0.2 mac and everything grinds to a stop.

You’ve cleared out the easy compartments, and now the sevo is eeking into the blood slowly, at sort of the same speed you filled up those fat stores before you hit cruising altitude, they patient is hopefully doing the breathing themselves now.

Unfortunately this creeping trickle of Sevo from Fat to blood seems to be Enough to keep most patients asleep. Because as it eeks into the blood, it also equilibrates with the brain. Dam !

The fun is not yet over you can hyperventilate someone at this depth and you may increase the plasma clearance of sevo enough to drop the CNS concentration and get the patient to stir and wake,

The pickle here is once you’ve whipped out that airway, and the patient returns to their basal spontaneous breathing the sevo oozes from the fat, and the conscious state diminishes as plasma sevo mischief /concentration increases, oops. this may be your problem or recoveries problem (soon to be yours) depending on the individual patient.

Breaking up how volatiles possess and dispossess patients is an excellent way to think compartmentally......

I find this an excellent way to think about pharmacokinetics and introduce yourself to compartmental models. It is worth repeatedly looking at the patients eyes as they emerge as they do a variety of entertaining things, as various bits of brain get progressively less anaesthetised.

Yes you could even split the brain into compartments based on their respective perfusion and or susceptibility to anaesthetic agents, this must occur to some degree as why else would you get different signs in the eyes at different depths / there is some evidence to suggest that inhibitory interneurons are more susceptible and that’s why they get all excitable/wriggly with gas induction and why you might get brief epileptiform activity with propofol or etomidate.

• A side note – pulling a tube/LMA at the wrong time in this journey to waking may cause laryngospasm, ive done this when rolling a patient post bum abscess with an iGel in, its certainly important to spot this and handle it calmly.
• Its important when dropping flows to monitor your respective concentrations of o2 / Anaesthetic agent/CO2.
• Achieving a rapid descent into anaesthesia with volatile gets riskier as the patient gets frailer.

Application clinically.

Clinically, you now know why you get stuck in MAC 0.2 land and have a conceptual model to understand why some patients might be anaesthetised more quickly than others.

Summarise

Try and apply this as its happening, and think about the flows of volatile in and out of the patient. This will put you in good stead for understanding TIVA models as well as cementing the volumes of distribution learning from earlier.

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"Thanks for listening guys... Every day you are getting better at this. Take it day by day, don't overcook yourself, don't freak out, and keep studying!"

Podcast Information

Transcript Compartmentalised Volatiles and a brief jaunt with Sevoflurane

Introduction and Podcast Overview

00:00-00:37

Hello and welcome to Gas, Gas, Gas, your one-stop podcast for the FRCA primary exam. This podcast will fill your brain with information. Listen to it, think about it, and check out the show notes on the website. There you will find the core diagrams you need to be able to draw and describe for the exam. This podcast can squeeze into your day - listen while you're driving to work, cooking dinner, maybe when you're on call, or in the gym. Eventually, the revision is going to end, but for now, expect facts, concepts, model answers, and the odd tangent. Remember to rate and follow the show to hear much, much, much more.

Topic Introduction: Volatile Anaesthetics and Compartmental Models

00:37-01:22

Hello, everyone. This is James at Gas, Gas, Gas. Welcome to another episode where we're going to discuss volatile anaesthetics a little bit and then consider how administering them to achieve and maintain and emerge from anaesthesia can be compared to the ever-exciting compartmental model.

I think this is a good way to open the door to thinking about pharmacokinetics for TIVA, and also it's a model that you can actually directly fiddle with and manipulate in order to get more of a feel about A) how volatiles work, but B) to get your mind around the concepts of multiple compartments and the interactions that occur within them that subsequently yield the effects that drugs have on humans.

Sevoflurane Overview and Comparisons

01:22-02:22

So a little bit more about sevoflurane. In the UK, it seems to be the most commonly used volatile inhalational anaesthetic. It has friends, chiefly isoflurane. It's cheaper, but it takes longer to wear off. It's also a little bit more irritant and smells not so nice, so not really your best choice for a gas induction.

Its other friend, which was perhaps far more commonly used a few years ago is desflurane. Well loved by the archaic dinosaurs of multiple departments, I'm sure. Wears off a teensy bit quicker, but may or may not kill polar bears - its equivalence in CO₂ is astronomical, and you have to use more of it for the same effect.

I think generally on paper, if you do all the maths, sevoflurane at low flow anaesthesia rates works out to be the least bad of isoflurane, sevoflurane, desflurane.

Volatile Properties and Partition Coefficients

02:22-03:21

When you're thinking about volatiles, you have the delight of multiple parameters and numbers which influence how it behaves in a physical environment, i.e., when it boils, when it might become a liquid, what its saturated vapour pressure might be. And then there's some more words: blood gas partition coefficients, i.e., how it behaves between lungs and blood, or oil gas coefficients, which I imagine this is how it behaves between brain and blood, and those are important numbers, and you have to get a bit of a feel for how they behave in relation to one another, i.e., is desflurane more oil gas partition coefficienty than sevoflurane? That's stuff you kind of have to go and learn to have a ranking in your head of what's what.

Model Answer: Factors Influencing Onset Time

03:21-06:13

Now for that time in the podcast where someone asks us an awkward question and we have to think about how to approach it.

"Hello, doctor. This is your pharmacology viva. What influences the onset time of volatile anaesthetic agents?"

"Ah, okay. There are many factors that influence the onset of volatiles. I break this down into circuit and ventilatory factors and then patient factors."

Circuit Factors:

So considering the circuit, onset time is reliant on the concentration of anaesthetic delivered to the patient, as well as the amount of fresh gas administered to that circuit. It's dependent on the size of the circuit and presence of any leaks within that circuit, i.e., the fewer leaks and the smaller the circuit, the faster the onset time.

Patient Factors:

It's also influenced by patient lung factors, so the size of their FRC, the alveolar minute ventilation you're delivering, i.e., have you minimised dead space, as well as the patient's cardiovascular state, i.e., the cardiac output. It seems almost contradictory in that a lower cardiac output actually yields a faster onset of anaesthesia. This is considered due to slower flows across capillaries facilitates diffusion of agent from plasma into effect site.

Another factor to consider with the circuit is the presence of a second gas that would facilitate uptake.

Patient Condition Factors:

Then I like to think about factors within the patient that may influence the amount of agent required to achieve depth of anaesthesia. Factors which increase the amount of anaesthetic required: on a spectrum the younger the patient classically the more agent is necessary; if they are in an anxious or increased state of catecholamine activity or sympathetic nervous system activity; if they are hyperthermic, hypernatraemic, or if they are a chronic user of alcohol or opiates and their basal neuronal excitatory state is higher because they've abstained from those two agents for their anaesthetic.

Situations that reduce MAC requirements are almost the opposite here. So older patients need less agent. If they are hypothermic or hyponatraemic, if they're pregnant, as well as if they are critically unwell, i.e., hypotensive, septic, their anaesthetic requirements are less.

And also if there's presence of synergistic agents on board, so if the patient's acutely intoxicated or has taken a number of opiates, benzos or tricyclic antidepressants, you can find that they require less anaesthesia.

Pharmacological Adjuncts:

There are a number of drugs that we may introduce to the patient that would also reduce MAC requirement or anaesthetic dose requirement. Classically consider these as sedatives, so opiates, alpha-2 agonists, as well as magnesium and some drugs that they may be prescribed, like antipsychotics and lithium.

Agent Properties:

And then there are factors based around the agent that you choose. Some anaesthetic agents have faster or slower onset times. This is governed classically by the blood gas coefficient - the lower the better, and the oil gas coefficient, which the higher the better in the context of rapidity of onset.

Deep Dive: FRC and Onset Time

06:13-07:33

"So, Doctor, you mentioned that FRC plays a role in onset time of volatile anaesthetic. Why is this?"

I like to think about this as a situation with volumes and concentrations. So in a patient with a high FRC - functional residual capacity - you find yourself in a situation where you have a greater volume of lung that you need to maintain a high concentration of anaesthetic agent in. This is critical because the concentration of anaesthetic agent in the lung could be sometimes considered equitable with the concentration in the brain.

Now this is perhaps slightly not accurate during induction of anaesthesia because of the rapidity of uptake from the lung and deposition into the target tissues. Having a smaller functional residual capacity means that the total volume of lung that you are seeking to achieve an anaesthetic agent concentration in is lower. Therefore, you can maintain a higher concentration and achieve onset of anaesthesia quicker.

Partition Coefficients Explained

08:12-11:16

I'm going to focus on a few things, ones that bamboozled me. Definitions of things: blood gas partition coefficient. I imagine this as the willingness of the sevoflurane that you've got into someone's lungs to stay in the plasma. And this begins to illustrate compartments. We're going to describe three compartments briefly here: lung, plasma, effect site brain.

If you have a low blood gas partition coefficient, the sevoflurane does not want to be in the blood. It hates its life when it's in there and it's really miffed. But it has no choice but to go in the blood if the lungs are full of 8% sevoflurane and there's 0% sevoflurane in the blood. So it has to go there.

However, at the first opportunity, it wants to leg it, so it's dumped in the blood and it leaves the lungs. And now that plasma full of 8% sevoflurane, although it'll be a bit less because there's a concentration gradient removed, remember, is being pumped off around the rest of the body mucho rapido, and it's going to wang past the brain, kidneys. There's going to be some perfusion of the heart through the coronaries, perfusion of the lungs through those bronchial arteries, and other important tissues that are vascular. The more vascular you are, the more blood you get from that cardiac output squeeze - that stroke volume.

So now that blood full of mostly sevoflurane has been fired off to the brain and the brain has no sevoflurane in it, and the sevoflurane is like, "Thank hecking God, I don't want to be in this blood. I'm much happier in a bit of brain," and it goes into the brain. This is why having a low blood gas partition coefficient, i.e., having lower solubility, yields a faster onset because it just doesn't want to be in there.

Oil Gas Partition Coefficient:

The next partition coefficient is the oil gas partition coefficient. This is the ability of the agent to dissolve into fat. Now you'd think if it dissolves into fat - great. The more it wants to jump into the brain, which as you know is quite a lot of fat, myelin, etc., floating about, the faster the onset time. And it is: a higher oil gas partition coefficient, i.e., the more lipid soluble the agent is, the faster the onset time is because it wants to get out into tissues.

The trouble arises when that partition coefficient is so high, you basically fill that patient with agent, and then it's got to come out again. You can use the oil gas coefficient as a surrogate for potency, i.e., the lower that number, the less the potency is.

You can see this working when you compare desflurane and sevoflurane. So desflurane, oil gas partition coefficient twenty-nine, sevoflurane eighty. So to achieve the same depth of anaesthesia, you need proportionally more desflurane than sevoflurane. And you can see this because the MAC, i.e., the end tidal sevoflurane concentration required to keep fifty percent of patients wriggle free with a standard incision: the MAC of desflurane is 6.6% of their expired gases, whereas the MAC of sevoflurane, 1.8%. So you need much more desflurane to achieve the same depth of anaesthesia because the brain soaks up plenty. If the brain soaks up plenty, getting the concentration high in the brain is harder, because more of it fits.

Compartmental Model: Gas Induction Case Study

11:47-17:59

Now I'm very excited to talk to you about the delights of a real hands-on compartmental model that you can fiddle with as an anaesthetist to your heart's content. You can measure it through surrogates and truly begin to understand A) how drugs get into people, and B) how they come back out again. Super cool. One of my favourite things to think about.

And that is the patient who is induced, maintained, and emerges from a volatile anaesthetic. And we'll take the example of an eight-year-old child having a gas anaesthetic for dental anaesthesia, because that's probably where you're going to be doing a number of gas anaesthetics.

The Compartments:

So I like to think about this as multiple compartments all chained together that yield interesting things. These are the circuit, so your circle circuit. Sometimes you might be using a Mapleson D to induce your anaesthesia, or a Humphrey ADE if you're really feeling cool and old fashioned. So you've got a circuit, and I consider this volume or this compartment up to the airway device, and then I think about the airway device, i.e., your face mask, then it might become your iGel or tube, and consider the dead space in that device plus the patient's dead space.

Next compartment, the patient's lungs, naturally. Next compartment, the patient's blood, and also you need to think about how much blood is going past those lungs, and then their brain, their heart, kidneys, liver, their muscle, and then their fat space.

Tommy's Gas Induction:

So here we are. We've got little Tommy. Tommy has come in and he's taken one look at that cannula, and he's on the ceiling, but he needs his teeth out 'cause they're awfully rotten. Mum agrees that, yeah, let's get on with it and do a gas anaesthetic and we start wafting some gas at Tommy.

And you might be thinking we're in the nineteen fifties and we're going to clamp that mask on Tommy's face, but we're not. We're going to waft that mask at him with maybe some nitrous, because we hate polar bears, and subsequently some anaesthetic gas.

Factors During Induction:

Number of factors influencing onset time here. If you're wafting and you're not getting a seal, then they're going to get less dose. So you're filling the room with nitrous and volatile. So you need to think about the atmosphere very adjacent to that child's face, and go fairly high on the flows. It'd be sensible to open with nitrous and bamboozle them a little bit, and then introduce the sevoflurane slowly. As you do this, you can then slowly creep that mask closer, get that mask over their face, and off we go to sleep.

Now, if Tommy's wailing and howling and starts crying, taking huge lungfuls, that increases the dose, but also increases their cardiac output because they're upset and increases their stress response because their sympathetic nervous system activates, they're terrified, which slows your onset time. Tricky.

Achieving Sealed System:

So now we're going to assume that we've got a sealed face mask attached to the patient, and now that they're exhaling gases that also contain sevoflurane and nitrous, that also returns to our circle circuit. We now can increase the concentration within our circuit compartment and speed up our onset because we can actually reuse some of that agent and know that we're delivering a higher concentration of agent to the child.

Excitatory Phase:

We've got a face mask, so now we're just thinking about the dead space within that mask cavity and the dead space between his lips and his alveoli. And he keeps chuntering away breathing, because they naturally tend to breathe when you do a gas induction. However, his breathing then changes and it becomes quite rapid, quite shallow, and his airway gets noisy because he's in that excitatory phase, whereby he's getting some agent, it's gone to his brain, it's anaesthetised some of him, but not all of him, and he's making that descent into the depths of anaesthesia.

Sometimes you might think about an airway adjunct at this point, but they're excitable. You could cause laryngospasm and make your life very awkward, especially when you've not got a cannula in little Tommy currently. So you've got to grit it out, sat there knowing that their shallow, rapid breathing means that actually they're just ventilating a lot more of their dead space and a lot less of their alveoli, which isn't helpful, but you've just got to grit it out and keep going with high concentration agent.

Deep Anaesthesia:

Then he dips into that lovely deep anaesthesia. His breathing slows down, his airway gets less noisy, he gets more relaxed with lower tone, and you either stick an airway device in at this point, or cannulate and propofol and stick an airway device in.

So now we know that we're in a state where we've got good concentrations in our circuit, good concentrations in our lungs out into the depths of his alveoli, and likely sufficient concentrations in his noodle that are giving us a decent depth of anaesthesia.

However, whilst he's got some blood going to his brain delivering anaesthetic agent, he's also got blood leaving his brain carrying anaesthetic agent elsewhere, and the brain will want to equilibrate with the rest of the body. If you were to stop delivering agent at this point, just give them oxygen, they will actually quite rapidly wake up, because they're going to clear agent through their lungs back into the circuit, they're going to pick up high concentrations of agent from their brain and distribute it around to the rest of their body, i.e., we're dropping the effect site concentration.

And they're young, 'cause Tommy's having his teeth out and he's ten, so actually, he needs quite a lot of anaesthetic agent to keep him asleep. We don't want that. So you have to keep maintaining a fair dose of volatile at this point in time, knowing that there's lots of re-equilibration of agent that's going to occur, and you want to land into that nice sweet spot whereby you're giving just about enough agent to maintain anaesthesia, can get your flows down and feel very smug. Admittedly, if it's dental, it's probably quite a short anaesthetic.

Compartmental Model: Maintenance Case Study

18:02-26:08

Right, so let's go to another case and talk about cruising altitude with volatile anaesthetics. So here we are, it's eight p.m. You've just finished your dinner and you're off to theatre, your first appendix, and they're a fit and well twenty-four-year-old lad.

And you've decided propofol induction with a bit of fentanyl maintenance with volatile and then wake-and-wake at the end and you're going to intubate them. So you've given them propofol, you've given them fentanyl, you've paralysed them, you've conducted some sort of modified RSI, and you've intubated them, and you've whacked up the sevoflurane.

Initial High Concentration Phase:

You're in the anaesthetic room and you're thinking, "Oh, should I put temperature probe in? Do I want another cannula?" And all those sorts of things. We're going to assume that you've gone for 5% sevoflurane, you might have gone for 6%, with maybe a fresh gas flow of eight litres. And you might tweak it down so it's not all oxygen, but some air as well, so you avoid the harms that pure oxygen have to the lungs.

What do you see? Well, the patient starts soaking up that volatile, like you might expect. Hoovering it up, because you've got a lovely concentration gradient between the lung and the plasma, and you think, "Tickety boo, great, let's go into theatre."

Transport to Theatre:

So you turn off the circuit, turn off the fresh gas flow, turn off the sevoflurane, and off you go into theatre. And then you get into theatre having thought, "Well, you know, my end tidal's 3.5, my MAC was one and a bit. Yeah, I'm fine." And you get them into theatre, attach them to the new circuit, turn on the gases to those rates and concentrations, and actually you realise your MAC's 0.6, your end tidal is 1.8, and you're thinking, "Oh God."

This is because you've got a fit young gentleman who has re-equilibrated between his various internal compartments during that trip from anaesthetic machine number one in the anaesthetic room to anaesthetic machine number two in theatre. We're recalling that when you are giving a nice concentration, a lot of it goes to the brain, and then often a portion of that's blown back out, a portion ends up in other tissues in the body, like muscle, and some is eking out into the fat, although only a little bit, because there's a sort of a fixed rate of how much ends up in the fat, depending on how much is in the plasma and the cardiac output.

Re-establishing Anaesthesia:

So you sorted that out, you cranked up the sevoflurane, you made sure no one was poking and prodding the patient too much. And if you find yourself in this situation and if the MAC is very low, you could give a little bit of extra propofol just to make yourself happy. We're back to a sensible situation. The surgeon's scrubbing up, you've tucked the patient in, connected them all up, checked the monitoring, and you're happy.

Flow Reduction Effects:

And you're running your sevoflurane at 4%, and you've come down from your eight litres of gas flow to your four litres of gas flow. You try and start writing your notes because you're desperate, you don't want to forget anything of what you've done, and you look up, and there's another dip, and this is because you're delivering the same concentration or maybe a bit of a lesser concentration of sevoflurane, but I like to think about it: 4% of eight litres is quite a lot of drug, whereas 4% of four litres is less drug.

You need to titrate this to the individual patient because they're all different shapes and sizes with different cardiac outputs, and you tweak up the concentration, knowing that you'd rather not use the fresh gas, and hopefully, you can find that sweet middle ground. His MAC is still one, and you're happy with that.

Compartment Filling:

So you start writing your notes proper, the surgeon's fiddling around, and they've insufflated the abdomen, and it's all fine. And then you look up and you realise that the patient's got a MAC of one point five. And you're like, "Hang on, what's going on there?" You've done a very good job of filling the patient. You've filled up their brain, their heart, their lungs, their muscle stores, and you've started filling up their fat stores.

And now you're eking agent into their fat, and the rest of it is accumulating in the plasma, which means when they exhale, they exhale a higher concentration, and that is what the MAC is derived from. So you tweak down the flows and you go to 400 mils or so and get back to doing your notes.

Steady State Achievement:

You look up again twenty to thirty minutes time, and that damn pesky MAC is up at one point five again, despite coming down on your flows and presumably delivering the right amount of agent. And this is because at this point in time, and you'll see it, you've actually filled up their fat stores now with volatile, or at least got very near to filling their fat stores. This means that you now have the plasma filling up because it can't, the sevoflurane can't go anywhere else.

So you have to come down even more. You can come down on your concentration. You could edge down your fresh gas flow a little bit further. Patients need at least 250mls of oxygen per minute, and here we are, and they're flopping around with the appendix. It's stuck to the liver, the caecum, and they're not quite sure where it is, so they're flaffing and prevaricating for a reasonable period of time as you're sat at maximal cruising altitude with filled brain, heart, lungs, liver, muscles, fat stores and plasma.

"Great," you think? "I can use very little anaesthetic now because it's all in the patient." And you're right. With sevoflurane particularly, about 3-5% is cleared by the liver, the rest only comes out when you breathe it out. You need to account for any losses in your circuit through leaks or scavenging. And at this point it might be sensible to make sure your alarms are nice and tight so that you can keep your flows low and not miss anything going a bit pear shaped.

Emergence and the Fat Compartment Problem

26:08-28:39

And then the surgeon turns around and says, "Ah, I'm all done." And you're thinking, "Oh crap," because now you know that you've got a patient who is exceedingly full of sevoflurane. And that means they're going to take ages to wake up. So you now need to think about ways to influence the situation in order to speed waking, because you don't want to be sat around for hours, you need a coffee.

Initial Emergence Strategies:

So you turn off the sevoflurane, you ramp up the fresh gas flows. Naturally, you check to make sure the patient's not paralysed, etcetera, etcetera. A number of situations can occur here to think about from a compartmental perspective. So you ramp up the flows and turn off the sevoflurane. So now you're recreating a concentration gradient in the opposing direction. A minimally sevoflurane-ish set of lungs and a highly sevoflurane-filled patient means that it's going to start coming out again.

There are things you can do to influence how quickly that does. You don't want the patient to be inhaling any sevoflurane, so you keep your flows up. You might turn up your respiratory rate and maybe creep up your tidal volumes ever so slightly in order to increase your alveolar minute ventilation. This means that the lungs spend a greater amount of time with a lower concentration of sevoflurane in them, therefore facilitating elimination through the lungs.

Initial Success:

And you think you're doing great because that MAC rapidly starts plummeting. It's pouring down. And you get yourself to 0.2 thinking, "Oh, this is great, actually. Maybe I've got away with it. Patient's going to wake up. Going to get coffee. Going to be great." You think you're king of the world.

The Fat Store Problem:

However, you get stuck at the classic 0.2 MAC. And here is the situation: you have cleared sevoflurane from all the highly perfused bits of this patient. So there's a bit in their brain now, there's a bit in their muscle, but mostly they're fairly empty. They're not completely empty, because we find ourselves in a situation of irritating, equilibrating compartments within the patient. The offender is the fat store chiefly.

This is because it is full of sevoflurane. It might be there's quite a lot of sevoflurane in there. And there is a rate of clearance from that compartment that is slow enough that it's boring, but sufficient enough that it means that you're depositing sevoflurane to the plasma that then gets distributed to the lungs, but also back to the brain, back to the muscle. So this is your rate limiting step, and you can get stuck there for a very boringly large amount of time.

Limited Options:

There are things you could do to try and speed things along, but you need to bear in mind that you've basically got like a depot injection of sevoflurane in the patient, and it's going to keep emptying until it's empty. And the patient's always going to be a bit anaesthetised until they're not, i.e., once the fat stores are empty, the patient is going to wake.

You could hyperventilate them at this point, and you may find that you can achieve a higher elimination rate from the plasma than the clearance from this fat store to the plasma. The patient might stir a bit and you think, "Ah, this is great." Unfortunately, the patient isn't breathing as quickly as you're making them breathe, and they're just going to re-equilibrate back to being dozy.

All patients are different. Some you might be able to safely extubate at this point in time, others you might not. That's the nuance of anaesthesia and emergence.

Clinical Observations and Planes of Anaesthesia

28:39-28:45

Volatiles are a great way to think about compartments. The important thing to know is that there are the excitable phases on falling asleep and waking up that can trigger laryngospasm if you're not careful. We also know that if you're frail and old, giving someone 8% sevoflurane is probably a recipe for quite a lot of paperwork.

And there are things you can do to while away the time while your patient is waking up from 0.2 MAC to awake MAC, and what I like to do is repeatedly look at their eyeballs, because it's quite hilarious. It always makes me chuckle. And you can see them descend from depths of anaesthesia to wakefulness, which is an excellent example of the planes of anaesthesia that you need to learn about - from like dilated, staring ahead, injected looking eyeballs, to squints of convergent and divergent and wonky eyeball natures that then come back to the midline with pupils that are now a bit smaller and a bit more normal looking. It's always funny to look at what their eyes are doing whilst you're whiling away the time.

Summary and Key Learning Points

28:45-29:14

So this is a long one, actually. I might cut some bits out of it, because I've got carried away. But we've talked about sevoflurane. We've compared and contrasted in brief some of the volatile agents, talked about the factors that influence onset, some factors that influence offset, discussed what a gas anaesthetic might look like and how those compartments are behaving then, and then a cruising altitude anaesthetic and emergence and how compartments behave then.

We've also covered partition coefficients, which are important. You've got to learn them. You might even have to learn numbers depending on how you're feeling. And the crux of all this: A) this is a compartmental model that you can actually fiddle with and influence based on the equipment and style of anaesthesia that you choose to apply, and it's an excellent way to think about compartments, which you're going to have to do for TIVA. Fun times.

Conclusion and Call to Action

29:14-29:14

Thank you very much for listening, guys. This is James with Gas Gas Gas and I hope that you're gonna have a nice day today. Enjoy. 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.