Ep.34 – Lidocaine For The FRCA Primary

00:30-02:28 | Introduction and Basic Properties

Hello everyone, this is James at Gas Gas Gas. This is another episode of the Local Anaesthetics series, and I’m sure you’ve all been super excited, absolutely waiting for it, because today we are talking lidocaine. Before we get into the bulk of the show, we’re doing a series on all the local anaesthetic agents. We’ve done an intro to local anaesthetics, we’ve covered bupivacaine, cocaine, and the last episode was prilocaine. So if this is your first time listening to Gas Gas Gas, make sure to go back and touch on that introduction to local anaesthetics episode as well. It really does set the scene for everything you need to get on with.

Now, if you’re finding this show absolutely riveting and you think, “Yeah, Dr Gas works really hard and I’d like to show my appreciation,” feel free to click that donate button at the bottom of the show notes and fire off a couple of million pounds. That’ll be very nice of you. Thank you very much.

Right, lidocaine. So we’re going to go through all the data and then we’re going to talk about a few interesting points. Its name is lidocaine. Its brand name was xylocaine and you might hear that being bandied around, and also historically it was called lignocaine. So it’s got three names, but what it really is is a local anaesthetic agent or a class 1b antiarrhythmic agent in our Vaughan Williams classification of antiarrhythmics. If you’ve got no amiodarone somehow in your hospital, which is a situation that wouldn’t be completely unlikely in the current state of healthcare in the UK, you can reach, as per ALS guidelines, for lidocaine in a VT or VF arrest situation. Although I’m sure you’d instil terror in everyone around you if you were reaching for that.

It’s a tertiary amine, therefore it’s an amide local anaesthetic agent. And for all those diehard delighters of pharmacology, it is derived from diethylaminoacetic acid, which just rolls off the tongue quite beautifully. It is a clear, colourless solution. It comes in a number of concentrations, classically 1% or 2% solutions, plus or minus 1 in 200,000 adrenaline.

02:28-04:04 | Formulations and Molecular Properties

However, we all know that lidocaine is superbly pervasive in our practice. It comes as an ointment, 5%, a 10% spray, a 4% aqueous solution for topicalisation, and also it is found in Instillagel. Instillagel is 2% lidocaine and chlorhexidine, so it sterilises, anaesthetises, and lubricates. Great. But also you get a 5% spray with 0.5% phenylephrine. It also comes in lidocaine patches.

These are patches about the size of your hand that are classically used in rib fractures. Now whether or not they actually convey any benefit or they just entertain us and the patient whilst we scrabble around until we start PCA or start erector spinae plane blocking or epidurals is another question. I don’t think it actually gets that deep and therefore probably doesn’t really help unless someone is skin and bones, then maybe it might help a little bit. I think it might have been Voltaire who said the role of a doctor is to entertain a patient whilst the disease takes its course. And I feel that that is where lidocaine patches in rib fracture management really comes in. It’s just something to do. And we shouldn’t do that really. Anyway, but I don’t know the evidence, so I’m going to ramble. So I’m going to move on.

So the next logical cognitive step you need to take is, gosh, if it comes in so many different shapes, forms and preparations, including EMLA, then it must have a painfully extensive range of uses, which you could therefore be asked about in an exam. And you’re not wrong. And we’ll get to that in a moment.

To tidy up and finalise that, we definitely need to all know that it has a molecular weight of 234 grams per mole, which seems to be in the same sort of ballpark as all these other amide local anaesthetic agents, actually.

04:04-05:29 | Mechanism of Action

And we all know the mechanism of action of local anaesthetic agents now. And if you don’t, I’m going to tell you, but clearly you need to go and listen to those other episodes as well. Local anaesthetic agents act upon the internal aspect of a sodium channel in a nerve axon, therefore it has to get there. It will only transition across the plasma membrane of the neuron in its unionised form, so therefore you’ve already got a fraction of that agent which works whilst the other fraction does not, so to speak. That’s based on the pKa of the drug. There’s an episode on pKa if that has left you surprised. It’s early on this podcast journey that we’re all on together.

Once that local anaesthetic agent is inside the nerve cell, its journey is yet to finish because it then needs to return to being ionised or becoming a cation. It does this generally by binding to a hydrogen ion inside the nerve. And then our fortunate local anaesthetic agent in its ionised form on the inside of the cell finally binds to that sodium channel.

As a little additional aside, it tends to like to bind to channels that have been activated because it’s more pleasingly shapely for said local anaesthetic agent. This is what we describe as use-dependent block. And actually, if you stick some local anaesthetic around a nerve and then try and use it, you generally result in a slightly faster onset of action.

As an aside, I’m super excited to learn about how many different ways I can describe the mechanism of action of local anaesthetics with greater and greater verbosity. So keep tuned for all that.

05:29-08:27 | Clinical Uses, Onset, Duration and Dosing

Clinical uses of lidocaine are extensive, as we mentioned earlier. You can infiltrate it under the skin. You can use it for regional nerve blocks, epidural top-ups, field blocks or ring blocks, airway topicalisation, urethral topicalisation, and also intravenous infusions for pain control. And don’t forget, there’s an IV bolus with a dysrhythmia, although that’s a bit niche.

As with all local anaesthetics, there’s a maximum dose, and then there’s some recommended doses depending on where you’re putting the lidocaine. As we all know, absorption of local anaesthetic agent is dictated by the vascularity of the space, as well as the particular properties of that local anaesthetic agent, i.e. how lipid soluble it is, how much protein binding it can undergo, if it is inherently vasodilatory in itself or not. Cocaine being a vasoconstrictor, whereas bupivacaine tends to cause some capillary vasodilatation.

But before we talk about all those doses, how long does it take to work? Well, lidocaine is quicker than bupivacaine and it depends on what you’re blocking as to the onset. If you’re sticking a bit under the skin to numb up an area for a blood gas, and I would implore everyone to use lidocaine whenever you’re doing an arterial blood gas, your patient will thank you and it just makes your life easier. Tell all the new F1s: use some local anaesthetic, it’ll make it less challenging for you because the patient won’t be writhing in agony as you’re trying to dig around and find that artery. Use local anaesthetic for arterial blood gases.

Well, that was another digression. The onset time, if you’re trying to block the very fine and minimally myelinated nerves in your skin that are detecting pain and pressure and vibration and cold and all that jazz, the onset at times is really quite fast, maybe even like 20 or 30 seconds. Very easy to test. If you’re blocking a nerve, it takes about three to five minutes to work. And that’s because if you imagine the nerves in distal skinny tissues, you’re going to be in the situation of those fine nerves that have not very much in the way of myelin sheath, etc. Whereas big chunky nerve that’s quite good at conducting and is very busy conducting robust signals around with a nice thick myelin sheath takes longer to numb up.

How long does it last? So plain lidocaine, i.e. sans adrenaline, 90 minutes to three hours, probably depending on how much you’ve stuck in and how vascular the site is. Lidocaine with adrenaline, you’re talking maybe four to five hours.

So what about doses? Neat lidocaine, do not use more than three milligrams per kilo. That means for a 75 kilo patient, 22 and a half mils is your max dose of 1% lidocaine. So you shouldn’t be using more than four or five mil ampoules in a normal, approximately normal sized human. If you’re needing to use that much lidocaine to numb someone up for a central line, are you sure you’re definitely not just being handed normal saline?

And then with adrenaline you can get away with more than double that at seven milligrams per kilo of lidocaine, which is cracking. Now I’m not going to break down all the different doses of where you can put lidocaine in what amount to achieve what effect. If you’re really interested in that, there’s a summary of all that in the show notes because I don’t really want to get bogged down telling you a load of numbers all the time.

Why don’t we stick it in spinals? Because it causes those transient neurological symptoms we spoke about in the prilocaine episode, and it’s the chief offender of that, so you’d be mad to use it for a spinal anaesthetic.

08:27-09:11 | Enhancing Efficacy

Can you make lidocaine work faster? Yes, you can add sodium bicarbonate to your lidocaine mix. That alters the pH of the agent, but also alters the pH of the tissue you’ve injected it into, increasing the unionised fraction of lidocaine, subsequently improving onset. You might be able to just about get away with sticking a bicarb lidocaine mix in and around an abscess to numb it up sufficiently. But as we know, the pH of the tissues around an abscess is more acidic, and therefore there’s a smaller unionised fraction of lidocaine. So you just find yourself not really winning, but you can give it a go if it’s small.

09:11-12:37 | Side Effects by System

As with everything, when we’re talking pharmacodynamics and we’ve tapped on dose and route and purpose, we need to think about side effects. So we’re always, always in the exam, and we’re going to be breaking down side effects into their systems because it helps us remember. Also, the examiner will probably start falling asleep if you start quietly reeling off a very neat and structured approach to this bit of your conversation.

Cardiovascular Side Effects

So cardiovascular side effects stand more or less the same as the other local anaesthetic agents. It decreases the rate of rise of phase zero of the cardiac action potential by blocking sodium channels. If given enough, you end up in the world of local anaesthetic toxicity, and this will lead to a plethora of dysrhythmias from VF/VT to asystole. Don’t give too much local anaesthetic folks, and don’t stick it in someone’s vein or artery.

Low toxic doses lead to a slight increase in systemic vascular resistance. However, once you’re in the high-dose territory, you will drop that systemic vascular resistance, and obviously it has negative inotropic effects.

Respiratory Effects

Respiratory perspective? Interestingly, lidocaine is a bronchodilator at sub-toxic doses, but trying to shoehorn that into a conversation about life-threatening asthma probably will raise some eyebrows because there’s a number of other lower hanging fruit options for drugs in asthma until lidocaine. I don’t think anyone’s used that. Naturally, in toxic doses, you’re just going to anaesthetise that respiratory centre and you’re going to get respiratory depression.

CNS Side Effects

The CNS side effects, again, we’ve mentioned this before, but it’s biphasic. So you get an initial excitatory response. Patients get light-headed, dizzy. They get visual and auditory disturbances. They get that tingly mouth or circumoral tingling. And then in higher doses, you end up with progressive sedation of the brain, leading from being dozy and confused and disorientated to a coma. Somewhere between these two stages, you might also see a seizure, which is a fairly common element of local anaesthetic toxicity, and you should either treat that with benzodiazepines or propofol. Intralipid technically won’t treat the seizure, but would treat the toxicity. But propofol is fair game, or thiopentone in that situation. I’m getting ahead of myself.

GI Side Effects

GI side effects. It depresses your bowel contractility, and that’s because it’s going to anaesthetise your enteric nervous system. Ta-da! You can work this all out, guys, on the fly.

Other Side Effects

For other or interesting allergic reactions to amide local anaesthetics are very rare. You’re more likely to have an allergic reaction or rash-like reaction to ester anaesthetics. Lidocaine can cause methaemoglobinaemia, much like prilocaine, although I think rarer. So if you’ve got a patient who’s predisposed to that or on other drugs that might predispose your patient to methaemoglobinaemia, perhaps large doses of lidocaine wouldn’t be a smart move.

Now, the other interesting side effect situation of lidocaine with adrenaline depends on if you’re sticking it into a relatively vascular area. So it’s seen in neurosurgery where they are numbing up the scalp to slice into it with lidocaine plus adrenaline to try and impair how much blood starts pouring out the scalp because it is just a very, very vascular place. But what you get is systemic uptake of adrenaline. And because it’s in relatively low concentrations, you see an interesting set of autonomic nervous system mediated responses.

So actually you get a drop in blood pressure as that adrenaline starts soaking into the person because adrenaline tends to like beta-1 adrenoceptors, which cause vasodilatation and tachycardia. So you get vasodilatation, which is a drop in blood pressure, plus tachycardia. Patient looks a bit ropey. And then you get a subsequent improvement in blood pressure, courtesy of adrenaline now tickling those alpha adrenoceptors as well. And that is just cool, isn’t it?

12:37-14:17 | Pharmacokinetics

So the pharmacokinetics of lidocaine.

Absorption

, well it really does depend on where you’ve gone and injected it, squirted it or sprayed it. That same old string of words applies, so from most absorbed to least absorbed would be intercostal, caudal, epidural, brachial, subcutaneous. But we also know that we stick it into a lot of other places. So if you spray it into someone’s airway down their trachea, the uptake is actually quite rapid and you can hit quite high peak concentrations. So you definitely need to be thoughtful about how many sprays of local anaesthetic, of what concentration you are administering to someone’s airway to sufficiently numb it up. That is beyond the scope of this episode.

Distribution

So its pKa is 7.7 and it is 25% unionised at physiological pH. How do you remember all these pKas? Well, you need to figure out some sort of complicated system yourself. But I just think that lidocaine starts with an L and a 7 looks like an L backwards. So therefore the one that is 7.7 must be lidocaine, which is a long-winded way to try and remember a pKa. It is 64 to 70% protein bound and again it is chiefly friends with alpha-1 acid glycoproteins and it has quite a small volume of distribution actually, 0.7 to 1.5 litres per kilo.

Metabolism

How is it metabolised? Well you rightly ask that and you know the answer because it’s an amide so it’s metabolised in the liver by N-dealkylation and it’s hydrolysed then into something called monoethylglycine and xylidide, and there is some rumbling suggestion that these metabolites might drop your seizure threshold. But again, I think you’d be having to give quite a bit of lidocaine to achieve that. 10% is excreted unchanged in the urine. It has a clearance of 6.8 to 11.6 ml per kilo per minute, and its elimination half-life is 90 to 100 minutes.

14:17-17:04 | IV Lidocaine Infusions for Pain

So that was a whistle-stop tour of all the blurb of lidocaine. Could you get all of that out in an exam? Probably not, but if you can have a structured approach to talking through any sort of drug in this sort of manner, you’re going to be halfway there, folks.

Now for the interesting part of the episode is thinking about this malarkey with IV infusions of lidocaine to treat pain, because what I’ve told you is that lidocaine can be toxic, it has loads of side effects, and actually it bears out with pain infusions as well because there’s a narrow therapeutic window and there’s a lot of variability between all your patients as to how they metabolise it, how much free lidocaine is in their plasma, and if you inadvertently under or overdose them.

There’s a great article from the AAGBI that’s like a consensus statement built on oodles of meta-analyses, etc., to come to some sort of sensible conclusions. But in terms of dosing, so if you’re doing this, you’d need to dose it on ideal body weight. Now you might be asked how to calculate that in an exam, and it’s simply the patient’s height in centimetres minus 100 if you’re a man and 105 if you’re a woman. If the patient’s less than 40 kilos, don’t do a lidocaine infusion. And then there are some cut-offs for how much you should infuse per hour. So no more than 120 milligrams per hour infused. Now if you’re using 1% lidocaine here, which is 10 milligrams per mil, that means that the infusion rate can’t be any more than 12 mls per hour. And that’s regardless of weight.

How do you dose it if you’re venturing off into this unknown realm, which I think is fairly common in some centres and then completely uncommon in other centres? But you load the patient over 10 minutes with 1.5mg per kilo of lidocaine based on their ideal body weight. And then you start an infusion of 1.5mg per kilo per hour. They recommend in this consensus statement that you shouldn’t really be doing this for more than 24 hours. There’s some other caveats they mentioned.

So outside of the theatre complex, a patient on a lidocaine infusion should be in a monitored bed space. Lipid emulsion should be readily available. That seems very common sense. And that you shouldn’t be mixing and matching a lidocaine infusion with a multitude of other local anaesthetic nerve blocks. And that you should wait four hours before starting an infusion if you’ve done a block or port site infiltration. But single shot spinals are less of an issue because that’s such a small dose.

Fortunately, the effects of a lidocaine infusion persist for a fair time after cessation of that infusion.

Mechanism of Pain Relief

So why on earth does lidocaine, which blocks sodium channels, somehow treat pain? And they actually purport that it is an anti-inflammatory, mitigates hyperalgesia, and is an analgesic. So lidocaine blocks muscarinic receptors, M1 and M3, blocks our friendly NMDA receptor, which we know ketamine likes, but also our dear friend methadone likes to block the NMDA receptor. And in really high doses, lidocaine blocks a load of other stuff, which I’ve never heard of, which I’m not going to tell you about. But if you give enough of any drug, then it’ll start shoehorning its way into receptors that it doesn’t tend to quite fit in because there’s just so much floating around.

17:04-18:37 | Safety and Efficacy of IV Infusions

So do lidocaine infusions work? This consensus statement kind of returns to the fence and says, in the gist of it, the heterogeneity of these papers and the resultant meta-analyses leave ultimately a lot to be decided because there’s so much variability between all the papers and it is not clear if it does have a distinct benefit.

Are the infusions safe? Well unfortunately symptoms of toxicity don’t correlate to plasma concentration, that’s one headache, and there are a number of variables that influence that free fraction of lidocaine in the plasma which is the fraction that’s up to mischief because it’s bound to glycoprotein and maybe a little bit of albumin in the plasma. It depends on the patient’s cardiac index because if they’ve got a high cardiac output then they’re going to clear more through their liver. If their cardiac output is low because they’re sickly poorly then they’re going to accumulate more. If they’re a bit acidotic or they’ve got a bit dozy and stopped breathing sufficiently then an acidosis shifts more lidocaine off of plasma proteins. If a patient is beta blocked it can reduce lidocaine metabolism and as you might expect lidocaine plus amiodarone are going to lead to some cardiac mischief. That’s not recommended.

They do go on to say that across the board, the studies that they’ve reviewed, most of the catastrophic events actually bore out human error in dosing calculations than a perfectly organised and appropriately dosed lidocaine infusion. So we are our own worst enemies as always folks. We should never rush when we’re doing maths, we should never allow ourselves to be distracted when we’re drawing up a drug, we should create that silent cockpit that they talk about.

My singular and last thought on that is, is lidocaine a prevailing punter for an Eleveld-esque TCI model and you just tap your patient’s details and the machine doses the patient appropriately. Wouldn’t that be great? One day.

18:37-20:22 | Key Points Recap

So you might now actually be listening to this episode and this is the first Gas Gas Gas episode you’ve listened to. And welcome if you have, you should definitely go back and listen to some other ones. So I’m just going to quickly remind everyone about the key points of local anaesthetics to remember.

Onset and length of action are dependent on the pKa, the lipid solubility and protein binding of the drug. As you can imagine, a large unionised fraction and high lipid solubility yields a rapid onset. And if there’s robust protein binding, you tend to see a longer duration of action.

The compounds themselves would be described as amphipathic compounds, which is a bit of a mouthful, but it goes to describe that there’s a hydrophilic end and a hydrophobic end. And in the exam, you might get asked to describe the overall structure of a local anaesthetic molecule. The fat-loving hydrophobic end is a benzene ring or a lipophilic aromatic ring, whereas the amino group on the other side of the molecule is the more water-soluble element of that molecule, and then they are joined together by either an ester or an amide linkage.

We know that ester local anaesthetic compounds break down quite quickly because of plasma esterases that go around mopping things up at a howling speed, whereas amides need to be toddled off to the liver to be broken down.

20:22-22:18 | Clinical Tips and Conclusion

Now my final Gas Gas Gas top tip of the day, alongside you should use it for ABGs and encourage everyone to do the same, is that if you’ve got a patient who is really not terribly keen on an NG tube because it feels like someone’s trying to jam a copper pipe down their nose, which it probably does feel quite awful, especially if you’re very hypersensory and overstimulated, having been fiddled around with, operated on, feeling like you’re half dead. No one wants an NG tube shoved up their nose.

So the solution, the bargaining chip, as long as your patient isn’t obtunded, is to use lidocaine with phenylephrine in it. It’s called cophenylcaine. Theatres should have it. It comes in a little blue box and you prep it together and you squirt it in their nose a couple of times, you get them to sniff a bit so that hopefully it numbs the back of their throat and larynx. You end up with a patient with a numb nose but also that vasoconstriction creates a bit more space in their nose and therefore you can sneak that NG tube down with less of that gibbering discomfort and agony.

Now if you go a bit overboard with the lidocaine spray you might numb up their oropharynx a bit, they might end up becoming a bit discordant when you’re trying to get them to swallow, and much like if you topicalise an airway they shouldn’t be eating or drinking for the next hour or two afterwards because they’re less able to prevent it going down the wrong way. But if you’ve got someone who’s had a rotten time and they really need an NG and everyone’s saying “oh so and so needs an NG but they don’t want it blah blah blah” you can go in and say “hey I can make it quite a bit more comfortable, shall we give it a go?”

Right, well I’ve talked far too much as always. I hope you enjoyed the episode guys. Next week we are covering the other ester local anaesthetic agent. I’m sure we might talk about topicalising eyeballs and not with cocaine, because we know that’s not very good. Anyway, I hope you have a nice week. Check out the show notes. There’s a couple of useful links on there about methaemoglobinaemia and lidocaine, and lidocaine as a pain infusion, as well as a link to the godly bible of all things intensive and anaesthetic medicine flavoured, the Deranged Physiology local anaesthetic pharmacology page, which is a dreamboat.

There’s also a link to a Bayesian network meta-analysis, which is a mouthful, looking at which local anaesthetic agent yields fastest onset for epidural anaesthesia for emergent caesarean section. Because some places use a confusing mix of lidocaine, bicarb, and adrenaline, which yields a rip-roaringly fast onset time, whereas most places I’ve worked just stick 0.5% bupivacaine in, but start topping it up in the delivery room as you transfer to theatre. I’m getting carried away again. Have a nice week. I’ll see you next time. Cheers.

Thanks for listening, guys. I hope you found it useful, but if you found it awful, do let me know. Please like and subscribe, register with whichever podcast platform you find yourself using, and leave a comment if you think I need to square something away. I just want to make sure that you guys know that every day you are getting better at this. There is a bucket of content to try and consume, and it is like drinking from a fire hose. Take it day by day, don’t overcook yourself, don’t freak out, and keep studying.

This is the full Show Transcript – Courtesy of Whisper LLM

00:00-00:01
Please listen carefully.

00:30-00:36
new shape and let’s get on with the show. Hello everyone, this is James at Games Gas Gas. This

00:37-00:42
is another episode of the Local Anesthetics series and I’m sure you’ve all been super excited,

00:42-00:46
absolutely waiting for it, because today we are talking lidocaine. Before we get into the bulk of

00:46-00:51
the show, we’re doing a series on all the local anaesthetic agents. We’ve done an intro to local

00:51-00:56
anaesthetics, we’ve covered bupivocaine, cocaine and the last episode was prilocaine. So if this

00:56-01:01
is your first time listening to Gas, Gas, Gas, make sure to go back and touch on that introduction

01:01-01:05
to local anaesthetics episode as well. It really does set the scene for everything you need to

01:05-01:09
get on with. Now, if you’re finding this show absolutely riveting and you think, yeah, yeah,

01:09-01:14
Dr. Gas works really hard and I’d like to show my appreciation, feel free to click that donate

01:14-01:19
button at the bottom of the show notes and fire off a couple of million pounds. That’ll be very

01:19-01:24
nice of you. Thank you very much. Right, lidocaine. So we’re going to go through all the data and

01:24-01:28
then we’re going to talk about a few interesting points. So its name is lidocaine. Its brand name

01:28-01:34
was xylocaine and you might hear that being bandied around and also historically it was called

01:34-01:39
lignocaine. So it’s got three names but what it really is is a local anaesthetic agent or a class

01:40-01:45
1b antiarrhythmic agent in our Vaughan Williams classification of antiarrhythmics because if

01:46-01:51
you’ve got no amiodarone somehow in your hospital which is a situation that wouldn’t be completely

01:51-01:56
unlikely in the current state of healthcare in the UK, you can reach, as per ALS guidelines,

01:56-02:03
for lidocaine in a VT or VF rest situation. Although I’m sure you’d instill terror to everyone around

02:03-02:08
you if you were reaching for that. It’s a tertiary amine, therefore it’s an amide low-climacetic

02:08-02:16
agent. And for all those diehard delighters of pharmacology, it is derived from diethylaminacetic

02:16-02:20
acid, which just rolls off the tongue quite beautifully. It is a clear, colourless solution.

02:20-02:28
It comes in a number of concentrations, classically 1% or 2% solutions, plus minus 1 in 200,000

02:28-02:28
adrenaline.

02:28-02:33
However, we all know that lidocaine is superbly pervasive in our practice.

02:33-02:40
It comes as an ointment, 5%, a 10% spray, a 4% aqueous solution for topication, and also

02:41-02:42
it is found in instilagel.

02:43-02:49
Instilagel is 2% lidocaine and chlorhexidine, so it sterilizes, anesthetizes, and lubricates.

02:49-02:49
Great.

02:49-02:54
But also you get a 5% spray with 0.5% phenylmephrine.

02:54-02:56
It also comes in lidocaine patches.

02:57-03:01
These are patches about the size of your hand that are classically used in rib fractures.

03:01-03:05
Now whether or not they actually convey any benefit or they just entertain us and the patient

03:05-03:10
whilst we scrabble around until we start PCA or sticker rectospine plane blocking

03:11-03:13
or epiduralin is another question.

03:13-03:16
I don’t think it actually gets that deep and therefore probably doesn’t really help

03:17-03:18
unless someone is skin and bones.

03:18-03:21
then maybe it might help a little bit.

03:21-03:24
I think it might have been Voltaire who said the role of a doctor

03:24-03:27
is to entertain a patient whilst the disease takes its course.

03:28-03:32
And I feel that that is where lidocaine patches in rib fracture management really comes in.

03:32-03:33
It’s just something to do.

03:33-03:34
And we shouldn’t do that really.

03:34-03:36
Anyway, but I don’t know the evidence, so I’m going to ramble.

03:36-03:37
So I’m going to move on.

03:37-03:40
So the next logical cognitive step you need to take is, gosh,

03:40-03:44
if it comes in so many different shapes, forms and preparations, including EMLA,

03:45-03:48
then it must have a painfully extensive range of uses,

03:48-03:51
which you could therefore be asked about in an exam.

03:51-03:52
And you’re not wrong.

03:52-03:53
And we’ll get to that in a moment.

03:53-03:54
To tidy up and finalise that,

03:55-03:56
we definitely need to all know

03:56-03:59
that it has a molecular weight of 234 grams per mole,

03:59-04:01
which seems to be in the same sort of ballpark

04:02-04:04
as all these other amide local anaesthetic agents, actually.

04:04-04:06
And we all know the mechanism of action

04:06-04:08
of local anaesthetic agents now.

04:08-04:09
And if you don’t, I’m going to tell you,

04:09-04:11
but clearly you need to go and listen

04:11-04:12
to those other episodes as well.

04:12-04:15
Local anaesthetic agents act upon the internal aspect

04:16-04:18
of a sodium channel in a nerve axon.

04:18-04:23
therefore it has to get there. It will only transition across the plasma membrane of the

04:23-04:29
neuron in its unionised form so therefore you’ve already got a fraction of that agent which works

04:29-04:34
whilst the other fraction does not so to speak. That’s based on the PKA of the drug. There’s an

04:34-04:40
episode on PKA if that has left you surprised. It’s early on this podcast journey that we’re all on

04:40-04:45
together. Once that local anaesthetic agent is inside the nerve cell its journey is yet to finish

04:45-04:49
because it then needs to return to being ionised or becoming a cation.

04:50-04:54
It does this generally by binding to a hydrogen ion inside the nerve.

04:54-05:00
And then our fortunate local anaesthetic agent in its ionised form on the inside of the cell

05:00-05:01
finally binds to that sodium channel.

05:02-05:06
As a little additional aside, it tends to like to bind to channels that have been activated

05:07-05:10
because it’s more pleasingly shapely for said local anaesthetic agent.

05:10-05:13
This is what we describe as use-dependent block.

05:13-05:16
And actually, if you stick some local anaesthetic around a nerve and then try and use it,

05:16-05:19
you generally result in a slightly faster onset of action.

05:19-05:25
As an aside, I’m super excited to learn about how many different ways I can describe the mechanism of action of local anaesthetics

05:25-05:27
with greater and greater verbosity.

05:27-05:29
So keep tuned for all that.

05:29-05:32
Clinical uses of lidocaine are extensive, as we mentioned earlier.

05:32-05:34
You can infiltrate it under the skin.

05:34-05:39
You can use it for regional nerve blocks, epidural top-ups, field blocks or ring blocks,

05:39-05:45
airway topicalisation, urethra topicalisation, and also intravenous infusions for pain control.

05:46-05:50
And don’t forget, there’s an IV bolus with a dysrhythmia, although that’s a bit niche.

05:51-05:56
As with all local anaesthetics, there’s a maximum dose, and then there’s some recommended doses

05:56-06:00
depending on where you’re putting the lidocaine. As we all know, absorption of local anaesthetic

06:01-06:06
agent is dictated by the vascularity of the space, as well as the particular properties of that local

06:06-06:11
anesthetic agent, i.e. how solubility is, how much protein binding it can undergo, if it is inherently

06:12-06:16
vasodilatory in itself or not. Cocaine being a vasoconstrictor, whereas bupivacaine tends to

06:17-06:22
cause some capillary vasodilation. But before we talk about all those doses, how long does it take

06:22-06:27
to work? Well, lidocaine is quicker than bupivacaine and it depends on what you’re blocking as to the

06:27-06:32
onset. If you’re sticking a bit under the skin to numb up an area for a blood gas, and I would

06:32-06:36
implore everyone to use lidocaine whenever you’re doing an arterial blood gas, your patient will

06:36-06:42
you and it just makes your life easier tell all the new f1s use some local anesthetic it’ll make

06:42-06:46
it less challenging for you because the patient won’t be writhing in agony as you’re trying to

06:46-06:51
dig around and find that artery use local anesthetic for arterial blood gases well that was another

06:51-06:58
digression the onset time if you’re trying to block the very fine and minimally myelinated nerves in

06:58-07:03
your skin that are detecting pain and pressure and vibration and cold and all that jazz the onset

07:03-07:08
at times really quite fast, maybe even like 20 or 30 seconds. Very easy to test. If you’re blocking

07:08-07:12
a nerve, it takes about three to five minutes to work. And that’s because if you imagine the

07:12-07:19
nerves in distal skinny tissues, you’re going to be in the situation of those fine nerves that have

07:19-07:24
not very much in the way of myelin sheath, etc, etc. Whereas big chonking nerve that’s quite good

07:24-07:30
at conducting and is very busy conducting robust signals around with a nice thick myelin sheath

07:30-07:35
takes longer to numb up. How long does it last? So plain lidocaine, i.e. sans adrenaline, 90 minutes

07:35-07:40
to three hours, probably depending on how much you’ve stuck in and how vascular the site is.

07:41-07:45
Lidocaine with adrenaline, you’re talking maybe four to five hours. So what about doses? Neat

07:46-07:51
lidocaine, do not use more than three milligrams per kilo. That means for a 75 kilo patient,

07:51-07:57
22 and a half mils is your max dose of 1% lidocaine. So you shouldn’t be using more than four or five

07:57-08:01
mil ampoules in a normal approximately normal sized human if you’re needing to use that much

08:02-08:06
lidocaine to numb someone up for a central line are you sure you’re definitely not just being handed

08:06-08:11
normal salinas and then with adrenaline you can get away with more than double that at seven

08:11-08:15
milligrams per kilo of lidocaine which is cracking now i’m not going to break down all the different

08:15-08:19
doses of where you can put lidocaine in what amount to achieve what effect if you’re really

08:19-08:23
interested in that there’s a summary of all that in the show notes because i don’t really want to

08:23-08:27
it bogged down and telling you a load of numbers all the time. Why don’t we stick it in spinals?

08:27-08:31
Because it causes those transient neurological symptoms we spoke about in a prilocane episode,

08:31-08:35
and it’s the chief offender of that, so you’d be mad to use it for a spinal anaesthetic.

08:35-08:41
Can you make lidocane work faster? Yes, you can add sodium bicarbonate to your lidocane mix.

08:42-08:47
That alters the pH of the agent, but also alters the pH of the tissue you’ve injected it into,

08:47-08:52
increasing the unionised fraction of lidocane, subsequently improving onset. You might be able

08:52-08:58
to just about get away with sticking a bicarby lidocaine mix in and around an abscess to numb

08:58-09:03
it up sufficiently. But as we know, the pH of the tissues around an abscess is more acidic,

09:03-09:08
and therefore there’s a smaller unionised fraction of lidocaine. So you just find yourself

09:08-09:11
not really winning, but you can give it a go if it’s small. As with everything,

09:11-09:15
when we’re talking pharmacodynamics and we’ve tapped on dose and root and purpose,

09:16-09:20
we need to think about side effects. So we’re always, always in the exam,

09:20-09:24
And we’re going to be breaking down side effects into their systems because it helps us remember.

09:24-09:31
Also, the examiner will probably start falling asleep if you start quietly reaming off a very neat and structured approach to this bit of your conversation.

09:31-09:36
So cardiovascular side effects stand more or less the same as the other local anesthetic agents.

09:37-09:42
It decreases the rate of rise of phase zero of the cardiac action potential by blocking sodium channels.

09:43-09:45
If given enough, you end up in the world of local anesthetic toxicity.

09:46-09:51
and this will lead to a plethora of dysrhythmias from VFVT to asystole.

09:52-09:53
Don’t give too much local aesthetic folks,

09:54-09:56
and don’t stick it in someone’s vein or artery.

09:56-10:01
Low toxic doses lead to a slight increase in systemic vascular resistance.

10:01-10:03
However, once you’re in the high-dose territory,

10:03-10:05
you will drop that systemic vascular resistance,

10:05-10:07
and obviously it has negative inotropic effects.

10:08-10:08
Respiratory perspective?

10:09-10:12
Interestingly, lidocaine is a bronchodilator at sub-toxic doses,

10:13-10:16
but trying to shoehorn that into a conversation about life-threatening asthma

10:16-10:20
Probably will raise some eyebrows because there’s a number of other lower hanging fruit options

10:20-10:22
for drugs in asthma until lidocaine.

10:22-10:24
I don’t think anyone’s used that.

10:24-10:28
Naturally, in toxic doses, you’re just going to anaesthetise that respiratory centre

10:28-10:29
and you’re going to get respiratory depression.

10:30-10:34
The CNS side effects, again, we’ve mentioned this before, but it’s biphasic.

10:34-10:37
So you get an initial excitatory response.

10:37-10:38
Patients get lightheaded, dizzy.

10:39-10:40
They get visual and auditory disturbances.

10:41-10:43
They get that tingly mouth or circumoral tingling.

10:44-10:48
And then in higher doses, you end up with progressive sedation of the brain,

10:49-10:53
leading from being dozy and confused and disorientated to a coma.

10:53-10:56
Somewhere between these two stages, you might also see a seizure,

10:56-10:59
which is a fairly common element of low-cylactic toxicity,

10:59-11:02
and you should either treat that with benzodiazepines or propofol.

11:02-11:05
Intralipid technically won’t treat the seizure, but would treat the toxicity.

11:06-11:09
But propofol is fair game, or thiopentone in that situation.

11:09-11:10
I’m getting ahead of myself.

11:10-11:11
GI side effects.

11:11-11:16
It depresses your bowel contractility, and that’s because it’s going to anesthetize your enteric nervous system.

11:16-11:19
Ta-da! You can work this all out, guys, on the fly.

11:19-11:24
For other or interesting allergic reactions to amide local anesthetics are very rare.

11:24-11:29
You’re more likely to have an allergic reaction or rash-like reaction to ester anesthetics.

11:29-11:34
Lidocaine can cause methemoglobinemia, much like prilocaine, although I think rarer.

11:34-11:40
So if you’ve got a patient who’s predisposed to that or on other drugs that might predispose your patient to methemoglobinemia,

11:40-11:44
perhaps large doses of lidocaine wouldn’t be a smart move.

11:44-11:46
Now, the other interesting side effect situation

11:47-11:48
of lidocaine with adrenaline

11:49-11:50
depends on if you’re sticking it

11:50-11:52
into a relatively vascular area.

11:52-11:53
So it’s seen in neurosurgery

11:53-11:55
where they are numbing up the scalp

11:55-11:57
to slice into it with lidocaine plus adrenaline

11:58-11:59
to try and impair how much blood

12:00-12:00
starts pouring out the scalp

12:01-12:03
because it is just a very, very vascular place.

12:03-12:05
But what you get is systemic uptake of adrenaline.

12:06-12:08
And because it’s in relatively low concentrations,

12:08-12:13
you see an interesting set of autonomic nervous system mediated responses.

12:13-12:17
So actually you get a drop in blood pressure as that adrenaline starts soaking into the person

12:17-12:21
because adrenaline tends to like beta-1 adrenoceptors,

12:21-12:23
which cause vasodilation and tachycardia.

12:23-12:27
So you get vasodilation, which is a drop in blood pressure, plus tachycardia.

12:27-12:28
Patient looks a bit ropey.

12:28-12:31
And then you get a subsequent improvement in blood pressure,

12:31-12:35
courtesy of adrenaline now tickling those alpha adrenoceptors as well.

12:35-12:37
And that is just cool, isn’t it?

12:37-12:42
So the pharmacokinetics of lidocaine absorption wise, well it really does depend on where you’ve

12:42-12:48
gone and injected it, squirted it or sprayed it. That same old string of words applies so from

12:49-12:54
most absorbed to least absorbed would be intercostal, caudal, epidural, brachial, subcutaneous but we

12:54-12:58
also know that we stick it into a lot of other places. So if you spray it into someone’s airway

12:58-13:03
down their trachea the uptake is actually quite rapid and you can hit quite high peak concentrations

13:03-13:07
So you definitely need to be thoughtful about how many sprays of local anaesthetic,

13:07-13:11
of what concentration you are administering to someone’s airway to sufficiently numb it up.

13:11-13:12
That is beyond the scope of this episode.

13:13-13:13
Distribution.

13:14-13:20
So its pKa is 7.7 and it is 25% unionised physiological pH.

13:20-13:21
How do you remember all these pKa’s?

13:21-13:24
Well, you need to figure out some sort of complicated system yourself.

13:24-13:28
But I just think that lidocaine starts with an L and a 7 looks like an L backwards.

13:28-13:31
So therefore the one that is 7.7 must be lidocaine,

13:31-13:37
which is a long-winded way to try and remember a pKa. It is 64 to 70% protein bound and again it

13:37-13:42
is chiefly friends with alpha-1 acid glycoproteins and it has quite a small volume of distribution

13:42-13:47
actually 0.7 to 1.5 litres per kilo. How is it metabolised? Well you rightly ask that and you

13:47-13:52
know the answer because it’s an amide so it’s metabolised in the liver by N-dealkylation and

13:52-13:58
it’s hydrolyzed then into something called monoethylglycine and xylodide and there is some

13:58-14:02
rumbling suggestion that these metabolites might drop your seizure threshold. But again, I think

14:02-14:07
you’d be having to give quite a bit of lidocaine to achieve that. 10% is excreted unchanged in the

14:07-14:13
urine. It has a clearance of 6.8 to 11.6 mL per kilo per minute, and its elimination half-life is

14:13-14:17
90 to 100 minutes. So that was a whistle-stop tour of all the blurb of lidocaine. Could you get all

14:18-14:22
of that out in an exam? Probably not, but if you can have a structured approach to talking through

14:23-14:26
any sort of drug in this sort of manner, you’re going to be halfway there, folks. Now for the

14:26-14:32
interesting part of the episode is thinking about this malarkey with IV infusions of lidocaine to

14:32-14:36
treat pain because what I’ve told you is that lidocaine can be toxic it has loads of side

14:36-14:40
effects and actually it bears out with pain infusions as well because there’s a narrow

14:40-14:46
therapeutic window and there’s a lot of variability between all your patients as to how they metabolize

14:46-14:51
it how much free lidocaine is in their plasma and if you inadvertently under or overdose them

14:51-14:56
there’s a great article from the AAGBI that’s like a consensus statement built on oodles of

14:56-15:00
meta-analyses, etc, etc, to come to some sort of sensible inclusions. But in terms of dosing,

15:01-15:05
so if you’re doing this, you’d need to dose it on ideal body weight. Now you might be asked how to

15:05-15:10
calculate that in an exam, and it’s simply the patient’s height in centimetres minus 100 if you’re

15:10-15:15
a man and 105 if you’re a woman. If the patient’s less than 40 kilos, don’t do a lidocaine fusion.

15:15-15:20
And then there are some cut-offs for how much you should infuse per hour. So no more than 120

15:20-15:25
milligrams per hour infused. Now if you’re using 1% lidocaine here, which is 10 milligrams per mil,

15:25-15:28
that means that the infusion rate can’t be any more than 12 mls per hour.

15:28-15:29
And that’s regardless of weight.

15:29-15:32
How do you dose it if you’re venturing off into this unknown realm,

15:33-15:35
which I think is fairly common in some centres

15:35-15:38
and then completely uncommon in other centres.

15:38-15:43
But you load the patient over 10 minutes with 1.5mg per kilo of lidocaine

15:43-15:45
based on their ideal body weight.

15:45-15:49
And then you start an infusion of 1.5mg per kilo per hour.

15:50-15:51
They recommend in this consensus statement

15:51-15:53
that you shouldn’t really be doing this for more than 24 hours.

15:53-15:55
There’s some other caveats they mentioned.

15:55-16:00
So outside of the theatre complex, a patient on a lidocaine infusion should be in a monitored bed space.

16:01-16:03
Lipid emulsion should be readily available.

16:03-16:04
That seems very common sense.

16:04-16:09
And that you shouldn’t be mixing and matching a lidocaine infusion with a multitude of other local anesthetic nerve blocks.

16:10-16:15
And that you should wait four hours before starting an infusion if you’ve done a block or port site infiltration.

16:15-16:19
But single shot spinals are less of an issue because that’s such a small dose.

16:19-16:25
Fortunately, the effects of a lidocaine infusion persist for a fair time after cessation of that infusion.

16:25-16:29
So why on earth does lidocaine, which blocks sodium channels, somehow treat pain?

16:29-16:35
And they actually purport that it is an anti-diplamatory, mitigates hyperalgesia, and is an analgesic.

16:35-16:41
So lidocaine blocks muscarinic receptors, M1 and M3, blocks our friendly NMDA receptor,

16:41-16:47
which we know ketamine likes, but also our dear friend methadone likes to block the NMDA receptor.

16:47-16:51
And in really high doses, lidocaine blocks a load of other stuff, which I’ve never heard of,

16:51-16:54
which I’m not going to tell you about. But if you give enough of any drug, then it’ll start

16:54-16:58
shoehorning its way into receptors that it doesn’t tend to quite fit in because there’s just so much

16:59-17:04
floating under. So do lidocaine infusions work? This consensus statement kind of returns to the

17:04-17:10
fence and says, in the gist of it, the heterogeneity of these papers and the resultant meta-analyses

17:10-17:14
leave ultimately a lot to be decided because there’s so much variability between all the papers

17:14-17:20
and it is not clear if it does have a distinct benefit. Are the infusions safe? Well unfortunately

17:20-17:24
symptoms of toxicity don’t correlate to plasma concentration, that’s one headache, and there are

17:24-17:30
a number of variables that influence that free fraction of lidocaine in the plasma which is the

17:30-17:35
fraction is up to mischief because it’s bound to glycoprotein and maybe a little bit of albumin in

17:35-17:39
the plasma. It depends on the patient’s cardiac index because if they’ve got a high cardiac output

17:39-17:42
then they’re going to clear more through their liver. If their cardiac output is low because

17:42-17:46
they’re sickly poorly then they’re going to accumulate more. If they’re a bit acidotic or

17:46-17:51
they’ve got a bit dozy and stopped breathing sufficiently then an acidosis shifts more lidocaine

17:52-17:57
off of plasma proteins. If a patient is beta blocked it can reduce lidocaine metabolism and

17:57-18:01
as you might expect lidocaine plus amyorone are going to lead to some cardiac mischief. That’s not

18:02-18:07
recommended. They do go on to say that across the board the studies that they’ve reviewed most of the

18:07-18:13
catastrophic events actually bore out human error in dosing calculations than a perfectly organized

18:14-18:19
and appropriately dosed lidocaine infusion so we are our own worst enemies as always folks we should

18:20-18:23
never rush when we’re doing maths we should never allow ourselves to be distracted when we’re drawing

18:23-18:27
a drug we should create that silent cockpit that they talk my singular and last thought on that is

18:28-18:34
is lidocaine a prevailing punter for a eleveld-esque tci model and you just tap your patient’s detail

18:34-18:36
and the machine doses the patient appropriately.

18:36-18:37
Wouldn’t that be great?

18:37-18:37
One day.

18:37-18:39
So you might now actually be listening to this episode

18:40-18:42
and this is the first gas, gas, gas episode

18:42-18:43
you’ve listened to.

18:43-18:44
And welcome if you have,

18:44-18:45
you should definitely go back

18:45-18:46
and listen to some other ones.

18:46-18:47
So I’m just going to quickly remind everyone

18:48-18:50
about the key points of local anaesthetics to remember.

18:50-18:52
Onset and length of action

18:52-18:53
are dependent on the PKA,

18:54-18:56
the solubility and protein binding of the drug.

18:56-18:57
As you can imagine,

18:57-18:59
a large unionised fraction

18:59-19:01
and high solubility yields a rapid onset.

19:01-19:03
And if there’s robust protein binding,

19:04-19:08
you tend to see a longer duration of action. The compounds themselves would be described as

19:09-19:15
amphipathic compounds, which is a bit of a mouthful, but it goes to describe that there’s a hydrophilic

19:15-19:20
end and a hydrophobic end. And in the exam, you might get asked to describe the overall structure

19:20-19:26
of a local anaesthetic molecule. The fat-loving hydrophobic end is a benzene ring or a lipophilic

19:26-19:32
aromatic ring, whereas the amino group on the other side of the molecule is the more water-soluble

19:32-19:37
element of that molecule and then they are joined together by either an ester or an amide linkage.

19:37-19:42
We know that ester, local anesthetic compounds, break down quite quickly because of plasma esterases

19:42-19:47
that go around mopping things up at a howling speed whereas amides need to be toddled off to

19:47-19:52
the liver to be broken down. Now my final gas gas gas top tip of the day alongside you should use

19:52-19:57
it for ABGs and encourage everyone to do the same is that if you’ve got a patient who is really not

19:57-20:02
terribly keen on an NG tube because it feels like someone’s to try and jam a copper pipe down their

20:03-20:06
nose, which it probably does feel quite awful, especially if you’re very hypersensory and

20:07-20:11
overstimulated, having been fiddled around with, operated on, feeling like you’re half dead. No one

20:11-20:15
wants an NG tube shoved up their nose. So the solution, the bargaining chip, as long as your

20:15-20:21
patient isn’t uptundered, is to use lidocaine with phenylnephrin in it. It’s called cophenylcaine.

20:22-20:26
Theatres should have it. It comes in a little blue box and you prep it together and you squirt it in

20:26-20:30
their nose a couple of times you get them to sniff a bit so that hopefully it numbs the back of their

20:30-20:35
throat attach and lytic hook you end up with a patient with a numb nose but also that vasoconstriction

20:35-20:41
created a bit more space in their nose and therefore you can sneak that ng tube down with

20:41-20:46
less of that gibbering discomfort and agony now if you go a bit overboard with the lidocaine spray

20:46-20:52
you might numb up their oropharynx a bit they might end up becoming a bit discordant when you’re trying

20:52-20:56
to get them to swallow and much like if you topicalize an airway they shouldn’t be like

20:56-21:01
eating or drinking for like the next hour or two afterwards because they’re less able to prevent it

21:01-21:05
going down the wrong way but if you’ve got someone who’s had a rotten time and they really need ng

21:05-21:09
and everyone’s saying oh so and so needs an ng but they don’t want it blah blah blah you can go in

21:09-21:13
and say hey i can make it quite a bit more comfortable shall we give it a go right well

21:14-21:18
i’ve talked far too much as always i hope you enjoyed the episode guys next week we are covering

21:18-21:21
the other ESTA local anesthetic agent.

21:21-21:23
I’m sure we might talk about topicalising eyeballs

21:24-21:24
and not with cocaine,

21:25-21:26
because we know that’s not very good.

21:26-21:28
Anyway, I hope you have a nice week.

21:28-21:29
Check out the show notes.

21:29-21:31
There’s a couple of useful links on there

21:31-21:33
about methicrobaglobinemia and lidocaine,

21:34-21:35
and lidocaine as a pain infusion,

21:35-21:37
as well as a link to the godly bible

21:38-21:40
of all things intensive and anesthetic medicine

21:41-21:42
flavoured the deranged physiology

21:43-21:45
local anesthetic pharmacology page,

21:45-21:46
which is a dreamboat.

21:46-21:50
There’s also a link to a Bayesian network meta-analysis,

21:50-21:51
which is a mouthful,

21:51-21:53
looking at which local anaesthetic agent

21:53-21:56
yields fastest onset for epidural anaesthesia

21:56-21:58
for emergent caesarean section.

21:58-22:01
Because some places use a confusing mix

22:01-22:03
of lidocaine, bicarb, and adrenaline,

22:03-22:05
which yields a rip-waringly fast onset time,

22:06-22:07
whereas most places I’ve worked

22:07-22:09
just stick 0.5% bubivacaine in,

22:10-22:12
but start topping it up in the delivery room

22:12-22:13
as you transfer to theatre.

22:14-22:15
I’m getting carried away again.

22:15-22:15
Have a nice week.

22:16-22:16
I’ll see you next time.

22:16-22:17
Cheers.

22:17-22:18
Thanks for listening, guys.

22:18-22:19
I hope you found it useful,

22:19-22:20
but if you found it awful,

22:20-22:21
do let me know.

22:21-22:22
Please like and subscribe,

22:23-22:24
register with whichever podcast platform

22:25-22:26
you find yourself using,

22:26-22:27
and leave a comment

22:27-22:28
if you think I need to square something away.

22:28-22:30
I just want to make sure

22:30-22:30
that you guys know

22:31-22:32
that every day you are getting better at this.

22:32-22:35
There is a bucket of content to try and consume,

22:35-22:37
and it is like drinking from a fire hose.

22:37-22:38
Take it day by day,

22:38-22:39
don’t overcook yourself,

22:39-22:40
don’t freak out,

22:40-22:41
and keep studying.