Metaraminol for the FRCA Primary + indirect vs direct mechanisms

Gas Gas Gas, Episode 59: Metaraminol

Episode overview

00:46-01:37

• Metaraminol is used constantly in anaesthetic practice, yet the published evidence base is remarkably thin.
• Episode structure: physicochemical properties, pharmacodynamics and pharmacokinetics, direct versus indirect acting agents, mechanism of action, then exam questions.

Hello everyone, and welcome to Gas Gas Gas. Today we’re covering metaraminol. This is a drug we use left, right and centre, but as you will ultimately come to learn across the course of this episode, there really isn’t that much published work on metaraminol, yet we seem to use it quite competently and confidently.

We’re going to cover the physicochemical properties of metaraminol, and then the pharmacodynamics and pharmacokinetics. Going to touch on indirect versus direct acting agents. The mechanism of action of metaraminol, which is not the easiest thing to identify through the joys of the internet, but I’ve had a good go. And then maybe a couple of questions at the end on metaraminol. You’re also going to find a question courtesy of the Teach Me Anaesthetics folks on metaraminol, just to, you know, try and focus on that exam as well.

What is metaraminol?

01:38-02:36

• Brand name: Aramine.
• A direct and indirectly acting alpha agonist that liberates catecholamines from neuronal stores.
• Used as a bolus and as an infusion intraoperatively to maintain blood pressure.
• Deranged Physiology (Dr Alex Yartsev) is the recommended source for wider reading.

Right oh. So, metaraminol. Brand name Aramine. And that’s an important one to know for those who are perplexed when the boss says, “Give me some Aramine.” Although you would probably have to be a near-retirement cardiac anaesthetist to be calling it Aramine.

Metaraminol is a direct and indirectly acting alpha agonist, liberating catecholamines from neuronal stores. It’s used as a bolus drug and as an infusion intraoperatively to maintain blood pressure, and to manage those pesky vasodilatory anaesthetic agents, and the vasoplegic sepsis in your patient who requires a laparotomy.

As I’ve already caveated, there is a paucity of data on metaraminol. The Deranged Physiology article, courtesy of Dr Alex Yartsev, is definitely a place to go for some additional interesting reading, if you’re curious, of course.

Physicochemical properties

02:37-03:50

• Synthetic sympathomimetic; structurally resembles a catecholamine but is not one.
• Stereoisomer: laevo- and dextro-isomers exist.
• Presented as a clear, colourless solution at 10 mg/mL, classically diluted to 0.5 mg/mL.
• Molecular weight 167 g/mol.
• Exam focus: name, isomer status, presentation. Molecular weight is unlikely to be asked.

Let’s get in amongst it with the pharmacology. We’re going to do physicochemical properties first. This drug’s name is metaraminol, brand name Aramine, and it is a synthetic sympathomimetic.

Its chemical makeup: I’m not going to go into excessive detail here, you certainly won’t get asked this in the exam, but it looks a little bit like a catecholamine, but not quite.

Its isomer status: indeed, it is a stereoisomer. There are laevo- and dextro-isomers of metaraminol.

It’s presented as a clear, colourless solution, 10 milligrams per mL, which is classically diluted to half a milligram per mL, or if you’re of the neuroanaesthetic variety in one of the local teaching hospitals to me, 0.2 milligrams per mL, because it’s more titratable. Which, you know, maybe it is, maybe it isn’t. I think it just makes it more confusing. But there we are. I would say 0.5 milligrams per mL, totally fair game.

And its molecular weight is 167 grams per mole. Simple enough.

In the exam, quick fire this, if you’re asked “tell me about metaraminol”: its name, its isomer status, how it is presented. They’re unlikely to ask you about molecular weight.

Pharmacodynamics and side effects

03:51-06:25

• Mild, clinically indistinguishable direct effects at alpha and beta adrenoceptors; chiefly an indirectly acting alpha agonist.
• Acts by displacing noradrenaline from catecholaminergic nerve endings.
• Onset 1–2 minutes IV; duration 20–30 minutes.
• Chief effect: increased SVR via vasoconstriction.
• Dosing: 0.5 mg bolus, or up to 15–20 mL/hour of a 0.5 mg/mL infusion.
• Effects: raised blood pressure, reflex bradycardia, increased myocardial contractility, reduced tidal volume and respiratory rate, reduced cerebral blood flow, increased glycogenolysis, inhibited insulin release.
• Cautions: uncontrolled hyperthyroidism, MAOIs, carcinoid syndrome. Phenylephrine is the safer choice in these patients.

Pharmacodynamics and side effects. So remember, this is what the drug does to the person. I would generally break it down into how the drug works, how long it takes to work, and how long it lasts, its chief effect, dosing, and then side effects.

So, metaraminol’s mechanism of action. It has mild and clinically indistinguishable direct effects on alpha and beta adrenergic receptors. So it is chiefly an indirectly acting alpha agonist. It does this by displacing noradrenaline from catecholaminergic nerve endings.

Onset time for an IV dose, 1 to 2 minutes. Duration of action, 20 to 30 minutes. You’re going to see it tapering off, obviously. And its chief effect is increasing systemic vascular resistance through vasoconstriction.

Dosing: generally half a milligram as a bolus, or up to 15 to 20 mL an hour of a standard 0.5 milligram per mL solution as an infusion.

As an aside, and do not say this in the exam, it has been administered to reasonable effect intramuscularly and subcutaneously. But do note there are also reports of extravasation necrosis with metaraminol.

Side effects, or effects, depending on how you look at it. You will see an increase in blood pressure and a reflexive drop in heart rate. It also causes increased contractility of myocardium, because it’s releasing noradrenaline. From a respiratory perspective, it may reduce tidal volumes and respiratory rate, but this is irrelevant in clinical practice. CNS-wise, you may see a reduction in cerebral blood flow due to the vasoconstriction. It can increase glycogenolysis and inhibit insulin release. Remember, these are noradrenergic effects.

And chief cautions: it doesn’t mix with patients who are in a heightened catecholamine state, i.e. patients with uncontrolled hyperthyroidism, patients on monoamine oxidase inhibitors, or those with rip-roaring carcinoid syndrome. Phenylephrine is a safer choice, because phenylephrine is pure, direct-acting alpha agonism.

I keep talking about direct and indirect. I’m going to cover this in a minute, okay?

Pharmacokinetics

06:26-08:02

• The literature is extremely sparse: roughly 1,290 Google Scholar results, against 139,000 for halothane.
• Absorption: given IV, so bioavailability is not a concern.
• Distribution: volume of distribution perhaps 4 L/kg (derived from rats); protein binding perhaps 45%. Think of nerve endings as the key compartment.
• Metabolism: essentially not metabolised. MAO and COMT do not touch it.
• Elimination: rapid redistribution into catecholaminergic neurons, then slow release over days, with clearance probably renal.

So, pharmacokinetic data on metaraminol. The literature is decidedly more arid than Kent in a heatwave. Really, scraping the barrel, which is an absolute juxtaposition to the frequency with which we use metaraminol.

If you search for metaraminol, or Aramine for example, on Google Scholar, you will see 1,290 results. Whereas if you’re looking for halothane, you’re looking at 139,000 results. That was in August. Absolutely bonkers that this is a drug we use every day when actually the paucity of data on it is astounding.

Anyhow, absorption. You’re going to give it IV. That means that you don’t need to worry about bioavailability, or how quickly it gets from a muscle to your effect site. We’re not worrying about that.

Distribution. Perhaps four litres per kilo, although that is calculated from rats. And its protein binding, perhaps 45%. From a distribution perspective, you need to envisage the fact that it is ending up in nerve endings. So that’s the compartment where you will find it slowly sequestering away.

Metabolism-wise, it is not really metabolised. Monoamine oxidase and catechol-O-methyltransferase don’t touch it. It’s not really metabolised.

Elimination-wise, no real numbers on this, but the thing to think about is that it quite rapidly redistributes in the human because it’s being sucked up by your catecholaminergic neurons. And it slowly ekes back out over days and is cleared, as far as I can figure out, renally. But don’t quote me on that.

Sponsor: Teach Me Anaesthetics

08:03-09:30

• Single best answer question bank written from the ground up for the FRCA Primary, with explainers, over 1,100 questions.
• Links from Gas Gas Gas are affiliate links and support the podcast.

Anyhow, time for a brief mention about the sponsors of Gas Gas Gas: Teach Me Anaesthetics. These guys are behind an excellent single best answer question resource.

Firstly, I took the joyful, challenging and intermittent bashing through their 1,100-plus questions, which they have written for the FRCA Primary exam. Now, I secretly loved it, and there are plenty of questions to test your knowledge.

When I was studying for the FRCA Primary it did not exist, but there were other packages online. These cost a lot more, and they didn’t really seem to reflect the content of the exams. Whilst doing them I came across rehashed MRCP questions, which was not terribly inspiring and left me pretty cheesed off. Whereas these single best answer questions have been built from the ground up. They have not sniffed an MCQ in a past life. They are based on the anaesthetic science you need to know, and there are explainers with all the questions, so it builds your knowledge as you work through them.

There is a multitude of ways you can study these questions. You could choose to do a random battle with 1,100-plus questions, or split them into subject area, or you can go back and redo the ones you’ve got wrong. It’s very malleable. So if you’ve been thinking about which question resource you might want to get your hands on for the exam, you shouldn’t really look any further than Teach Me Anaesthetics.

All the links to Teach Me Anaesthetics from Gas Gas Gas are affiliate links, so if you’re signing up through one of those, you’re helping to support Gas Gas Gas. So if you think you’re going to go for it, click a link with me. You know you want to. You’ll not only be supporting your exam preparation, but you’ll be supporting your 100% favourite tell-your-nan-over-Sunday-lunch podcast, which is of course Gas Gas Gas.

Direct versus indirect acting agents

09:31-12:35

• A direct agent reliably works on receptors when they are available to it.
• An indirect agent depends on the neuron having appropriate substrate or a primed enzyme available.
• Neither is inherently better. Direct agents are subject to receptor downregulation (dobutamine tachyphylaxis) and upregulation (cardiac transplant patients are exquisitely catecholamine-sensitive).
• Indirect agents fail at both extremes: overly primed tissue (carcinoid syndrome) or depleted neuronal stores, which is probably where metaraminol tachyphylaxis lives.

Okay, we probably need to think in a bit more detail about what indirect versus direct means, and perhaps think a little bit more closely about the mechanism by which metaraminol works, because that’s going to be some building blocks for thinking about noradrenaline, adrenaline, etc. later. When I say later, I mean in future episodes.

Direct versus indirect. When I started anaesthetic training, this constantly made my head hurt, because you’re talking about a drug and then you’re trying to remember, “Bloody hell, does that work on a receptor? Does that do something weird with an enzyme?” And it wasn’t until I sort of sat down and worked from back to front, as opposed to “think of a drug, how does it work”, to thinking about the mechanism and attaching a drug to it, that it really stuck in my mind.

So why do we care? The crux of what caring boils down to for direct versus indirect is two things. A direct agent reliably works on the receptors when they are available to it. Whereas indirect agents are reliant on the neuron having appropriate substrate, or an enzyme being available and primed, ready for action.

One is not better than the other necessarily, because there are caveats. From a receptor perspective, you can get receptor downregulation. You see this as a tachyphylaxis to dobutamine, and we’re going to touch on dobutamine later. Or upregulation of the receptor. So cardiac transplant patients are incredibly responsive to catecholamines, because their heart is relatively starved of sympathetic stimulus, so it sticks a ton more G protein coupled receptors of the alpha and beta adrenergic variety on its myocardial cells, because it’s craving them. So you give them a snifter of adrenaline and you see a massive response.

And then thinking about caveats of indirect agents. You can end up with overly primed neurons, or excessive tissues in the body being ready for action. Carcinoid syndrome is a great example: they’ve got a lot of ticklish cells that are pretty labile and ready to spaff out glorious quantities of neurotransmitters that can cause all sorts of mischief. Or your neurons are completely depleted of their catecholamines. There’s nothing left in the tank, you’re running on fumes. This might be where metaraminol tachyphylaxis lives.

So remember: direct, the drug acts on a receptor. Indirect, the drug is reliant on an endogenous system to mediate its action. In the case of metaraminol, displacing noradrenaline from vesicles. Or drugs which inhibit reuptake and thus lead to increased availability of catecholamines in synaptic clefts, like cocaine. Ephedrine’s a tricksy one, because it has mixed effects.

Mechanism of action: the noradrenaline switcheroo

12:36-15:15

• Metaraminol is taken up into the sympathetic neuron by the Uptake 1 system.
• From the cytoplasm it is loaded into storage vesicles by VMAT, the vesicular monoamine transporter, which relies on a proton gradient generated by a vesicular ATPase.
• Exactly why metaraminol then displaces noradrenaline is not well explained in the literature.
• The evidence is essentially black box: give metaraminol, measure noradrenaline, infer the mechanism.
• Exam tip: if you’re this deep, you’ve either passed or been led down a rabbit hole. Read the examiner’s body language and let them speak.

Right, so how is metaraminol achieving its switcheroo with noradrenaline? Where is this noradrenaline? It is in the little vesicles storing neurotransmitter near the synaptic clefts of the sympathetic nervous system.

How does it do it? So, we’ve given a bolus of metaraminol that’s soaking into your patient. It’s been well distributed, and it finds itself adjacent to a neuron in your sympathetic nervous system. That neuron, normally minding its own business, looking around for noradrenaline that it has released in order to take it back up again and use it again, inadvertently takes up the metaraminol using its Uptake 1 system. What is Uptake 1? We’re going to cover that in a second.

So this metaraminol now finds itself inadvertently floating around in the cytoplasm of our so-named sympathetic nerve. It minds its own business here until it is inadvertently taken up into a vesicle within that terminal bouton of our synaptic nerve. This is done by something called a VMAT protein, or a vesicular monoamine transporter protein. The clue’s in the name here: monoamine. Typically this would be looking around for adrenaline, noradrenaline, maybe a spot of dopamine, but it spots that metaraminol and says, “Oh well, gosh, you look a little bit like something I need. In you go.”

Now, VMATs move monoamines from cytoplasm to storage vesicles. They rely on a proton gradient courtesy of an ATPase you find on that vesicle. That proton gradient is used to pull noradrenaline in.

Why does metaraminol, when it’s in that vesicle, kick out noradrenaline? Is it just stopping those vesicles from taking up noradrenaline that they have been releasing of their own volition? I don’t think there’s a good answer to that. And if you’re being asked about that in the exam, you have definitely passed that station, or they’ve let you go down a massive rabbit hole. Always be guided by their body language and their ums and uhs, and if it looks like they’re trying to get a word in edgeways, let the examiner get a word in edgeways.

Hard to be 100% sure here. There is some research we’re going to go into a bit later that describes it in a sort of black box manner: I’ve given metaraminol, I’ve measured the noradrenaline in the patient, therefore something must occur that leads to this outcome. If you go deep enough, the science always seems to fizzle out with most things in anaesthesia.

Uptake 1 and Uptake 2

15:16-16:39

• Uptake 1: noradrenaline is pulled back into the neuron by NET, the noradrenaline transporter on the cell membrane, then stored in vesicles by VMAT for reuse.
• Uptake 2: extraneuronal clearance. Noradrenaline diffuses away into plasma and is broken down by MAO, or more often COMT.
• Net result: metaraminol displaces noradrenaline, which agonises alpha receptors, raising SVR and increasing myocardial contractility.

Anywho, earlier I mentioned Uptake 1. This is something we’re going to touch on in more detail when we look at adrenaline and noradrenaline, but the gist of it is that we are thinking about what happens to the adrenaline or noradrenaline that is released into the synaptic cleft in a patient.

Uptake 1 is the concept that the noradrenaline is pulled back into that neuron and squirrelled away in a vesicle for reuse. It does that through the NET, the noradrenaline transporter, found on the cellular membrane of that neuron. It then gets squirrelled away by VMAT into vesicles for reuse.

Whereas Uptake 2 is the clearance of adrenaline and noradrenaline from that site in an extraneuronal manner, i.e. the noradrenaline manages to diffuse away from the synaptic cleft, ends up in the plasma, and subsequently gets broken down by MAO, or more often COMT, which is your catechol-O-methyltransferase.

So the crux of it is: metaraminol displaces noradrenaline from vesicles. That noradrenaline goes off and agonises alpha receptors, which leads to an increase in vasoconstriction, i.e. SVR going up, but also mediates increased contractility of the myocardium. In a nutshell. Glorious.

If you just say it works indirectly, you could probably move on in the exam. But now you know a little bit more. Fun times.

Does metaraminol exhibit tachyphylaxis?

16:40-18:15

• The two camps: it’s useless after a few doses, versus it has direct action and lasts for ages.
• The middle ground: direct effects exist, but require a massive and unsafe dose.
• If you’re scraping the barrel early and late in an infusion, pick a different drug.
• Practical aside: peripheral noradrenaline can buy time while a central line is sited, subject to trust policy. A Leeds guideline exists describing how to do this relatively safely. Do not do it without consultant backing.

So now let’s move on to the question that does seem to bounce around: does metaraminol exhibit tachyphylaxis?

Some people say yes, it absolutely does, it’s a useless drug if you’ve given it for more than three and a half seconds, although I’m being hyperbolic there. And others say no, no, no, it has direct action as well as indirect action, it lasts for ages.

I would argue that we need to be a bit more in the middle, because it does have direct effects, but you have to give a massive dose, and a massive dose is not safe. Early in an infusion and later in an infusion, if you’re really scraping the heck out of the barrel, then you need to pick a different drug.

Which, in an emergency, as an aside: if you’re on ITU and you stumble across a patient who’s been on metaraminol all night and actually maybe shouldn’t have been, and now their systolic is something like 70, and you’re trying to get a central line in and it’s an absolute mess, you can run peripheral noradrenaline, depending on your trust. There is a guideline on the internet from Leeds which describes how to do it with a relative degree of safety, and it will buy you a little bit of time, and you’ll actually have a blood pressure to work with instead of the patient sitting with a systolic of 70 whilst you’re rushing to try and whack a central line in, that really it’d be better if you could do calmly and in a controlled manner. Your trust might not appreciate it, though, so don’t just pile in and do that without thinking a lot first. I do not recommend doing that without the boss’s backing. Unless you are the boss, of course, in which case, check out the guidelines.

The evidence: Harrison, Chidsey and Braunwald, 1963

18:16-23:48

• Anaesthetised, open-chest dogs. Systolic pressure and right ventricular contractile force measured. Two groups: reserpine-depleted and unreserpinised controls.
• Metaraminol produced a 125% increase in contractile force in controls, versus only 22% in the depleted animals. That 22% may represent the direct effect.
• Infusing noradrenaline into the reserpinised dogs progressively restored the response to metaraminol.
• Bolus arm: 500 µg/kg. Coronary sinus noradrenaline rose from 0.36 µg/L at baseline to 19.3 µg/L at 2 minutes, and was 3.23 µg/L at 15 minutes. Roughly a tenfold increase at 15 minutes.
• Scaled to a 75 kg adult, that bolus is 37.5 mg, almost four ampoules. Clinically indefensible.
• Infusion arm: 50 µg/kg/min. Pressor response fell to 10–20% of baseline by two hours, with tissue noradrenaline falling from 2.68 to 0.97 µg/g. Scaled to an adult, that is 225 mg/hour, over 20 ampoules.
• Take-home: there is evidence that metaraminol releases noradrenaline, that responses diminish over time, and that noradrenaline infusion reinvigorates the response.

Good. So, now that we’re imagining our septic patient on metaraminol who now has a really awful blood pressure: why has that occurred? The prevailing vibe is, well, they’ve just run out of noradrenaline in their nerve endings, and therefore it’s not working any more. But is there any research evidence for such an occurrence? And the answer is yes.

Harrison and Chidsey, in 1963, were experimenting on dogs. They were anaesthetised, fortunately. They had open chests, and they were measuring their systolic pressure and their right ventricular contractile force. There were two groups: one which were depleted of their catecholamines using reserpine infusions, and the other were fresh, unreserpinised controls.

They gave doses of metaraminol, 30 micrograms per kilo, and noted in the control group a 125% increase in contractile force of myocardium. Whereas in the reserpinised doggos, they only saw a 22% increase. You might be able to say, well, that 22% increase might be the direct effects. But also, the question is how much reserpine were they given? Were they entirely depleted of noradrenaline? Not sure.

Interestingly, they then went on to infuse noradrenaline into the reserpinised pooches, and noted that they progressively saw a return of response to metaraminol.

They then continued in what seems like a somewhat elaborate research protocol, where they’ve just given some drugs to some dogs and then tried something else. They went on to think, well, let’s measure noradrenaline concentrations in these animals also. They gave the dogs 500 microgram per kilo boluses, so half a milligram per kilo boluses, a big dose, and measured noradrenaline levels chiefly in their coronary sinuses. The background levels were 0.36 micrograms per litre, and at time plus two minutes the noradrenaline concentration was 19.3 micrograms per litre. And actually, at T plus 15 minutes, they found 3.23 micrograms per litre of noradrenaline. So a tenfold increase in circulating noradrenaline between time zero and time 15 in these animals.

I’d point out that if you were to scale that dose up to a standard 75 kilo adult, you’d be giving them 37.5 milligrams, which is a lot. That’s almost four ampoules of metaraminol. Absolutely not a smart move to do that in a human. It would clearly lead to rip-roaring hypertension and badness, potentially stroke, potentially myocardial strain.

And then finally, they infused the dogs with an infusion of metaraminol, comparing noradrenaline concentrations at time zero and at two hours. They did an infusion of 50 micrograms per kilo per minute, and noted that the pressor response reduced to 10 to 20% of its original value from time zero to time at two hours, noting their starting concentrations of noradrenaline. And noting there are different units here, folks: 2.68 micrograms per gram of blood, presumably, versus at the end of the infusion 0.97 micrograms per gram. So quite a bit less.

I’ll point out that that 50 micrograms per kilo per minute infusion, if you were to try and scale that up to an adult over an hour, that would be equivalent to giving them 225 milligrams of metaraminol. So over 20 ampoules of metaraminol in an hour. Again, the nurses are certainly going to be looking at you with indescribable horror if you make them draw up that much metaraminol. And you just wouldn’t.

Now, they were a bit coy in the paper about describing how much blood pressure changed. But if you look at the graphs, you could see that the systolic pressure in these dogs went up by up to 100 millimetres of mercury. So if you’ve got an adult with a blood pressure of 80 systolic, you might get them to 180 systolic. Now, I know that if I were to give an adult that dose of metaraminol, you would just see a terribly massive high blood pressure, 200, 250, 300. Because these are in dogs, and dogs and humans are closely related but not entirely related. Who knows if they actually produce less noradrenaline, or store less noradrenaline in their sympathetic nervous systems compared to us? Who knows?

I suppose what you can draw from this information is that there is research evidence to say metaraminol causes noradrenaline release. You will see diminishing responses over time. But interestingly, if you perhaps infuse people with noradrenaline, you reinvigorate that response.

Just trying to think if there are any times where you might be thinking, “Oh well, you know, their blood pressure’s a bit crap, but I don’t want to give them an increased rate of noradrenaline infusion, I’m just going to give them a bolus of metaraminol just to nudge that blood pressure up.” Maybe if you’re sedating a patient who’s on a noradrenaline infusion for some sort of procedure on ITU, you might think, well, metaraminol probably will work actually if they have a low blood pressure, instead of doing the dance with the noradrenaline. But I’m struggling to really think of a time. But yeah, email me if you have thought of a time when that may or may not be a thing.

SBA question: alpha-1 receptor signalling

23:49-26:41

Quick question: metaraminol up the nose

26:42-27:46

• Intranasal metaraminol vasoconstricts and reduces mucosal mass burden, improving visualisation of intranasal structures.
• Phenylephrine, not metaraminol, is the agent used clinically. Co-phenylcaine is lidocaine plus phenylephrine.
• Practical use: anaesthetising a sore nose to get an NG tube in.

Okay, next question. Very brief question, hopefully you’ll be able to answer this off the top of your nose. What effect does metaraminol have if squirted up the nose? And I can tell you, it’s vasoconstricting, as you might expect, and it reduces the mucosal mass burden in your schnoz.

Why is that useful? Well, better visualisation of intranasal structures, a bit like when they pack the nose full of cocaine.

And this is why you will find phenylephrine, not really metaraminol, phenylephrine, in Co-phenylcaine, a nasal spray that is lidocaine and phenylephrine. That is useful for anaesthetising the nose if you’re trying to put an NG tube in someone who has a really sore nose because they’ve had a bunch of NG tubes shoved in there, and you’re finding it not the most spacious of experiences for yourself and not very pleasant for your patient. Numbing up their nose is an excellent bargaining chip for trying to get that NG tube back in.

Summary

27:47-29:50

• Ubiquitous and generally safe at everyday anaesthetic doses.
• The ampoule is not one standard adult dose, unlike, say, 4 mg ondansetron. Inadvertent administration of a whole ampoule can cause a hypertensive episode, stroke, myocardial strain or MI, and per the eMC, vasoconstriction leading to convulsions.
• Indirect alpha agonist releasing noradrenaline in the sympathetic nervous system.
• 0.5 mg bolus, or up to 15 mg/hour as an infusion.
• Not readily metabolised. Sequestered by the sympathetic nervous system and released over days.
• Avoid in uncontrolled hyperthyroidism, carcinoid syndrome and patients on MAOIs.

Okay, so in summary, we know that metaraminol is a ubiquitous and generally safe drug in the doses we use day to day in anaesthetic practice.

It’s important to point out that, as with other vasoactive agents, the ampoule does not represent one standard adult dose. You know, four milligrams of ondansetron, you give the ampoule, don’t you? And inadvertent administration of an ampoule of metaraminol will certainly cause a hypertensive episode. You could certainly lead to stroke, myocardial strain, MI, etc. Or vasoconstriction that leads to convulsions, if you’re reading the eMC compendium website on metaraminol.

It is an indirect alpha agonist, releasing noradrenaline in the sympathetic nervous system. 0.5 milligram bolus, or up to 15 milligrams per hour as an infusion.

It is not readily metabolised. It is generally sequestered by the sympathetic nervous system and ekes out and is released over days after administration.

Its side effect profile is generally well tolerated, and you shouldn’t mix it with uncontrolled hyperthyroid patients, those with carcinoid syndrome, or those on monoamine oxidase inhibitors.

Certainly have a look at the references in the show notes for the available literature on metaraminol that has some interest.

And that’s it, folks. Thanks again for listening to another episode of Gas Gas Gas. I’ve now somehow managed to end up with 2,100 people just on Spotify who are following, subscribed, whatever you want to call it, which is mad. I hope you all are getting something out of it. See you next time.

Outro

29:51-30:41

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Reference cited in this episode

Harrison DC, Chidsey CA, Braunwald E. Studies on the mechanism of action of metaraminol (Aramine). Annals of Internal Medicine 1963;59(3):297–305. doi:10.7326/0003-4819-59-3-297