sugammadex dosing

[coffeebythelake]

Per sugammadex labeling we are told to use 2 mg/kg for 1-2 twitches, 4 mg/kg for 1-2 PTC, and 16 mg/kg for RSI rocuronium reversal. I understand the simplistic nature of this to combine drug dose given and pharmacokinetics/pharmacodynamics, but I can only think how irrelevant this type of dosing is especially in patients with profound neuromuscular disease (e.g., myasthenia gravis), where you could obtain very significant weakness even with minimal doses of rocuronium.

From a theoretical perspective, we know that sugammadex has an incredibly high affinity constant to rocuronium, and given the 1:1 encapsulation we have a theoretical dose ratio of 3.57 mg sugammadex : 1 mg rocuronium.

Thoughts?

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[dchz]

Need source on molecular weight of roc and sugammadex.

Too lazy to look it up, but if you have the molecular weight it's just easy math imo.

 

[coffeebythelake]

Need source on molecular weight of roc and sugammadex.

Too lazy to look it up, but if you have the molecular weight it's just easy math imo.

based on molecular weights
3.57 mg sugammadex : 1 mg rocuronium

 

[dchz]

based on molecular weights
3.57 mg sugammadex : 1 mg rocuronium

sorry i lied.

That is only true when YOU GIVE BOTH DRUGS AT THE SAME TIME. But the pharmacokinetics of roc is WAY faster than that of sugammadex (which is inert and doesn't break down if i recall correctly, can stay upto 6hrs in the intravascular space with no significant metabolism (don't have source but i read it in a reliable source somewhere)). By the time you reverse, a majority of the roc is metabolized. So it's probably 10:1 or 20:1. 🙂

Furthermore, Sugammadex acts as another compartment to sink more aminosteroids into, rather than the classic drug that competitively antagonizes.

Key point: Sugammadex does not diffuse into another compartment, so the intravascular compartment is always constant. but the pharmacokinetics of the amino steroids are different, they get broken down very fast.

That's one of the key advantages of the cyclodextrins, they are there constantly to act as a sink while neo/glyco only competitively antagonizes and has much faster pharmacokinetics (shorter effect time) compared to sugammadex.

I do agree that the sugammadex dose of 2mg/kg of ACTUAL body weight is an overdose. But the side effect profile of the drug is so low that over dosing an inert cyclodextrin isn't that big of a deal.

Even if you give in a dose of 1:1 instead of 3.57:1, the above advantages of acting as a constant inert sink while the aminosteroids are metabolized still makes it extremely effective. (which is also a very interesting thought experiment. I didn't pursue this as a research project/real experiment because the effective cost saving would be very minimal unless you are multi-dosing a 200mg vial of sugammadex.)

 

[deleted697535]

Practically speaking having used it on every patient for 6 months, it all.depends on the need and how quick you need it.

Failed rsi with cico is 16 per kg but I've never seen that.

Anything else just give 50 or 100mg and wait a few mins longer. Say if I had 4 patients for the day I'd give 50 roc for each case to tube, then 50mg each of suggamadex 2 mins prior to extubate. That's all the avg dude needs. And you only need 1 200mg vial for the day then. It's amazing how quickly and well it works!

 

[coffeebythelake]

sorry i lied.

That is only true when YOU GIVE BOTH DRUGS AT THE SAME TIME. But the pharmacokinetics of roc is WAY faster than that of sugammadex (which is inert and doesn't break down if i recall correctly, can stay upto 6hrs in the intravascular space with no significant metabolism (don't have source but i read it in a reliable source somewhere)). By the time you reverse, a majority of the roc is metabolized. So it's probably 10:1 or 20:1. 🙂

Furthermore, Sugammadex acts as another compartment to sink more aminosteroids into, rather than the classic drug that competitively antagonizes.

Key point: Sugammadex does not diffuse into another compartment, so the intravascular compartment is always constant. but the pharmacokinetics of the amino steroids are different, they get broken down very fast.

That's one of the key advantages of the cyclodextrins, they are there constantly to act as a sink while neo/glyco only competitively antagonizes and has much faster pharmacokinetics (shorter effect time) compared to sugammadex.

I do agree that the sugammadex dose of 2mg/kg of ACTUAL body weight is an overdose. But the side effect profile of the drug is so low that over dosing an inert cyclodextrin isn't that big of a deal.

Even if you give in a dose of 1:1 instead of 3.57:1, the above advantages of acting as a constant inert sink while the aminosteroids are metabolized still makes it extremely effective. (which is also a very interesting thought experiment. I didn't pursue this as a research project/real experiment because the effective cost saving would be very minimal unless you are multi-dosing a 200mg vial of sugammadex.)

I agree with your statements. we expect rocuronium levels to decrease over time such that the ratios would skew even more in favor of less sugammadex. Agree side effect profile is minimal. But the sugammadex dosing as recommended is overdose, and potentially COSTLY

 

[stepone2015]

I've only used it on one patient with mg but there were no issues with standard dosing.

Is it super expensive where you work? My hospital system, it's slightly more expensive. No attending cares which you do as long as you know how to use both. I get a handful of vials every day, and there are some surgeons that are like 'HOLY ****, HE'S POST TETANIC, HOW AM I SUPPOSED TO OPERATE???!@?!?', so I keep 'em super paralyzed and just sugammadex the **** out of 'em. This is only when their pressures don't tolerate more anesthesia...

Also, I do use that dosing strategy by twitches, but I usually round up a fair bit, by 50-100 mg usually because their weights are never accurate.

 

[yobynaes]

... some surgeons that are like 'HOLY ****, HE'S POST TETANIC, HOW AM I SUPPOSED TO OPERATE???!@?!?'

There are surgeons who are able to say the words "post tetanic?" I thought they are only able to utter "ehh.. patient is awake."

 

[fakin' the funk]

Gave 3/kg sugammadex to a pt with 0/4 TOF and 10 PTC the other day and --> 4/4 with 5sec tetany and no fade in 120 seconds.

That **** is amazing.

 

[Psai]

Has anyone used neostigmine/glyco then sugammadex because the patient looked floppy or not ready for extubation for whatever reason?

 

[deleted126335]

Has anyone used neostigmine/glyco then sugammadex because the patient looked floppy or not ready for extubation for whatever reason?

Yes. Neostigmine failure is our most common reason for using suggsmadex. (Pharmacy is all over us on this drug). If not for pressure from pharmacy we would use it routinely.


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[Mman]

I agree with your statements. we expect rocuronium levels to decrease over time such that the ratios would skew even more in favor of less sugammadex. Agree side effect profile is minimal. But the sugammadex dosing as recommended is overdose, and potentially COSTLY

are you using the vials as multipatient multidose vials?

 

[Psai]

Yes. Neostigmine failure is our most common reason for using suggsmadex. (Pharmacy is all over us on this drug). If not for pressure from pharmacy we would use it routinely.


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I've only had two issues with neo likely due to timing of roc/patient comorbidities (neuromuscular disease) but I was wondering if the dose of sugammadex should change since you already "reversed".

Also I don't get where they get 16 mg/kg for reversal after giving double dose roc, seems like papers that study its pharmacodynamics say you need about 6 mg/kg for full reversal of roc. This seems to jive with the 3.57:1 that people are saying above if I did the math right.

 

[Mman]

Also I don't get where they get 16 mg/kg for reversal after giving double dose roc, seems like papers that study its pharmacodynamics say you need about 6 mg/kg for full reversal of roc. This seems to jive with the 3.57:1 that people are saying above if I did the math right.

I believe it is from dose finding studies in patients. I participated in some of those as a resident. We'd be blinded to what dose we were giving and the patients had very fancy NMB monitors hooked up. They'd keep track of time from various twitch levels to full reversal.

 

[narcotics999]

Has anyone used neostigmine/glyco then sugammadex because the patient looked floppy or not ready for extubation for whatever reason?

y, I usually gave 50mg. Worked very well.

 

[deleted875186]

I remember a study on dosing showing times to full reversal with 0.5, 1, 2, 4 mg/kg. From what I recall, even 0.5 mg/kg worked if there were twitches but just took a bit longer. I personally never use more than 200 mg vial, even if I have a 150 kg morbidly obese patient. Just make sure to check for sustained tetany after reversal.

 

[AdmiralChz]

Has anyone used neostigmine/glyco then sugammadex because the patient looked floppy or not ready for extubation for whatever reason?

Yes, several times as staff. It works wonders!

I remember a study on dosing showing times to full reversal with 0.5, 1, 2, 4 mg/kg. From what I recall, even 0.5 mg/kg worked if there were twitches but just took a bit longer. I personally never use more than 200 mg vial, even if I have a 150 kg morbidly obese patient. Just make sure to check for sustained tetany after reversal.

Totally agree. Unless it’s the mega rare instance where you just gave a huge induction dose and you need emergent reversal immediately, 200 mg is all you’d really ever need.

Don’t fall for the trap, the 500 mg vial is much more expensive than the 200 for a reason.

 

[Hork Bajir]

Anyone worry about the fact that overdose of neostigmine itself can cause paradoxical neuromuscular weakness? If you reverse with neostigmine, then give sugammadex and soak up all the remaining roc, isn’t this pharmacologically equivalent to giving a large dose of neostigmine alone? I guess as long as you’re monitoring block at least semi-quantitatively you’re prob gonna be fine, but at least an interesting theoretical concern, no?

 

[Psai]

Thanks guys. Also about the post tetanic, it's amazing that surgeons used to operate without anesthesia but nowadays, a pinkie toe twitches and the surgeons are falling all over themselves complaining that they can't put the head dressing on properly. Dawg you don't need negative twitches to wrap some kerlix jesus christ

 

[MirrorTodd]

How often are you all seeing anaphylaxis using sugammadex? My attending last night quoted me an incidence of 1:300 when I used it after a lap appy, she would've much preferred I use glyc/neo.

 

[Psai]

How often are you all seeing anaphylaxis using sugammadex? My attending last night quoted me an incidence of 1:300 when I used it after a lap appy, she would've much preferred I use glyc/neo.

More like 1:3000.

That's why I don't use ancef or roc. Because of the risk of anaphylaxis.

 

[nimbus]

How often are you all seeing anaphylaxis using sugammadex? My attending last night quoted me an incidence of 1:300 when I used it after a lap appy, she would've much preferred I use glyc/neo.

That sounds awfully high. I should have seen at least a couple cases by now. I’ve seen none. It’s hard to know the true incidence of anaphylaxis but it seems very low.


Sugammadex: The Anaphylactic Risk - Anesthesia Patient Safety Foundation

Sugammadex and rocuronium-induced anaphylaxis


Sugammadex-induced anaphylaxis
Confirmed cases of allergic reactions to clinical doses of sugammadex have been recently reported [11, 12]. However, the number of reports of sugammadex-induced anaphylaxis is much less than those for NMBAs [12, 13]. To date, the Japanese Society of Anesthesiologists has issued a warning about sugammadex-induced anaphylactic shock five times since March 2011. The third one, issued in June 2013, included 95 cases of sugammadex-related allergies that occurred between April 2010 and January 2013, although with no incidents of death. In all 95 cases, the relationship between the reaction and sugammadex was definitively ascertained by the attending anesthesiologists. Seventy-eight of the 95 cases fulfilled the validation criteria for anaphylaxis. The incidence rate of anaphylactic reactions due to sugammadex was estimated as 29 per million cases (1:34,483), based on the estimated number of patients (3.09 millions) in whom sugammadex was injected during the survey period. The alert also pointed out that the incidence rate may have been underestimated, because the survey was based on spontaneous reports from anesthesiologists and not on prospective studies. It is uncertain whether this incidence rate is higher in Japan than in other countries, because there is no epidemiological survey regarding this so far. The other possibility is that these warnings may simply reflect a high level of sugammadex usage in Japan. The drug company, MSD (Tokyo, Japan), has reported that sugammadex usage in Japan in 2010, in terms of monetary value, was more than four times higher than that in Spain, the country that showed the second-highest usage in the world [11].

 

[btbam]

Isn't the supposed high rate of anaphylaxis the reason it took so long to get approved in the U.S. market?

 

[anbuitachi]

i know some people that just give 500 to everyone (unless need more) because the vial they have is 500 and it's 1 vial per patient

 

[26B]

i know some people that just give 500 to everyone (unless need more) because the vial they have is 500 and it's 1 vial per patient

That's how it is where I train, but with 200 mg vials. We have 200 and 500mg vials of Sugammadex. Most patients get 200mg because once you've given 2 mg/kg, you've given most of the vial anyway.

On a few occasions I've given a small bolus of 50 mg prior to giving the rest of the 2 mg/kg dose, and every single time the patient achieved 4/4/tetany/no fade within 2-3 minutes even before the remainder of the Sugammadex was given.

 

[Gern Blansten]

i know some people that just give 500 to everyone (unless need more) because the vial they have is 500 and it's 1 vial per patient

If they didn't want you to give it all, they wouldn't have put it in the vial...

 

[Iso4ane]

If they didn't want you to give it all, they wouldn't have put it in the vial...

I say they are already paying for the full vial if you crack it open. What’s the difference between 150mg at 2mg/kg and 200mg at 2.66mg/kg.

The only reason why we dose it mg/kg is that’s how the studies were done. Arguably we should be able to dose the Suga based off total NMBs given. And thinking off the wall, if 200mg is good enough for Roc. 50mg or even less should be good enough for Vec.

 

[Urzuz]

I say they are already paying for the full vial if you crack it open. What’s the difference between 150mg at 2mg/kg and 200mg at 2.66mg/kg.

I think you should make it a point to use the minimum amount of drug necessary to achieve a desired effect. Though I'm certain you it would be tough be able to detect a difference in side effects/morbidity between 2 mg/kg and 2.66 mg/kg of sugammadex, as a general policy when it comes to injecting people with drugs, less is more.

The same reasoning you presented is what causes some people to give 90 year old grandmas 2 mg of midazolam before the start of a case...

 

[deleted162650]

or even less should be good enough for Vec.

I thought binding affinity for vec was less than for roc??

 

[drmwvr]

I think you should make it a point to use the minimum amount of drug necessary to achieve a desired effect. Though I'm certain you it would be tough be able to detect a difference in side effects/morbidity between 2 mg/kg and 2.66 mg/kg of sugammadex, as a general policy when it comes to injecting people with drugs, less is more.

The same reasoning you presented is what causes some people to give 90 year old grandmas 2 mg of midazolam before the start of a case...

Except with versed in that case is none is more.

 

[Psai]

I say they are already paying for the full vial if you crack it open. What’s the difference between 150mg at 2mg/kg and 200mg at 2.66mg/kg.

The only reason why we dose it mg/kg is that’s how the studies were done. Arguably we should be able to dose the Suga based off total NMBs given. And thinking off the wall, if 200mg is good enough for Roc. 50mg or even less should be good enough for Vec.

I use the same reasoning with phenylephrine and epi

 

[Iso4ane]

I thought binding affinity for vec was less than for roc??

It is. But how much less is it? Is it more than a factor of 10? The MoA is binding 1:1 with Roc. Vec roughly the same MW as Roc (off anything it heavier), but we dose it by a factor of 10 less than Roc. So if it was as effective binding Roc the theoretically we should be able to get by with ~a tenth of the dose.