Why don't paralytics stop the heart?

[FiremedicMike]

With the exception of succs and degenerative muscular disorders, why don't paralytics also effect the muscle tissue in the heart?

I figured I'd ask here since you guys/gals are not only the physiology experts, but also the ones who use paralytics more than anyone else.

Thanks!

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[G0S2]

With the exception of succs and degenerative muscular disorders, why don't paralytics also effect the muscle tissue in the heart?

I figured I'd ask here since you guys/gals are not only the physiology experts, but also the ones who use paralytics more than anyone else.

Thanks!

Does the cardiac tissue contract due to nicotinic stimulation?

 

[periopdoc]

The quick and dirty...

Paralytics work at the nicotinic acetylcholine receptor in the neuro-muscular junction of skeletal muscle tissue to inhibit transmission of stimulatory impulses from the nervous system to the muscle.

Cardiac muscle fibers have intrinsic automaticity (and some other unique physiologic features) and do not require the same type of stimulation from the nervous system for organized beat to beat contraction.

The nervous system acts on the heart to increase or decrease this baseline contractile function and it does so through a different type of receptor than is used at the neuromuscular junction of skeletal muscle.

Therefore, the drugs that are designed to inhibit transmission of impulses at the nicotinic acetylcholine receptor do not have an effect on the heart. The examples you gave of an effect on the heart do not happen because of a direct effect of the drug on the heart, they are an effect of the physiologic derangement brought about by the influence of these drugs.


- pod

 

[pgg]

To expand on what's already been written -

Nondepolarizing drugs (like rocuronium, vecuronium, cis-atracurium, etc) block the nicotinic receptor at the neuromuscular junction. Succinylcholine is a depolarizing muscle relaxant that is an agonist at the nicotinic receptor.

There are acetylcholine receptors in the heart and smooth muscle elsewhere but they're muscarinic receptors, and not directly tied to contraction - they're part of the parasympathetic ANS.

This is why when we reverse neuromuscular blockade with neostigmine (an acetylcholinesterase inhibitor that results in more acetylcholine being around) we also give glycopyrrolate (a muscarinic receptor blocker) ... otherwise the muscarinic effects of the neostigmine would cause bradycardia (and other effects like nasty abdominal cramps and poopin').


A fun rookie mistake is to reverse a patient with only neostigmine because they're tachycardic and you think you don't "need" the glycopyrrolate to prevent bradycardia. 🙂

 

[Yangkower]

Guilty, did it in a young trauma patient when I was a CA1. His HR was 110-120 throughout the case despite treatment (Fluids, Beta Blocker, opioids), so I reversed with Neo only. I fixed his fast heart rate (for several minutes he was in the 60s) : ) It was pretty harmless for this kid, but I have been very careful every since.

 

[FiremedicMike]

Thanks guys, I knew you'd not disappoint me!

 

[Mman]

This is why when we reverse neuromuscular blockade with neostigmine (an acetylcholinesterase inhibitor that results in more acetylcholine being around) we also give glycopyrrolate (a muscarinic receptor blocker) ... otherwise the muscarinic effects of the neostigmine would cause bradycardia (and other effects like nasty abdominal cramps and poopin').

Glycopyrrolate does not prevent the muscarinic effects of neostigmine on the colon.

 

[pgg]

Glycopyrrolate does not prevent the muscarinic effects of neostigmine on the colon.

Really? Guess I need to open a text again. 🙂

 

[Mman]

I didn't think they did because of anecdotal stories from ICU nurses who could always tell which patients we reversed prior to dropping off and which we didn't. Browsed the lit and found some small studies on GI patients describing infusions of glycopyrrolate and neostigmine to treat bowel obstruction successfully.

 

[Bertelman]

I wouldn't generally trust ICU RN anecdotes to supplement my medical knowledge.

 

[pgg]

I didn't think they did because of anecdotal stories from ICU nurses who could always tell which patients we reversed prior to dropping off and which we didn't. Browsed the lit and found some small studies on GI patients describing infusions of glycopyrrolate and neostigmine to treat bowel obstruction successfully.

I haven't looked it up yet, being between cases ... but I do remember an occasion when I was doing a ward month way back, the GI guys treated a case of Ogilvie syndrome / colonic pseudo-obstruction with 1 mg of neostigmine because the fellow didn't feel like doing a decompressing colonoscopy at 3 AM. She did NOT give the patient glyco also. That patient was cured but didn't enjoy the experience...

A classmate of mine tried the neostigmine without glyco reversal one day and code brown'd in what was reported to be spectacular fashion. I think the glyco must do something for postganglionic parasympathetics in the colon.

 

[Mman]

I wouldn't generally trust ICU RN anecdotes to supplement my medical knowledge.

Nor would I. But you'd be stupid to ignore tidbits from smart people with 30 or more years experience with what they do.

That's why you then go research it and see the evidence for yourself. There is decent evidence in the medical literature that glyco doesn't prevent the GI effects of Neostigmine.

 

[Bertelman]

Nor would I. But you'd be stupid to ignore tidbits from smart people with 30 or more years experience with what they do.

That's why you then go research it and see the evidence for yourself. There is decent evidence in the medical literature that glyco doesn't prevent the GI effects of Neostigmine.

Help us out, then, since you've made the definitive statements here. What small studies did you browse, what did they say, and how exactly did these experienced nurses know which patients were reversed? What objective data were they using?

Your original statement was an absolute, which isn't necessarily supported with your report of "decent evidence." What you seem to be saying is there is anecdotal ICU experience as well as decent medical evidence that suggests glyco may not prevent muscarinic s/e in the gut. That's very different than your original statement, so maybe excuse us just a little for challenging your assertions.

 

[Mman]

Help us out, then, since you've made the definitive statements here. What small studies did you browse, what did they say, and how exactly did these experienced nurses know which patients were reversed? What objective data were they using?

Your original statement was an absolute, which isn't necessarily supported with your report of "decent evidence." What you seem to be saying is there is anecdotal ICU experience as well as decent medical evidence that suggests glyco may not prevent muscarinic s/e in the gut. That's very different than your original statement, so maybe excuse us just a little for challenging your assertions.

testy aren't we?

http://www.nimbot.com/Med/Articles/Other/Neostigmine–Glycopyrrolate for Bowel Evacuation in SCI.pdf

http://www.nejm.org/doi/full/10.1056/NEJM199911183412115

http://rd.springer.com/article/10.1007/s10620-008-0216-z

I'm not at work so I can't go do a PubMed search for you. Maybe you could do it yourself and get back to us.

But the moral of the story is glyco doesn't prevent the GI effects of neostigmine.



As to my tale of the ICU nurses making jokes about which patients got reversal and which didn't, they noticed the frequent code browns on some patients that happened to have been given NMB reversal as opposed to the ones left paralyzed. When somebody that's been doing something a long time makes a clinical observation, it'd be stupid to totally ignore it.

 

[Impromptu]

Has anyone ever given neostigmine to a patient who has had a heart transplant? I did at the end of a diagnostic cath/biopsy in an 8 year old and the heart rate decreased from a pre-neostigmine steady rate of 67 bpm the entire case down to 47 bpm post-neostigmine. I wasn't expecting that and hadn't given glycopyrrolate, because I didn't think it would have done any good.

In my brief search since then it is thought that the transplanted heart, though denervated, has post-ganglionic parasympathetic ganglia which may spontaneously release acetylcholine or be stimulated by an increase in acetylcholine from neostigmine (edrophonium in the studies I looked at). The bradycardia is not as significant as in normal hearts, but can occur in the transplanted heart. Also, atropine and probably glycopyrrolate may prevent that.

 

[Robert Loblaw]

testy aren't we?

http://www.nimbot.com/Med/Articles/Other/Neostigmine–Glycopyrrolate for Bowel Evacuation in SCI.pdf

http://www.nejm.org/doi/full/10.1056/NEJM199911183412115

http://rd.springer.com/article/10.1007/s10620-008-0216-z

I'm not at work so I can't go do a PubMed search for you. Maybe you could do it yourself and get back to us.

But the moral of the story is glyco doesn't prevent the GI effects of neostigmine.



As to my tale of the ICU nurses making jokes about which patients got reversal and which didn't, they noticed the frequent code browns on some patients that happened to have been given NMB reversal as opposed to the ones left paralyzed. When somebody that's been doing something a long time makes a clinical observation, it'd be stupid to totally ignore it.

Haven't reviewed the citations and have no interest in playing favorites, but I would anticipate that a reversed patient is more likely to cough/valsalva and that the suvsequent rise in IA pressure/vagal tone could be an additional causative 'agent.'.

 

[soorg]

One thing I never understood is if paralytics only work on skeletal muscle, then why does a patient stop breathing if they are given them? The diaphragm is smooth muscle.

 

[btbam]

One thing I never understood is if paralytics only work on skeletal muscle, then why does a patient stop breathing if they are given them? The diaphragm is smooth muscle.

It's skeletal.

 

[soorg]

Oops. Too much beer in my cereal this morning...

 

[epidural man]

A fun rookie mistake is to reverse a patient with only neostigmine because they're tachycardic and you think you don't "need" the glycopyrrolate to prevent bradycardia. 🙂

Not so fun if the resident makes your patient asystolic - which I have seen from lack of glyco.

 

[BobBarker]

Oops. Too much beer in my cereal this morning...

and all along I thought I was the only one who drowned his raisin bran in coors original.

 

[jetproppilot]

A fun rookie mistake is to reverse a patient with only neostigmine because they're tachycardic and you think you don't "need" the glycopyrrolate to prevent bradycardia. 🙂

HUH?

A fun ROOKIE mistake?

Dude you are

HILARIOUS!!!!

AND WRONG!!!!!



There is no

ROOKIE

in decreasing or eliminating glycopyrrolate in the tachycardic, dude.

Why are you propagating that?

That's simply

NOT TRUE.

Tachycardia doesn't need muscarinic receptor blockade concerning neuromuscular blockade reversal.

BTW, ASK NOYAC ABOUT HIS USE OF NEOSTIGMINE

IN CABG CASES.

 

[jetproppilot]

Not so fun if the resident makes your patient asystolic - which I have seen from lack of glyco.

Yes, but not in a
tachycardic patient.

With tachycardia and neuromuscular reversal, one can

EXPLOIT

the bradycardic tendencies of neostigmine!

TURNS OUT, SOMETIMES YOU CAN EXPLOIT THE "BAD" PART OF A DRUG, AND TURN IT INTO A POSITIVE.

A patient with a heart rate of 130 (assuming you want to decrease the heart rate...i.e. heart rate is not due to hypovolemia, low hematocrit, etc)

WILL BENEFIT BY GIVING A REVERSAL OF NEOSTIGMINE.

In this clinical setting you

WANT

a slower heart rate,

SO WHY NOT EXPLOIT THE PHARMACOLOGIC

"downside"

OF THE DRUG?

SANS GLYCO?

 

[MTGas2B]

Has anyone ever given neostigmine to a patient who has had a heart transplant? I did at the end of a diagnostic cath/biopsy in an 8 year old and the heart rate decreased from a pre-neostigmine steady rate of 67 bpm the entire case down to 47 bpm post-neostigmine. I wasn't expecting that and hadn't given glycopyrrolate, because I didn't think it would have done any good.

.

Yes.

60 some year old, ten years out from his heart transplant, back for his kidney transplant. Ten year of tacro knocked off his beans.

Hemodynamically stable throughout the case. Neostigmine knocked him down. A whiff of epi works nice in that case.

 

[MTGas2B]

Yes, but not in a
tachycardic patient.

With tachycardia and neuromuscular reversal, one can

EXPLOIT

the bradycardic tendencies of neostigmine!

TURNS OUT, SOMETIMES YOU CAN EXPLOIT THE "BAD" PART OF A DRUG, AND TURN IT INTO A POSITIVE.

A patient with a heart rate of 130 (assuming you want to decrease the heart rate...i.e. heart rate is not due to hypovolemia, low hematocrit, etc)

WILL BENEFIT BY GIVING A REVERSAL OF NEOSTIGMINE.

In this clinical setting you

WANT

a slower heart rate,

SO WHY NOT EXPLOIT THE PHARMACOLOGIC

"downside"

OF THE DRUG?

SANS GLYCO?

Almost routinely I will decrease my neo/glyco ratio below the classic 1/0.2. I usually put 0.8 mg of glyco with 5 mg neostigmine. For the markedly tachy patient, I'll give even less. For the frighteningly brady, but stable, I'll go back to the 1 to 0.2.

And not revisit an old issue, I am a mixer.

 

[jetproppilot]

Almost routinely I will decrease my neo/glyco ratio below the classic 1/0.2. I usually put 0.8 mg of glyco with 5 mg neostigmine. For the markedly tachy patient, I'll give even less. For the frighteningly brady, but stable, I'll go back to the 1 to 0.2.

And not revisit an old issue, I am a mixer.

Would you

EVER CONSIDER THE

SCANDULOUS

administration of

NAKED NEOSTIGMINE??



(btw sometimes it's ok dude)

 

[pgg]

HUH?

[...]

Tachycardia doesn't need muscarinic receptor blockade concerning neuromuscular blockade reversal.

You're right, it doesn't; I never said it did.

The risk with 'naked neostigmine' as you put it, in tachycardic patients, is the non-cardiac muscarinic effects. Salivation (slobbery airway), GI tract effects (abd cramps), etc.

It's just an unpleasant way to wake up.

I almost never give a 1:1 ratio of neostigmine:glycopyrrolate. If I give a full 5 mg of neostigmine, usually I'm looking at 0.4 mg of glycopyrrolate. Though I'll adjust that based on HR, I never skip the glycopyrrolate entirely.

Of course, I try not to have undesired tachycardia when it's reversal time, and so I very rarely find myself needing to really exploit neostigmine's effects on HR.

I've seen enough code browns and snotty patients in the PACU from other people getting cute with the 'naked neostigmine' trick (at least the HR is 60 🙂) to have no real desire to play that game.

 

[MTGas2B]

Would you

EVER CONSIDER THE

SCANDULOUS

administration of

NAKED NEOSTIGMINE??



(btw sometimes it's ok dude)

Reminds me of a story a Navy general surgeon told me. Some SEAL/spec ops super fit secret squirrel kind of dude is in the surgeon's office as a patient. Surgeon asks him to remove his pants for an exam. Patient does, no underwear. Surgeon looks perplexed. Patient responds, "Doc, panties are for chicks."

Anyway, random thought when you mentioned naked.

Back to the thread.

 

[Mman]

I've seen enough code browns and snotty patients in the PACU from other people getting cute with the 'naked neostigmine' trick (at least the HR is 60 🙂) to have no real desire to play that game.

There is no evidence in the literature that glyco prevents the GI effects of Neostigmine. There is evidence that it does not.

 

[soonerfrog]

I would argue glyco does not prevent but rather attenuates the cholinergic effects of neostigmine. Are you saying that by the time you see brady effects from Neostigmine you're not also going to have an aggregated an noticeable triggered parasympathetic GI surge as well? Those symptoms are cholinergic in nature, specifically muscarinic. I can't help but believe the addition of glyco is essentially a class 2b intervention at this point ie, can't hurt, may or may not help. Besides, isn't this the reason he good Lord gave us drugs like Esmolol?

 

[pgg]

There is no evidence in the literature that glyco prevents the GI effects of Neostigmine. There is evidence that it does not.

I did look at the articles you posted earlier, and especially the 3rd one has some interesting things to say, namely

Facial and tongue fasciculations
were noted by 92% of subjects who received neostigmine
alone. Addition of glycopyrrolate did not change the likelihood
of this reaction (89%). This was also the case for other
symptoms, such as diaphoresis and salivation.

I've seen patients get 1 mg of 'naked neostigmine' from the GI guys to treat Ogilvie's and for the next 30 minutes they have gut-wrenching abd cramps and usually their GI motility kicks in quick.

So why we don't see the same thing every time we reverse NMBDs with neostigmine, if not for the glycopyrrolate? Is there something else we're doing that prevents patients from getting all the unpleasant cholinergic side effects despite receiving up to ~5 mg of neostigmine?

I have difficulty accepting that the glyco does nothing, given the times I've seen the 'naked neostigmine' trick result in a PACU patient enduring some clearly cholinergic symptoms, whereas other patients who received the usual reversal simply don't. Perhaps the glyco doesn't prevent, but still significantly reduces neostigmine's other effects.

But I do appreciate your data driven comments.

 

[dhb]

Naked neostigmine = code brown in my experience

 

[jetproppilot]

Reminds me of a story a Navy general surgeon told me. Some SEAL/spec ops super fit secret squirrel kind of dude is in the surgeon's office as a patient. Surgeon asks him to remove his pants for an exam. Patient does, no underwear. Surgeon looks perplexed. Patient responds, "Doc, panties are for chicks."

Anyway, random thought when you mentioned naked.

Back to the thread.

 

[jetproppilot]

There is no evidence in the literature that glyco prevents the GI effects of Neostigmine. There is evidence that it does not.

Ummmmm...

pgg?

 

[jetproppilot]

I did look at the articles you posted earlier, and especially the 3rd one has some interesting things to say, namely

I've seen patients get 1 mg of 'naked neostigmine' from the GI guys to treat Ogilvie's and for the next 30 minutes they have gut-wrenching abd cramps and usually their GI motility kicks in quick.

So why we don't see the same thing every time we reverse NMBDs with neostigmine, if not for the glycopyrrolate? Is there something else we're doing that prevents patients from getting all the unpleasant cholinergic side effects despite receiving up to ~5 mg of neostigmine?

I have difficulty accepting that the glyco does nothing, given the times I've seen the 'naked neostigmine' trick result in a PACU patient enduring some clearly cholinergic symptoms, whereas other patients who received the usual reversal simply don't. Perhaps the glyco doesn't prevent, but still significantly reduces neostigmine's other effects.

But I do appreciate your data driven comments.

DUDE

all kidding aside,

we are talking hemodynamics and you are pontificating about academic, dogmatic worries about a patient s h itting their pants.

WTF?

PRIORITIES MAN!

A...B....C....

Priorities man.

 

[pgg]

all kidding aside,

we are talking hemodynamics and you are pontificating about academic, dogmatic worries about someone s h itting their pants.

WTF?

🙄

So in one breath, you're telling me that exploiting neostigmine's hemodynamic side effects is good, but in the next you're arguing that avoiding neostigmine's undesirable side effects is bad.

Or are you telling me that a drug's side effects shouldn't have any bearing on which one you use to accomplish a hemodynamic goal? (This is CRNA think.)

Or are you telling me that it's not possible to lower heart rate with neostigmine, unless you give it without glycopyrrolate? (This is wrong of course; most everyone can and does reduce the amount of glyco given to achieve some HR reduction, if desired.)

Or are you telling me that neostigmine is a superior way to control tachycardia at the end of a case when it's reversal time? (I disagree.)


Look, taking advantage of neostigmine's effect on HR at the end of a case is NOT some super slick, clever, crafty, pearl of anesthesia. It's something most of us picked up as CA1s. In fact, many of us picked it up so early and so well that we tried the 'naked neostigmine' unopposed reversal method ourselves ... if we didn't have the good fortune of learning from a classmate's bad experience there first.


Regardless,
1) I prefer not having tachycardia needing treatment in the first place, because everything I did during the case leading up to reversal made it unnecessary - ie, enough fentanyl, or beta blocker, or depth of anesthesia, or whatever

2) If the patient's HR is higher than I want it at that time, I'll reduce my dose of glycopyrrolate somewhat, but not eliminate it, because neostigmine alone DOES produce unpleasant side effects in some patients

3) Esmolol is a cleaner drug for the kind of rapid, usually short-term HR reduction I need or want at the end of case


There's a certain amount of personal preference and style to the way everyone practices anesthesia, and getting cute with reversal drugs solely for the sake of getting cute, despite real drawbacks in patient comfort, isn't my style.