Succinylcholine and hyperkalemia

[DrPak]

A question I came across on qbank describes a burn victim being given succinylcholine and subsequently developing hyperkalemia. The explaination to the question states that during the prolonged muscle depolarization (caused by succinylcholine) the muscle releases a lot of K+ and this caused the hyperkalemia.

I don't get how depolarizing the muscle will cause it to release K+. In depolarization, the Na+ floods inside the cell, and K+ is KEPT out, it's not that K+ is actively pumped out of the cell. Could some one clarify?

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[Krazykritter]

Sorry I don't have an answer for you but...how do you get access to Qbank?? Is it something your school has to activate? Thanks.

 

[DrPak]

No, I pay, and they give me access.

 

[Doc Ivy]

A question I came across on qbank describes a burn victim being given succinylcholine and subsequently developing hyperkalemia. The explaination to the question states that during the prolonged muscle depolarization (caused by succinylcholine) the muscle releases a lot of K+ and this caused the hyperkalemia.

I don't get how depolarizing the muscle will cause it to release K+. In depolarization, the Na+ floods inside the cell, and K+ is KEPT out, it's not that K+ is actively pumped out of the cell. Could some one clarify?

It's my understanding that succ can cause a malignant hyperthermia reaction which is associated with rhabdomyolysis-- rhabdo basically causes muscle fiber trauma and releases K from the myocytes leading to hyperkalemia and potentially acute kidney failure from myoglobin injury of renal tubules.

 

[HamOnWholeWheat]

I think the mechanism behind the madness is the following:

In severe burn injury or severe trauma you get muscle denervation. In response to the denervated muscle the mRNA of acetylcholine receptors is upregulated and an increasing number of nAchRs are present throughout the denervated muscle NMJ spreading away from the end plates. This results in a much larger area of membrane with the potential to be sensitive to suxamethonium, a depolarising paralytic.

The action of succinylcholine (suxamethonium) is to depolarise the nAchR resulting in a non specific cation influx (Na+ and Ca2+) and efflux (K+). eventually the muscle is not longer able to fire because the gradient is lost, initially you get the fasciculations because of the depolarization. If we have more nAchR on the muscle we increase the amount of "pores" through which K+ can leave the cell, causing a life threatening arrythmia or cardiac arrest due to the hyperkalemia. In normal individuals this is not important because we do not have an upregulation of nAchR across the NMJ and the transient increase in K+ is handled by the conductance of potassium and the active transport back into the cell.

Does that make sense?

Wow. Good answer if its correct.

 

[DrPak]

what is the nAchRs?

 

[Jack P]

nAchR - nicotinic Acetylcholine receptors...just checked in Rang in Dale Pharmacology and it describes a similar scenario with respect to the mechanism behind hyperkalemia. Just to be thorough check out the abstract to Succinylcholine-induced hyperkalemia in acquired pathologic states: etiologic factors and molecular mechanisms. Anesthesiology. 2006 Jan;104(1):158-69.


Here is the link to the abstract

 

[ice_maiden34567]

Just wondering, can it be explained by the fact that---prolonged depolarisation causes increased mucle contraction and ultimately acidosis,which causes hyperkalemia?

 

[DrPak]

Thank you Jack P for looking it up

@ice_maiden, succinylcholine doesn't really cause big contractions, just fasiculations. I don't think that's nearly enough to cause an acidosis.

 

[Jack P]

No worries, it cleared the fog for me as well

 

[beastmaster]

the mechanism of hyperkalemia is the extra nicotinic receptors. The reason they cause a problem is because, in dystrophy/burns/etc, they are outside the neuromuscular junction. recall that in depolarization Na+ comes in; and in repolarization K+ goes out. Normally this is contained within the NMJ and corrected by the refractory period. But in these medical conditions the receptors are all over the membrane of the muscle fiber and, and there is no correction because of the succinylcholine block. Hence K+ is dumped into the extracellular space.

 

[DrPak]

@beastmaster: Yes, in repolarization, K+ does go out, but succinyl choline doesn't cause repolarization\hyperpolarization, it causes prolonged DEpolarization, meaning that it will allow tons of Na+ into the muscle. K+ is not affected because that only moves out in the repolarization part, as you said. My question was that if succinyl choline causes prolonged DEpolarization, and involving just the Na+ channels, why would there be hyperkalemia?

 

[beastmaster]

@beastmaster: succinyl choline doesn't cause repolarization\hyperpolarization, it causes prolonged DEpolarization

you're wrong, sorry. go back and re-study how succinylcholine works and then re-read my post and all will be clear

 

[HamOnWholeWheat]

you're wrong, sorry. go back and re-study how succinylcholine works and then re-read my post and all will be clear

Better yet, scroll up and read Jack P's answer. Its better and has a reference.

 

[PuGanDoo]

Dr. Pak,

Depolarization and repolarization are not separate phenomena. They are all part of the action potential. When ligand and receptor bind, sodium is allowed into the cell and this electrical potential change triggers further depolarization with sodium influx. At the same time, these electrical changes trigger not only the sodium channel opening, but also the potassium channel opening. Physiologically you cannot have sodium channel opening (depolarization) without potassium channel opening (repolarization).

 

[DrPak]

@PuGanDoo: Thanks, that clears it up. I had forgotten both channels are opened up almost at once.

 

[sukanya7p]

The upregulation of ACh receptors takes place just as after dennervation.They occur at sites immediately beneath & distant from the burn.There is a positive correlation between hyperkalemia intensity & Achr number after succinyl choline administration.
The upregulation of Achr is profound & occurs as early as72 hrs after burn.There may be upregulation of immature isoform provided by the assessment of mRNA for the gamma subunit When depolarised the immature isoform has a prolonged open channel time ,which exaggerates the K efflux that occurs with depolarisation.

 

[Idiopathic]

NO INCREASED HYPERKALEMIA RISK IN ACUTE BURN OR PARALYSIS (remember that

Chronic muscle/tissue wasting (burns, atrophy, etc.) however will cause upregulation of ACh receptors and the rest has already been explained.

In a 'normal' patient, K+ can be expected to rise by 0.5 after a therapeutic dose of succ. Ive seen it more than double when given to someone with prominent LE muscle atrophy.

A good follow up series would be:

a) what EKG changes would be observed (and in what order)?

b) what are the treatments for a K+ high enough to cause EKG changes?

 

[surgical06]

A question I came across on qbank describes a burn victim being given succinylcholine and subsequently developing hyperkalemia. The explaination to the question states that during the prolonged muscle depolarization (caused by succinylcholine) the muscle releases a lot of K+ and this caused the hyperkalemia.

I don't get how depolarizing the muscle will cause it to release K+. In depolarization, the Na+ floods inside the cell, and K+ is KEPT out, it's not that K+ is actively pumped out of the cell. Could some one clarify?

this questions isn't as complicated as some have put it. there is an overephasis on succinylcholine, its more of a membrane physio question

1)at the the end of depolarization there is K+ efflux into the ECF, this helps return the ICF to a negative resting potential. K channels are slower than Na channels to open but both are stimulated by depolarization. thus massive depolarization as with the use of succ does cause increased ECF K, but remember the role of Na/K pump, which returns the ECF K to the ICF. in a normal person with healthy membrane physiology (elctrically and chemically intact), K theorhetically would be transiently elevated but quickly returned to normal with use of succinylcholine.

2) anytime you have cellular injury, intracellular contents are released. since K+ is an intracellular ion (145meq), it is released from a cell. massive tissue (cell) injury (NOT JUST SEVERE BURN, but a large burn surface area) causes release of K from MANY CELLS, which is additive, thus creating a higher serum K. burn patients have lost their membrane integrity , no gradient, and thus, serious electrolyte issues independent of succinylcholine usually occur.

succinylcholine does exacerbate an already present problem in burn patients

 

[surgical06]

furthermore, succinylcholine is usually used in a rapid induction intubation, used in acute situations (1-5hrs post injury) receptor upregulation takes days, so its unlikely that receptors would play a role in an acute injury (first 12hrs) situation.

this questions isn't as complicated as some have put it. there is an overephasis on succinylcholine, its more of a membrane physio question

1)at the the end of depolarization there is K+ efflux into the ECF, this helps return the ICF to a negative resting potential. K channels are slower than Na channels to open but both are stimulated by depolarization. thus massive depolarization as with the use of succ does cause increased ECF K, but remember the role of Na/K pump, which returns the ECF K to the ICF. in a normal person with healthy membrane physiology (elctrically and chemically intact), K theorhetically would be transiently elevated but quickly returned to normal with use of succinylcholine.

2) anytime you have cellular injury, intracellular contents are released. since K+ is an intracellular ion (145meq), it is released from a cell. massive tissue (cell) injury (NOT JUST SEVERE BURN, but a large burn surface area) causes release of K from MANY CELLS, which is additive, thus creating a higher serum K. burn patients have lost their membrane integrity , no gradient, and thus, serious electrolyte issues independent of succinylcholine usually occur.

succinylcholine does exacerbate an already present problem in burn patients

 

[Idiopathic]

2) anytime you have cellular injury, intracellular contents are released. since K+ is an intracellular ion (145meq), it is released from a cell. massive tissue (cell) injury (NOT JUST SEVERE BURN, but a large burn surface area) causes release of K from MANY CELLS, which is additive, thus creating a higher serum K. burn patients have lost their membrane integrity , no gradient, and thus, serious electrolyte issues independent of succinylcholine usually occur.

succinylcholine does exacerbate an already present problem in burn patients

Actually the correct concept is receptor upregulation. Thats why patients with perfectly intact membrane integrity can have this problem (paraplegics, for instance) and this is not an issue with acute burn, so your theory doesnt really tell the whole story. Its not the physical manifestation of the burn that explain this effect, although burn patients definitely will have electrolyte abnormalities.

 

[Idiopathic]

furthermore, succinylcholine is usually used in a rapid induction intubation, used in acute situations (1-5hrs post injury) receptor upregulation takes days, so its unlikely that receptors would play a role in an acute injury (first 12hrs) situation.

And this is why you dont see this abnormality (hyperkalemia with succ) until 72+ hours after the denervation injury, usually.

 

[Gasboy07]

Very easy question if you're studying for you anaesthesiology exam...

The nicotinic acetylcholine receptor (nACHR) is a transmembrane pentameric ligand gated ion channels. The five subunits are two alpha1s, a beta1, a delta and the last one is variable. The main ion conducted is Na+ but, some Ca++ enters and some K+ exits.

The foetal form has a gamma subunit.

Under the influcence of growth factors secreted by the motor neurone, adult type (with an epsilon) subunit nACHR proliferate at the NMJ, while growth of foetal type extrajunctional nAChR are inhibited by electrical activity.

The foetal type receptor opens for longer, but has a lower conductance per unit time than the adult receptors.

These foetal receptors proliferate if denervated - nobody is sure how long this takes to happen, somewhere between 2 days and 2 weeks?

Administration of Sux would cause all of these extra receptors to open, causing a much larger potassium efflux than normal - raising serum potassium, the main problem resulting from this is cardiac arrythmias.

 

[Jack P]

I think the mechanism behind the madness is the following:

In severe burn injury or severe trauma you get muscle denervation. In response to the denervated muscle the mRNA of acetylcholine receptors is upregulated and an increasing number of nAchRs are present throughout the denervated muscle NMJ spreading away from the end plates. This results in a much larger area of membrane with the potential to be sensitive to suxamethonium, a depolarising paralytic.

The action of succinylcholine (suxamethonium) is to depolarise the nAchR resulting in a non specific cation influx (Na+ and Ca2+) and efflux (K+). eventually the muscle is not longer able to fire because the gradient is lost, initially you get the fasciculations because of the depolarization. If we have more nAchR on the muscle we increase the amount of "pores" through which K+ can leave the cell, causing a life threatening arrythmia or cardiac arrest due to the hyperkalemia. In normal individuals this is not important because we do not have an upregulation of nAchR across the NMJ and the transient increase in K+ is handled by the conductance of potassium and the active transport back into the cell.

Does that make sense?