Succinylcholine: Termination of Blockade

Basic, Basic Sciences

Succinylcholine is a depolarizing neuromuscular blocker that is composed of two molecules of acetylcholine linked through their acetyl methyl groups. This molecule exerts its mechanism of action at the nicotinic junction of the neuromuscular endplate, opening predominantly sodium channels, then allowing the release of calcium from the sarcoplasmic reticulum to then allow neuromuscular contraction and fasciculation. With a dose of 1 mg/kg, the neuromuscular junction cannot be re-activated in any capacity for at least 60 seconds and can take anywhere from 9-13 minutes to regain full recovery as the membrane will remain depolarized above the re-activation threshold. This is the formation of the drug’s primary effect, known as the phase I block. The phase I block dissipates when plasma cholinesterase (or pseudocholinesterase) hydrolyzes the drug after it leaves the junction (with usually 50% hydrolyzed 5 minutes after administration). It should be noted that this enzyme is usually not present at the junction and the acetylcholine molecule must diffuse away from the junction first for the block to start wearing off.

Succinylcholine, if administered in higher concentrations or as a continuous infusion (usually total greater than 4 mg/kg) can also result in what is called a “Phase II block.” After the neuromuscular membrane has been depolarized, due to the activity of Na-K channels, the membrane continuously moves back in the direction of its baseline electric potential. Thus, with higher infusions, it is pushed back to being depolarized, but simultaneously cannot fully recover, resulting in a block with tetanic fade, similar to a non-depolarizing neuromuscular block. A Phase II block could be antagonized either through cholinesterase inhibitors like with a non-depolarizing neuromuscular block or by waiting until it resolves.

Succinylcholine is a depolarizing neuromuscular blocking agent. It is a correlate of acetylcholine (ACh), consisting of two ACh molecules bound at their acetyl methyl groups. It facilitates rapid neuromuscular blockade (usually within 60 seconds) by binding post-synaptic cholinergic receptors at the motor endplate, causing sustained depolarization of the postjunctional membrane (rendering it unable to respond to subsequent release of ACh).

As mentioned previously, succinylcholine is metabolized by pseudocholinesterase in the blood plasma; thus, individuals with lower-than-normal pseudocholinesterase levels can have prolonged blockade in response to succinylcholine administration. This can be caused by genetic variants (e.g. homozygous atypical cholinesterase gene), medications that inhibit plasma cholinesterases (such as neostigmine and cyclophosphamide), as well as certain conditions (such as pregnancy, severe liver or kidney disease, and hypothyroidism).

The dibucaine number is a laboratory test that can be used to assess pseudocholinesterase deficiency. Normally, the local anesthetic dibucaine inhibits pseudocholinesterase by 80% (hence a “normal” dibucaine number of 80); however, in cases of homozygous atypical cholinesterase, it is only inhibited by 20% (dibucaine number of 20). Thus, an individual with a dibucaine number of 20 would be expected to have a severely prolonged blockade in response to succinylcholine administration.


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Rashid Hussain, MD and Tyler Johnson, MD