Search on website
Filters
Show more
chevron-left-black Summaries

Succinylcholine: Termination of Blockade

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.

Updated definition 2020:

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).

Succinylcholine is rapidly metabolized by pseudocholinesterase in the bloodstream. Only a small fraction of succinylcholine is delivered to the motor endplate, with most being metabolized prior to reaching it. The fraction of succinylcholine that does reach the motor endplate rapidly dissociates from the neuromuscular junction, and is subsequently metabolized by pseudocholinesterase. In normal rapid sequence intubation doses (~1-1.5 mg/kg), succinylcholine causes a “phase I block,” which is defined by transient muscle fasiculations followed by relaxation, absence of fade to tetanic or train of four stimulation, and absence of post-tetanic potentiation. This generally lasts up to six minutes. However, in excessive doses (>3-5 mg/kg), succinylcholine can cause a “phase II block” which more closely resembles a non-depolarizing neuromuscular blockade with fade after tetanic or train of four stimulation and the presence of post-tetanic potentiation. This is a prolonged blockade, thought to be due to repeated channel opening, desensitizing the junctional membrane to further depolarization. It may be possible to reverse a phase II block with acetylcholinesterase inhibitors such as neostigmine; however, this practice is controversial due to unpredictable response to antagonism (as acetylcholinesterase inhibitors will prolong a phase I block), and some sources recommend allowing the block to wear off naturally.

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.

References

  1. Hilgenberg JC, Stoelting RK. Characteristics of succinylcholine-produced phase II neuromuscular blockade during enflurane, halothane, and fentanyl anesthesia. Anesthesia and Analgesia. 1981 Apr;60(4):192-6 PubMed Link
  2. Naguib M, Samarkandi AH, El-Din ME, et al. The dose of succinylcholine required for excellent endotracheal intubating conditions. Anesth Analg 2006;102:151–5. PubMed Link

Other References

  1. Keys to the Cart: A 5-minute review of ABA Keywords Link
  2. Hager HH, Burns B. Succinylcholine Chloride. [Updated 2019 Mar 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan Link
  3. Pino, Richard M., editor. "Neuromuscular Blockade." Clinical Anesthesia Procedures, 9th ed., Wolters Kluwer, 2019. Anesthesia Central Link
  4. Trujillo R, West, DO WP. Pseudocholinesterase Deficiency. [Updated 2019 Jun 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan Link