Neuromuscular Blockade – How Depolarizing and Non-Depolarizing Agents Work


Author: Tracy Evans, MBA, RN, EMT-P

Now, with two short-acting neuromuscular blocking agents available to prehospital providers today, succinylcholine and the newer agent rapacuronium, it is more important than ever that we understand the mechanism of action for each of the nondepolarizing agents and the one depolarizing agent.

How do muscles contract?


A neuromuscular junction. Note the chemical transmitter, acetylcholine between the junction.

Muscles receive the impulse to contract from a neuron. The interesting part is that muscles and neurons do not touch. The  gap between them is called the neuromuscular junction. The impulse is carried across the neuromuscular junction (gap) by acetylcholine (ACh) which is stored at the motor endings.

As soon as ACh reaches the muscle, it stimulates cholinergic receptors on the muscle cells, triggering depolarization, which causes the muscle to contract. Acetylcholinesterase (AChE) rapidly breaks down the ACh, and the muscle returns to the resting state.

What does non-depolarizing mean?

Neuromuscular blocking agents act competitively with ACh. All of the agents except one are nondepolarizing, which means that they work by binding to the ACh receptors on the muscle side of the junction. With these receptors blocked, ACh cannot transmit the nerve impulse, so the muscle cannot depolarize and contract.

Progressive paralysis results. It starts with the smaller muscles in the eyelids and face and then moves to the larger muscle groups including the tongue, neck and shoulder, and finally to the respiratory muscles: the intercostals, the larynx and diaphragm. Examples of non-depolarizing agents are vecuronium (Norcuron) and the new short-acting non-depolarizing agent rapacuronium (Raplon).

Recovery from neuromuscular blocking drugs occurs in the reverse order, with diaphragmatic function returning first. Anticholinesterase drugs like neostigmine (Prostigmin) can be given to reverse the effects of nondepolarizing agents. The practical problem with reversal is that they can take a long time to achieve reversal.


Succinylcholine mimics ACh by competitive inhibition of the receptor.

Depolarizing  is different.

There is only one depolarizing agent, succinylcholine (Anectine), which mimics ACh but stays at the neuromuscular junction (the gap) for a longer period of time. At first, succinylcholine stimulates the muscles, causing transient twitching and can cause painful fasciculations. As it sits in the junction, it prolongs depolarization. The muscles are paralyzed because they cannot repolarize.

Depolarizing neuromuscular blockade cannot be chemically reversed: succinylcholine must wear off on its own.

Another classification: Short versus Long?

Neuromuscular blockers can also be classified as short acting or long acting. Short acting agents like rapacuronium (Raplon) and succinylcholine (Anectine) begin working in as little as 30 seconds and last from 4-16 minutes.  Long acting agents such as pancuronium (Pavulon) and vecuronium (Norcuron), take as long as six minutes to work and can last up to 45 minutes or even three hours.

Coming in August:

Although neuromuscular blocking agents cause paralysis, they do not affect consciousness; nor do they control pain. It is therefore crucial that the patient be adequately sedated and given appropriate pain medication before any paralytic drug is given and during administration as needed. Next month we’ll take a look at options for sedation prior to RSI and for ongoing sedation.  We’ll also take a look at the pros and cons of using “High-dose Versed” as an option to facilitate intubation.

Drug

Onset

Duration

Adverse Effects

Paramedic Care Considerations

Causes Fasciculations

Reversible

Succinylcholine (Anectine or Quelicin)

30 to 60 seconds

4 to 6 minutes

Increased Intracranial Pressure

Cardiac Dysrhythmias

Increased Ocular Pressure

Malignant Hyperthermia

Can cause cells to release potassium, so avoid use in patients with crush injuries or severe burn injuries.

YES

NO

Rapacuronium (Raplon)

1.5 to 2 minutes

12 to 16 minutes

Hypotension

Bronchospasm

Bradycardia

Tachycardia

Procainamide and Magnesium may increase duration of action

Carbamazepine and Phenytoin may reduce duration of action

NO

YES

Vecuronium

(Norcuron)

1½ to 3 minutes

25-40 minutes

Excessive salivation

Can be used to prevent fasciculations of depolarizing neuromuscular blocking agents (SCh)

Contrainidcated with neuromuscular disease. (Ex. Myasthenia gravis)

No

Yes

References:

  • Evans, T. (2000). Neuromuscular Blockade: When and How. RN. 63(5), 56.
  • Ford, E.V. (1995). Monitoring neuromuscular blockade in the adult ICU. Am J Crit Care, 4(2), 122.
  • Spratto, G.R. and Woods, A.L. (2000). PDR: Nurses Drug Handbook. Montvale, NJ: Delmar Publishers.
  • Zellinger, M. (1995). Paralytics and sedatives in the ICU. In Current issues in critical care nursing (pp. 17-20). New York: Medical Information Services, Inc.