S3E2 - Neuromuscular Blocking Agents

Neuromuscular blocking agents are used to chemically paralyze skeletal muscle during surgery to: 

1. Provide paralysis of the vocal cords for intubation 
2. Enhance operating conditions for surgeons 

How does skeletal muscle work normally? 

An action potential triggers the release of acetylcholine into the neuromuscular junction, which binds to nicotinic receptors on the muscle and causes contraction. As acetylcholine is then degraded, the muscle can begin to respond to stimulation again. 

How do neuromuscular blocking agents work? 

Neuromuscular blocking agents work by interfering with the acetylcholine signaling mechanism and there are two types: 

1. Non-depolarizing (e.g. rocuronium): These are competitive antagonists with acetylcholine and bind to nicotinic receptors preventing muscle contraction. 
2. Depolarizing (e.g. succinylcholine): These act similarly to acetylcholine, as nicotinic receptor agonists, but are not metabolized by acetylcholinesterase and therefore inhibit further acetylcholine-mediated contraction. 

How are neuromuscular blocking agents reversed? 

• Non-Depolarizing 
  • Neostigmine/Glycopyrrolate: This method increases the amount of acetylcholine to outcompete the blockade.
  • Sugammadex: This method directly inactives the non-depolarizing neuromuscular blocking agent 
• Depolarizing 
  • Quickly broken down by plasma cholinesterases and do not require reversal agents 

How to choose a neuromuscular blocking agent? - Questions to consider 

1. Duration of action 
   • Are you doing a RSI or not? 
   • How long do you require skeletal muscle paralysis? 
2. Route of excretion 
   • How is the NMB metabolized/excreted and does you patients have any conditions that would prolong the action? 
3. Adverse reactions and contraindications 
   • Rocuronium: a common cause of allergic reactions in the OR 
   • Succinylcholine (the 4 H’s) 
     1. Malignant Hyperthermia
     2. Hyperkalemia 
     3. High ocular pressure
     4. Higher post-op muscle pain