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A 22 year old male patient presents to the emergency room with 12 hours of severe hematemesis and hematochezia. The patient is stabilized in the ICU overnight and undergoes an upper endoscopy the following morning. Anesthesia is induced and maintained with midazolam and propofol. The patient is at aspiration risk, so he is intubated with succinylcholine used for neuromuscular blockade. 45 minutes later the procedure is complete, and anesthesia is stopped, but 5 minutes later the patient is not making any respiratory effort. Train of four monitoring reveals 0 out of 4 twitches. What is your next best step in the management of this patient?
Content Reviewers:Yifan Xiao, MD
Okay, first things first. In order for a skeletal muscle to contract, your brain sends a signal, in the form of an action potential in an upper motor neuron.
The upper motor neuron then activates a lower motor neuron in the spinal cord.
From here, the action potential is sent through an axon down to its ending branches, called axon terminals, to muscle fibers which they innervate.
The place where an axon terminal meets the muscle fiber is the neuromuscular junction.
The neuromuscular junction has three main parts: a presynaptic membrane, which is the membrane of an axon terminal; a postsynaptic membrane, which is the membrane of a skeletal muscle fiber and is also called a motor end-plate; and a synaptic cleft, which is the gap between the presynaptic and postsynaptic membranes.
When an action potential reaches the axon terminal, synaptic vesicles that contain neurotransmitters, called acetylcholine, fuse with the cell membrane of the axon terminal, releasing the acetylcholine into the synaptic cleft.
The acetylcholine then diffuses over to the motor end plate on the muscle fiber and binds to ligand-gated ion channels, also called nicotinic receptors.
When that happens, these ligand-gated ion channels open up, letting lots of sodium ions rush into the skeletal muscle fiber, and a few potassium ions leak out of the cell as well. But overall there’s an increase in positive charge on the inside of the muscle fiber causing it to depolarize.
This causes the voltage-gated sodium ion channels on the membrane to open up, and there’s a huge influx of sodium ions into the muscle fiber.
This leads to a generation of an action potential, which rapidly spreads along the entire membrane, causing the whole muscle fiber to contract.
When the signal sent from the lower motor neuron stops, this causes synaptic vesicles full of acetylcholine to stop fusing with the membrane, while molecules of acetylcholine that are left behind within the synaptic cleft, are chopped up by an enzyme called acetylcholinesterase. And muscle contraction stops.
Alright, so neuromuscular blockers are medications that block the interaction between acetylcholine and nicotinic receptors at the neuromuscular junction. This leads to skeletal muscle relaxation.
And based on their mechanism of action, they’re classified into non- depolarizing and depolarizing blockers.
So, non-depolarizing neuromuscular blockers can bind to the same binding sites on the receptor as acetylcholine, but they don’t trigger the opening of ion channels.
So when administered, they compete for these binding sites on the receptors, which leads to decreased depolarization of the muscle fiber and weaker contraction.
Clinically, they are usually used to relax the muscles before surgery or during intubation for mechanical ventilation, which is when someone is connected to a ventilator machine that helps them breathe.
They can also be used as general anesthetics during surgical procedures.
So typically, non-depolarizing neuromuscular blockers are injected intravenously, and in less than a couple of minutes, they begin paralyzing small muscles of the face and fingers; then larger muscles in the neck, torso, and limbs; then finally, the diaphragm.
Gradually, in about 40 to 90 minutes, these muscles start recovering in the reverse order, so first the diaphragm, then the limbs, torso, neck, and then fingers and the face.
Now for side effects, they occur more frequently with atracurium.
Specifically, atracurium induces histamine release, which causes bronchoconstriction, or narrowing of the airways; as well as vasodilation, or blood vessel relaxation; and thus causing hypotension, reflex tachycardia, and flushing, or reddening of the face.
At the same time, it produces a toxic metabolite, called laudanosine.
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