Steph’s Note: It’s been a little bit since we’ve had a post from our good friend, Dr. Josef Nissan. (Not because he hasn’t been writing! Au contraire, he’s been working up a storm on our pharmacotherapy pocket guides like medical emergencies and antibiotics. Dude is seriously PRODUCTIVE, I’m envious.)

But anyways, this week we are privileged to have his brain laid out on a topic you definitely want to have in your acute care arsenal: rapid sequence intubation. When you need this info, you need it - and rapidly (har har). So take it away, Joe, and tell us what we need to know!

Let’s be real for a second. I am going to take a wild guess and say that if you’re reading this, then you likely:

Have an RSI topic discussion tomorrow morning in which you have yet to prepare for, OR
Recently were thrown into a rapid sequence intubation scenario and did not feel clinically comfortable, OR
You’re a nerd like me and just enjoy reading tl;dr posts.

(Or maybe none of the above fit you, and I should just stop guessing.)

Anyway, regardless of why you’re here, you clearly want a refresher on rapid sequence intubation (RSI). While this post will provide you with a basic overview of RSI, you may want to check out our RSI Cheat Sheet and/or Acute Medical Emergency Pocket Guide for a more comprehensive (yet quicker) review of RSI as well as many other acute medical emergencies (shameless plug). But seriously, that way you can always have a quick reference for when you’re stuck in these emergency situations.

Shall we begin?

To Intubate or Not To Intubate?

Just making sure we’re all on the same page… Intubation is the process for inserting a breathing tube. Note how the tube needs to be guided into the trachea, NOT the esophagus. (Image)

Before we can understand RSI, we need to first understand why we even intubate somebody in the first place. I pretty much sum all the reasons for intubation into three main categories:

Lung Injury: malfunction of the lungs resulting in poor oxygen exchange (e.g., pneumonia, COPD exacerbation, asthma exacerbation, COVID-19, etc)
Altered Mentation/Inability to Protect Airway: neurological dysfunction in which your brain forgets to tell your lungs to breathe (e.g., opioid overdose, benzodiazepine overdose, seizure, meningitis, etc)
Upper Airway Obstruction/Injury: trauma or injury leading to a blockage of your upper airway (e.g., trauma, anaphylaxis, angioedema, etc)

Pretty simple, right? If the patient can’t breathe sufficiently on their own due to lung damage, altered mentation, or upper airway obstruction, let’s intubate.

The Seven P’s of Rapid Sequence Intubation

So we’ve deemed that it is necessary to intubate someone. Next steps?

Let’s follow the “7 P’s”. While there are 7 whole P’s, we, as pharmacists, will primarily be involved in 3 of these P’s. But nonetheless, let’s review all 7 P’s briefly because it’s good to have an idea of what everybody on the team is up to in these situations.

Preparation: assemble all the equipment and medications needed for intubation
Pre-Oxygenation: use the lungs as an oxygen reservoir to help avoid the use of bag mask ventilation during RSI
Pre-Treatment: certain medications may be administered to help prevent adverse physiologic effects associated with RSI
Paralysis with Induction: sedate the patient prior to paralysis to help ease intubation and avoid complications
Positioning: elevate the patient’s head, extending the head at the neck and aligning the ears horizontally
Placement with Proof: confirm the correct placement of the endotracheal tube using a colorimetric CO2 detector or continuous capnography
Post-Intubation Management: begin sedation and analgesic infusions to ensure the patient’s comfort while intubated

So, which three steps do you think pharmacists are heavily involved in? That’s right, all the steps that deal with medications, including pre-treatment, paralysis with induction, and post-intubation management.

The Myths of Pre-Treatment

I am Will Smith and Pre-Treatment is Chris Rock. (Image)

Personally, I hate this step. (We all kind of ignore it like Chris Rock ignoring that fact that Will Smith smacked him on live TV.)

Let me preface this by saying there is very poor clinical evidence that supports the use of pre-treatment drugs in RSI. The majority of patients don’t need pre-treatment, and this step should be skipped entirely.

However, there may be some clinical scenarios in which pre-treatment may be appropriate.

And on the off chance you have that one oddball that may benefit from a pre-treatment drug, I will review them for you (you’re welcome).

IV Atropine 20 mcg/kg
- Potential Candidate: children receiving succinylcholine
- Potential Benefit: may prevent bradycardia associated with intubation in children
IV Lidocaine 1.5 mg/kg
- Potential Candidate: patients with elevated intracranial pressure or bronchospasms
- Potential Benefit: may provide neuroprotection and decrease airway reactivity
IV Fentanyl 1-2 mcg/kg
- Potential Candidate: patients with elevated intracranial pressure, pain, or tachycardia
- Potential Benefit: provides adequate analgesia and neuroprotection in head injury
IV Vecuronium 0.01 mg/kg
- Potential Candidate: patients expected to experience fasciculations with succinylcholine administration
- Potential Benefit: may prevent fasciculation with associated with succinylcholine

Paralysis with Induction

Another thing that I strongly dislike about the 7 P’s (other than the pre-treatment step) is the fact that the word paralysis is written before the word induction. I get it though. They’re called the “7 P’s” not the “6 P’s plus one I”.

But put yourself in the patient’s shoes. Imagine you receive a paralytic while you’re fully awake and conscious. You can still hear everything, feel everything, think normally, but you can’t move…

Sounds like something out of a nightmare, huh? Exactly. So hopefully I haunted you enough to the point where you NEVER forget to adequately sedate someone BEFORE you paralyze them.

Sedation (aka induction in this case) is an INTEGRAL step in RSI. Not only is it inhumane to paralyze someone who is fully conscious, but sedation has also been proven to provide amnesia (as a patient, wouldn’t you rather forget this experience??), blunt sympathetic response, and improve intubating conditions and laryngoscopic view. Fun fact, there are a multitude of studies that report the prevalence of patients developing long-term PTSD from not being adequately sedated prior to paralysis during RSI.

Alright, I don’t want to beat a dead horse. Actually, maybe one more time. Provide adequate sedation BEFORE paralyzing the patient. Okay cool. So what can we use for sedation in RSI? Let’s look below:

Alright, so which sedative should you use? Well, it depends. Every patient scenario is different.

Depending on the situation, one sedative agent may be more appropriate than the other. Every agent has advantages and disadvantages (as I clearly listed above). So use those advantages when applicable, and avoid the disadvantages when able. But to make it easier for you (because I am awesome), I have listed common scenarios in which certain sedative agents are preferred over others in RSI.

Do you see a recurrent theme? Looks like etomidate and ketamine are generally the most applicable in the above patient situations. Hence why they’re usually my go-to sedatives in RSI.

Paralytic Agents

Okay, so now that we’ve adequately sedated the patient, it’s time to paralyze. Much like sedation, paralysis is also an integral step in this sequence as it has shown to improve RSI success rates and reduce complications. When considering paralytic agents, we must first refresh ourselves with the pathophysiology of the somatic nervous system.

Let’s take for example, Mr. Potato Head. For Mr. Potato Head to voluntarily move his arm, his brain must release a neurotransmitter called acetylcholine. Acetylcholine then binds to nicotinic muscarinic (Nm) receptors in Mr. Potato Head’s arm. Once the Nm receptors are agonized, this will result in the voluntary movement of his arm.

So, what’s one way to cause paralysis?

Block those Nm receptors to prevent acetylcholine from binding to them. As long as acetylcholine can’t agonize the Nm receptors, the patient will lose all voluntary skeletal muscle control, leading to paralysis.

And that, ladies and gentleman, is how non-depolarizing neuromuscular blockers work. Buh bam. So what are the options?

Non-Depolarizing Neuromuscular Blockers (NMBAs)

Agent: rocuronium
- Mechanism of Action: antagonizes Nm receptors at the motor end plates → prevents endogenous acetylcholine from binding to Nm receptors → loss of voluntary skeletal muscle movement → paralysis\
- Dose (IV): 0.6 to 1.2 mg/kg

Now let’s talk about the other paralytic drug class: Depolarizing Neuromuscular Blockers. Their mechanism of action is fairly unique. Let’s take a look.

Depolarizing Neuromuscular Blockers (NMBAs)

Agent: succinylcholine
- Mechanism of Action: analogue of acetylcholine (Ach) → binds directly to the postsynaptic acetylcholine receptors of the motor endplate → continuous stimulation → leads to transient fasciculation followed by muscle paralysis
- Dose (IV): 1 to 1.5 mg/kg

Once again, I present to you multiple options. Which should we use? Again, it depends.

Succinylcholine is generally the more attractive agent given its faster time to effect and much shorter duration of action compared to rocuronium. But as with most drugs, it comes with a laundry list of contraindications and adverse effects.

One of the biggest downsides of succinylcholine is its notorious ability to cause hyperkalemia. A single dose of succinylcholine is estimated to increase serum potassium by up to 0.5 mEq/L. Hyperkalemia can lead to ECG changes and life-threatening arrhythmias. Additionally, succinylcholine has been shown to induce malignant hyperthermia in patients predisposed to this condition.

Given these risks, succinylcholine is generally contraindicated in patients with a history of:

Malignant hyperthermia (personal or family)
Neuromuscular disease involving denervation
Muscular dystrophy
Stroke over 72 hours old
Rhabdomyolysis
Burn over 72 hours old
Significant hyperkalemia

Additionally, given it’s an analogue of acetylcholine, succinylcholine can lead to bradycardia, increased intraocular pressure, hyperkalemia, trismus, and fasciculations. Does that mean we should never use succinylcholine? Not at all. While it may carry more contraindications and side effects than rocuronium, its much shorter duration of action (~10 minutes vs ~45 minutes) makes it the more attractive option when a patient doesn’t have any of the above contraindications.

Remember, the entire RSI sequence takes about ~5-15 minutes. You really only need the patient paralyzed for ~10 minutes. The ~45 minutes duration of rocuronium is excessive and can delay neurological testing in a lot of patients.

So let’s review the benefits of both paralytic agents:

Succinylcholine benefits:
- Rapid onset
- Shorter duration of action allowing for faster return of neuromuscular function
Rocuronium benefits:
- Carries fewer contraindications than succinylcholine
- Can be used in patients at risk of hyperkalemia on admission
- Does NOT carry a risk for trismus or fasciculations
- Less likely to cause bradycardia

The tl;dr of Rapid Sequence Intubation

Primary literature and treatment guidelines recommend against the routine use of pre-treatment drugs in rapid sequence intubation. Sedatives are integral to the performance of rapid sequence intubation with typical 1st-line agents being etomidate and ketamine. Midazolam and propofol tend to be second line for most patients.

Neuromuscular blocker use in RSI is necessary as these medications render a patient flaccid to facilitate emergency endotracheal intubation, mitigate unwanted physiological responses to laryngoscopy and intubation, and minimize the risk of aspiration. Both depolarizing and nondepolarizing neuromuscular blockers can be used as first-line for paralysis in RSI.

There you have it, folks! A basic overview of RSI. Again, if you want a more comprehensive review of RSI that reviews pharmacokinetics, pharmacodynamics, clinical applicability, paralytic reversal agents, and post-intubation sedation and analgesia, check out our RSI cheat sheet (shameless plug, again).

The Pharmacist's Dos & Don'ts of Rapid Sequence Intubation (RSI)