K.O. Induction & Paralysis
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In some of my previous blogs, I discussed other “P’s” of RSI including pre-oxygenation and pre-intubation optimization, found HERE and HERE, respectively. If you haven’t read them, I suggest giving them a gander as many will consider them “prerequisites” prior to the next “P” on the list, Paralysis with Induction.
* Induction should occur before paralysis for ethical reasons, but it doesn’t fit the 7 P’s of the RSI mnemonic otherwise *
Once we have prepped our equipment, appropriately pre-oxygenated, and adequately optimized our patient's hemodynamics, we then move on to paralysis with induction -- The ole "1-2" leading to the K.O.
Depending on the literature you reference, this phase of RSI involves administration of a potent sedative induction agent in order to produce prompt loss of consciousness and is immediately followed by a neuromuscular blocking agent (NMBA) to produce paralysis, with both medications given IV push. This is done to rapidly render the patient unconscious and flaccid to facilitate optimal intubation conditions of patients requiring emergency endotracheal intubation while also minimizing the risk of aspiration [1, 2].
In this blog, we will discuss the process of paralysis with induction by answering the following questions:
Which medication should I choose?
What order do I give the medications?
But before I answer those questions, I’d like to give an overview of what sedative induction agents and NMBAs are, and the commonly used medications from each, in the pre-hospital and critical care transport setting.
Sedative Induction Agents:
Medications used to produce prompt loss of consciousness, or “induce,” our patients for the rapid sequence induction procedure are referred to as “induction” agents. These agents can also provide amnesia, blunt the sympathetic (pain) response, and improve intubating conditions .
In the perfect and most ideal world, induction agents would quickly render a patient deeply unconscious, create amnesia, and provide analgesia, have minimal to no poor hemodynamic effects, be immediately reversible, and have few (if any) physiologic effects… but unfortunately, that doesn’t exist; or, at least no medication currently meets this full list of criteria [1,5].
Many induction agents, however, will fit the first criteria of quickly rendering the patient unconscious. And if you’re familiar with paralytics, this is a nice quality for the drug to have. We all likely know (or hopefully know) that using a paralytic without an induction agent leaves the patient fully aware of his or her environment including feelings of pain, claustrophobia, and suffocation… Quite simply, the patient is unable to respond while able to feel, hear, and perceive EVERYTHING. Scary 💩 !
The most commonly used induction agents used for RSI include Etomidate, Ketamine, Propofol, and Versed. Etomidate and Ketamine are the usual go-to’s for RSI as they have a rapid onset and maintain relative hemodynamic stability (while also being more available amongst pre-hospital and critical care transport clinicians). Propofol is most often used by anesthetists and anesthesiologists but has been used more and more outside of surgical suites, but is limited by its associated vasodilation and hypotension. Versed, as well as other benzodiazepines, have a longer onset time AND are often associated with vasodilation, making them less “attractive” as induction agents for RSI.
Neuromuscular Blocking Agents:
Neuromuscular blockade is the cornerstone of RSI, optimizing conditions for tracheal intubation while minimizing the risks of aspiration or other physiologic events. Neuro-muscular blocking agents (NMBAs/paralytics) DO NOT provide analgesia, sedation, or amnesia. As a result, they are paired with sedative induction agents for RSI .
The neuromuscular blocking agents render the patient unresponsive and flaccid (paralyzed) in order to facilitate intubation. There are multiple randomized control trials and observational studies demonstrating that the use of paralytics improves success rates for emergency intubation and reduces the risks of complications .
The most common NMBAs used in the pre-hospital and critical care environment for RSI include Succinylcholine and Rocuronium. Both of the medications produce paralysis, but each of the medications paralyzes the patient in a different manner, either through depolarization or non-depolarization. Succinylcholine, the depolarizing paralytic, works by rapidly depolarizing the neuromuscular end-plate (postsynaptic acetylcholine receptors of the motor end-plate), causing resistance to further stimulation. Whereas, Rocuronium is non-depolarizing, which blocks the binding site of acetylcholine to receptors at the neuromuscular end-plate. The duration of these medications varies as well, with succinylcholine lasting for only a short length of time, and Rocuronium (and other non-depolarizing NMBAs) lasting much longer.
** Don't take the "intentionally left blank" too literally. Fellow FOAMfrat content creator, Jake Good, will dive more in-depth into each of these medications. It's more of a "There are very minimal pitfalls to Rocuronium" statement. **
I know, you’d all like a more in-depth look, or dive, into these medications. But, for the sake of keeping the blog of appropriate length, this in-depth dive is left out. The info in this blog serves as a quick hit, or “pearls” of the mentioned medications. Also, our FOAMfrat educator Jake Good has taken on the task of adding an additional look into these medications in his series, “Pharmacology NOT Taught in Paramedic School.” Keep your eyes peeled for those blogs here in the future.
Pharmacology Not Taught in Medic School
** These blogs are "in progress," we will hyperlink them as they release **
RSI has many different iterations of the term, all of which seem to mean the same thing to some, while to others, have different “approaches” or small variations to the procedure. These different iterations include, but is not limited to:
Rapid Sequence Intubation (RSI)
Rapid Sequence Induction (RSI)
Resuscitation Sequence Intubation (RSI)
Resuscitation Intubation Procedure (RIP)
Delayed Sequence Intubation (DSI)
Rapid Sequence Airway (RSA)
For the purpose of this blog, I will be cover “Rapid Sequence Intubation” and “Delayed Sequence Intubation” as it has been taught to me and how the resources I am using for this blog portray them. AND we will stick to the induction and paralysis side of the procedure within this writing — FOAMfrat has many other blogs covering other parts of the RSI procedure. I recommend the Airway Manifesto series written by Adam LaChapelle 😊 .
The information given in this blog should NOT replace your employer's policies, procedures, protocols, or guidelines regarding the RSI procedure. This is simply a rundown of the induction and paralysis procedure performed during RSI.
Which Medications Should I Choose?
This is where learning the “pros” and “cons” to the medications in your RSI tackle box comes into play and critical thinking becomes imperative. Simply put, you need to invest your time into knowing the medications found in your supply.
It’s hard to say that there is any perfect medication or perfect combo, although you’ll find a vast majority of providers automatically selecting Ketamine and Rocuronium. This is both due to a large number of potential benefits and minimal contraindications to both.
Certain induction and paralyzing agents may offer benefits, or advantages, over others in varying clinical settings . We need to consider the benefits, considerations, and adverse effects of each to make an educated medication selection. We must also perform a good assessment and obtain a thorough history (if possible) prior to medication selection.
Specific Clinical Settings for Induction Agents:
Head Injury or Stroke
When a patient suffers from a stroke, head injury, or potentially elevated intracranial pressure (ICP), adequate cerebral perfusion pressure must be maintained to prevent secondary brain injury. Avoiding elevation in ICP and maintaining an adequate MAP is of importance. Ideally, we should choose a medication that is capable of improving or maintaining cerebral perfusion pressure (CPP).
Etomidate is recommended in these scenarios with Ketamine as a reasonable alternative. When signs of herniation are present, it’s often recommended to avoid Ketamine .
When significant hypertension is present (MAP > 120 mmHg), Etomidate is preferable to Ketamine, as it may further elevate the blood pressure. In normotensive patients, Etomidate or Ketamine may be used. For hypotensive patients, Etomidate or Ketamine may be used, although a reduced dose is typically recommended.
In hemodynamically unstable, head-injured patients, both Versed and Propofol should be avoided due to the risk of hypotension-induced brain injury. If no other agents are available, consider reducing the dose of Versed and Propofol to minimize the risk of exacerbating hypotension.
For this subset of patients, Propofol, Etomidate, or Versed are all acceptable options [1,3]. Ketamine has also been shown to be effective at terminating status epilepticus, especially in children, and would be a good fourth option .
Propofol is a potent anticonvulsant, but doses should be carefully considered to avoid dose-dependent hypotension . Little data exists on Propofol as an induction agent with seizures, but evidence does exist demonstrating that it provides rapid suppression of seizure activity after a bolus and infusion when used in refractory status epilepticus .
Etomidate is a good induction agent if there is associated hypotension and it may raise the seizure threshold (inhibiting seizure activity) in generalized seizures .
Versed may be used for induction with appropriate dose selection, however, using a lower dose in hemodynamically unstable patients means that it functions poorly as an induction agent [1,3].
Reactive Airway Disease
For patients experiencing severe bronchospasm requiring advanced airway management, Ketamine and Propofol are suggested because of their bronchodilators properties .
The Manual of Emergency Airway Management labels Ketamine the induction agent of choice in this subset of patients. Ketamine stimulates the release of catecholamines and also has a direct bronchial smooth muscle relaxing effect .
Etomidate is the induction agent of choice for these patients. Etomidate provides hemodynamic stability with the absence of induced hypertension that may be unwanted when intubating this group of patients.
SHOCK -- The Unstable Patient
All sedative induction agents can cause hypotension (repeat that previous sentence, then do it again). If you haven’t gathered from pretty much all of the previous reading, Etomidate and Ketamine are suggested in the unstable patient population, or those with expected post-intubation hypotension (PIH). A reduction in the normal dosing regime is recommended in these patients.
I suggest reading my previous blog on pre-intubation optimization HERE for further info on suggested interventions in the shock patient during airway management.
** This information was obtained from UpToDate - RSI for Adults Outside of the Operating Room and The Manual of Emergency Airway Management. Keep in mind, Succinylcholine has a large number of contraindications and relative contraindications related to potassium abnormalities, be sure to include those possible clinical scenarios as well. **
Specific Clinical Settings for Neuromuscular Blocking Agents:
Again, the use of NMBAs are an integral component in the performance of RSI. They improve success rates and reduce the risk for complications. When no contraindications exist, Succinylcholine or Rocuronium can be used.
Non-depolarizing NMBAs, such as Rocuronium, is recommended when the following conditions are present:
Stroke Over 72 Hours Old
Burns Over 71 Hours Old
In a previous photo on NMBAs, under considerations for Succinylcholine, I used the verbiage, “Instances where increases in potassium may cause harm, Rocuronium should be considered.” Hyperkalemia can be due to many different reasons such as rhabdomyolysis, burns, denervation, crush injuries, and myopathies. While those aren’t “absolute contraindications” per se, further information about each of them is needed and in the pre-hospital environment and may be difficult to obtain. When encountering any condition that may increase or affects potassium levels, Rocuronium becomes an easier selection and leads to cognitive offloading during a potentially task saturating procedure such as RSI.
Another “pearl” regarding the Succ VS. Roc debate is the time to desaturation after administration. It is reported in the EMcrit Annals of Emergency Medicine paper, “Preoxygenation and Prevention of Desaturation During Emergency Airway Management,” that desaturation occurs faster with the use of Succinylcholine versus that of Rocuronium. Desaturation to 95% or lower was seen in 242 seconds (4 minutes) with Succinylcholine and desaturation to 95% or lower was seen in 378 seconds (6.3 minutes) with Rocuronium; both of which were following adequate preoxygenation measures.
What Order Do I Give The Medications?
This question has had some controversy in recent times as blogs supporting ideas that Etomidate or Ketamine can be given after administration of a paralytic has seen some popularity. I’ve seen many references to the Rocuronium administration prior to Ketamine called something like, “The RocKetamine Approach.” This thought process has stemmed from the idea that the induction agents have a faster onset than that of the paralytics, namely rocuronium, and less apnea time is encountered with the onset of each medication occurring at closer intervals.
“Drug Order in Rapid Sequences Intubation,” a secondary analysis of an already completed randomized control trial, demonstrated that the administration of either a NMBA or sedative induction agent first, are both acceptable. They also go on to say, “Administering the NMBA first may result in modestly faster time to intubation. For now, it is reasonable for physicians to continue performing RSI in the way they are most comfortable with.” 
But even with that being said, standard practice still remains with the “traditional,” give the sedative induction agent prior to the paralyzing agent. The definition of RSI, per the Manual of Emergency Airway Management, is, “The administration, after pre-oxygenation and patient optimization, of a potent induction agent, followed immediately by a rapidly acting NMBA to induce unconsciousness and motor paralysis for tracheal intubation.”
It is common practice to administer the sedative induction agent first, immediately followed by the NMBA; this is “traditional” rapid sequence induction.
BONUS QUESTION: What is Delayed Sequence Intubation?
The purpose of RSI is to render the patient unconscious and paralyzed and then to intubate the trachea, with the patient as oxygenated and optimized as possible, without the use of bag-mask ventilation, which may cause gastric distention and increase the risk for aspiration .
But, modifications of this approach have been implemented and variations of the “traditional” RSI have been made, such as ventilation during apnea, titration of induction agents, and sedation utilized to facilitate pre-oxygenation.
DSI, or delayed sequence intubation, is one of those modifications. DSI is the addition of procedural sedation, where the procedure is pre-oxygenation . When a patient is consistently hypoxemic or at risk of precipitous desaturation, and is unable to cooperate with clinicians in achieving appropriate oxygenation, delayed sequence intubation may be appropriate. In DSI, the induction agent is given in the hopes of facilitating oxygenation of an uncooperative patient .
The technique involves the administration of a dissociative dose of ketamine followed by several minutes of pre-oxygenation. Ketamine is given to provide sedation in attempts to better pre-oxygenate our patients, who otherwise we're unable to be appropriately pre-oxygenated; use that sedation time to apply our pre-oxygenation technique for our uncooperative or combative patients. When optimal oxygenation has been obtained, the NMBA may be pushed, and the intubation procedure continues as normal.
Ketamine is the ideal DSI induction agent due to its ability to provide sedation, but also preserve airway reflexes and respiratory drive.
Jared Patterson, CCP-C, FP-C, One Rad Medic
Killin' It Since 1989
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