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Selection of Paralytic and Induction Agents in RSI

Updated: Apr 9, 2023



What is Rapid Sequence Intubation

Rapid Sequence Intubation (RSI) is a technique that involves administering an induction agent and a neuromuscular blocking agent simultaneously to induce unconsciousness and paralysis. This makes it easier to intubate the patient quickly and minimizes the risk of aspiration.

Before administering drugs, it is essential to do maximal preoxygenation and hemodynamic optimization. Preoxygenation is an important step of RSI that creates a large intrapulmonary reservoir of oxygen. This allows patients to tolerate a period of apnea without clinically significant oxygen desaturation. Bag-mask ventilation should be avoided with high-risk patients to minimize gastric insufflation and the risk of aspiration between drug administration and tracheal tube placement. RSI is associated with a higher rate of successful tracheal tube placement on the first attempt, and fewer complications overall [1,2].


Choices of Induction Agents

Although RSI is associated with less rate of complications, however, patients who are critically ill may experience hypotension as a result of the rapid induction. Therefore, the choice of induction medication should be done carefully to minimize these risks and cardiovascular status should be optimized with crystalloids, blood products, vasopressors, or inotropes before beginning RSI. We choose agents for paralysis and induction with the intent of causing unconsciousness and full muscle relaxation rapidly. RSI does not entail titration of these agents to reach this state. Instead, we calculate the dose of each agent ahead of time to get the desired effect. The length of time it takes for the drugs to take action after administration varies depending on which agent is selected, but regardless, our objective is to achieve adequate sedation and paralysis in 45-60 seconds. We will now go over the three most typical induction agents—etomidate, ketamine, and propofol—and discuss their possible side effects and the best clinical setting for each agent.


Propofol

Propofol is a highly lipid-soluble, alkylphenol derivative that acts at the GABA receptor causing sedation and amnesia. Sedation occurs through direct suppression of brain activity, while amnesia appears to result from interference with long-term memory creation. Induction doses of 1.5 to 3 mg/kg IV can be used, with a time to effect of approximately 15 to 45 seconds, and a duration of action of 5 to 10 minutes. Propofol does not provide analgesia.


Propofol is a highly lipid-soluble, alkylphenol derivative that acts at the GABA receptor and provides sedation through direct suppression of brain activity. Propofol can also cause amnesia by interfering with long-term memory creation, however, no analgesic properties. Induction doses of 1.5 to 3 mg/kg IV with a time to effect of 15 to 45 seconds, and duration lasting 5 to 10 minutes.

Children appear to metabolize propofol slightly differently than adults, resulting in a longer time to peak serum concentration. Propofol reduces airway resistance and can be an effective induction agent for patients with bronchospasm undergoing RSI. Propofol's neuroinhibitory properties make it ideal for patients with intracranial pathology who are hemodynamically stable. Propofol suppresses sympathetic activity and causes cardiac suppression and vasodilation. A decrease in mean arterial pressure (MAP) from propofol can reduce cerebral perfusion pressure and worsen the neurologic injury. The typical MAP reduction is about 10 mmHg.


Etomidate

Etomidate is an imidazole drug that affects the gamma-aminobutyric acid A (GABAA) receptor complex. It has a quick onset and short duration of action, similar to propofol. However, etomidate does not cause vasodilation or myocardial depression. This makes it safer for patients who are at increased risk for hypotension. The induction dose of etomidate for RSI is 0.2 to 0.4 mg/kg IV, with rapid onset (30 to 45 seconds) and a duration of action of 5 to 15 minutes.


A single dose of etomidate has been shown to cause adrenal suppression in the first 12 hours after administration, but it may help prevent a rise in cortisol levels in response to stressful stimuli. However, according to a systematic review that included six trials and 772 patients, using etomidate for endotracheal intubation is not associated with increased mortality compared to other induction agents [3].


Ketamine

Ketamine works by blocking NMDA receptors. It has mild direct cardiovascular effects, but in patients with an intact autonomic nervous system, ketamine can actually cause sympathetic stimulation and an increase in blood pressure, heart rate, and cardiac output. For this reason, ketamine may be a better choice than etomidate for patients who are at risk of hypotension. However, it is only possible to stimulate the sympathetic nervous system with ketamine if there is enough sympathetic reserve. If a patient has already maximally activated the sympathetic response and depleted all of their reserve (for example, patients in profound hypovolemic shock), administering ketamine may cause them to experience low blood pressure. The RSI induction dose of ketamine is 1 to 2 mg/kg IV. In patients with hypertension or when ICP elevation is suspected, ketamine should be avoided as it can worsen blood pressure. Ketamine has a time to effect of 45 to 60 seconds, and a duration of action of 10 to 20 minutes.


Selection of Induction Agents

In most cases, etomidate 0.3 mg/kg IV or ketamine 1 to 2 mg/kg IV are the better choices; however, depending on the clinical scenario, different sedatives may be preferred for RSI.


To prevent secondary brain injury in patients with head injuries or potentially elevated ICP, cerebral perfusion pressure must be maintained at an adequate level. Etomidate or ketamine is therefore preferred for the induction of these patients during RSI, even if they are hypotensive. However, ketamine should be avoided in cases where the patient has hypertension (MABP >120 mmHg) or signs of cerebral herniation are present.


For those suffering from Status epilepticus, propofol or etomidate are preferred for assistance during RSI. However, if the patient is also experiencing hemodynamic compromise, only then should etomidate be used. Ketamine should not be used due to its stimulant effects. Although midazolam is acceptable, one must take care when administering the appropriate induction dose (0.1-0.3mg/kg) so as not to cause hypotension with larger doses.


In patients with severe bronchospasm and hemodynamically stable, ketamine or propofol is preferred due to their bronchodilatory effects. Etomidate or midazolam can be used as an alternative option. For those who are hemodynamically unstable and have severe bronchospasm, ketamine or etomidate is preferred.


In patients with cardiovascular compromise (i.e., ACS, aortic dissection) without cardiogenic shock, etomidate is the preferred agent due to its hemodynamic stability profile.

In patients with shock, propofol should be avoided as it induces hypotension. A low dose of IV etomidate (0.15 mg/kg) or IV ketamine (1 mg/kg) can be used as an alternative. If etomidate is used on a patient that has sepsis and is unresponsive to treatment via fluid resuscitation and a vasopressor, a single dose of 100 mg glucocorticoid hydrocortisone intravenously may be given for the possibility of adrenal suppression.


In awake intubation, ketamine is preferred unless the patient has cardiovascular disease or hypertension. Finally, etomidate is the preferred agent in geriatric patients and the dose should be reduced to half in fragile or hypotensive patients.

Agent

Onset of Action

Duration of Action

Propofol

15-45 seconds

5-10 minutes

Etomidate

30-45 seconds

5-15 minutes

Ketamine

45-60 seconds

10-20 minutes

Succinylcholine

45-50 seconds

6-10 minutes

Rocuronium

45-60 seconds

45 minutes

Paralytic Agents

The cornerstone of RSI is a neuromuscular blocking agent (NMBA) given with a sedative. In the context of RSI, only two NMBAs have short onset times: succinylcholine and rocuronium.


Succinylcholine

The depolarizing agent succinylcholine (SCh) is an analog of acetylcholine (ACh). SCh binds directly to the postsynaptic ACh receptors on motor endplates, causing continuous stimulation of these receptors. This leads to muscle fasciculations followed by paralysis. SCh is commonly used in emergency settings because it works rapidly and provides dependable intubating conditions. Given as a 1.5 mg/kg intravenous (IV) dose (except in myasthenia gravis where a higher dose at 2 mg/kg IV should be used), paralysis sets in 45 to 60 seconds after dosing for rapid sequence intubation and generally lasts for 6 to 10 minutes. SCh is contraindicated in malignant hyperthermia, hyperkalemia, and in conditions that upregulate the ACh receptors and increase the risk of hyperkalemia. These conditions constitute denervating diseases (eg, multiple sclerosis, amyotrophic lateral sclerosis), inherited myopathies (eg, Duchenne muscular dystrophy), burns, after 72 hours, crush injuries after 72 hours, rhabdomyolysis, prolonged total body immobilization and severe, prolonged intraabdominal infections.


Rocuronium

The other agent that has a rapid onset is rocuronium which is a nondepolarizing neuromuscular blocking agent (NMBAs). The recommended dose for this neuromuscular blocking agent (NMBAs) is 1.5 mg/kg, given intravenously (IV), according to the patient's total body weight (except in myasthenia gravis where a lower dose of 0.6 mg/kg IV should be used). A higher dose usually results in more consistent paralysis and allows for easier laryngoscopy due to the added mechanical advantage of having the patient completely paralyzed from the start. The time it takes to reach intubation-level paralysis is approximately 45 to 60 seconds, with a duration of action lasting around 45 minutes. The most common reason why nondepolarizing NMBAs shouldn't be used for RSI is when the airway is predicted to be difficult. If the preintubation examination predicts a difficult airway, the clinician may select an alternative method to RSI. They might also modify the sequence of drugs for RSI or develop a more detailed backup plan in case of failed intubation.


In the absence of contraindication to succinylcholine, what is your preferred choice of paralytic agent in RSI?

  • Rocuronium

  • Succinylcholine


Selection of a Paralytic Agent

In general, succinylcholine is the preferred paralytic agent for RSI in the absence of any contraindication. This is due to its rapid onset, short duration, and overall efficacy and safety profile. In case of a difficult airway and inability to intubate, the paralytic effect is abolished in 6-10 minutes as opposed to at least 45 minutes in rocuronium. In addition, this guarantees that the patient does not wake up while he is still paralyzed with a longer-acting agent.


On the other hand, rocuronium is the preferred agent if a contraindication to succinylcholine exists or the clinician is not sure of the presence of any of these contraindications. In case the patient could not be intubated, sugammadex (16 mg/kg IV) can be used as a reversal agent. If sugammadex is used, full ECG monitoring should be continued during and after the administration of sugammadex due to the risk of bradycardia and anaphylaxis. Atropine and epinephrine should be immediately available.


Finally, if the clinician suspects difficult intubation, he or she may elect not to use a paralytic agent and decide to use an "awake look" first by using ketamine and topical anesthesia (nebulized 4 percent lidocaine). This allows the practitioner to examine the visibility of the laryngeal structure before committing to using a paralytic agent.


Watch the full presentation on RSI by Dr. Hasan Hawa here



References
  1. EFERENCESWilcox SR, Bittner EA, Elmer J, Seigel TA, Nguyen NT, Dhillon A, Eikermann M, Schmidt U. Neuromuscular blocking agent administration for emergent tracheal intubation is associated with decreased prevalence of procedure-related complications. Crit Care Med. 2012 Jun;40(6):1808-13. doi: 10.1097/CCM.0b013e31824e0e67. PMID: 22610185.

  2. Mosier JM, Sakles JC, Stolz U, Hypes CD, Chopra H, Malo J, Bloom JW. Neuromuscular blockade improves first-attempt success for intubation in the intensive care unit. A propensity matched analysis. Ann Am Thorac Soc. 2015 May;12(5):734-41. doi: 10.1513/AnnalsATS.201411-517OC. PMID: 25719512; PMCID: PMC5466156.

  3. Bruder EA, Ball IM, Ridi S, Pickett W, Hohl C. Single induction dose of etomidate versus other induction agents for endotracheal intubation in critically ill patients. Cochrane Database Syst Rev. 2015 Jan 8;1(1):CD010225. doi: 10.1002/14651858.CD010225.pub2. PMID: 25568981; PMCID: PMC6517008.


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