Residency · Residency · Emergency Medicine
Rapid Sequence Intubation: Pharmacology and Technique
Overview
Definition
Rapid sequence intubation (RSI) is the near-simultaneous administration of a potent induction agent and a neuromuscular blocking agent to facilitate endotracheal intubation. The goal is to achieve rapid onset of unconsciousness and complete paralysis, creating optimal intubating conditions while minimizing the risk of aspiration. RSI is the most common method of emergency airway management in the ED, used in more than 80 percent of emergency intubations.
Indications for Intubation
The core indications for endotracheal intubation include failure to maintain or protect the airway, failure of ventilation or oxygenation, an anticipated clinical course that will require airway control (such as an expanding neck hematoma or worsening burns), and the need to facilitate workup or management (such as CT scanning or operative planning).
Pre-Oxygenation
Purpose
Pre-oxygenation replaces nitrogen in the functional residual capacity (FRC) with oxygen, creating an oxygen reservoir that extends safe apnea time from roughly one minute to three to eight minutes. In a standard patient with good pre-oxygenation, safe apnea time is approximately eight minutes. In obese or critically ill patients, it may be less than three minutes even with optimal technique.
Techniques
The standard approach is a non-rebreather mask at 15 L/min flush rate for at least three minutes, targeting an end-tidal oxygen above 90 percent. A bag-valve mask with a PEEP valve can be added for obese patients or those with shunt physiology. High-flow nasal cannula (HFNC) at 40 to 70 L/min provides both pre-oxygenation and apneic oxygenation simultaneously. BiPAP or CPAP should be used for patients who cannot maintain adequate SpO2 on a non-rebreather alone.
Apneic Oxygenation
Keeping a nasal cannula at 15 L/min or HFNC running during laryngoscopy extends safe apnea time by providing passive oxygen flow to the alveoli. The FELLOW trial showed no significant difference in lowest SpO2 in ICU patients, but the ENDAO trial and other studies support its use. Given its low cost and minimal risk, apneic oxygenation is standard practice at most institutions.
Patient Positioning
Ramped Position
The head of the bed should be elevated 20 to 30 degrees, with the external auditory meatus aligned horizontally with the sternal notch — an enhanced version of the classic "sniffing position." This is particularly critical in obese patients, where it improves FRC, extends apnea time, and improves the laryngoscopic view. Towels or blankets stacked under the shoulders and head create the ramp.
Head-Elevated Laryngoscopy
Even modest head-up positioning at 20 degrees improves the laryngoscopic view, reduces the risk of passive regurgitation, and decreases intracranial pressure (relevant in traumatic brain injury).
Induction Agents
Ketamine
Ketamine is dosed at 1 to 2 mg/kg IV, with 1.5 mg/kg being the typical RSI dose. Onset is 45 to 60 seconds, and duration is 10 to 15 minutes. Its advantages include preservation of respiratory drive at lower doses, bronchodilation, hemodynamic stability, and analgesic properties. Disadvantages include emergence phenomena (which can be reduced with a concurrent benzodiazepine), increased secretions (treatable with glycopyrrolate 0.2 mg if needed), and a theoretical concern about elevating intracranial pressure — though this has been largely debunked, and ketamine may actually reduce ICP by maintaining MAP. Ketamine is best suited for hemodynamically unstable patients, those with asthma or bronchospasm, and general-purpose induction. It is now the most commonly used induction agent in emergency RSI.
Etomidate
Etomidate is dosed at 0.3 mg/kg IV, with an onset of 15 to 45 seconds and a duration of 5 to 15 minutes. It is hemodynamically neutral with a rapid, predictable onset. Its main disadvantage is adrenal suppression through inhibition of 11-beta-hydroxylase for 24 to 48 hours. Whether this single-dose adrenal suppression is clinically significant in sepsis remains debated — multiple studies have produced conflicting results. The trend is toward avoiding etomidate in septic patients, but the evidence of harm from a single dose is weak. Etomidate is best for hemodynamically stable patients and cardiac patients who need neutral hemodynamics.
Propofol
Propofol is dosed at 1 to 2 mg/kg IV, with the dose reduced to 0.5 to 1 mg/kg in elderly or hemodynamically unstable patients. Onset is 15 to 45 seconds, and duration is 5 to 10 minutes. It provides excellent intubating conditions and has anticonvulsant, ICP-lowering, and antiemetic properties. However, it causes dose-dependent hypotension and myocardial depression and provides no analgesia. It is best suited for hemodynamically stable patients, status epilepticus, and elevated ICP without hypotension.
Midazolam
Midazolam at 0.1 to 0.3 mg/kg IV has an onset of 60 to 90 seconds and a duration of 15 to 30 minutes. Its slow onset, unpredictable depth of sedation, significant hypotension, and lack of analgesic properties make it generally unsuitable as a primary induction agent for RSI. Its role is limited to adjunctive sedation post-intubation and pre-procedure anxiolysis.
| Induction Agent | RSI Dose | Onset | Duration | Key Advantage | Key Disadvantage | Best Use |
|---|---|---|---|---|---|---|
| Ketamine | 1.5 mg/kg IV | 45–60 sec | 10–15 min | Hemodynamic stability, bronchodilation | Emergence phenomena, increased secretions | Hemodynamically unstable, asthma |
| Etomidate | 0.3 mg/kg IV | 15–45 sec | 5–15 min | Hemodynamically neutral | Adrenal suppression (24–48 hr) | Stable patients, cardiac patients |
| Propofol | 1–2 mg/kg IV | 15–45 sec | 5–10 min | Anticonvulsant, lowers ICP | Dose-dependent hypotension | Stable patients, status epilepticus |
| Midazolam | 0.1–0.3 mg/kg IV | 60–90 sec | 15–30 min | Anxiolysis | Slow onset, unpredictable | Generally not recommended for RSI |
Neuromuscular Blocking Agents
Succinylcholine
Succinylcholine is dosed at 1.5 mg/kg IV (or 2 mg/kg IM if no IV access is available). Onset is 45 to 60 seconds, and duration is 6 to 10 minutes. As a depolarizing agent, it binds nicotinic acetylcholine receptors, causing initial fasciculations followed by paralysis. Its key advantages are the fastest onset and shortest duration of any paralytic, allowing spontaneous recovery if intubation fails. Contraindications include hyperkalemia or conditions predisposing to it (burns or crush injuries beyond 48 hours, denervation injuries, prolonged immobilization, renal failure with potassium above 5.5), personal or family history of malignant hyperthermia, and myopathies such as Duchenne or Becker muscular dystrophy. Penetrating eye injury is a relative contraindication due to transient IOP elevation. Side effects include fasciculations, a potassium rise of 0.5 to 1 mEq/L, bradycardia (especially with repeat doses in children), masseter spasm, and malignant hyperthermia (rare, approximately 1 in 50,000 to 100,000).
Rocuronium
Rocuronium at the RSI dose of 1.2 mg/kg IV has an onset of 60 to 90 seconds and a duration of 45 to 70 minutes. A lower dose of 1 mg/kg provides slower onset and should not be used for RSI. As a non-depolarizing agent — a competitive antagonist at nicotinic acetylcholine receptors — it avoids the hyperkalemia risk, fasciculations, and contraindications associated with succinylcholine. Its main disadvantage is the long duration, which is problematic if intubation fails and ventilation cannot be maintained. However, sugammadex at 16 mg/kg provides immediate reversal, restoring spontaneous breathing within 2 to 3 minutes.
| Paralytic | RSI Dose | Onset | Duration | Key Advantage | Key Disadvantage |
|---|---|---|---|---|---|
| Succinylcholine | 1.5 mg/kg IV | 45–60 sec | 6–10 min | Fastest onset, shortest duration | Hyperkalemia risk, malignant hyperthermia |
| Rocuronium | 1.2 mg/kg IV | 60–90 sec | 45–70 min | No hyperkalemia risk, reversible with sugammadex | Long duration without reversal agent |
Succinylcholine vs. Rocuronium
At proper RSI doses, intubating conditions are equivalent between the two drugs. Rocuronium is increasingly preferred because sugammadex availability provides a safety net for failed intubation. Succinylcholine is still used when rapid offset is desired and sugammadex is unavailable. As the cost of sugammadex continues to decrease, practice is shifting further toward rocuronium.
Adjunctive Medications
Fentanyl
Fentanyl at 1 to 3 mcg/kg IV, given 3 minutes before induction, blunts the sympathetic response to laryngoscopy. It is indicated for patients with elevated ICP, aortic dissection, or cardiovascular disease where tachycardia and hypertension are harmful. Risks include chest wall rigidity at high doses, respiratory depression, and hypotension.
Lidocaine
Lidocaine at 1.5 mg/kg IV, given 3 minutes before induction, theoretically blunts the ICP rise and bronchospasm associated with laryngoscopy. However, the evidence for both indications is weak, and the drug is largely falling out of favor. Some clinicians still use it for reactive airway disease.
Atropine
Atropine at 0.02 mg/kg IV (minimum 0.1 mg) was historically given to children under one year before succinylcholine to prevent bradycardia. Current AHA guidelines no longer recommend routine atropine pretreatment, but it should be available and given if symptomatic bradycardia occurs.
The RSI Sequence (7 P's)
The RSI sequence follows seven steps. Preparation involves equipment checks (SOAP-ME: suction, oxygen, airway equipment, pharmacology, monitoring/end-tidal CO2), establishing monitoring and IV access, and drawing up medications. Pre-oxygenation takes at least three minutes with a non-rebreather, HFNC, or BVM with PEEP. Pretreatment with fentanyl or lidocaine, if indicated, is given three minutes before induction. Paralysis with induction involves giving the induction agent immediately followed by the paralytic. Protection and positioning entails avoiding bag-mask ventilation if possible to reduce aspiration risk and optimizing patient position. Placement of the endotracheal tube occurs after fasciculations cease (with succinylcholine) or at approximately 60 seconds (with rocuronium). Post-intubation management includes confirming placement with end-tidal CO2, securing the tube, obtaining a chest X-ray, initiating a sedation and analgesia infusion, and setting the ventilator.
Post-Intubation Sedation and Analgesia
Paralysis without sedation is a medical emergency — awareness under paralysis must always be prevented. Common regimens include propofol infusion at 5 to 50 mcg/kg/min (monitoring for hypotension), ketamine infusion at 0.1 to 0.5 mg/kg/hr, fentanyl at 25 to 100 mcg/hr combined with midazolam at 1 to 4 mg/hr, and dexmedetomidine at 0.2 to 0.7 mcg/kg/hr (which avoids respiratory depression but carries a bradycardia risk). An analgesia-first approach — using an opioid with a low-dose sedative — is preferred.
<image>A pharmacology comparison table rendered as a visual infographic showing the four main induction agents for RSI (ketamine, etomidate, propofol, midazolam) in four columns. Each column displays: the drug name, standard RSI dose, onset time, duration, a bar graph showing relative hemodynamic effect (from most depressant to most neutral), key advantages listed as green checkmarks, key disadvantages listed as red crosses, and ideal clinical scenario at the bottom. The hemodynamic comparison is the visual centerpiece, showing propofol with the most depression and ketamine/etomidate as most neutral.</image>
<image>A step-by-step illustration of the ramped intubation position for an obese patient. Side-view cross-section showing a patient on a hospital bed with progressive towel/blanket stacking under the shoulders and upper back, creating a ramp so that the external auditory meatus aligns horizontally with the sternal notch. A dashed horizontal line connects these two landmarks. The head of bed is elevated 20-30 degrees. An inset shows the improved laryngoscopic view achieved with this positioning compared to the standard supine position, with the vocal cords more visible.</image>
<image>A timeline diagram showing the RSI sequence along a horizontal time axis. Key moments are marked: T-3 minutes (preoxygenation begins and pretreatment drugs given), T-0 (induction agent given), T+10 seconds (paralytic given), T+45-60 seconds (onset of paralysis, begin laryngoscopy), T+90 seconds (tube placed, cuff inflated), T+2 minutes (ETCO2 confirmed, tube secured). Below the timeline, continuous apneic oxygenation via nasal cannula is shown as a green bar spanning the entire period. Monitoring parameters (SpO2, ETCO2, BP) are shown being tracked throughout.</image>
Clinical Pearls
Pre-oxygenation is the most important step in RSI because it determines how much time is available for laryngoscopy before desaturation. Ketamine has largely replaced etomidate as the default induction agent because it offers hemodynamic stability without the concern for adrenal suppression. Always use the RSI dose of rocuronium at 1.2 mg/kg — underdosing results in suboptimal paralysis and poor intubating conditions. Sugammadex at 16 mg/kg can reverse rocuronium within 2 to 3 minutes, which has made rocuronium the preferred paralytic at many institutions. Apneic oxygenation with nasal cannula at 15 L/min during laryngoscopy is a low-risk intervention that should be standard practice. Post-intubation sedation must be initiated immediately, as paralysis without sedation constitutes awareness under paralysis. Ramped positioning is critical in obese patients and beneficial in all patients. Push-dose vasopressors should be drawn up before intubating any hemodynamically tenuous patient.
References
- Brown CA, et al. National Emergency Airway Registry (NEAR) data on RSI practices. Multiple publications.
- Mosier JM, et al. The physiologically difficult airway. West J Emerg Med. 2015;16(7):1109-1117.
- Driver BE, et al. Bougie-first intubation. NEJM. 2021;384:1901-1908.
- April MD, et al. Ketamine versus etomidate for RSI. Ann Emerg Med. 2020;76(4):444-453.
- Sakles JC, et al. Apneic oxygenation during emergency intubation. Acad Emerg Med. 2016;23:703-710.
- Tran DTT, et al. Rocuronium vs. succinylcholine for RSI. Cochrane Database Syst Rev. 2015;CD002788.
