Rapid sequence induction

In advanced airway management, rapid sequence induction (RSI) - also referred to as rapid sequence intubation or as rapid sequence induction and intubation (RSII) - is a special process for endotracheal intubation that is used where the patient is at a high risk of pulmonary aspiration or impending airway compromise. It differs from other forms of general anesthesia induction in that artificial ventilation is generally not provided from the time the patient stops breathing (when drugs are given) until after intubation has been achieved. This minimizes insufflation of air into the patient's stomach, which might otherwise provoke regurgitation.

Rapid sequence induction/intubation

"Classic" RSI involves pre-filling the patient's lungs with a high concentration of oxygen gas, followed by applying cricoid pressure, administering rapid-onset sedative or hypnotic and neuromuscular-blocking drugs that induce prompt unconsciousness and paralysis, inserting an endotracheal tube with minimal delay, and then releasing the cricoid pressure. "Modified" RSI refers to changes that deviate from the classic pattern, usually to reduce acidosis or improve oxygenation in case of cardiac, neurological and asthmatic patients, but at the expense of increased regurgitation risk [citation needed!!]; examples of modifications include giving ventilations before the tube has been placed, or not using cricoid pressure. The induction agents and muscle relaxants differ in each cases.

The procedure is used where general anesthesia must be induced before the patient has had time to fast long enough to empty the stomach; where the patient has a condition that makes aspiration more likely during induction of anesthesia, regardless of how long they have fasted (such as gastroesophageal reflux disease or advanced pregnancy); or where the patient has become unable to protect their own airway even before anesthesia (such as after a traumatic brain injury).

The induction drugs traditionally used for RSI have short durations of action, wearing off after only minutes. This confers a degree of fault tolerance on the procedure when it is used in elective or semi-elective settings: if intubation is unsuccessful, and if the clinical condition allows it, the procedure may be abandoned and the patient should regain the ability to protect their own airway sooner than would be the case under routine methods of induction. Conversely, in emergency settings where the patient's condition does not allow for them to be woken up immediately, a failed intubation under RSI places them at very high risk for respiratory compromise.

Common medications


Premedication is used to reduce anxiety of those who are going to be intubated and to reduce the anticipated physiological response of the patient during intubation.[1]

  • Midazolam - It is a fast-acting and the most lipophilic of all benzodiazepine and rapidly crosses the blood–brain barrier. It is a gamma-aminobutyric acid (GABA) agonist. Usual doses for midazolam are 1 mg to 2 mg where the older people receive smaller doses and obese people receive higher doses. Midazolam is metabolised in the liver and is excreted through the kidneys. When midazolam is used alone, it has few side effects, but can cause respiratory depression if being used together with fentanyl.[1]
  • Fentanyl - It is a synthetic, centrally-acting opioid. It suppresses pain and sympathetic stimulation. Sympathetic stimulation can cause further injury to those with heart disease, aortic dissection, and aortic aneurysm. Fentanyl is ideal because of its rapid onset, lack of histamine release, high lipophilicity, and short duration of action. The dosage is between 1 and 3 μg/kg. It is metabolised by liver. The most significant side effect is respiratory depression.[1]
  • Atropine — The process of intubation can cause massive stimulation to vagus nerve, causing bradycardia (low heart rate). The people who are at increased risk of bradycardia are neonates and children. This does not happen in adults because sympathetic stimulation overpowers the vagal response. However, for those adults who have received drugs such as beta blocker, calcium channel blocker, and digoxin has an increased risk of developing bradycardia. Atropine is a muscarinic receptor antagonist, thus blocking the vagal response. The dose is 0.01 mg/kg. It has quick onset of action, and common side effects are: increased heart rate, dry mouth, flushing, and urinary retention.[1]
  • Lidocaine - It is used to reduce the sympathetic response in those who has suspected raised intracranial pressure (ICP) or those who received succinylcholine which also causes increase ICP or those with underlying asthma that have bronchospasm. Administration of lidocaine can causes reduction in mean arterial pressure (MAP). The dosage is 1.5 mg/kg. This drug is metabolised by liver. The side effects are: hypotension, arrythmia (irregular heart beat). Lidocaine can further interact with other drugs such as amiodarone and monoamine oxidase inhibitor to cause hypotension, and dronedarone to cause arrhythmia.[1]

Induction agents

Administration of induction agents followed by neuromuscular blockade agents helps to achieve optimal conditions for intubation.[1]

  • Etomidate - It is an imidazole-derivative that stimulates GABA receptors. The dosage is between 0.2 and 0.6 mg/kg (commonly 20 to 50 mg doses). Dose reduction maybe required in those with hypotension. Etomidate has minimal cardiovascular side effects, reduces intracerebral pressure (by reducing cerebral blood flow), and does not cause histamine release. It has quick onset of action, short duration of action, and undergoes hepatic elimination. Myoclonus, pain at the site of the injection, post-operative nausea and vomiting are common. It can also suppresses the production of cortisol and aldosterone.[1]
  • Ketamine - It is highly lipophilic and crosses the blood-brain barrier. It inhibits the binding of glutamine to N-Methyl-D-aspartic acid (NMDA) receptors in Thalamocortical radiations and limbic system, causing amnesia. Through the same blockade of NMDA receptor, ketamine is also effective as a painkiller. The dosage is 1 to 2 mg/kg, usually given at 100 mg. Ketamine is metabolised by liver and excreted through kidneys. The drug lessen the reuptake of the catecholamine, increases heart rate, blood pressure, and cardiac output, thus suitable for those with hypotension. However, it can worsen the cardiac depression and hypotension for those with depletion of catecholamines. Thus, maximum dose of 1.5 mg/kg is need for this situation. For those with head injuries, ketamine does not appear to increase intracranial pressure, while able to maintain the mean arterial pressure. Ketamine also relieves bronchospasm by dilating bronchial smooth muscles. However, it increases oral secretions during intubation. Ketamine is associated with nightmares, delirium, and hallucinations.[1]
  • Propofol - It is a highly lipid-soluble, GABA agonist. The dosage is 1.5 mg/kg (usually 100 to 200 mg). It has quick onset of action, can cross the blood-brain barrier, wide tissue distribution, and can be cleared by the body quickly. In old people, the rate of propofol clearance is low. Therefore, lower doses of propofol (50 to 100 mg) should be given. It is suitable in those with kidney or liver impairment and decreases intra-cranial pressure. For those with bronchospasm, propofol also has mild bronchodilating effect. However, propofol can induce hypotension and bradycardia due to its calcium channel blocker and beta blocker properties. At prolonged high propofol dosages, it can induce propofol infusion syndrome. Pain during peripheral administration of propofol can be reduced by using a large bore cannula.[1]
  • Midazolam - Apart as a premedication, midazolam can be used as an induction agent at the dose of 0.2 to 0.3 mg/kg. It has slow onset of action when used alone, but the onset can be improved when using together with an opioid. However, for those with hypotension, midazolam can further reduce the blood pressure and has cardiac depressive effects. Therefore, dose reduction is required for the elderly, and for those with heart and liver failure.[1]
  • Methohexital - This is a GABA agonist. It works by reducing the dissociation of GABA from its receptors. The dosage is 1.5 mg/kg. It is metabolised in liver. However, methohexital can cause respiratory depression, venodilatation, myocardial depression, and hypotension. Additionally, it can also cause reduced cerebral blood flow and histamine release. It can cause distal thrombosis and tissue necrosis if given into the arterial system.[1]
  • Phenylephrine - This drug is administered to those with hypotension post intubation as a result of lidocaine, midazolam, fentanyl, propofol, and ketamine. The dosages range from 50 to 200 μg in adults. It has quick onset and quick elimination. The common side effect is reflex bradycardia.[1]


Paralytics are also known as neuromuscular-blocking drugs (NMB). NMB can reduce the complication rates of rapid sequence induction such as inadequate oxygenation of the blood, airway complications, and instability of the cardiovascular system. NMB can be divided into two types: depolarising and non-depolarising blockers. Depolarising blockers resembles the acetylcholine and activates the motor end-pate of the neuromuscular junction (NMJ). Meamwhile, non-depolarising blockers competitively blocks the NMJ without activating the motor end plate.[1]

Depolarising blockers

  • Succinylcholine - This drug has rapid onset of action and fast duration. It dosages is between 1 and 2 mg/kg body weight with common dosages of 100 mg. The drug can only be kept under room temperature for 14 days. Therefore, for longer shelf life, it has to be kept under temperatures from 3.3 °C (37.9 °F) to 8.7 °C (47.7 °F) When the intravenous access is not obtainable, the 3 to 4 mg/kg of intramuscular doses can be given (usual doses of 300 mg). However, duration of onset will be delayed to 3 to 4 minutes. Repetitive dosages of succinylcholine is discouraged to prevent vagal stimulation which lead to bradycardia.[1]

In myasthenia gravis, the number of acetylcholine receptors is reduced due to antibodies attack. Therefore, dosages greater than 2 mg/kg is required for these people. In Lambert Eaton syndrome, the number of acetylcholine receptors is upregulated. Although this condition has increased response to the non-dopolarsing NMB, it does not shows increased response to depolarsing blockers. Therefore, acetylcholine dose reduction is not needed for Lambert Eaton syndrome. For those with pseudocholinesterase enzyme deficiency, the person can remain paralysed up to 6 to 8 hours because there is not enough enzymes to break down acetylcholine. Therefore, acetylcholine should be avoided in these people. On the other hand, although there is also a relative decrease in pseudocholinesterase enzymes in those with liver disease, kidney disease, anemia, pregnancy, chronic cocaine use, amphetamine abuse, increased age, and connective tissue disease, the acetylcholine effect is minimal and dose reduction is not needed.[1]

The most significant side effect of acetylcholine is malignant hyperthermia and hyperkalemia. In malignant hyperthermia, mutation of ryanodine receptor at chromosome 19 is responsible for the increased release of calcium from the calcium channels, thus triggering increase in muscle contraction and temperature rise. This only happens when acetylcholine is administered. For those who had history of receiving succinylcholine and developed fever, tachycardia, and muscle rigidity. Muscle rigidity in the masseter muscle causes intubation to be impossible. Rhabdomyolysis of the muscles also occurs which lead to increase in calcium, potassium, and creatine kinase concentrations. Blood gas analysis which cause mixed respiratory and metabolic acidosis. Dantrolene (dose at 2.5 mg/kg) is the treatment of choice that binds to ryanodine receptors that inhibits calcium release from the sacroplamic reticulum. However, such drug is labour-intensive for pharmacy to prepare. Other physiological derangements should be treated supportively. The serum potassium levels typically increase by 0.5 to 1 mEq/L and is not contraindicated in those with diabetic ketoacidosis and acute kidney failure. Only if the person has symptomatic hyperkalemia, then rocuronium should be considered. In those with prolonged immobilisation, crush injuries, burns, and myopathies, there is increase in extrajunctional cholinergic receptors, thus potential potassium rise is higher in these people. For those with acute nerve injuries or stroke, the increase in acetylcholine receptors will only occurs after five to fifteen days after injury. Therefore, succinylcholine can be given within the first 24 hours of injury. The increase in succinylcholine sensitivity remains elevated after 2 to 6 months after the injury. Other side effects of succinylcholine includes increase in intraocular pressure (IOP) and increase in intracranial pressure (ICP).[1]

Non-depolarising blockers

  • Rocuronium - The dosage of rocuronium is between 0.6 and 1.2 mg/kg. Since rocuronium has longer duration of onset, caution should be taken for those who is difficult to bag-mask ventilate.[1]
  • Vecuronium - The dosage of this drug is between 0.08 and 0.1 mg/kg. Vecuronium is only used when there is a shortage of drugs such as succinylcholine and rocuronium.[1]

Reversal agents

  • Sugammadex - It is used as a reversal agent for rocuronium and vecuronium. It works by encapsulating the paralytic thus preventing it from acting on the binding sites. The dose of 16 mg/kg is used for immediate reversal after administration such as during RSI. Doses of 2 mg/kg and 4 mg/kg are used if the patient has twitches evident on a twitch monitor. and terminates the rocuronium action within 3 minutes. The FDA initially did not approve Sugammadex due to concerns over potential allergic reactions, however it was subsequently approved on December 15, 2015 for use in the United States.
  • Neostigmine - It is can be used to reverse nondepolarizing neuromuscular blocking agents which cannot be reversed with sugammadex, although its onset is much slower. It works by competing with acetylcholine for the binding sites of acetylcholinesterase, which in turn prevents the breaking down of the acetylcholine. The dosage is between 0.03 and 0.07 mg/kg. The side effect of this drug is bradycardia. Therefore, glycopyrrolate should be given together with neostigmine to prevent bradycardia.[1]

Other medications


Rapid sequence intubation refers to the pharmacologically induced sedation and neuromuscular paralysis prior to intubation of the trachea. The technique is a quicker form of the process normally used to induce general anesthesia. A useful framework for describing the technique of RSI is the "seven Ps".[2]


The patient is assessed to predict the difficulty of intubation. Continuous physiological monitoring such as ECG and pulse oximetry is put on the patient. The equipment and drugs for the intubation are planned, including the endotracheal tube size, the laryngoscope size, and drug dosage. Drugs are prepared in syringes. Intravenous access is obtained to deliver the drugs, usually by placing one or two IV cannulae.


The aim of preoxygenation is to replace the nitrogen that forms the majority of the functional residual capacity with oxygen. This provides an oxygen reservoir in the lungs that will delay the depletion of oxygen in the absence of ventilation (after paralysis). For a healthy adult, this can lead to maintaining a blood oxygen saturation of at least 90% for up to 8 minutes.[3] This time will be significantly reduced in obese patients, ill patients and children. Preoxygenation is usually performed by giving 100% oxygen via a tightly fitting face mask. Preoxygenation or a maximum of eight deep breaths over 60 seconds results in blood oxygenation is not different from that of quiet breathing volume for 3 minutes.[4]

Newer methods of pre oxygenation include the use of a nasal cannula placed on the patient at 15 LPM at least 5 minutes prior to the administration of the sedation and paralytic drugs. High flow nasal oxygen has been shown to flush the nasopharynx with oxygen, and then when patients inspire they inhale a higher percentage of inspired oxygen. Small changes in FiO2 create dramatic changes in the availability of oxygen at the alveolus, and these increases result in marked expansion of the oxygen reservoir in the lungs prior to the induction of apnea. After apnea created by RSI the same high flow nasal cannula will help maintain oxygen saturation during efforts securing the tube (oral intubation).[5][6] The use of nasal oxygen during pre-oxygenation and continued during apnea can prevent hypoxia before and during intubation, even in extreme clinical cases.[7]


Pretreatment consists of the medications given to specific groups of high-risk patients 3 minutes before the paralysis stage with the aim of protecting the patient from the adverse effects of introducing the laryngoscope and endotracheal tube. Intubation causes increased sympathetic activity, an increase in intracranial pressure and bronchospasm. Patients with reactive airway disease, increased intracranial pressure, or cardiovascular disease may benefit from pretreatment. Two common medications used in the pretreatment of RSI include Lidocaine and Atropine. Lidocaine has the ability to suppress the cough reflex which in turn may mitigate increased intracranial pressure. For this reason Lidocaine is commonly used as a pretreatment for trauma patients who are suspected of already having an increase in intracranial pressure. Although there is not yet definitive evidence to support this, if proper dosing is used it is safe. The typical dose is 1.5 mg/kg IV given three minutes prior to intubation.[8] Atropine may also be used as a premedication agent in pediatrics to prevent bradycardia caused by hypoxia, laryngoscopy, and succinylcholine. Atropine is parasympathetic blocker. The common premedication dose for atropine is 0.01-0.02 mg/kg.

Paralysis with induction

With standard intravenous induction of general anesthesia, the patient typically receives an opioid, and then a hypnotic medication. Generally the patient will be manually ventilated for a short period of time before a neuromuscular blocking agent is administered and the patient is intubated. During rapid sequence induction, the person still receives an IV opioid. However, the difference lies in the fact that the induction drug and neuromuscular blocking agent are administered in rapid succession with no time allowed for manual ventilation.

Commonly used hypnotics include thiopental, propofol and etomidate. The neuromuscular blocking agents paralyze all of the skeletal muscles, most notably and importantly in the oropharynx, larynx, and diaphragm. Opioids such as fentanyl may be given to attenuate the responses to the intubation process (accelerated heart rate and increased intracranial pressure). This is supposed to have advantages in patients with ischemic heart disease and those with brain injury (e.g. after traumatic brain injury or stroke). Lidocaine is also theorized to blunt a rise in intracranial pressure during laryngoscopy, although this remains controversial and its use varies greatly. Atropine may be used to prevent a reflex bradycardia from vagal stimulation during laryngoscopy, especially in young children and infants. Despite their common use, such adjunctive medications have not been demonstrated to improve outcomes.[9]


Positioning involves bringing the axes of the mouth, pharynx, and larynx into alignment, leading to what's called the "sniffing" position. The sniffing position can be achieved by placing a rolled towel underneath the head and neck, effectively extending the head and flexing the neck. You are at proper alignment when the ear is inline with the sternum.[10]

The Sellick's maneuver, or cricoid pressure, may be used to occlude the esophagus with the goal of preventing aspiration.

Placement of tube

During this stage, laryngoscopy is performed to visualize the glottis. The endotracheal tube is then passed in between the vocal cords, and a cuff is inflated around the tube to hold it in place and prevent aspiration of stomach contents.

The position of the tube in the trachea can be confirmed in a number of ways, including observing increasing end tidal carbon dioxide, auscultation of both lungs and stomach, chest movement, and misting of the tube.

Postintubation management

Malpositioning of the endotracheal tube (in a bronchus, above the glottis, or in the esophagus) should be excluded by confirmation of end tidal CO2, auscultation and observation of bilateral chest rise.

One important difference between RSI and routine tracheal intubation is that the practitioner does not typically manually assist the ventilation of the lungs after the onset of general anesthesia and cessation of breathing, until the trachea has been intubated and the cuff has been inflated.[11]

Additional considerations

Age can play a role in whether or not the procedure is warranted, and is commonly needed in younger persons.[12] The clinician that performs RSI must be skilled in tracheal intubation and also in bag valve mask ventilation. Alternative airway management devices must be immediately available, in the event the trachea cannot be intubated using conventional techniques. Such devices include the combitube and the laryngeal mask airway. Invasive techniques such as cricothyrotomy must also be available in the event of inability to intubate the trachea by conventional techniques.

RSI is mainly used to intubate patients at high risk of aspiration, mostly due to a full stomach as commonly seen in a trauma setting. Bag ventilation causes distention of stomach which can induce vomiting, so this phase must be quick. The patient is given a sedative and paralytic agent, usually midazolam / suxamethonium / propofol and intubation is quickly attempted with minimal or no manual ventilation. The patient is assessed for predictable intubation difficulties. Laryngoscope blades and endotracheal tubes smaller than would be used in a non-emergency setting are selected.

If the patient on initial assessment is found to have a difficult airway, RSI is contraindicated since a failed RSI attempt will leave no option but to ventilate the patient on bag and mask which can lead to vomiting. For these challenging cases, awake fiberoptic intubation is usually preferred.


Since the introduction of RSI, there has been controversy regarding virtually every aspect of this technique, including:[13]

  • choice of intravenous hypnotic agents as well as their dosage and timing of administration
  • dosage and timing of administration of neuromuscular blocking agents
  • avoidance of manual ventilation before tracheal intubation
  • optimal position and whether the head-up, head-down, or horizontal supine position is the safest for induction of anesthesia in full-stomach patients
  • application of cricoid pressure, which is also referred to as the Sellick maneuver.


  1. Joanna L, Stollings; Danie A, Diedrich; Lance J, Oyen; Daniel R, Brown (2014). "Rapid-Sequence Intubation: A Review of the Process and Considerations When Choosing Medications". Annals of Pharmacology. 48 (1): 62–76. doi:10.1177/1060028013510488. PMID 24259635.
  2. Cooper, Angus. "Rapid Sequence Intubation - A guide for assistants" (PDF). Scottish Intensive Care Society Education. NHS - Education for Scotland. Retrieved 31 March 2013.
  3. Benumof, J. L.; Dagg, R.; Benumof, R. (1997). "Critical hemoglobin desaturation will occur before return to an unparalyzed state following 1 mg/kg intravenous succinylcholine". Anesthesiology. 87 (4): 979–982. doi:10.1097/00000542-199710000-00034. PMID 9357902.
  4. "Preoxygenation". 2010-10-04.
  5. Binks MJ, Holyoak RS, Melhuish TM, Vlok R, Bond E, White LD. Apneic oxygenation during intubation in the emergency department and during retrieval: a systematic review and meta-analysis. Am J Emerg Med 2017. https://dx.doi.org/10.1016/j. ajem.2017.06.046.
  6. Pavlov I, Medrano S, Weingart S. Apneic oxygenation reduces the incidence of hypoxemia during emergency intubation: A systematic review and meta-analysis. Am J Emerg Med 2017.
  7. "No Desat!".
  8. Hampton, J. P. (2011). Rapid-sequence intubation and the role of the emergency department pharmacist. American Journal of Health-System Pharmacy, 68(14), 1320-1330. doi:10.2146/ajhp100437
  9. Neilipovitz, DT; Crosby, ET (2007). "No evidence for decreased incidence of aspiration after rapid sequence intubation". Canadian Journal of Anesthesia. 54 (9): 748–64. doi:10.1007/BF03026872. PMID 17766743.
  10. Nancy Caroline: Emergency Care in the Streets 7th Ed. Jones & Bartlett Learning. 2013. p. 780.
  11. Stone DJ and Gal TJ (2000). "Airway management". In Miller, RD (ed.). Anesthesia, Volume 1 (5th ed.). Philadelphia: Churchill Livingstone. pp. 1414–51. ISBN 978-0-443-07995-5.
  12. Warner KJ, Sharar SR, Copass MK, Bulger EM (April 2009). "Prehospital management of the difficult airway: a prospective cohort study". The Journal of Emergency Medicine. 36 (3): 257–65. doi:10.1016/j.jemermed.2007.10.058. PMID 18439793.
  13. El-Orbany, MI; Connolly, LA (2010). "Rapid Sequence Induction and Intubation: Current Controversy" (PDF). Anesthesia & Analgesia. 110 (5): 1318–25. doi:10.1213/ANE.0b013e3181d5ae47. PMID 20237045.
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