Rapid Sequence Induction

Aka: Rapid Sequence Induction, Rapid Sequence Intubation, Pharmacologic Management during Endotracheal Intubation, Peri-Intubation Hypotension

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II. Precautions

  1. Rapid Sequence Intubation (RSI) is a high risk procedure
  2. Must be able to completely control airway and ventilation after use
  3. Use a checklist!
  4. Peri-intubation Cardiac Arrest is predicted by 3 highest risk factors
    1. Preintubation shock or Hypotension (RR 6)
    2. Preintubation Hypoxemia (RR 3)
    3. Forced to act scenarios

III. Indications

  1. Preparation for intubating a conscious patient

IV. Protocol

  1. Walls protocol describes all steps in Endotracheal Intubation
    1. This page focuses on pharmacologic strategies in RSI (steps 3, 4 and 7)
    2. Endotracheal Intubation Preparation describes a safety checklist for readying for intubation
    3. Endotracheal Intubation Preoxygenation - prevent Hypoxia during intubation (including Apneic Oxygenation)
    4. Endotracheal Intubation describes techniques for maximal laryngeal visualization and ET insertion, confirmation
  2. Mnemonic: 7Ps (Walls)
    1. Preparation - step 1
      1. See Endotracheal Intubation Preparation
      2. Includes SOAP-ME Mnemonic
      3. See Endotracheal Tube
        1. Includes size and length selection of Endotracheal Tubes
      4. See Direct Laryngoscope
        1. Includes sizes of Miller Blade and Macintosh Blade
      5. See Video Laryngoscope
        1. Includes Video Laryngoscopy devices such as Glidescope, C-MAC, MacGrath
    2. Preoxygenation - step 2
      1. See Endotracheal Intubation Preoxygenation (includes Apneic Oxygenation)
      2. Significantly extends duration of safe apnea during intubation
    3. Physiologic Optimization - step 3 (CRASH Mnemonic)
      1. See Physiologic Optimization Prior to Intubation
      2. See below
    4. Paralysis with Induction - step 4
      1. See below
    5. Positioning - step 5
      1. See Endotracheal Intubation
    6. Placement with Proof - step 6
      1. See Endotracheal Intubation
    7. Postintubation Management - step 7
      1. See Endotracheal Intubation
      2. Also see post-intubation agents described below
  3. Alternatives
    1. See Extraglottic Device
      1. Includes Laryngeal Mask Airway or LMA
      2. Consider as emergency device in case of Endotracheal Intubation failure
    2. See Nasotracheal Intubation
      1. May be considered in anticipated difficult airway of a conscious patient

V. Protocol: Physiologic Optimization - Step 3 (Mnemonic: CRASH)

  1. Background
    1. Physiologic factors are the greatest threat to safe intubation (esp. Saturation/Hypoxemia and Hypotension)
  2. Consumption of Oxygen Increased (outpaces Oxygen Delivery)
    1. Causes: High demand states (e.g. ARDS, Sepsis, pregnancy, children, Thyroid Storm)
    2. Endotracheal Intubation Preoxygenation (includes Apneic Oxygenation)
  3. Right Ventricular Failure
    1. See Acute Right Ventricular Failure Management
    2. Right ventricle poorly compensates for increased right-sided Afterload (pulmonary vascular resistance)
      1. RV has only Tachycardia and a marginal increase in contractility for compensation
      2. Pulmonary pressures further increase with hypercapnia, Hypoxia, Atelectasis and PPV
      3. Catastrophic decompensation and Cardiac Arrest may follow
  4. Acidosis Metabolic
    1. Hypercapnea during intubation may worsen an already severe Metabolic Acidosis
    2. Acidosis may precipitate further decreased inotropy and ventricular Arrhythmias
  5. Saturation of oxygen may fall with even brief intubation attempts
    1. See Endotracheal Intubation Preoxygenation (includes Apneic Oxygenation)
    2. Preoxygenation is limited in severe airspace diseases where FRC Is low (e.g. ARDS) or low V/Q (shunt)
    3. Continue Apneic Oxygenation throughout intubation (e.g. Nasal Cannula at 15 lpm)
    4. Adequate preoxygenation (tight oxygen mask at 100% FIO2) allows for a safe apneic period during intubation
      1. Leads to denitrogenation, improved Functional Residual Capacity (FRC), decreased V/Q mismatch
  6. Hypotension
    1. See Prevention of Post-Intubation Hypotension
    2. Optimize underlying conditions before intubation and have Vasopressors readily available
  7. References
    1. Brown (2022) Walls Manual of Emergency Airway Management, LWW, p. 21-2

VI. Protocol: Paralysis with Induction - step 4

  1. Sedation with paralysis (standard, recommended protocol)
    1. Ensure adequate sedation to prevent awareness while paralyzed (painful, horrible torture)
      1. Paralysis with awareness occurs in 2.6% of patients
      2. Pappal (2021) Ann Emerg Med 77(5): 532-44 [PubMed]
    2. Can never over-dose paralytics
      1. Best to over-estimate than under-estimate dose (e.g. 2 mg/kg of Succinylcholine or Rocuronium)
        1. Paralytics should be dosed at actual body weight (total body weight)
        2. Succinylcholine and Rocuronium can both be dosed at 1.5 mg/kg
      2. Low Cardiac Output may reduce effect and delay onset of action (overcome by higher dose)
      3. Re-dose fully in reliable IV if suspected infiltration of first dose via a poorly placed IV
    3. Consider half dose or lower of induction agents in Hypotension
      1. All induction agents should be dosed at Lean Body Mass
      2. Indicated in Hypotension
      3. Midazolam, Propofol and Barbiturates doses should be lowered
        1. Decrease induction dose to 10 to 20% standard dose (avoid >50% of standard dose)
      4. Alternatively, use Etomidate or Ketamine for induction
        1. Etomidate or Ketamine do not lower Blood Pressure and may be given at full dose
      5. References
        1. Driver (2023) Ann Emerg Med 82(4):417-24 +PMID: 37389494 [PubMed]
  2. Sedation without paralysis (facilitated intubation, use only with caution in difficult airway)
    1. See Difficult Airway for other ways to approach a patient with risk of failed airway
    2. Precaution: May significantly Handicap intubation technique
      1. RSI with sedation only (without paralytic) is not recommended
        1. Risk for adverse outcome (multiple intubation attempts, airway injury, aspiration, death)
        2. Bozeman (2006) Prehosp Emerg Care 10(1): 8-13 [PubMed]
      2. Sedation without paralysis may lead to inadequate Muscle relaxation for intubation
        1. Etomidate is short acting
          1. May not allow for adequate intubation attempt without paralysis
        2. Propofol is longer acting, but risks Hypotension
      3. Risk of Emesis and aspiration
        1. Consider pretreatment with Ondansetron to suppress Gag Reflex
      4. Full dose paralytics are recommended for even the lowest GCS scores (outside of crash airway)
        1. Avoid half-dose paralytics or defasciculating dose
    3. Indications
      1. Patients who are not resisting stabilization measures AND
      2. Difficult Airway (with risk of a unsupportable patient if intubation unsuccessful)
        1. Otherwise complete paralysis for 8 minutes (Succinylcholine) to 45 minutes (Rocuronium)
        2. A patient aware, "locked-in", paralyzed without sedation or Analgesic is torture
          1. Avoid, unless the only alternative is death
    4. Alternatives
      1. Dissociative Awake Intubation
      2. Awake Nasotracheal Intubation
    5. Technique
      1. Prepare Paralytic Agent for injection (even if not immediately injected)
      2. Consider pretreatment with Ondansetron to suppress Gag Reflex
      3. Administer sedation (e.g. Etomidate) at standard dosing
        1. Dissociative Awake Intubation with Ketamine 1-2 mg/kg
        2. Consider adding Etomidate 0.1 mg/kg to suppress Gag Reflex
    6. References
      1. Braude in Herbert (2013) EM:Rap 13(11): 14
      2. Weingart in Majoewsky (2012) EM:Rap 12(2): 8
  3. Preferred Sedation/Induction agents (preferred)
    1. General
      1. Dose at Lean Body Weight (Lean Body Mass)
    2. Etomidate
      1. Dose: 0.2 to 0.3 mg/kg
        1. Dose of 0.3 mg/kg is most common (24 mg for an 80 kg adult)
        2. Compromised patients: 0.15 to 0.2 mg/kg
      2. Agent of choice in most cases
        1. Most hemodynamically stable agent (more than Ketamine)
      3. Preferred in Hemorrhagic CVA with increased Blood Pressure
      4. Possible increased mortality in Rapid Sequence Intubation (RSI)
        1. Meta-analysis number needed to harm (NNH): 31
        2. Kotani (2023) J Crit Care 77:154317 +PMID: 37127020 [PubMed]
      5. May cause adrenal suppression (which may impact survival in Sepsis)
        1. Consider Ketamine as an alternative induction agent in Sepsis
        2. Not Clinically Significant if used in single dose as induction agent for intubation
          1. McPhee (2013) Crit Care Med 41(3): 774-83 [PubMed]
        3. Avoid in Sepsis for any longer use than brief
          1. Cuthbertson (2009) Intensive Care Med 35(11): 1868-76 [PubMed]
          2. Jabre (2009) Lancet 374(9686): 293-300 [PubMed]
    3. Ketamine
      1. Dose: 1.5 mg/kg (120 mg for an 80 kg adult)
        1. Do not exceed 1.5 mg/kg in shock cases
        2. Compromised patients: 0.5 to 1 mg/kg
      2. Preferred agent in copd, Asthma, Angioedema (and possibly Sepsis)
        1. Ketamine is not associated with apnea, regardless of dose
        2. Ketamine also has Bronchodilator properties (ideal for COPD, Asthma)
      3. Not contraindicated in Closed Head Injury (previously thought to increase Intracranial Pressure)
        1. Appears to be neuroprotective by increasing Cerebral Perfusion Pressure
        2. Does not lower Seizure threshold
      4. Consider administration with Zofran (due to associated Vomiting)
      5. Not contraindicated in Coronary Artery Disease, Congestive Heart Failure or Hypertension
      6. Avoid concurrent Atropine (or glycopyrrolate) to dry secretions
        1. Worsens increased airway secretions by thickening them
  4. Other sedation/induction agents
    1. Propofol (Diprivan)
      1. Dose: 1.5 mg/kg
        1. Compromised patients: 0.5 to 1 mg/kg
      2. Consider for Status Epilepticus
      3. Contraindicated in hypotensive patients
      4. Although common use in post-intubation sedation, rare use in emergency RSI
    2. Thiopental (Pentothal)
      1. Older agent, rarely used in U.S. in 2013
      2. Consider for Status Epilepticus (Fast-acting anti-epileptic)
      3. Consider Increased Intracranial Pressure (Fastest lowering of ICP of any induction agent)
      4. Contraindicated in hypotensive patients or porphyria
      5. Risk of skin necrosis if infiltrates (highly alkalotic agent with pH 10)
    3. Midazolam (Versed)
      1. Considered a poor agent for RSI
      2. Rarely given at adequate doses (a typical adult dose for RSI is an astounding 8-10 mg)
      3. Could be considered in Status Epilepticus
      4. Risk of Hypotension at induction doses
      5. Risk of Agitation in the elderly and those with liver disease
  5. Paralysis agents
    1. General
      1. Dose at actual body weight (total body weight)
    2. Succinylcholine 1.5 mg/kg (120 mg for an 80 kg adult)
      1. Contraindicated if Hyperkalemia risk (see Succinylcholine for a list of risks)
        1. Do not re-dose Succinylcholine (Hyperkalemia risk increases)
        2. If longer paralysis is needed, use Rocuronium instead
      2. Wait at least one minute for defasciculation prior to intubating (risk of Emesis)
      3. Oxygen Saturation drops more quickly with Succinylcholine due to oxygen utilization for paralysis
        1. Use Apneic Oxygenation
      4. Duration or paralysis: 8 minutes (far shorter than Rocuronium)
        1. Optimal duration to reduce the risk of patient awareness without adequate sedation
        2. Allows for earlier resumption of Neurologic Exam (e.g. Status Epilepticus, head or neck Trauma)
        3. Some prefer in anticipated difficult airway
          1. However, return of spontaneous breathing in 8 minutes is a poor back-up strategy
          2. An Advanced Airway is needed regardless of failed intubation (see Difficult Airway Assessment)
    3. Rocuronium 1 to 1.2 mg/kg (80-96 mg for 80 kg adult)
      1. Agent of choice in children (and in adults if Succinylcholine contraindicated)
      2. Many recommend Rocuronium for all intubations as the safest option in undifferentiated ED presentations
      3. Inadequate sedation and analgesia is common following Rocuronium (due to long duration)
        1. Err on the side of more aggressive sedation and analgesia while patient is paralyzed
        2. Awareness of intubation (paralysis persists longer than sedation) should NEVER be allowed to occur
        3. Initiate bolus and infusion of Sedative (e.g. Propofol) immediately after intubation (prepare before)
        4. Korinek (2014) Eur J Emerg Med 21(3): 206-11 +PMID:23510899 [PubMed]
      4. Duration of paralysis: 45 minutes
        1. Sugammadex tightly binds Rocuronium and Vecuronium to reverse paralysis
      5. Some prefer in difficult airway due to longer duration of action
        1. Positive Pressure Ventilation may be easier with paralysis
        2. Longer duration allows for repeat attempt without re-dosing in case of failed intubation

VII. Protocol: Post-intubation Management - step 7

  1. See Post-Intubation Sedation and Analgesia

VIII. Management: Special Circumstances

  1. Status Asthmaticus
    1. Sedation: Ketamine
  2. Congestive Heart Failure
    1. Sedation: Etomidate
  3. Status Epilepticus
    1. Sedation: Thiopental, Midazolam, Propofol
  4. Multiple Trauma or Hemorrhagic Shock
    1. Sedation: Etomidate
  5. Shock
    1. Use lower induction agent doses (e.g. half dose)
      1. Etomidate 0.15 to 0.2 mg/kg
        1. Preferred induction agent (most hemodynamically stable induction agent)
      2. Ketamine 0.5 to 1 mg/kg
        1. May be used as an alternative to Etomidate (e.g. in Asthma, COPD)
    2. Use increased paralytic doses
      1. Rocuronium 2 mg/kg
      2. Succinylcholine 3-4 mg/kg
    3. References
      1. Orman and Hayes in Herbert (2017) EM:Rap 17(1): 10
      2. Heier (2000) Anesth Analg 90(1): 175-9 +PMID:10625000 [PubMed]

IX. Management: Pretreatment (primarily historical, not recommended in most cases)

  1. Pretreatment medications that have largely fallen out of favor (no evidence, possible harm)
  2. Perintubation Pretreatment (Fentanyl, Lidocaine) is rarely if ever indicated
    1. Indications are listed below for completeness, but are not generally recommended
    2. ABC Mnemonic was used to guide pretreatment (not indicated in most cases)
    3. No evidence of benefit for any of these agents (except possibly for Atropine in infants)
  3. ABC Mnemonic for pretreatment is listed (with the evidence against its use)
    1. Asthma or COPD
      1. Lidocaine 1.5 mg/kg (120 mg for 80 kg adult)
    2. Brain (prevention of Intracranial Pressure increase with intubation)
      1. Fentanyl 4-5 mcg/kg (320 mcg for 80 kg adult) given slowly over 1-2 minutes
        1. More than twice the Analgesic dose
      2. Lidocaine 1.5 mg/kg (no longer recommended)
        1. Multiple studies show no benefit for neurologic outcome
        2. Lin (2012) Am J Emerg Med 30(9): 1782-7 +PMID:22633717 [PubMed]
        3. Robinson (2001) Emerg Med J 18(6): 453-7 +PMID:11696494 [PubMed]
    3. Cardiovascular disease (Ischemic Heart Disease, aortic aneurysm, Aortic Dissection)
      1. Fentanyl 3 mcg/kg
    4. Children under age 12 months (optional for ages 1 to 5 years)
      1. Greatest predictive factor for Bradycardia on intubation is Hypoxia
        1. Apneic Oxygenation (Nasal Cannula delivered High Flow Oxygen throughout intubation)
        2. Prolongs safe intubation time (see above)
      2. Atropine 0.02 mg/kg
        1. Atropine has historically been used to prevent Bradycardia when intubating children
          1. Still used in pediatric EDs as of 2024 for intubation of age <6-12 months (high vagal tone)
        2. However, mixed evidence and some references do not routinely recommend for any age
          1. Fleming (2005) CJEM 7(2): 114-7 +PMID:17355661 [PubMed]
        3. Consider Atropine ready at the time of intubation in case of Symptomatic Bradycardia
          1. However, Atropine activity may have too delayed an effect to be used prn
        4. If Atropine used in cases of suspected Non-accidental Trauma
          1. Consider performing Retinal Exam immediately after RSI with Atropine
        5. Avoid Atropine to dry secretions with Ketamine (results in thicker secretions)

X. Resources

  1. Rapid Sequence with Rocuronium and Ketamine Video (Sacchetti)
    1. http://www.youtube.com/watch?v=kTd7km_jnKw
  2. RSI Calculator (slide-rule bedside calculator for RSI drugs)
    1. http://www.RSIcalculator.com

XI. References

  1. Herbert (2012) EM: RAP-C3 2(5): 3-4
  2. Swaminathan and Weingart in Herbert (2019) EM:Rap 19(5): 11-12
  3. Levitan (2013) Practical Airway Management Course, Baltimore
  4. McClain, Lawner and Butler (2019) Crit Dec Emerg Med 33(12): 19-27
  5. McCollum (2024) EM:Rap, published 3/25/2024
  6. Walls (2012) Emergency Airway Management, 3rd Ed, Lippincott, Philadelphia, p. 24-35
  7. Walker L. A. (1993) Emerg Med Rep, 14(15):127-32 [PubMed]

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