Acute Airway Management & RSI — Part 2: RSI Protocol & Medications

1. Rapid Sequence Intubation: Definition and Rationale

Rapid sequence intubation (RSI) is the near-simultaneous administration of a potent induction (sedative-hypnotic) agent and a neuromuscular blocking agent to produce rapid onset of unconsciousness and complete neuromuscular paralysis for the purpose of tracheal intubation.^{1 2} RSI is the technique of choice for emergency intubation in patients who have not fasted and are at risk for aspiration of gastric contents. It differs from standard induction in the operating room by the emphasis on:

• Zero apnea time — induction and paralysis are given in rapid succession (not titrated)
• Full paralysis dose — neuromuscular blockers are given at the higher end of the dosing range for rapid onset
• Avoidance of positive-pressure ventilation — traditionally, BVM ventilation is avoided between induction and intubation to minimize gastric insufflation and aspiration risk (although recent evidence from the PreVent trial supports gentle BVM with PEEP)³
• Cricoid pressure — the application of posterior force on the cricoid cartilage (Sellick maneuver) to compress the esophagus, although its efficacy is debated⁴

2. The “Seven P’s” of RSI: Systematic Preparation

2.1 Overview

A structured preparation protocol ensures that all necessary elements are in place before induction. The “Seven P’s” framework provides a time-based checklist.¹

2.2 Equipment Preparation

Before induction, the following equipment must be immediately available and checked:

3. Pretreatment Agents

Pretreatment agents are administered 3 minutes before induction to mitigate specific physiologic responses to laryngoscopy and intubation. Their routine use is controversial; current evidence supports selective use in specific clinical scenarios.^{1 5}

3.1 Pretreatment Agent Summary

3.2 Detailed Pretreatment Considerations

Fentanyl:

• Primary use: blunting the hypertensive/tachycardic response to laryngoscopy in patients where sympathetic surge is dangerous
• Critical caution: Fentanyl itself can cause hypotension (especially in hypovolemic patients) and apnea — give slowly and monitor
• Dose reduction in hemodynamically compromised patients: 0.5–1 mcg/kg
• Administer 3 minutes before induction for peak effect at time of laryngoscopy
• Not routinely recommended for all intubations; only when sympathetic attenuation is specifically indicated

Lidocaine:

• Primary use: suppression of cough reflex and bronchospasm during airway manipulation
• For asthma/COPD: may reduce bronchospasm triggered by intubation
• For ICP: evidence for ICP attenuation is weak and inconsistent; should not delay intubation
• Administer 3 minutes before induction

Atropine:

• Primary use: prevent bradycardia in young children receiving succinylcholine
• Children < 1 year: routine atropine before succinylcholine is recommended by multiple pediatric guidelines
• Children 1–5 years: consider atropine, especially if repeat doses of succinylcholine may be needed
• Adults: not routinely recommended; succinylcholine-associated bradycardia in adults is rare and usually transient
• Minimum dose of 0.1 mg to avoid paradoxical bradycardia

4. Induction Agents

The induction agent produces rapid loss of consciousness, facilitating laryngoscopy and preventing the patient from experiencing paralysis while awake. The ideal agent provides rapid onset (< 60 seconds), brief duration, hemodynamic stability, and favorable side-effect profile. No single agent meets all criteria; selection is based on clinical context.^{1 5 6}

4.1 Complete Induction Agent Comparison Table

4.2 Detailed Agent Profiles

4.2.1 Ketamine

Ketamine is an NMDA-receptor antagonist that produces a “dissociative” state characterized by profound analgesia, amnesia, and sedation while preserving respiratory drive and pharyngeal reflexes at sub-induction doses.⁷

Dosing:

• RSI induction: 1.5–2.0 mg/kg IV push
• IM (when IV unavailable): 4–5 mg/kg IM (onset 3–5 min)
• Dose reduction in shock/catecholamine depletion: 1.0–1.5 mg/kg IV
• IN (intranasal, pediatric/backup): 3–4 mg/kg IN (onset 5–10 min)

Key pharmacology:

• Mechanism: NMDA antagonist, produces “dissociative” state; stimulates catecholamine release from adrenal medulla and sympathetic nerve terminals
• In catecholamine-depleted patients (prolonged septic shock, decompensated heart failure), the direct myocardial depressant effect of ketamine may predominate, causing hypotension — use lower doses and have vasopressors ready
• ICP: Historical concerns about ketamine raising ICP have been largely refuted; current evidence suggests ketamine is safe in head injury when used with controlled ventilation⁸
• Bronchodilation: Ketamine causes bronchial smooth muscle relaxation, making it the preferred agent in status asthmaticus
• Secretions: Increases oral and bronchial secretions; consider co-administration of glycopyrrolate 0.2 mg IV (optional, not required in RSI)

4.2.2 Propofol

Dosing:

• RSI induction: 1.5–2.0 mg/kg IV push
• Elderly/hemodynamically compromised: 0.5–1.5 mg/kg IV (titrate to effect if time permits)
• Obese patients: dose on lean body weight (LBW), not total body weight

Key pharmacology:

• Mechanism: GABA-A receptor agonist; produces rapid unconsciousness
• Reduces cerebral metabolic rate and ICP — useful in status epilepticus and elevated ICP (if blood pressure can be maintained)
• Causes dose-dependent vasodilation and myocardial depression — avoid or dose-reduce in hypotension, hypovolemia, sepsis, elderly
• BP decrease of 25–40% is common at induction doses
• No analgesic properties — pain on injection common through peripheral IV (can attenuate with lidocaine 20–40 mg IV administered through same IV 30 seconds before propofol)

4.2.3 Etomidate

Dosing:

• RSI induction: 0.3 mg/kg IV push
• No dose adjustment typically required for obesity (some practitioners use ideal body weight)

Key pharmacology:

• Mechanism: GABA-A receptor modulation at a unique binding site
• Minimal hemodynamic effect — preserves sympathetic tone, produces negligible changes in heart rate, blood pressure, or cardiac output
• Adrenal suppression: A single induction dose of etomidate inhibits 11-beta-hydroxylase, suppressing cortisol synthesis for 12–24 hours. The clinical significance of this transient suppression remains debated.⁹
  • In the landmark KETASED trial, ketamine was compared to etomidate for RSI in critically ill patients; no significant difference in mortality or organ failure was found¹⁰
  • Current consensus: etomidate remains a reasonable choice for RSI, particularly in hemodynamically unstable patients; the adrenal suppression from a single dose is likely clinically insignificant in most patients
  • Consider ketamine as an alternative if adrenal suppression is a concern (septic shock)
• Myoclonus occurs in 30–60% of patients but is eliminated by neuromuscular blockade in RSI

4.2.4 Midazolam

Dosing:

• RSI induction: 0.1–0.3 mg/kg IV (at the higher end for reliable unconsciousness)
• Elderly: 0.05–0.1 mg/kg IV

Key pharmacology:

• Mechanism: GABA-A receptor agonist (benzodiazepine binding site)
• Rarely used as first-line RSI induction agent due to slow onset (60–90 sec), unpredictable depth of anesthesia, and prolonged duration
• May be considered when ketamine, propofol, and etomidate are all unavailable
• Causes moderate hypotension via vasodilation
• Reversible with flumazenil (0.2 mg IV, repeat q1 min to max 1 mg) — but flumazenil reversal in the post-intubation patient is rarely indicated and carries seizure risk

4.3 Induction Agent Selection by Clinical Scenario

5. Neuromuscular Blocking Agents

Neuromuscular blockers (NMBAs) produce complete skeletal muscle paralysis, abolishing protective reflexes (gag, cough, swallowing) and creating optimal conditions for laryngoscopy and intubation. In RSI, they are given immediately after the induction agent.^{1 5 11}

5.1 NMBA Comparison Table

5.2 Succinylcholine — Detailed Profile

Mechanism: Depolarizing neuromuscular blocker; binds acetylcholine receptors at the neuromuscular junction, causing initial depolarization (fasciculations) followed by sustained depolarization and desensitization block (paralysis).¹¹

Dosing:

• Adults: 1.5 mg/kg IV (based on total body weight)
• Children: 2.0 mg/kg IV (higher dose due to larger volume of distribution)
• IM (when no IV access): 4 mg/kg IM (onset 3–4 min; useful in laryngospasm, pediatric emergencies)
• Obese patients: dose on total body weight (TBW) — plasma cholinesterase activity correlates with TBW

Fasciculations:

• Occur 10–15 seconds after administration; visible as transient muscle twitching
• Followed by complete paralysis within 45–60 seconds
• May cause transient increase in intragastric pressure, intraocular pressure, and intracranial pressure
• Can be prevented with a “defasciculating dose” of a non-depolarizing agent (e.g., rocuronium 0.06 mg/kg) given 3 min before — rarely done in emergency RSI

Absolute Contraindications to Succinylcholine:

Relative contraindications:

• Open globe injury (transient IOP increase — controversial; many experts consider acceptable if intubation is needed)
• Renal failure with normal potassium (safe if K⁺ is not elevated)
• Pregnancy: safe in all trimesters; plasma cholinesterase levels may be slightly reduced but clinically insignificant

Key pearl: Succinylcholine is safe in acute burns (< 5 days), acute crush injury (< 5 days), acute stroke (< 5 days), and acute spinal cord injury (< 5 days). The receptor upregulation that causes dangerous hyperkalemia requires several days to develop.

5.3 Rocuronium — Detailed Profile

Mechanism: Competitive (non-depolarizing) antagonist at nicotinic acetylcholine receptors at the neuromuscular junction. Competes with acetylcholine for receptor binding without causing depolarization.^{11 12}

Dosing:

• RSI dose: 1.2 mg/kg IV (based on ideal body weight in obese patients)
• Standard intubation dose: 0.6 mg/kg (onset 90–120 sec; not for RSI)
• Obese patients: dose on ideal body weight (IBW) — rocuronium distributes to lean tissue; TBW dosing causes prolonged paralysis

Ideal body weight calculation:

• Males: IBW (kg) = 50 + 2.3 × (height in inches − 60)
• Females: IBW (kg) = 45.5 + 2.3 × (height in inches − 60)

No contraindications comparable to succinylcholine (no hyperkalemia risk, no MH trigger, no fasciculations). Safe in:

• Hyperkalemia
• Burns, crush injury (any time frame)
• Neuromuscular disease
• Malignant hyperthermia susceptibility
• Renal/hepatic impairment (may prolong duration)

Reversal with Sugammadex:

Sugammadex is a modified gamma-cyclodextrin that encapsulates rocuronium (and vecuronium) molecules in a 1:1 complex, rapidly and completely reversing neuromuscular blockade regardless of depth.¹³

Key pharmacology of sugammadex:

• Weight-based dosing uses total body weight (not ideal body weight)
• Onset is rapid (full reversal in < 3 min at 16 mg/kg dose)
• No muscarinic side effects (unlike neostigmine — no need for co-administration of glycopyrrolate or atropine)
• Contraindication: severe renal impairment (GFR < 30) — sugammadex-rocuronium complex is renally excreted; may have prolonged effect
• Drug interaction: may reduce efficacy of hormonal contraceptives for 7 days
• CICO rescue role: If a patient has received rocuronium and develops a “cannot intubate, cannot oxygenate” scenario, sugammadex 16 mg/kg can reverse paralysis and potentially restore spontaneous ventilation — however, this should NOT delay front-of-neck access if oxygenation is critical

5.4 Succinylcholine vs. Rocuronium: Selection Guide

Current practice trend: Rocuronium has increasingly become the default NMBA for emergency RSI in many institutions, particularly where sugammadex is readily available, due to the absence of contraindications and comparable onset time at the 1.2 mg/kg dose.¹²

6. Paralysis Verification

After administration of the induction agent and NMBA, paralysis must be confirmed before attempting laryngoscopy:

• Time-based: Wait at least 45–60 seconds after succinylcholine or rocuronium 1.2 mg/kg administration
• Clinical assessment:
  • Loss of fasciculations (succinylcholine): fasciculations begin at ~15 sec and resolve by ~45 sec
  • Loss of jaw tone: test by attempting to open the mouth — if jaw is relaxed and moves freely, paralysis is adequate
  • Loss of movement: no spontaneous movement, no response to jaw thrust
• Peripheral nerve stimulator (train-of-four): If available, apply to ulnar nerve at wrist and stimulate; zero twitches (0/4) = complete paralysis. Most useful in OR and ICU settings; in the ED, clinical assessment is usually sufficient given the time-based approach.

Critical pearl: Do not attempt laryngoscopy before paralysis is complete. Premature attempts on a partially paralyzed patient result in poor intubating conditions (residual jaw tone, patient movement, cough), leading to failed first-pass attempts and complications.

7. Cricoid Pressure (Sellick Maneuver)

Cricoid pressure involves the application of 30–40 N (approximately 3–4 kg) of posterior force on the cricoid cartilage ring to compress the esophagus against the cervical vertebral body, theoretically preventing passive regurgitation of gastric contents.⁴

Current evidence and recommendations:

Practical approach:

• If your institution protocol includes cricoid pressure, apply correctly identified force (30 N — “firm enough that it’s uncomfortable if applied to your own cricoid”)
• Release immediately if laryngoscopic view is poor, if ventilation is impaired, or if SGA placement is attempted
• Many emergency airway experts have abandoned routine cricoid pressure based on current evidence

8. Confirmation of Intubation

8.1 Waveform Capnography — The Gold Standard

Continuous waveform capnography (quantitative end-tidal CO₂ monitoring) is the single most reliable method for confirming correct endotracheal tube placement and is the standard of care.^{14 15}

Criteria for confirmation:

• Presence of a sustained, repetitive waveform for at least 5–6 breaths with appropriate waveform morphology (the “shark fin” or rectangular CO₂ waveform)
• Quantitative ETCO₂ value — typically 35–45 mmHg in a patient with normal metabolism and circulation
• An ETCO₂ reading alone (colorimetric) without waveform is less reliable — colorimetric detectors can give false positives (gastric CO₂, carbonated beverages) and false negatives (low cardiac output, cardiac arrest)

False negatives (no CO₂ despite correct placement):

• Cardiac arrest (absent or minimal pulmonary blood flow → minimal CO₂ delivery to alveoli) — ETCO₂ may be < 10 mmHg
• Massive pulmonary embolism
• Contamination or malfunction of the capnography sensor

False positives (CO₂ detected with esophageal placement):

• CO₂ from recent carbonated beverage ingestion or BVM ventilation of the stomach — diminishes rapidly over 5–6 breaths (esophageal CO₂ will decrease to zero; tracheal CO₂ maintains plateau)

8.2 Additional Confirmation Methods

8.3 Confirming Proper Depth

After confirming tracheal placement, verify appropriate depth:

• Adults: ETT tip should be 3–5 cm above the carina (approximately 21–23 cm at the lip in adult males, 19–21 cm at the lip in adult females)
• Verify with chest radiograph — the ETT tip should project over T2–T4 vertebral bodies with the head in neutral position
• Right mainstem intubation is the most common malposition — suspect if breath sounds are absent on the left; withdraw ETT 2 cm and reassess

9. Drug-Assisted Intubation Without Paralysis (Delayed Sequence Intubation / DSI)

9.1 Concept

Delayed sequence intubation (DSI) is a technique in which a dissociative dose of ketamine is used to produce a sedated but spontaneously breathing state that allows the patient to tolerate preoxygenation measures (NIV, HFNC, NRB) that they would otherwise not tolerate due to agitation or combativeness.¹⁶

DSI is NOT intubation without paralysis — the patient receives a dissociative dose of ketamine, tolerates aggressive preoxygenation, and then undergoes standard RSI (with paralysis) once oxygenation has been optimized.

9.2 DSI Protocol

9.3 Indications for DSI

• Agitated, hypoxic patient who will not tolerate preoxygenation (e.g., delirium, excited delirium, head injury with agitation)
• SpO₂ < 93% with inability to preoxygenate due to patient combativeness
• The patient who “needs to be intubated but can’t be safely preoxygenated”

9.4 Cautions

• Ketamine at dissociative doses may cause transient apnea — be prepared to assist ventilation
• DSI does not replace standard RSI — it is a pre-oxygenation facilitation strategy
• Not indicated when the airway is imminently threatened (e.g., expanding hematoma, complete obstruction)

10. Awake Intubation

10.1 Indications

Awake intubation is performed with the patient conscious, breathing spontaneously, and maintaining their own airway while the clinician secures the trachea under direct or indirect vision. It is the safest approach when the predicted airway anatomy is severely difficult and the clinician cannot confidently rescue a failed intubation with BVM, SGA, or FONA.^{2 17}

Primary indications:

• Known or predicted difficult airway where Plan B/C are also predicted to fail (LEMON + MOANS + RODS + SHORT all abnormal)
• Previous documented difficult/failed intubation
• Significant upper airway distortion (tumor, abscess, angioedema, radiation changes)
• Severe cervical spine instability (unstable C-spine fracture with neurologic deficit)
• Morbid obesity with multiple difficult airway predictors
• Patient refusal of general anesthesia with request for awake technique (elective)

10.2 Topicalization of the Airway

Successful awake intubation requires adequate local anesthesia of the oropharynx, hypopharynx, and larynx to suppress gag, cough, and laryngospasm.

Total lidocaine dose limit: 4.5 mg/kg without epinephrine; 7 mg/kg with epinephrine. Topical absorption is variable; conservative approach is to limit total topical lidocaine to 4–5 mg/kg.

10.3 Sedation for Awake Intubation

Light sedation improves patient tolerance without abolishing protective reflexes or respiratory drive:

10.4 Techniques for Awake Intubation

• Awake fiberoptic intubation (FOI): Gold standard for predicted difficult airway; flexible bronchoscope passed through nose or mouth into trachea; ETT railroaded over scope
• Awake video laryngoscopy: Hyperangulated VL blade with topicalized airway; increasingly popular in ED
• Awake tracheostomy: For severe upper airway obstruction where even awake oral/nasal intubation is unsafe (e.g., massive laryngeal tumor, severe tracheal stenosis)

11. Post-Intubation Immediate Priorities

Immediately after confirmation of tracheal intubation, the following must occur:

11.1 Post-Intubation Sedation and Analgesia

Key principle — “Analgesia first”: The modern approach to ICU sedation prioritizes analgesia (pain control) before sedation. An adequately analgesed patient requires less sedation. Target a light sedation level (RASS 0 to -2) unless deep sedation is specifically required (e.g., paralysis, severe ARDS, elevated ICP).¹⁸