Which medications are recommended for rapid‑sequence intubation (RSI) in adult patients, including the short‑acting analgesic, induction agent, and neuromuscular blocker, and what are the relevant contraindications?

Medications for Rapid Sequence Intubation

For rapid sequence intubation in adult patients, you must administer a sedative-hypnotic induction agent (etomidate 0.2-0.3 mg/kg, ketamine 1-2 mg/kg, or propofol 2 mg/kg) immediately followed by a neuromuscular blocking agent (succinylcholine 1-1.5 mg/kg or rocuronium 0.9-1.2 mg/kg), with etomidate plus succinylcholine being the preferred combination for hemodynamically unstable patients. 1, 2

Mandatory Three-Drug Sequence

1. Short-Acting Analgesic (Optional Pretreatment)

• Administer fentanyl 2-5 mcg/kg IV three minutes before induction to blunt the sympathetic response to laryngoscopy, particularly in patients with cardiovascular disease or elevated intracranial pressure. 1, 3, 4
• This pretreatment step attenuates hypertension and tachycardia during intubation but increases the risk of apnea, so use cautiously. 1

2. Sedative-Hypnotic Induction Agent (Mandatory)

You must always give a sedative-hypnotic agent before the neuromuscular blocker to prevent awareness during paralysis—this is a best practice statement from the Society of Critical Care Medicine. 1, 2

Etomidate (First-Line for Unstable Patients)

• Dose: 0.2-0.3 mg/kg IV 2, 3
• Etomidate is the preferred agent for hemodynamically unstable patients because it causes minimal cardiovascular depression through GABA-A receptor enhancement. 2
• The 2023 Society of Critical Care Medicine guidelines found no difference in mortality or vasopressor requirements between etomidate and other induction agents, making it safe for critically ill patients. 1
• Critical pitfall: Etomidate's duration is only 3-12 minutes, far shorter than long-acting paralytics (25-73 minutes), creating a high risk of awareness if post-intubation sedation is delayed. 5, 6

Ketamine (Alternative for Agitated Patients)

• Dose: 1-2 mg/kg IV 2, 7, 3
• Ketamine is an NMDA receptor antagonist that maintains respiratory drive and increases catecholamine release, making it ideal for medication-assisted preoxygenation in agitated or combative patients. 1, 2, 7
• Contraindication: In critically ill patients with depleted catecholamine stores, ketamine can cause paradoxical hypotension and cardiac arrest despite its sympathomimetic properties. 1, 2

Propofol (Use Only in Stable Patients)

• Dose: 2-2.5 mg/kg IV 8, 3, 4
• Propofol causes the most profound hypotension of all induction agents through venodilation, limiting its use to hemodynamically stable patients. 1
• It suppresses airway reflexes more effectively than other agents, which can be advantageous if intubation fails. 7

3. Neuromuscular Blocking Agent (Mandatory)

The Society of Critical Care Medicine strongly recommends administering an NMBA when a sedative-hypnotic agent is used—this is a Class I strong recommendation. 1, 2

Succinylcholine (First-Line for Stable Patients)

• Dose: 1-1.5 mg/kg IV 2, 7, 8, 3
• Succinylcholine provides the fastest onset (45-60 seconds) and shortest duration (5-10 minutes), making it the preferred agent when there are no contraindications. 1, 2
• Absolute contraindications: Burns >24 hours old, renal failure >24 hours, crush injuries, denervation injuries, or hyperkalemia—all can cause fatal hyperkalemic cardiac arrest. 7, 8

Rocuronium (Alternative When Succinylcholine Contraindicated)

• Dose: 0.9-1.2 mg/kg IV for RSI (not the 0.6 mg/kg dose used for routine intubation) 2, 7, 8
• High-dose rocuronium (0.9-1.2 mg/kg) provides onset comparable to succinylcholine (median 1 minute) but with a much longer duration (58-67 minutes). 2, 8
• Mandatory requirement: Sugammadex must be immediately available at bedside for rapid reversal (within 3 minutes) in "cannot intubate/cannot oxygenate" scenarios. 2, 7
• The FDA label explicitly states rocuronium 0.6 mg/kg is not recommended for rapid sequence induction in Cesarean section patients due to poor intubating conditions when combined with lower thiopental doses. 8

Evidence-Based Selection Algorithm

For Hemodynamically Unstable Patients:

• Induction agent: Etomidate 0.2-0.3 mg/kg 2
• NMBA: Succinylcholine 1-1.5 mg/kg (if no contraindications) 2
• Rationale: This combination provides the fastest intubation with minimal cardiovascular depression. 2

For Hemodynamically Stable Patients:

• Induction agent: Etomidate or ketamine 2
• NMBA: Either succinylcholine or rocuronium 0.9-1.2 mg/kg 1, 2
• Rationale: The 2023 Society of Critical Care Medicine guidelines suggest no difference between these agents in stable patients. 1

For Agitated/Combative Patients Unable to Preoxygenate:

• First: Ketamine 1-2 mg/kg IV for medication-assisted preoxygenation 1, 2, 7
• Wait 3 minutes for preoxygenation while patient is dissociated 7
• Then: Administer NMBA (succinylcholine or rocuronium) 7
• Rationale: This "delayed sequence intubation" approach increases oxygen saturation by 8.9% before paralysis. 7

For Patients with Renal Failure:

• Induction agent: Etomidate 0.2-0.3 mg/kg (no dose adjustment needed) 7
• NMBA: Rocuronium 0.9-1.2 mg/kg only—never succinylcholine after 24 hours of renal failure 7
• Rationale: Succinylcholine causes life-threatening hyperkalemia in renal failure due to upregulated acetylcholine receptors and baseline hyperkalemia. 7

Critical Timing Requirements

• Administer the induction agent and NMBA in rapid succession with immediate endotracheal tube placement before any assisted ventilation to minimize aspiration risk. 2, 7
• Wait at least 60-90 seconds after NMBA administration before attempting intubation to allow full paralysis. 7, 8
• Post-intubation sedation must be given within 10-15 minutes of etomidate administration to prevent awareness during ongoing paralysis, as etomidate's duration (3-12 minutes) is far shorter than rocuronium's (58-67 minutes). 5, 6

Common Contraindications

Succinylcholine Contraindications:

• Burns or crush injuries >24 hours old 7
• Renal failure >24 hours 7
• Denervation injuries (stroke, spinal cord injury) >72 hours 7
• Known hyperkalemia or malignant hyperthermia history 7

Ketamine Relative Contraindications:

• Severe catecholamine depletion (septic shock, cardiogenic shock) where paradoxical hypotension may occur 1, 2

Rocuronium Special Requirement:

• Cannot be used unless sugammadex is immediately available for emergency reversal 2, 7

Most Dangerous Pitfall

The single most dangerous error is administering a long-acting NMBA (rocuronium) with a short-acting induction agent (etomidate) and then failing to provide post-intubation sedation within 10-15 minutes. Studies show 63% of patients receive delayed sedation (>15 minutes) and 13% receive no additional sedation at all, resulting in prolonged periods of paralysis with awareness. 5, 6 This is medical malpractice—set a timer and administer continuous sedation (propofol or midazolam infusion) immediately after confirming tube placement. 5, 6