Describe delayed sequence intubation.

Delayed Sequence Intubation (DSI)

Delayed sequence intubation is a technique in which a dissociative dose of ketamine (1–2 mg/kg IV) is administered to facilitate adequate preoxygenation in agitated or delirious patients who cannot tolerate standard preoxygenation, followed 3 minutes later by administration of a neuromuscular blocking agent and intubation. 1, 2

Core Concept and Rationale

DSI is essentially procedural sedation where the "procedure" is preoxygenation itself. 2 The technique addresses a critical clinical problem: patients with altered mental status, agitation, or delirium who actively resist preoxygenation efforts, creating high risk for severe hypoxemia during intubation. 1

• The British Journal of Anaesthesia guidelines explicitly describe DSI as a practical solution when pre-induction oxygenation becomes difficult in agitated patients. 1
• DSI allows clinicians to convert an uncooperative, hypoxemic patient into one who can receive optimal preoxygenation before paralysis and intubation. 2

The DSI Protocol: Step-by-Step

Step 1: Patient Assessment and Preparation

• Identify patients who are agitated, delirious, or combative and cannot tolerate facemask preoxygenation despite their need for definitive airway management. 2, 3
• Ensure all intubation equipment, rescue devices, and vasopressors are immediately available before beginning. 1

Step 2: Ketamine Administration

• Administer ketamine 1–2 mg/kg IV (mean effective dose approximately 1.4 mg/kg when titrated). 4, 2
• Ketamine is preferred because it preserves spontaneous respirations and airway reflexes while providing dissociative sedation. 4
• The dissociative state typically occurs within 30–60 seconds of administration. 2

Step 3: Preoxygenation Phase (3 Minutes)

• Once the patient is dissociated and cooperative, apply high-flow nonrebreather mask at 15 L/min or noninvasive positive pressure ventilation (NIPPV) for 3 minutes. 2, 3
• In critically injured trauma patients, this 3-minute preoxygenation window after ketamine administration significantly improves oxygen saturation levels. 3
• The British Journal of Anaesthesia recommends using a tight-fitting facemask with CPAP 5–10 cm H₂O if oxygenation is impaired. 1
• Target end-tidal oxygen fraction (FetO₂) ≥90% or oxygen saturation ≥98% before proceeding. 1, 2

Step 4: Induction and Paralysis

• After the 3-minute preoxygenation period, administer your neuromuscular blocking agent (succinylcholine 1–1.5 mg/kg IV or rocuronium 0.9–1.2 mg/kg IV). 4, 5
• No additional induction agent is typically needed because the ketamine provides ongoing sedation during the brief period until paralysis occurs. 2
• Wait for full neuromuscular blockade (30–45 seconds for succinylcholine, 60 seconds for rocuronium) before attempting laryngoscopy. 4

Step 5: Intubation

• Proceed with laryngoscopy and intubation using your standard technique. 2
• Continue nasal oxygen at 15 L/min during intubation attempts (apneic oxygenation). 1

Step 6: Post-Intubation Sedation

• Critical pitfall: Immediately administer protocolized post-intubation analgosedation, especially if rocuronium was used, because ketamine's dissociative effects wear off well before rocuronium's paralysis resolves (30–60 minutes), creating a high-risk window for awareness. 4
• Assign a dedicated team member to manage post-intubation sedation timing. 4

Evidence for Efficacy and Safety

Oxygenation Outcomes

• In a prospective multicenter study of 62 emergency department and ICU patients, DSI increased mean oxygen saturation from 89.9% to 98.8% (mean increase 8.9%, 95% CI 6.4–10.9%). 2
• Among 32 high-risk patients with baseline saturations ≤93%, 91% achieved saturations >93% after DSI. 2
• A randomized controlled trial in 200 critically injured trauma patients showed DSI reduced peri-intubation hypoxia from 35% (RSI group) to 8% (DSI group), P = .001. 3

Intubation Success

• First-attempt intubation success was 83% with DSI versus 69% with conventional RSI (P = .02) in trauma patients. 3
• All 40 patients receiving DSI from intensive care flight paramedics were successfully intubated with median post-DSI oxygen saturation of 100%. 6

Safety Profile

• No complications were observed in the original 62-patient DSI cohort. 2
• In the prehospital setting, only one patient experienced self-limiting apnea <15 seconds after ketamine; no patients required surgical airway or experienced cardiac arrest. 6
• Post-intubation complications (bradycardia, hypotension, tachycardia, transient desaturation) occurred at low rates comparable to standard RSI. 6

Clinical Indications for DSI

Use DSI when patients meet ALL of the following criteria:

• Require emergency airway management with definitive intubation. 2
• Are agitated, delirious, combative, or have altered mental status preventing cooperation. 1, 2, 3
• Cannot tolerate standard preoxygenation techniques (facemask, NIPPV, high-flow nasal oxygen). 1, 2
• Are hypoxemic or at high risk for critical desaturation during intubation. 2, 3

Common clinical scenarios include:

• Traumatic brain injury with agitation. 6, 3
• Hypoxemic respiratory failure with delirium. 2
• Intoxication or withdrawal states preventing cooperation. 2
• Combative patients requiring nasogastric tube placement before intubation. 2

DSI Versus Standard RSI: Key Distinctions

Feature	Standard RSI	Delayed Sequence Intubation
Timing	Induction agent and paralytic given simultaneously or in rapid succession [5]	Ketamine given first, then 3-minute preoxygenation, then paralytic [2,3]
Preoxygenation	Attempted before any medications [5]	Performed AFTER ketamine, during dissociation [2]
Patient cooperation	Required for effective preoxygenation [1]	Not required; ketamine enables cooperation [2]
Apnea risk	Begins immediately after paralytic [5]	Delayed until after optimal preoxygenation achieved [2]

Critical Pitfalls and How to Avoid Them

Pitfall 1: Inadequate Post-Intubation Sedation

• The problem: Ketamine's dissociative effects dissipate within 10–15 minutes, but rocuronium-induced paralysis lasts 30–60 minutes, creating a window where patients are paralyzed but inadequately sedated. 4
• The solution: Implement protocolized post-intubation analgosedation immediately after successful intubation, ideally managed by a dedicated team member or clinical pharmacist. 4
• Use standardized order sets that automatically trigger sedation protocols after rocuronium administration. 4

Pitfall 2: Using DSI When Standard RSI Is Appropriate

• The problem: DSI is NOT a replacement for standard RSI in cooperative patients who can tolerate preoxygenation. 2
• The solution: Reserve DSI specifically for agitated or delirious patients who actively resist preoxygenation efforts. 1, 2

Pitfall 3: Inadequate Preoxygenation Time

• The problem: Rushing through the 3-minute preoxygenation window defeats the entire purpose of DSI. 2, 3
• The solution: Use the full 3-minute preoxygenation period after ketamine administration to maximize oxygen reserves. 3
• Monitor oxygen saturation continuously and target ≥98% before administering the paralytic. 2

Pitfall 4: Ketamine Dose-Related Hypotension

• The problem: In critically ill patients with depleted catecholamine stores, ketamine may paradoxically cause hypotension despite its sympathomimetic properties. 4
• The solution: Have vasopressors immediately available and consider using the lower end of the ketamine dosing range (1 mg/kg) in hemodynamically compromised patients. 4

Pitfall 5: Awareness Risk with Rocuronium

• The problem: The incidence of explicit recall during emergency intubation is approximately 2.6%, and rocuronium's longer duration compared to succinylcholine (5–10 minutes) may prevent patient movement that would otherwise alert staff to inadequate sedation. 4
• The solution: Protocolized post-intubation analgosedation reduces awareness risk substantially. 4
• Have sugammadex 16 mg/kg available for reversal if a "can't intubate, can't ventilate" scenario develops. 5

Contraindications and Cautions

Relative contraindications to ketamine in DSI:

• Severe cardiovascular instability with depleted catecholamine stores (risk of paradoxical hypotension). 4
• Elevated intracranial pressure concerns are not an absolute contraindication, as ketamine's sympathomimetic properties help maintain cerebral perfusion pressure. 4

When DSI may not be appropriate:

• Patients who can cooperate with standard preoxygenation should receive conventional RSI. 2
• "Can't intubate, can't ventilate" scenarios require immediate front-of-neck access, not DSI. 5

Practical Implementation Tips

• Position the patient: Use semi-Fowler position (head and trunk elevated 20–25°) during DSI to improve oxygenation and reduce aspiration risk. 1, 5
• Optimize oxygen delivery: Apply nasal oxygen at 5 L/min during ketamine administration, then increase to 15 L/min after loss of consciousness and continue throughout intubation. 1
• Consider NIPPV: In patients with severe hypoxemia (PaO₂/FiO₂ <150), use NIPPV during the preoxygenation phase after ketamine administration. 4
• Team communication: Brief the team that you are performing DSI (not standard RSI) so everyone understands the 3-minute preoxygenation window before paralysis. 1
• Document clearly: Record baseline oxygen saturation, post-ketamine saturation, and pre-paralysis saturation to demonstrate the effectiveness of your preoxygenation. 2