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Bandyopadhyay A, et al. "Peri-Intubation Hypoxia After Delayed Versus Rapid Sequence Intubation in Critically Injured Patients on Arrival to Trauma Triage: A Randomized Controlled Trial". Anesthesia & Analgesia. 2023. 136(5):913-919.

Clinical Question

In adult, critically ill, trauma patients requiring intubation, does delayed-sequence intubation decrease peri-intubation hypoxia as compared to rapid-sequence intubation

Bottom Line

Delayed sequence intubation (DSI) was associated with less hypoxia, more first pass success, and fewer complications as compared to rapid sequence intubation.

Major Points

Intubating an agitated and/or delirious patient in the emergency department may pose a challenge and is not without some risk. Securing that airway in a trauma patient may be paramount. Several of the medications utilized in the intubation procedure may induce hypoxia (e.g. midazolam, propofol, thiopental, etomidate). Rapid Sequence Intubation (RSI) is commonplace in this setting where there is pre-oxygenation prior to sedation and paralysis to perform the manoeuvre. The Delayed Sequence Intubation (DSI) modifies this approach to first lightly sedate the patient to allow safer and easier pre-oxygenation prior to paralysis and intubation attempt.

This trial, an RCT conducted in a single academic centre in India, compared RSI (n=100, 3 minutes pre-oxygenation, ketamine 1.5 mg/kg IV with succinylcholine 1.5 mg/kg induction, then intubation) to DSI (n=100, ketamine 1.5mg/kg IV in 0.5mg/kg increments until dissociation, then 3 minutes pre-oxygenation, then paralysis with succinylcholine 1.5 mg/kg IV, then endotracheal intubation). This trial used direct laryngoscopy,

They found that DSI has less peri-intubation hypoxemia compared RSI (8% vs 35%; p=0.001) and a higher first-pass-attempt success rate (83% vs 69%; p=0.02). Hemodynamical parameters were not statistically different, nor were there any difference in airway adverse events or injuries. There are some potential issues with this trial, it was a small, single centre trial which may benefit from further study. All of the anestheologiests were in training and were unblinded (based on the protocol) and thus could have introduced bias. Unexpected difficult airways were also excluded after randomization, which may have bias towards the null. This trial suggests that DSI may increase success and potentially help protect patients and staff when a patient is agitated, more study is warranted.


As of July 2023, no guidelines have been published that reflect the results of this trial.


  • Multicenter, double-blind, parallel-group, randomized, controlled trial
  • N=200
    • Delayed Sequence Intubation (n=100)
    • Rapid Sequence Intubation (n=100)
  • Setting: single site in India
  • Enrollment: not declared
  • Analysis: Per-protocol
  • Primary Outcome: incidence of peri-intubation hypoxia (oxygen saturation of SpO2 <93% anytime from preoxygenation until 1 minute following intubation)


Inclusion Criteria

  • Adult
  • trauma
  • requiring definitive airway management

Exclusion Criteria

  • anticipated difficult airway (defined as difficulty in at least one of mask ventilation, laryngoscopy,

and tracheal intubation.)

  • extensive burns
  • active vomiting
  • crash intubation
  • cardiac arrest

Baseline Characteristics

Delayed Sequence Intubation Group displayed

  • Demographics: mean age 38.5 years, 16% female
  • Physiologic parameters: median GCS 6
  • Indication for intubation: 95% Poor GCS, 5% respiratory distress
  • Mode on Injuries: 82% MVA, 14% fall from height, 4% closed head injury
  • Comorbidities : 89% nil, 6% diabetes mellitus, 2% hypertension, 2% hypothyroid, 1% both DM and HTN


Pre-oxygenation done by face-mask, oxygenation at 10 L/minutes Intubation performed using direct laryngoscopy

  • Rapid Sequence Intubation (RSI): pre-oxygenation 3 minutes, inductions with IV ketamine 1.5 mg/kg and IV succinylcholine 1.5 mg/kg followed by endotracheal intubation
  • Delayed Sequence Intubation (DSI): IV ketamine 1.5mg/kg in 0.5mg/kg increments until dissociation (patient calm and spontaneously breathing), then pre-oxygenation for 3 minutes, then succinylcholine 1.5 mg/kg, then endotracheal intubation


Comparisons are Delayed Sequence Intubation (DSI) vs. Rapid Sequence Intubation (RSI).

Primary Outcomes

peri-intubation hypoxia (Spo2 <93% anytime from preoxygenation until 1 minute following intubation)
8% vs. 35% P < 0.001

Secondary Outcomes

First pass intubation success
83% vs. 69% (P = 0.02)
Use of airway adjuncts
9% vs. 39% (P = 0.13)

Subgroup Analysis

Multivariate analysis, predictor of peri-intubation hypoxia
DSI vs. RSI adjusted odds ratio 6.82 (95% CI 2.82–16.48) P = 0.001
Correlation of number of intubation attempts to airway injuries
8.5% on first attempt vs. 31.2% from multiple attempts (P = 0.001)

Adverse Events

Airway related adverse events
9% vs. 16% (P = 0.134)
Airway injuries
31% vs. 39% (P = 0.29)


  • External validity: agents were ketamine and succinylcholine, unclear if we can extrapolate to other sedatives and paralytics utilized for intubation
  • External validity: trial conducted on patients with structurally normal airways, unclear if we can extrapolate to other trauma patients (e.g. burns, difficult airways, etc)
  • end-tidal oxygenation was not measured
  • Investigator bias: anesthesiologist involved in the intubation was unblinded (due to protocol) and could have introduced bias
  • anesthesiologists were in training
  • airway adjuncts were not defined
  • patients with unanticipated difficult airways were excluded from the final analysis (and may have favoured DSI if included)


  • none declared

Further Reading