Critical Care Alert, Critical Care, EMS, Airway, Trauma

Critical Care Alert: Delayed Versus Rapid Sequence Intubation in Critically Injured Trauma Patients

ARTICLE: Bandyopadhyay A, Kumar P, Jafra A, Thakur H, Yaddanapudi LN, Jain K. Peri-Intubation Hypoxia After Delayed Versus Rapid Sequence Intubation in Critically Injured Patients on Arrival to Trauma Triage: A Randomized Controlled Trial. Anesth Analg. 2023;136(5):913-919. doi: 10.1213/ANE.0000000000006171. Epub 2023 Apr 14.

To compare the incidence of peri-intubation hypoxia after delayed versus rapid sequence intubation in critically injured trauma patients

Securing a definitive airway in trauma patients is daunting due to trauma-induced factors such as airways contaminated by blood or vomit as well as faciomaxillary, cervical spine, and head injuries. In addition, trauma patients may be agitated and delirious due to pain, altered mental status, and hypoxia. Many clinicians prefer rapid sequence intubation (RSI), which involves pre-oxygenation followed by near-simultaneous administration of an induction agent and a neuromuscular blocker to facilitate intubation without transitional ventilation.1 The pre-oxygenation step is critical since it allows for denitrogenation of the lungs and increases the oxygen content of functional reserve capacity, both creating a physiologic reserve that prevents hypoxia in the apneic phase of intubation. For the agitated or combative patients who do not tolerate pre-oxygenation, positive pressure ventilation with a bag valve mask (BVM) before intubation can be trialed; however, this can worsen the risk of gastric distension or aspiration and is often not tolerated by trauma patients either. Thus, adequate preoxygenation is often not achieved and a higher incidence of peri-intubation desaturation has been reported.2 This hypoxia can result in secondary injuries and worse outcomes, especially in trauma patients with associated head injury. Other peri-intubation adverse events have been reported like hemodynamic instability, direct airway trauma, and vomiting with or without pulmonary aspiration.3

Delayed sequence intubation (DSI) involves administering a dissociative dose of ketamine followed by goal-directed preoxygenation for a minimum of 3 minutes, neuromuscular blocker administration, and intubation. The advantage over RSI is that this dose of ketamine relieves agitation and pain while maintaining spontaneous respirations and airway reflexes. DSI has previously been studied in observational trials with ED patients (both medical and surgical) with improvements in mean O2 saturation from 89.9% to 98.8% after DSI,4 and it was hypothesized by these authors that these benefits may transfer to trauma patients requiring emergent airway management.

This was a randomized control trial at a level two trauma center in Chandigarh, India. Patients were randomized 1:1 to RSI or DSI groups via computer-generated random number codes. The codes were concealed in an opaque envelope which was opened up by the nursing officer before airway management. All intubations were performed by a 2nd-year postgraduate anesthesia resident on the airway response team. Another anesthesiologist administered the drug sequence as per random number and kept a record of the data. The intubator and the anesthesiologist injecting the medications were not blinded to group allocation, though patients and the data analyzer were blinded to the group allocation. The groups were split as follows:

  • Group RSI: preoxygenation for 3 minutes followed by induction with intravenous (IV) ketamine 1.5 mg/kg and IV succinylcholine 1.5 mg/kg followed by endotracheal intubation
  • Group DSI: IV ketamine 1.5 mg/kg in 0.5-mg/kg increments until dissociation was achieved (patient is calm but spontaneously breathing) followed by preoxygenation for 3 minutes followed by IV succinylcholine 1.5 mg/kg and endotracheal intubation

Patients were preoxygenated via spontaneous tidal breathing for 3 minutes using a facemask, a Bain circuit, and oxygen at 10 liters per minute. Intubation was performed using direct laryngoscopy in both groups. An intubation attempt was defined as any insertion of laryngoscope beyond teeth irrespective of intubation success. Intubation was confirmed by bilateral chest auscultation, adequate chest rise, and mist in the endotracheal tube. O2 saturation values were recorded at baseline and then every 1 minute for 3 minutes during the preoxygenation period and thereafter 1 minute after intubation.

Adult trauma patients aged 18 to 80 who required definitive airway with endotracheal intubation


  • Patients with anticipated difficult airway (defined as any difficulty faced in one or more of the following: mask ventilation, laryngoscopy, and tracheal intubation)
  • Patients with extensive burns, active vomiting, crash intubations, or cardiac arrest
  • All patients with unanticipated difficult airway

Incidence of peri-intubation hypoxia (Spo2 <93%) from preoxygenation from baseline until 1 minute after intubation.

Hemodynamic data at predefined intervals of intubation, Cormack-Lehane (CL) grading, first-attempt success rate, use of airway adjuncts, incidence of airway injuries, and cardiac arrest.

In total, 100 patients were randomized to the DSI and RSI group each. Median ages were 38.5 and 39.3, respectively. For sex, 84% and 91% were male, respectively. The most common indication for intubation in both groups were poor GCS, with the median GCS in both groups being comparable at 6. The most common mode of injury by far was MVA (82/100 in both groups), followed by fall from height (14/100, 15/100 respectively) and closed head injury (4/100, 2/100 respectively).

Primary outcome
The Incidence of peri-intubation hypoxia was significantly higher in group RSI (35%) than in group DSI (8%); P = <.001. The median Spo2 values were significantly higher in group DSI compared to group RSI at all time points except at baseline, where Spo2 values were higher in group RSI.

Secondary outcomes

  • No statistically significant difference in hemodynamics measured in both groups
  • First-pass intubation success rate was higher in DSI (83%) versus RSI (69%); P = .020
  • CL grades were comparable between the 2 groups, with the majority of patients being grades I/II
  • Airway-related adverse events were also comparable (9% vs 16% in groups DSI and RSI, respectively; P = .134).
  • Fewer airway injuries were reported with successful first attempts (8.5% [13/152 of 200 patients]) such as lip injuries or bleeding; whereas multiple attempts correlated with a higher percentage of airway injuries (31.2% [15/48 of 200 patients]; P = <.001)
  • No reported episodes of hypotension, arrhythmias, or cardiac arrest
  • Multivariate analysis revealed DSI versus RSI to be a significant predictor of peri-intubation hypoxia (OR 6.82 [2.82–16.48]; P = .001)


  • Study was conducted only on patients with structurally normal airways as the difficult airways were excluded
  • Study was not able to measure end-tidal oxygen as a target end point of preoxygenation or use end-tidal carbon dioxide for confirmation of correct endotracheal tube placement
  • The anesthesiologists were unblinded to group allocation
  • All intubating anesthesiologists were still in training. The results could be different for experienced physicians
  • Baseline agitation was not quantified in this study
  • Small study sample size (n = 200) at a single center

Consider DSI with ketamine in trauma patients requiring emergent airway intervention as it was associated with a reduction in the incidence of peri-intubation hypoxia compared to RSI. It also led to greater first-attempt success rate and was associated with fewer airway injuries while not having adverse effects on hemodynamics vs. RSI.


  1. Goto T, Goto Y, Hagiwara Y, Okamoto H, Watase H, Hasegawa K. Advancing emergency airway management practice and research. Acute Med Surg. 2019; 6:336–351.
  2. Bodily JB, Webb HR, Weiss SJ, Braude DA. Incidence and duration of continuously measured oxygen desaturation during emergency department intubation. Ann Emerg Med. 2016;67(3):389-395.
  3. Wahlen BM, El-Menyar A, Asim M, Al-Thani H. Rapid sequence induction (RSI) in trauma patients: insights from healthcare providers. World J Emerg Med. 2019;10(1):19–26.
  4. Weingart SD, Trueger NS, Wong N, Scofi J, Singh N, Rudolph SS. Delayed sequence intubation: a prospective observational study. Ann Emerg Med. 2015;65(4):349-355.

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