Peri-Intubation Hypoxia After Delayed Versus Rapid Sequence Intubation in Critically Injured Patients on Arrival to Trauma Triage: A Randomized Controlled Trial
Written by: Tina Anjali Jagtiani, DO, Edited by: Brian Smith, DO, MA, MMSc-Med
Background:
Securing a definitive airway through endotracheal intubation is a critical, life-saving intervention in trauma patients who present with compromised consciousness or inability to protect their airway. However, intubating agitated trauma patients is challenging, particularly because their agitation often prevents adequate preoxygenation, which is essential to reduce the risk of hypoxia during the procedure. Peri-intubation hypoxia is associated with increased morbidity and mortality in these critically ill patients.
The standard approach to intubation in trauma is rapid sequence intubation (RSI), which involves brief preoxygenation followed rapidly by administration of induction and paralytic agents to facilitate quick endotracheal tube placement. However, when patients are combative or delirious, RSI can be problematic because agitation may impair adequate preoxygenation, putting them at risk of desaturation during the intubation.
Delayed sequence intubation (DSI) is an alternative technique designed for such challenging cases. In DSI, a dissociative dose of ketamine is administered first to sedate the patient while maintaining their spontaneous respirations, allowing for a prolonged preoxygenation period before the administration of paralytics and intubation. While observational data suggested that DSI might improve oxygenation and intubation success, there is a lack of high-quality randomized controlled trials comparing DSI to RSI in critically injured trauma patients.
This study sought to answer the question: does delayed sequence intubation reduce the incidence of peri-intubation hypoxia compared to rapid sequence intubation in critically injured, agitated trauma patients who poorly tolerate preoxygenation?
The Study:
This research was conducted as a prospective, randomized controlled trial (RCT) at a single Level 1 trauma center emergency department. The investigators recruited 200 adult critically injured trauma patients who required emergent airway management on arrival to trauma triage. Eligible patients were those who were agitated or delirious and unable to tolerate effective preoxygenation necessary for intubation. Randomization occurred when the patient arrived and it was determined that airway management was needed. Patients were allocated via sealed envelopes into one of two groups:
DSI group: Patients received a dissociative dose of IV ketamine at 1.5 mg/kg in 0.5 mg/kg increments until sedation was achieved. Then, the patient underwent 3 minutes of preoxygenation via facemask breathing before administration of IV succinylcholine 1.5 mg/kg for paralysis, followed by intubation.
RSI group: Patients underwent the conventional RSI protocol consisting of 3 minutes of preoxygenation followed by rapid sequential administration of IV ketamine and IV succinylcholine, then intubation. The same doses were used in both groups.
Exclusion criteria included:
Patients with anticipated difficult airway identified before intubation (e.g., severe anatomical abnormalities)
Extensive burns
Active vomiting at presentation
Crash/emergency intubations without adequate preparation time
Cardiac arrest on arrival
Patients who developed an unanticipated difficult airway during the procedure were excluded from the primary analysis to maintain comparability.
The primary outcome was incidence of peri-intubation hypoxia, defined as a drop in oxygen saturation (SpO2) below 93% anytime from preoxygenation until 1 minute after intubation. Secondary outcomes were first-attempt intubation success rate, use of adjunct airway devices, airway injuries, and hemodynamic changes such as hypotension, tachycardia or even cardiac arrest.
The authors planned a sample size of approximately 100 patients per group to ensure adequate power (80%) to detect a clinically meaningful reduction (~20%) in hypoxia incidence from an expected baseline around 57%. Statistical analyses included Student’s t-test or Mann-Whitney U for continuous variables and Chi-square tests for categorical outcomes. Baseline demographic and clinical characteristics were similar between groups, ensuring comparability.
Results and Discussion:
The study found a highly significant reduction in peri-intubation hypoxia in the DSI group compared to the RSI group: only 8% of patients in the DSI group experienced hypoxia versus 35% in the RSI group (p < 0.001). This is an absolute risk reduction of 27%, which is both statistically and clinically meaningful.
In terms of procedural success, first-pass intubation success was higher with DSI at 83% compared to 69% in the RSI group (p = 0.02). Better oxygenation likely contributed to this improved first-attempt success, reducing the need for multiple intubation attempts.
Hemodynamic parameters, including rates of hypotension or arrhythmias, did not differ significantly between groups. No major airway injuries or adverse events related to ketamine were reported. In addition, the mean oxygen saturation improved from baseline only in the DSI group, demonstrating more effective preoxygenation.
Key limitations of the study include its single-center design, which may limit generalizability to other institutions or patient populations. The study was unblinded due to the visible effects of ketamine, potentially introducing performance bias. The exclusion of patients with difficult airways before or during the procedure also narrows applicability to complex airway scenarios.
The RCT design with adequate power, valid randomization, and appropriate statistical analysis provides strong internal validity. The results robustly indicate that DSI reduces peri-intubation hypoxia and enhances first-pass success compared to RSI in agitated trauma patients. From an external validity perspective, these findings are most applicable to adult trauma patients presenting with agitation or delirium that impairs preoxygenation. They may not apply to non-agitated patients, pediatric populations, or non-trauma critically ill patients. Nonetheless, the principle of ketamine-facilitated sedation to enable better preoxygenation aligns with current understanding of airway management physiology.
In the context of current knowledge, this study adds high-quality evidence supporting the incorporation of DSI into airway management protocols for challenging trauma cases. Prior literature had mainly consisted of observational studies or expert opinion. This trial challenges standard RSI practice by demonstrating a safer alternative in a specific high-risk group, highlighting the benefits of ketamine use to optimize oxygenation prior to paralysis and intubation.
Resources
Bandyopadhyay, A., Kumar, P., Jafra, A., Thakur, H., Yaddanapudi, L. N., & Jain, K. (2023). Peri-intubation hypoxia after delayed versus rapid sequence intubation in critically injured patients on arrival to trauma triage: A randomized controlled trial. Anesthesia & Analgesia, 136(5), 913–919. https://doi.org/10.1213/ANE.0000000000006171
Rezaie, S. (2023, August 7). REBEL Cast Ep122 – Delayed vs rapid sequence intubation in agitated trauma patients. REBEL EM. https://rebelem.com/rebel-cast-ep122-delayed-vs-rapid-sequence-intubation-in-agitated-trauma-patients/
Weingart, S. (2015). Delayed sequence intubation: a prospective observational study. Academic Emergency Medicine, 22(6), 734–740. https://doi.org/10.1111/acem.1265