Introduction

Airway management in pediatrics represents a sig­nificant challenge in the care of critically ill patients in emergency departments. This is due to physiological characteristics unique to this population, such as higher metabolic rate and oxygen consumption, lower function­al residual capacity, and, consequently, a greater propen­sity for hypoxemia. These factors result in poor tolerance to apnea and a higher risk of hypoxia, bradycardia, and cardiopulmonary arrest during endotracheal intubation (ETI)^(1,2).

Persistent hypoxemia before intubation is the stron­gest predictor of peri-intubation cardiac arrest in chil­dren, followed by pre-intubation hypotension, myocardial dysfunction, and repeated intubation attempts. This last factor has been shown to increase the risk of compli­cations from 6.6% on the first attempt to 18.4% on the second^(3–5). Hypoxemia is also the primary cause of inter­ruption of laryngoscopy or intubation, further increasing the number of attempts and the risk of peri-intubation complications^(4,5).

Rapid sequence intubation (RSI) aims to mitigate the potential risks associated with emergent airway manage­ment. This procedure includes the administration of a hyp­notic agent and a neuromuscular blocker in a standardized sequence, facilitating ETI and reducing the risk of compli­cations. However, there are clinical scenarios in which RSI is not feasible and alternative strategies are required.

Delayed sequence intubation (DSI) emerges as an option for patients who cannot tolerate conventional preoxygen­ation. It is indicated in agitated patients who do not allow preoxygenation. Its principle lies in administering sedation prior to anesthetic induction and neuromuscular blockade, allowing effective oxygen therapy while maintaining spon­taneous breathing. This ensures continuous oxygenation before and after anesthetic induction, helping prevent hy­poxemia and hypoventilation during the procedure⁽⁶⁾.

Most studies supporting DSI come from adult popula­tions. In pediatrics, there are no clinical trials or prospec­tive cohorts validating its use, although various reports, case series, and reviews document its practice with fa­vorable outcomes. In this context, DSI appears as a valid alternative in pediatric patients for whom conventional methods such as RSI are not viable.

The purpose of this article is to present a narrative re­view of the most relevant aspects related to DSI and its potential utility in pediatrics. Given that proficient airway management in emergency departments is a constant challenge, healthcare personnel must be familiar with and trained in different management alternatives, selecting the most appropriate strategy according to the clinical charac­teristics and context of each patient.

Materials and methods

A narrative review was conducted using the following MeSH terms and Boolean operators:

((“delayed sequence intubation” OR “delayed-sequence intubation” OR DSI) OR (“Intubation, Intratra­cheal” OR “endotracheal intubation” OR “rapid sequence intubation”)) AND (“Oxygen Inhalation Therapy” OR preoxygenat* OR “pre-oxygenation” OR “apneic oxy­genation” OR “apnoeic oxygenation” OR “high flow na­sal cannula”) AND (“Conscious Sedation” OR “Sedation” OR sedat* OR ketamine OR “procedural sedation”) AND (“Child” OR “Infant” OR “Adolescent” OR pediatric OR paediatric OR child*).

Searches were performed in PubMed/MEDLINE, Sco­pus (Elsevier), Embase (Elsevier), LILACS, and SciELO. Clinical reference resources and academic search en­gines were also consulted, including ClinicalKey (Elsevi­er), UpToDate, Ovid, and Google Scholar. Publications in English and Spanish were included, regardless of date. Priority was given to studies published within the last 10 years, with emphasis on pediatric populations, although adult studies providing relevant information were also included.

A total of 50 articles were identified. After screening titles and abstracts, 29 were excluded for not being direct­ly related to pediatric populations or to the DSI context. Twenty-one full-text articles were reviewed; 13 pertained exclusively to pediatric populations, and the remainder in­volved mixed populations (adults and pediatrics, or gener­al physiology applicable to both).

Anatomical Considerations of the Pediatric Airway

The airway in pediatric patients presents particular anatomical characteristics that differ from adults. Over fifty years ago, Eckenhoff et al. described its morphology as conical. However, with the advent of diagnostic tech­niques such as CT, MRI, and fiberoptic bronchoscopy, this concept was shown to be inaccurate. It is now recognized that the pediatric airway is predominantly cylindrical, with two points of maximal narrowing: at the vocal cords and at the cricoid ring. Additionally, the epiglottis is longer, stiffer, and shaped like a “U” or “omega”^(7,8).

Bronchial size correlates directly with age. In younger children, the reduced bronchial diameter increases airway resistance. Added to this is a looser and more vascularized mucosa, such that minimal inflammation or edema can rapidly generate significant obstruction^(8,9).

Furthermore, oxygen consumption in pediatric pa­tients is higher due to elevated basal metabolic rate. Combined with reduced functional residual capacity — defined as the air volume remaining in the lungs after a normal passive exhalation— this results in a smaller oxy­gen reserve. Consequently, children desaturate more rap­idly during apnea⁽⁸⁾.

Preoxygenation Methods During Endotracheal Intubation

Preoxygenation is essential to allow time for laryngos­copy and placement of the endotracheal tube without de­saturation. It involves administering oxygen until the onset of apnea, and even during apnea, to reduce the risk of car­diovascular collapse secondary to hypoxemia.

Preoxygenation is defined as the administration of oxygen before anesthetic induction or neuromuscular blockade, with the goal of replacing alveolar nitrogen with oxygen, increasing the alveolar reserve fraction and pro­longing the time before desaturation^(10,11).

The main mechanism of preoxygenation is airway denitrogenation, which aims to delay arterial desatura­tion during apnea following administration of anesthetic agents and prior to endotracheal tube placement. In oth­er words, it seeks to ensure a “safe apnea time,” defined as the interval until the patient reaches an oxygen satu­ration of 90%⁽¹¹⁾.

It is typically performed by administering 100% oxy­gen for 3 to 5 minutes with spontaneous ventilation via a well-fitted face mask. Alternatively, the vital capacity method may be used, in which the patient takes 8 to 10 deep breaths of 100% oxygen over 60 seconds^(12–14).

The target is an end-tidal oxygen fraction (FeO₂) ≥ 0.9, reflecting adequate nitrogen washout and optimal oxygen reserve. In pediatrics, due to higher metabolic demand, lower functional residual capacity, and reduced tolerance to apnea, preoxygenation is even more critical.

Delayed Sequence Intubation

DSI was developed to ensure adequate preoxygenation in agitated, hypoxemic, hypercapnic, or delirious patients who cannot tolerate conventional techniques such as RSI. In these cases, standard oxygen therapy devices, like face masks, may be ineffective because the patient may remove them or be unable to sustain continuous oxygen­ation, leading to intubation attempts without adequate preoxygenation.

In this context, the administration of a sedative agent can facilitate effective oxygenation.

The first adult study was published by Weingart et al. in 2015 in a cohort of 62 patients with altered mental status or medical conditions preventing optimal preoxygenation via classic techniques, including RSI. The authors reported im­proved peri- and post-intubation oxygenation without major complications, although the study was limited to adults and had inherent observational design constraints. Since then, case series, isolated reports, and narrative reviews have been published in both pediatric and adult populations^(6,15).

More recently, in 2023, Bandyopadhyay et al. conduct­ed the first randomized clinical trial in 200 critically injured adult trauma patients. Results showed significantly lower peri-intubation hypoxemia with DSI versus RSI (8% vs. 35%; p=0.001), along with higher first-attempt intubation success (83% vs. 69%; p=0.02)⁽¹⁶⁾.

This constitutes the first clinical trial supporting DSI as a valid alternative to RSI in patients in whom conventional preoxygenation is expected to be ineffective.

In DSI, ETI requires the initial use of an intravenous an­esthetic agent, as these patients are often uncooperative or present with altered mental status. Once a dissociative state preserving spontaneous breathing is achieved, oxy­gen is administered via non-rebreather mask or high-flow nasal cannula to maintain SpO₂ >95% for at least three minutes. Neuromuscular blockade is then administered, followed by ETI.

In summary, DSI can be understood as procedural se­dation in which the procedure is preoxygenation⁽¹⁷⁾.

Definition of DSI

Weingart et al. defined DSI as an alternative to RSI in which oxygenation is optimized before intubation and con­sists of two essential elements^(15,17):

• Sedation prior to anesthetic induction and neuromus­cular blockade, allowing oxygen delivery and secre­tion clearance using agents that preserve spontaneous breathing and airway protective reflexes.

• Oxygen therapy to prevent or delay hypoxemia be­fore and after anesthetic induction and neuromuscular blockade.

Indications of DSI in Pediatric Patients

• Healthy, uncooperative children who do not allow preoxygenation

• Children with special needs such as autism spectrum disorders or ADHD

• Children with altered mental status, agitation, confu­sion, or encephalopathy⁽¹⁷⁾

Sedative Agents for DSI

The anesthetic agents most commonly used for DSI are ketamine and dexmedetomidine. Ketamine is considered the agent of choice, as it is widely available and exten­sively used in pediatrics as a dissociative anesthetic that preserves respiratory drive and airway reflexes while main­taining cardiovascular stability⁽¹⁷⁾.

Doses for both drugs are summarized in Table 3.

DSI Step by Step

1. Patient selection

• Uncooperative child with agitation, delirium, or al­tered mental status

• Hypoxemia/hypercapnia preventing conventional preoxygenation

• High risk of desaturation with RSI

2. Preparation

• Full monitoring (pulse oximetry, heart rate, blood pressure, capnography if available)

• Airway equipment ready

• Oxygen source and devices prepared (NRB mask, HFNC, or NIV)

3. Initial sedation

• Administer IV ketamine (1–2 mg/kg) or dexmedeto­midine (0.5 mcg/kg), titrating subsequent doses as needed while allowing spontaneous breathing and tolerance of preoxygenation devices

4. Preoxygenation

• Non-rebreather mask (>15 L/min)

• HFNC (age/weight appropriate)

• NIV (CPAP/BiPAP) if available

• Maintain SpO₂ >95% for ≥3 minutes

5. Neuromuscular blockade

• Administer neuromuscular blocker

6. Endotracheal intubation

• Perform ETI during apnea

• Maintain supplemental oxygen (apneic oxygenation with NC/HFNC)

7. Verification and post-intubation care

• Confirm tube position (capnography, clinical assess­ment, auscultation)

• Adjust ventilator settings

• Monitor for complications

In Figure 1 the DSI algorithm is summarized.

Table 4 presents a comparison between RSI and DSI.

Is There Evidence Supporting DSI in Pediatrics?

Evidence supporting DSI in pediatric patients is ex­tremely limited. No prospective studies, randomized trials, or formal guidelines exist for children. Reports include the following successful pediatric cases:

• 16-month-old with RSV who did not tolerate a face mask⁽¹⁸⁾

• 11-year-old with cognitive delay and pneumonia; and an 11-month-old infant with intestinal obstruction and shock⁽¹⁹⁾

• 6-year-old obese child with adrenal insufficiency, hy­poventilation, severe hypoxemia, and combativeness⁽²⁰⁾

• 1.5-year-old child with esophageal perforation, pneu­momediastinum, pneumothorax, and subcutaneous emphysema⁽²¹⁾

Conclusion

Delayed sequence intubation is an emerging and potentially promising alternative for pediatric airway management, particularly in critically ill children where conventional preoxygenation is insufficient or agitation compromises procedural safety. Although early reports suggest benefits in oxygenation and hemodynamic stability, current evidence remains limited and largely extrapolat­ed from adult populations, preventing firm recommenda­tions in children.

Clinical implementation should therefore be restricted to trained teams and selected scenarios. Future research should focus on prospective multicenter pediatric studies to validate its efficacy, define indications, and establish standardized protocols.

Funding

This research received no specific grant from public, commercial, or nonprofit funding agencies.

Conflicts of Interest

The authors declare no conflict of interest.

Author Contributions

The authors certify equal contribution to the concep­tion, design, scientific and intellectual content, and manu­script writing.

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