Emergence delirium prevention through electroencephalogram-guided anesthesia: a new standard for pediatric care?

The study from Miyasaka et al. investigates electroencephalogram (EEG)-guided titration of sevoflurane to address emergence delirium (ED), a clinically relevant and challenging perioperative complication with an unclear etiology in young patients (1). It not only adds an option for preventing ED, but also exemplifies how technological advancements can bring measurable improvements to pediatric anesthesia care (1).

ED remains a clinically important postoperative phenomenon in pediatric anesthesia, particularly when not systematically assessed with validated tools. It is characterized by acute disturbances in a child’s awareness during awakening from anesthesia. Children with ED usually present with inconsolability, restlessness, non-purposeful movements, lack of eye contact, and unawareness of their surroundings (2). Although typically self-limited, the etiology remains unclear, and ED can be associated with negative postoperative behavioral changes—such as sleep disorders and anxiety—along with increased risk of injury, disruption of surgical repairs, and removal of medical devices, resulting in additional burden for caregivers and healthcare teams (3). ED is also a disruptive adverse event in post-anesthesia care units, which may require additional clinical resources and staff attention during recovery (2).

Several factors have been reported as associated with ED, including exposure to volatile anesthetics such as sevoflurane and individual patient characteristics. Proposed mechanisms remain largely speculative, and current evidence does not support a single explanatory pathway. Although transient epileptiform EEG patterns have been described during emergence in some studies, their role in the development of ED remains uncertain (4,5). Routine documentation and the use of validated tools such as the Pediatric Anesthesia Emergence Delirium (PAED) scale are essential for accurate recognition, diagnosis, and management of ED in children (6,7). Accurate identification of ED requires the use of these validated instruments, as postoperative pain can be mistaken for delirium if structured assessment is not employed.

While the pathophysiology of ED is not yet fully understood, structured screening and preventive strategies remain both feasible and essential in clinical practice. As ED is often considered a self-limited event, preventive strategies should focus on optimizing perioperative management and addressing modifiable risk factors. Although reduced exposure to volatile anesthetics through multimodal techniques has been associated with lower ED rates in some studies, current evidence does not establish ED as a strictly dose-dependent phenomenon. Associations between ED and specific surgical types—particularly adenotonsillectomy—may be confounded by postoperative pain, which can be difficult to distinguish from delirium when using behavioral scales (2,8,9). Preventive interventions such as the administration of propofol for hypnosis or the use of alpha-2 agonists like dexmedetomidine in combination with sevoflurane have been shown to reduce ED incidence (2,10). This is likely due to reduced requirements of halogenated anesthetics when multimodal hypnosis is used—consistent with Miyasaka’s findings that monitoring-guided anesthetic delivery allows the use of lower doses of sevoflurane (1).

The adoption of innovative technologies such as EEG monitoring represents a significant advance in pediatric anesthesia. EEG-based titration exemplifies how technology can enhance clinical care by offering real-time visualization of a child’s brain responses, enabling more accurate anesthetic dosing based on direct brain activity rather than cardiovascular variables or population-based models (11). The study demonstrates that individualized management guided by real-time EEG reduces both anesthetic exposure and the incidence of ED (1). Other studies have suggested that EEG-guided anesthesia may reduce total anesthetic exposure and help tailor anesthetic delivery to individual neurodevelopmental needs. Although reductions in intraoperative burst suppression have been reported in some settings, the randomized trial by Miyasaka et al. did not demonstrate a significant difference in burst suppression between groups, highlighting the need for further investigation of this outcome in diverse pediatric populations (1,12). EEG improves the precision, safety, and efficacy of pediatric anesthetic management and deepens insights into anesthesia-induced alterations in consciousness and arousal, which are especially dynamic in children (12).

The use of EEG-based markers aligns with the goals of precision medicine, contributes to advances in pediatric neurodevelopmental research, and may facilitate the development of guidelines for optimal anesthetic depth in children. Reduced reliance on volatile agents further supports global initiatives to minimize the environmental impact of inhaled anesthetics.

The use of EEG to guide hypnotic dosing has been investigated in various pediatric studies, though findings are sometimes conflicting (13,14). While reductions in anesthetic consumption are consistently demonstrated, clear evidence of reduced complications—including ED—remains insufficient (15). These discrepancies may relate to heterogeneity in monitoring approaches, diverse institutional practices, and the ongoing challenge of properly diagnosing and reporting ED. Furthermore, variability in reported ED incidence across studies may reflect differences in assessment methods, observer training, and local clinical protocols (16).

Several methodological aspects of the trial warrant cautious interpretation. Premedication with diazepam was routinely used, which could potentially influence EEG characteristics and anesthetic requirements. In addition, anesthetic concentrations employed in both study groups reflected local institutional practice and may differ from standards used in other countries, thereby limiting external generalizability. Postoperative pain scores were not reported, precluding analysis of the extent to which pain may have contributed to PAED assessments, particularly in procedures performed without regional anesthesia. Finally, subgroup analyses according to surgical category or analgesic technique were not powered to detect meaningful differences.

Furthermore, some elements of the original authors’ conclusions extend beyond the direct evidence provided by the trial. For example, statements regarding parental preferences for reduced anesthetic exposure and potential environmental benefits of lower volatile anesthetic use were not empirically evaluated and should be interpreted as broader contextual reflections rather than data-driven findings. Additionally, although EEG-guided titration aimed to maintain electrophysiologic patterns consistent with unconsciousness, the trial was not designed to assess intraoperative awareness or amnesia, and such outcomes were not formally tested. The absence of postoperative recall assessments means that the study cannot conclusively determine whether EEG-guided dosing ensured amnesia in all patients.

A key limitation of the present study also reflects a broader issue in pediatric anesthesia: the limited number of professionals experienced in interpreting EEG data from commercially available monitors. Given that the widespread adoption of this technology is relatively recent, misinterpretation of data remains common due to limited familiarity. Furthermore, EEG monitors represent an additional cost, potentially limiting access in resource-constrained environments and influencing education and competency development. Training programs have proven effective in improving anesthesiologists’ EEG interpretation skills, supporting safe and scalable implementation of these technologies (17).

In the trial by Miyasaka et al., EEG monitoring was performed using the Masimo (Irvine, CA, USA) Root^® platform with SedLine^® EEG technology, allowing continuous acquisition of both raw and processed EEG signals (1). Processed indices included the Patient State Index (PSI), Spectral Edge Frequency 95 (SEF95), burst suppression ratio, and artifact metrics, recorded at high temporal resolution, together with spectrogram-based analysis using multitaper spectral methods. EEG interpretation was based on frontal lead recordings with standardized amplitude and feed settings, enabling reproducible visualization of anesthetic depth and neurophysiologic state (1).

From a broader pediatric perspective, contemporary EEG-guided anesthesia practice emphasizes the use of non-proprietary EEG features, including density spectral array (DSA) analysis, SEF95, raw EEG waveform interpretation, and relative spectral power distribution across frequency bands (17,18). As highlighted by Yuan et al., EEG interpretation in children must be age-dependent, reflecting neurodevelopmental changes in thalamocortical connectivity, evolving frequency architecture, and the absence of stable alpha coherence in early infancy (18). Consequently, spectrogram-based interpretation combined with SEF95 and raw EEG visualization currently represents the most physiologically meaningful framework for EEG-guided anesthetic titration across pediatric age strata, rather than reliance on proprietary depth indices alone (18).

This trial features a rigorous methodological design—a randomized clinical trial with blinded outcome assessment and strong internal validity—which reinforces the reliability of its results. Major strengths include the use of validated ED assessment tools, appropriate patient selection, and comprehensive data analysis. Nevertheless, being single-center and conducted by clinicians with specific EEG expertise may limit the generalizability of the findings in settings where pediatric perioperative care and EEG proficiency are less standardized.

The findings underscore the strong potential of EEG monitoring to guide anesthetic practice, while highlighting the need for multicenter and population-diverse research before its adoption as universal standard of care. Further studies should help elucidate ED pathophysiology and determine optimal EEG parameters based on age, neurodevelopment, and surgical context. Development of standardized protocols for EEG-guided pediatric anesthesia should be prioritized, as this may enable guideline formation and improve outcomes across healthcare systems.

Looking ahead, future research should focus on implementing EEG-guided protocols in diverse practice environments and across wider pediatric populations. Studies should evaluate developmental changes in EEG patterns, compare anesthetic agents and delivery techniques, and incorporate both clinical and cost-effectiveness outcomes. Standardized, evidence-based guidelines for EEG use in pediatric anesthesia will depend on such expanded research, ultimately aiming to reduce drug exposure and postoperative complications while enhancing patient safety and recovery.

In conclusion, this trial adds important evidence supporting the use of emerging technologies to improve anesthetic care while addressing a frequent but still poorly understood perioperative event. As summarized in Figure 1, integrating risk prediction, preventive strategies, and physiologic monitoring may support more tailored anesthetic management. Continued research is needed to refine EEG-guided practices for broader clinical application and guideline development, with the overarching goal of delivering the highest-quality care to children undergoing general anesthesia.

Figure 1 Predictors, preventive strategies, and clinical implications of EEG-guided sevoflurane titration in children. AI disclosure: the infographic contained in this work was generated with the assistance of the Gemini AI model (version 3), developed by Google. The tool was used for visual data synthesis and graphic design, under the supervision and technical review of the authors to ensure scientific accuracy. ↓, decrease. AI, artificial intelligence; ED, emergence delirium; EEG, electroencephalography; ENT, ear, nose, and throat.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Translational Pediatrics. The article has undergone external peer review.

Peer Review File: Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-1-888/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-2025-1-888/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Miyasaka KW, Suzuki Y, Brown EN, et al. EEG-guided titration of sevoflurane and pediatric anesthesia emergence delirium: a randomized clinical trial. JAMA Pediatr 2025;179:704-12. [Crossref] [PubMed]
2. Mason KP. Paediatric emergence delirium: a comprehensive review and interpretation of the literature. Br J Anaesth 2017;118:335-43. [Crossref] [PubMed]
3. Quintão VC, Carlos RV, Cardoso PFN, et al. Comparison of intravenous and inhalation anesthesia on postoperative behavior changes in children undergoing ambulatory endoscopic procedures: A randomized clinical trial. Paediatr Anaesth 2023;33:229-35. [Crossref] [PubMed]
4. Lerman J. Induction of anesthesia with sevoflurane in children: Curiosities and controversies. Paediatr Anaesth 2022;32:1100-3. [Crossref] [PubMed]
5. Koch S, Rupp L, Prager C, et al. Emergence delirium in children is related to epileptiform discharges during anaesthesia induction: An observational study. Eur J Anaesthesiol 2018;35:929-36. [Crossref] [PubMed]
6. Sikich N, Lerman J. Development and psychometric evaluation of the pediatric anesthesia emergence delirium scale. Anesthesiology 2004;100:1138-45. [Crossref] [PubMed]
7. Quintão VC, César R, Carmona M, et al. A psychometric evaluation of the Brazilian versions of the Pediatric Anesthesia Emergence Delirium scale and Children's Hospital of Eastern Ontario Pain Scale. Paediatr Anaesth 2021;31:1366-7. [Crossref] [PubMed]
8. Quintão VC, Carlos RV, Kulikowski LD, et al. Association between adult and child behavioral interactions with preoperative anxiety and emergence delirium. Paediatr Anaesth 2023;33:402-4. [Crossref] [PubMed]
9. Ringblom J, Wåhlin I, Proczkowska M, et al. Measurement Properties of the Pediatric Anesthesia Emergence Delirium Scale: A Confirmatory Factor Analysis-Based Study. Paediatr Anaesth 2025;35:155-62. [Crossref] [PubMed]
10. Costi D, Cyna AM, Ahmed S, et al. Effects of sevoflurane versus other general anaesthesia on emergence agitation in children. Cochrane Database Syst Rev 2014;2014:CD007084. [Crossref] [PubMed]
11. Yuan I, Xu T, Kurth CD. Using Electroencephalography (EEG) to Guide Propofol and Sevoflurane Dosing in Pediatric Anesthesia. Anesthesiol Clin 2020;38:709-25. [Crossref] [PubMed]
12. Brown EN, Purdon PL, Akeju O, et al. Using EEG markers to make inferences about anaesthetic-induced altered states of arousal. Br J Anaesth 2018;121:325-7. [Crossref] [PubMed]
13. Han Y, Miao M, Li P, et al. EEG-Parameter-Guided Anesthesia for Prevention of Emergence Delirium in Children. Brain Sci 2022;12:1195. [Crossref] [PubMed]
14. Frederick HJ, Wofford K, de Lisle Dear G, et al. A Randomized Controlled Trial to Determine the Effect of Depth of Anesthesia on Emergence Agitation in Children. Anesth Analg 2016;122:1141-6. [Crossref] [PubMed]
15. Long MHY, Lim EHL, Balanza GA, et al. Sevoflurane requirements during electroencephalogram (EEG)-guided vs standard anesthesia Care in Children: A randomized controlled trial. J Clin Anesth 2022;81:110913. [Crossref] [PubMed]
16. Lerman J, Ingelmo P. Emergence delirium in children: Do the studies reflect reality? Paediatr Anaesth 2024;34:493-4. [Crossref] [PubMed]
17. Yuan I, Missett RM, Jones-Oguh S, et al. Implementation of an electroencephalogram-guided propofol anesthesia education program in an academic pediatric anesthesia practice. Paediatr Anaesth 2022;32:1252-61. [Crossref] [PubMed]
18. Yuan I, Bong CL, Chao JY. Intraoperative pediatric electroencephalography monitoring: an updated review. Korean J Anesthesiol 2024;77:289-305. [Crossref] [PubMed]