Impact of EEG-guided Sevofluorane on Opioid Consumption and Quality of Awakening

Impact of EEG-guided Sevoflurane Titration on Opioid Consumption and Emergency Quality in Pediatric Patients Undergoing Surgery Without Regional Anesthesia

This prospective, randomized, single-blind, two-arm parallel-group clinical trial evaluates whether EEG-guided sevoflurane titration affects intraoperative opioid consumption and emergence quality in children undergoing painful elective surgery without regional anesthesia. Children aged 2-8 years (ASA I-II) scheduled for elective tonsillectomy (±adenoidectomy) are randomized 1:1 to a Control Group (standard 1 age-adjusted MAC; EEG screen concealed) or a Study Group (sevoflurane titrated to a stable slow-delta/alpha EEG pattern, SEF 17-20 Hz, starting at ~0.7 MAC). In both arms, fentanyl (0.5-1 mcg/kg IV) is added when nociception signs occur. The primary outcome is intraoperative fentanyl consumption (mean mcg/kg rate). Secondary outcomes include sevoflurane exposure (EtSevo, MAC-hours), EEG burst suppression, emergence time, emergence delirium (PAED scale), postoperative pain and opioid use, and hemodynamic events. Sample size: 50 participants (25/arm; 90% power, α=0.05, expected difference 2 mcg/kg, SD=2). EEG spectral analysis is performed in MATLAB using multitaper frequency-domain bootstrap. The study has institutional ethics approval; parental consent and patient assent (≥7 years) are obtained prior to enrollment.

Study Overview

• Status: Not yet recruiting
• Conditions: Postoperative Pain; Pediatric Anesthesia; Tonsillectomy; Emergence Delirium, Anesthesia
• Intervention / Treatment: Procedure: Standard; Procedure: EEG-guided

Detailed Description

Electroencephalography (EEG)-guided anesthetic titration has demonstrated significant clinical benefits in both pediatric and adult patients. However, proprietary EEG-based indices widely used for monitoring anesthetic depth are affected by patient age and the specific anesthetic agent used, limiting their validity and generalizability. More recently, titrating anesthetics based on a specific interpretation of EEG waveforms and their oscillatory patterns observed on the spectrogram has gained popularity.

Previous studies indicate that sevoflurane titration based on specific EEG waveforms and oscillatory patterns yields more substantial reductions in sevoflurane exposure than previously reported with proprietary EEG indices. Furthermore, reducing sevoflurane exposure decreases the incidence of EEG burst suppression, results in faster emergence times, and reduces emergence delirium.

However, most of these benefits have been reported in the context of surgeries where intraoperative antinociception was provided via central or peripheral nerve blocks, in the absence of increased intraoperative analgesic and opioid requirements. It remains unclear whether the benefits associated with reduced sevoflurane exposure are also observed in surgeries where intraoperative antinociception cannot be provided through regional blocks. In such cases, antinociception depends primarily on the co-administration of inhaled anesthetics and opioids. Therefore, the clinical benefits of decreasing sevoflurane exposure via electroencephalographic guidance must be weighed against the side effects of higher perioperative opioid requirements.

What will be the impact of strict titration of the hypnotic component using electroencephalography in a painful surgery, in terms of intraoperative opioid consumption and the quality of anesthetic emergence? It is hypothesized that to adjust the sevoflurane dose according to EEG targets in children undergoing surgeries where intraoperative antinociception cannot be provided via regional blocks will result in a reduction of sevoflurane requirements. However, a compensatory increase in intraoperative opioid consumption is expected to be observed, which could subsequently affect the quality and duration of the anesthetic recovery period.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mauricio Ibacache, Phd; Phone Number: +56984421425; Email: mianesteman@gmail.com
• Study Contact Backup: Name: Ricardo Fuentes, MD; Phone Number: +56984421425; Email: rfuente@ucchristus.cl

Study Locations

• Chile
  • Santiago, Chile
    • Hospital UC Christus
    • Contact: Mauricio Ibacache, Phd; Phone Number: +56 9 8442 1425; Email: mianesteman@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 2-8 years
• ASA Physical Status I or II
• Elective tonsillectomy (±adenoidectomy)
• Signed parental consent (and assent ≥7 years)

Exclusion Criteria:

• Neurological or psychiatric disorders
• Growth or developmental delay
• Known allergy to study medications
• Coagulation disorders
• Parental or patient refusal

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control Group; Induction with sevoflurane 5% in O₂. Maintenance at fixed 1 age-adjusted MAC in O₂/air FiO₂ 60%. BIS monitor attached but screen concealed; anesthesiologist blinded to EEG data.	Procedure: Standard; Arm Description: Induction with sevoflurane 5% in O₂. Maintenance at fixed 1 age-adjusted MAC in O₂/air FiO₂ 60%. BIS monitor attached but screen concealed; anesthesiologist blinded to EEG data.
Experimental: Intervention Group; Induction with sevoflurane 3% in O₂. Maintenance titrated to the minimum concentration sustaining a continuous slow-delta/alpha EEG pattern (SEF 17-20 Hz), starting at 0.7 age-adjusted MAC in O₂/air FiO₂ 60%.	Procedure: EEG-guided; Induction with sevoflurane 3% in O₂. Maintenance titrated to the minimum concentration sustaining a continuous slow-delta/alpha EEG pattern (SEF 17-20 Hz), starting at 0.7 age-adjusted MAC in O₂/air FiO₂ 60%.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total intraoperative opioid consumption	Mean fentanyl rate (mcg/kg).	Intraoperative period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sevoflurane exposure	Age-adjusted MAC-hours	Intraoperative period
Sevoflurane exposure	EtSevo	Intraoperative period
EEG burst suppression	incidence	Intraoperative period
EEG spectral markers_TBP	Total band power	Intraoperative period
EEG spectral markers_MedF	Median frequency	Intraoperative period
EEG spectral markers_SEF95	SEF 95%	Intraoperative period
EEG burst suppression	Cumulative duration	Intraoperative period
hemodynamic, Bradicardia	Intraoperative bradycardia (HR<20% basaline) requiring intervention	Intraoperative period
hemodynamic, hypotension	intraoperative hypotension (MAP<20% basaline) requiring intervention	Intraoperative period
emergence time	Time from anesthesia discontinuation to extubation	From end of anesthesia period to extubation
Eye opening, emergence time	Time from anesthesia discontinuation to eye opening	From end of anesthesia period to extubation
emergence delirium	incidence by paed scale	Post anesthesia period
Postoperative pain	flacc/vas scores	Post anesthesia period
Rescue analgesia	Drug use for rescue analgesia non opioids (mg)	Post anesthesia period
postoperative opioid use	fentanyl use for pain rescue (mcg)	Post anesthesia period

Collaborators and Investigators

• Sponsor: Pontificia Universidad Catolica de Chile
• Investigators: Study Chair: Victor Contreras, MSN, RN, Researcher; Principal Investigator: Mauricio Ibacache, Phd, Professor

Publications and helpful links

General Publications

• Wang HY, Chen TY, Li DJ, Lin PY, Su KP, Chiang MH, Carvalho AF, Stubbs B, Tu YK, Wu YC, Roerecke M, Smith L, Tseng PT, Hung KC. Association of pharmacological prophylaxis with the risk of pediatric emergence delirium after sevoflurane anesthesia: An updated network meta-analysis. J Clin Anesth. 2021 Dec;75:110488. doi: 10.1016/j.jclinane.2021.110488. Epub 2021 Sep 1.
• Miyasaka KW, Suzuki Y, Brown EN, Nagasaka Y. EEG-Guided Titration of Sevoflurane and Pediatric Anesthesia Emergence Delirium: A Randomized Clinical Trial. JAMA Pediatr. 2025 Apr 21;179(7):704-12. doi: 10.1001/jamapediatrics.2025.0517. Online ahead of print.
• Sun Y, Ye F, Wang J, Ai P, Wei C, Wu A, Xie W. Electroencephalography-Guided Anesthetic Delivery for Preventing Postoperative Delirium in Adults: An Updated Meta-analysis. Anesth Analg. 2020 Sep;131(3):712-719. doi: 10.1213/ANE.0000000000004746.

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: June 23, 2026
• First Submitted That Met QC Criteria: July 14, 2026
• First Posted (Actual): July 20, 2026

Study Record Updates

• Last Update Posted (Actual): July 20, 2026
• Last Update Submitted That Met QC Criteria: July 14, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Electroencephalogram; Tonsillectomy; Pediatric Anesthesia; Sevoflurano
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Postoperative Complications; Pathologic Processes; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Emergence Delirium; Pain, Postoperative
• Other Study ID Numbers: 260319004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Study Protocol Statistical Analysis Plan Informed Consent Form Clinical Study Report

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No