Elucidating the Neural Correlates of Anesthesia-induced Unconsciousness in Neonates (NeoNCC)

This study will try to elucidate the neural responses of neonatal patients to surgery-level propofol infusions during induction and maintenance of anesthesia. The main objective is to elucidate the EEG patterns of neural activity that can reliably reflect the level of hypnotic depth in full term neonates undergoing propofol anesthesia based on the classification of EEG into states and the characterization of discrete neonatal EEG events.

Study Overview

• Status: Not yet recruiting
• Conditions: Anesthesia; Neonatal Surgery; Anesthesia Brain Monitor

Detailed Description

Appropriated dosage of anesthetic drugs is essential to reduce the incidence of negative outcomes during and after surgery. In neonates, this is of particular importance because of their intrinsic vulnerability. Administration of an insufficient dose of hypnotic drugs like propofol to a neonate can result in episodes of intraoperative awareness and strong pain responses that cause unnecessary physiological stress, which may be hard to detect intraoperatively because of muscle relaxants. On the other hand, excessive dosage of drugs like propofol for long periods of time can drastically disrupt ongoing spontaneous activity, which is essential for the normal development of synaptic connections within the cerebral cortex, especially around the time of birth. Also, it has been suggested that these drugs may have a neurotoxic effect in neonates. This highlights some of the reasons why the highest degree of precision is required when administering hypnotic anesthetic drugs to neonates.

In adults, intraoperative anesthesia monitoring provides an objective measure of the magnitude of the anesthetic effect achieved by directly evaluating the patient's brain activity in real time. With this information, anesthesiologists can continuously titrate the doses of hypnotic drugs required to produce an optimal effect. This monitoring is done by continuously recording electroencephalographic (EEG) activity and comparing that activity with known markers of hypnotic depth like oscillatory activity of different frequencies. Importantly, this is possible because we know to a great extent what patterns of brain activity are related to insufficient, optimal and excessive dosages of propofol in the adult brain. However, we do not currently have this information about neonates' brain during anesthesia.

Neonatal EEG activity is notoriously different to adults' EEG, both during anesthesia and without it. The EEG activity of adults under propofol anesthesia is dominated by either alpha (8 - 12 Hz, which is not present in neonates) and/or delta (1- 4Hz) oscillations that are relatively consistent in time. This means that the amplitude and frequency of these oscillations do not vary significantly in time but remain mostly constant unless there are changes in the patient's hypnotic depth because of a change in dosage. In contrast, neonatal EEG activity during anesthesia is notoriously discontinuous; it transitions from low to high amplitude activity, and is filled by discrete events including sharp waves, bursts and delta brushes. This makes the adult's EEG markers of anesthesia unusable in neonates. The specific characteristics of these discontinuities and discrete events have been mainly described by visual inspection or rough historical criteria, but not using modern data-driven EEG analysis techniques.

In this work the investigators will directly record EEG activity from neonates before anesthesia (baseline), during propofol induction and during surgery-level anesthesia. In this way the investigators will be able to evaluate how do the putative neural signatures of hypnotic depth behave, and how closely they follow propofol concentration and propofol effect (i.e. loss of consciousness/response). Because of this, the current study will be a prospective observational analytic cohort study.

The study will include full term neonates (37 - 42 weeks of gestational age) that require general anesthesia/deep sedation during their first 28 days of life because they require a surgery or a specific procedure. This will include patients from cardiac and non-cardiac surgeries like hernias, superficial abdominal surgery, radiological procedures, procedures related to airway assessment, among others. Exclusion criteria will include patients scheduled for neurological surgeries, with perinatal asphyxia, with evidence of neurological injury or pathology, suspected brain malformations, and patients with metabolic or hemodynamic instability at the time of the surgery or procedure.

A considerable number of neonatal surgeries and procedures are conducted in patients that are already partially sedated because their pathology or general medical condition requires it. This implies that EEG activity during baseline will depend on whether the patient was already sedated or not. To manage this, the investigators will separate patients into two groups: 1) a previously sedated group and 2) a not previously sedated group. Although we know that it will be harder to evaluate neural signatures of anesthesia in patients that are already sedated during baseline, we chose to include them in our study because we want our results to reflect the clinical reality of many neonatal patients. Also, at least in our institution, patients that require surgery or a procedure with anesthesia are more likely to be already sedated. We will record the drugs and doses administered to each patient in the previous 24 hours including vasoactive and sedatives.

Separating neonates based on their sedation state before the surgery or procedure will, at the same time, separate patients based on their level of severity of illness. The researchers will directly measure this possible confounding effect to include it in our models. They will quantify severity of illness with two indices, the "Neonatal therapeutic intervention scoring system" (NTISS) and the "Neonatal sequential organ failure assessment" score (nSOFA). These consider dozens of factors like if the patient requires supplemental oxygen, if they have required transfusions of any blood products or if they have a central venous line, among many others. Each one of these criteria is considered for the final score. In this way, we will have two objective measures of patient's severity of illness to be used as covariates in data analyses. They will help to better understand if a given EEG property is a marker of hypnotic depth or just a marker of severity of illness.

• Study Type: Observational
• Enrollment (Estimated): 64

Contacts and Locations

• Study Contact: Name: Gonzalo Boncompte, PhD; Phone Number: +569 64319979; Email: gnboncompte@uc.cl

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients of the Hospital Clinico UC-Christus.

Description

Inclusion Criteria:

• Full term neonates (37 - 42 weeks of gestational age)
• Require general anesthesia/deep sedation during their first 28 days of life because they require a surgery or a specific procedure (cardiac or non-cardiac)
• Scheduled for propofol induction

Exclusion Criteria:

• Neurological surgeries
• Perinatal asphyxia
• Evidence of neurological injury or pathology
• Suspected brain malformations
• Patients with metabolic or hemodynamic instability at the time of the surgery or procedure.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Main group; This main group will consist of neonatal patients that require general anesthesia for a surgery or procedure during their first 28 days of life.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Temporal distribution of EEG states	We will evaluate how the temporal distribution of particular EEG states changes across propofol doses. In particular we will evaluate the percentage of time spent by each patient in each EEG state and the transition probabilities between different EEG states during and after propofol induction. EEG states will be defined in two ways: based on peak amplitude of the EEG signal following our previous work (DOI: 10.1097/EJA.0000000000002208); based on data-driven clustering of spectral and non-spectral EEG features. These features will include spectral power in all canonical frequency bands (i.e. slow, delta, theta, alpha and beta bands) as well as entropy/complexity derived measures (e.g. permutation entropy and Lempel-ziv complexity). Each EEG state will be defined. The predictive power of both EEG states defining approach will be evaluated.	This will be collected during the anesthesia induction and the first minutes of maintenance of anesthesia
Distribution of discrete EEG events	We will evaluate how the distribution of EEG events changes across propofol doses. In other words we will quantify the probability of appearance of different EEG events such as k-complexes and delta brushes. The probability of these events will be evaluated as predictors of propofol dosage during and after induction. Time segments with EEG events will be classified as such based on their spectral profiles, which will be evaluated using both classical spectral estimations (multitapers) and also using Empirical Mode Decomposition. The two strategies will be compared.	This will be collected during the anesthesia induction and the first minutes of maintenance of anesthesia

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of illness - nSOFA	We will evaluate severity of illness of each patient using neonatal sequential organ failure assessment (nSOFA) instrument. The instrument scores range from zero to 15 points and higher scores indicate worst status.	At the time of surgery
Severity of illness - NTISS	We will evaluate severity of illness of each patient using the Neonatal therapeutic intervention scoring system (NTISS) instrument. The scores of this instrument typically range from 0 to 47 with higher scores suggesting greater severity of illness. Mean values of 12.3 (SD = 8.7) have been reported for NICU patients)	At the time of surgery
Age	We will evaluate the postnatal and postmenstrual age of patients.	At the time of surgery

Collaborators and Investigators

• Sponsor: Pontificia Universidad Catolica de Chile

Publications and helpful links

General Publications

• Wynn JL, Polin RA. A neonatal sequential organ failure assessment score predicts mortality to late-onset sepsis in preterm very low birth weight infants. Pediatr Res. 2020 Jul;88(1):85-90. doi: 10.1038/s41390-019-0517-2. Epub 2019 Aug 8.
• Gray JE, Richardson DK, McCormick MC, Workman-Daniels K, Goldmann DA. Neonatal therapeutic intervention scoring system: a therapy-based severity-of-illness index. Pediatrics. 1992 Oct;90(4):561-7.
• Boncompte G, Cortinez LI, Toso A, Giordano A, Cruzat F, Fuentes R, Pedemonte JC, Contreras V, Biggs D, Chiu E, Ibacache M. Differential effects of propofol anaesthesia across three amplitude-defined electroencephalographic states in sedated critically ill term neonates: An observational study. Eur J Anaesthesiol. 2025 Oct 1;42(10):889-898. doi: 10.1097/EJA.0000000000002208. Epub 2025 May 23.

Study record dates

Study Major Dates

• Study Start (Estimated): May 15, 2026
• Primary Completion (Estimated): May 15, 2028
• Study Completion (Estimated): May 15, 2029

Study Registration Dates

• First Submitted: April 14, 2026
• First Submitted That Met QC Criteria: May 18, 2026
• First Posted (Actual): May 22, 2026

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: propofol; neonatal anesthesia; brain monitoring; neonatal brain monitoring; neonatal brain states
• Other Study ID Numbers: FONDECYT Iniciacion N°11261085; Ethics committee: N°250421014 (Other Identifier: Comité Ético científico de Ciencias de la Salud, Pontificia Universidad Católica de Chile)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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