Heart Rate Variability and Processed EEG Features as Predictors of Postoperative Outcomes After Cranial Neurosurgery (HERO-PACU)

March 6, 2026 updated by: Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta

Heart Rate Variability and Processed EEG Features as Predictors of Postoperative Outcomes After Cranial Neurosurgery - A Prospective Observational Study in the Post-Anesthesia Care Unit

Patients undergoing cranial neurosurgery face a high-risk postoperative period, particularly during emergence from anesthesia and early recovery in the post-anesthesia care unit (PACU). Standard monitoring provides limited insight into brain and autonomic recovery processes. Heart rate variability (HRV) and processed electroencephalography (pEEG) may offer complementary markers of autonomic and cortical function, with potential to improve early detection of complications and guide individualized care.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Detailed Description

Patients undergoing cranial neurosurgery face a particularly vulnerable postoperative course. The immediate hours after surgery represent a high-risk window, as the transition from anesthesia to recovery is marked by abrupt physiological shifts and the potential for neurological or systemic instability. As patients transition from deep anesthesia to consciousness, dynamic fluctuations in autonomic tone and cortical activity reflect the brain's ability to recover from surgical and anesthetic stress. Smooth emergence and extubation are therefore essential: coughing, hypertension, or surges in intracranial pressure (ICP) can endanger hemostasis and compromise brain protection. Most serious complications-such as intracranial bleeding, cerebral edema, ischemia, hydrocephalus, or herniation-tend to arise within the first hours after surgery.

The Post Anesthesia Care Unit (PACU) constitutes a important window of observation. At this critical phase many strategies have been developed to protect the brain from complication triggering events. For example, remifentanil infusion-whether manual or target-controlled at effect-site concentrations, like adopted at our institution, titrated to suppress airway reflexes and blunt cardiovascular responses-have been shown to promote safe and controlled awakening while preserving prompt neurological evaluation(1-6), facilitating the identification of surgical from anesthetic causes of delayed recovery. Any unrecognized or delayed deterioration early after surgery may herald potentially warning signs, highlighting the need for accurate, physiology-based monitoring to support timely detection and intervention.

Standard monitoring-focused largely on vital signs-offers limited insight into the underlying brain and autonomic processes that govern recovery. Heat rate variability (HRV) and processed electroencephalography (pEEG) features, may provide novel means to characterize patient vulnerability in the PACU, improving risk stratification and guiding individualized perioperative care.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
300

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Elective Cranial Neruosurgical Patients with planned extubation in the Post-Anesthesia Care Unit (PACU)

Description

Inclusion Criteria:

  • Adult patients (≥18 years) scheduled for elective cranial neurosurgery.
  • Planned extubation in the PACU after surgery.
  • Ability to obtain high-quality ECG and EEG recordings intra- and postoperatively (≥60 min expected PACU monitoring).
  • Written informed consent signed preoperatively.

Exclusion Criteria:

  • Pre-existing severe cardiac arrhythmias (e.g., atrial fibrillation, frequent ectopy) or pacemaker dependence.
  • Known severe autonomic neuropathy (e.g., advanced diabetes, Parkinson's disease with autonomic failure).
  • Preoperative conditions associated with abnormal EEG (status epilepticus, uncontrolled seizures, sedative/hypnotic overdose).
  • Intraoperative or immediate postoperative events necessitating continued mechanical ventilation or ICU admission (e.g., massive bleeding, intraoperative arrest).
  • Inability to provide informed consent (e.g., cognitive impairment, language barrier without interpreter).
  • Refusal of informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Temporal trajectories of HRV and pEEG after Neurosurgery in the PACU
Time Frame: 1 year

Quantitative assessment of autonomic and cortical recovery during the entire period of PACU staying until 120 minutes after extubation or PACU discharge

  1. Heart Rate Variability (HRV) parameters derived from continuous ECG recording, including:

    Time-domain indices:

    RMSSD (ms) SDNN (ms)

    Frequency-domain indices:

    LF power (ms²) HF power (ms²) LF/HF ratio (dimensionless) HRV will be calculated from high-resolution ECG signals using validated software following international standards (Task Force of the European Society of Cardiology and North American Society of Pacing and Electrophysiology).

  2. Processed EEG (pEEG) parameters obtained from a commercial depth-of-anesthesia monitor, including:

Processed EEG index value (dimensionless scale, 0-100) Spectral edge frequency (Hz) Relative alpha and delta power (% of total EEG power) Measurements will be extracted in predefined 5-minute epochs during of PACU monitoring
1 year

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Correlation Between HRV/pEEG Parameters in PACU and Incidence of Early Postoperative Complications Within 48 Hours
Time Frame: 48 hours after surgery

Association between HRV and pEEG parameters (RMSSD, SDNN, LF/HF ratio, pEEG index, spectral edge frequency) measured during the first 60 minutes in PACU and the occurrence of predefined postoperative complications within 48 hours.

Postoperative complications will include:

  • Intracranial hemorrhage
  • Cerebral edema
  • Hydrocephalus
  • Ischemic events
  • Delirium
  • Reintubation
  • Unplanned ICU admission Complications will be recorded as a binary variable (presence/absence).

The strength of association will be quantified using:

  • Odds Ratios (OR) from multivariable logistic regression models
  • Area Under the Receiver Operating Characteristic Curve (AUC)

Unit of Measure:

  • Incidence (% of patients with complication)
  • Odds ratio (dimensionless)
  • AUC (0-1 scale)
48 hours after surgery
Correlation Between HRV/pEEG Parameters and Perioperative Drug Exposure
Time Frame: Intraoperative period

Correlation between HRV/pEEG parameters measured in PACU and intraoperative anesthetic and opioid exposure including:

  • Total propofol dose (mg)
  • Total remifentanil dose (µg)
  • Effect-site concentration at end of surgery (µg/mL or ng/mL)

The relationship will be quantified using:

  • Pearson or Spearman correlation coefficients (r)
  • Multivariable linear regression coefficients (β)

Unit of Measure:

  • Drug dose (mg, µg)
  • Effect-site concentration (µg/mL or ng/mL)
  • Correlation coefficient (r, -1 to +1)
Intraoperative period
Correlation Between HRV/pEEG Parameters and Perioperative Clinical Variables
Time Frame: Intraoperative period

Correlation between PACU HRV/pEEG parameters and:

  • Duration of surgery (minutes)
  • Intraoperative hypotension duration (minutes below MAP threshold)
  • Estimated blood loss (mL)
  • ASA physical status classification

Association will be assessed using:

  • Pearson/Spearman correlation
  • Multivariable regression models

Unit of Measure:

  • Minutes
  • mL
  • ASA class (categorical scale)
  • Correlation coefficient (r)
Intraoperative period
Feasibility and Data Quality of HRV and pEEG Monitoring in PACU
Time Frame: First 60 minutes of PACU stay

Assessment of feasibility and signal quality of ECG and pEEG recordings during PACU monitoring, including:

  • Percentage of analyzable ECG epochs (%)
  • Percentage of analyzable EEG epochs (%)
  • Artifact burden (% of recording time excluded)

Unit of Measure:

Percentage (%)
First 60 minutes of PACU stay

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta

Publications and helpful links

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General Publications

Study record dates

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Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 5, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 19, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 24, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 2, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 10, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 6, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2026

More Information

Terms related to this study

Keywords

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • HERO-PACU

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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