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

Recruiting

Conditions

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

Observational

Enrollment (Estimated)

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 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

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

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

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

Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 5, 2026

Primary Completion (Estimated)

February 1, 2027

Study Completion (Estimated)

February 1, 2027

Study Registration Dates

First Submitted

January 19, 2026

First Submitted That Met QC Criteria

February 24, 2026

First Posted (Actual)

March 2, 2026

Study Record Updates

Last Update Posted (Actual)

March 10, 2026

Last Update Submitted That Met QC Criteria

March 6, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Other Study ID 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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