qNOX Response to Nociceptive Motor Events During Procedural Sedation (MO-NOX)

Performance of the CONOX Monitor Without Neuromuscular Blockade: qCON and qNOX Responses to Nociceptive Motor Events During Procedural Sedation

The goal of this observational study is to evaluate whether the CONOX monitor can detect pain during sedation in patients undergoing urological procedures. The main questions it aims to answer are:

Does the qNOX index respond to pain-related motor responses during urological procedural sedation? Does the qNOX index show greater responsiveness to painful episodes compared to blood pressure and heart rate? Participants undergoing urological procedures (such as cystoscopy) under sedation as part of their regular medical care will have continuous brain activity monitoring with the CONOX device. All monitoring displays (CONOX monitor, vital signs monitor, and target-controlled infusion pump) will be video-recorded throughout the procedure to capture synchronized data including qCON, qNOX, EMG, heart rate, blood pressure, oxygen saturation, and drug concentrations. Researchers will analyze the relationship between these indices and spontaneous movements triggered by painful stimulation to evaluate the monitor's performance compared to traditional vital signs.

Study Overview

• Status: Recruiting
• Conditions: Procedural Sedation and Analgesia; Monitored Anesthesia Care; Monitoring Noxious Events Using EEG-Derived Pain Indices

Detailed Description

STUDY RATIONALE

Adequate monitoring of sedation depth and nociception is essential during monitored anesthesia care (MAC). While processed EEG monitors assess hypnotic depth, monitoring pain remains challenging. The CONOX monitor uniquely provides two indices: qCON for sedation depth and qNOX for nociception probability.

Most CONOX studies have used neuromuscular blockade, which prevents motor responses and limits validation of the qNOX index against observable pain reactions. Furthermore, data during procedural sedation and MAC is limited. The absence of neuromuscular blockade during MAC allows studying the relationship between qNOX values and actual pain-triggered motor responses, providing a concrete reference for nociception assessment.

This study evaluates whether an EEG-based nociception index can reliably detect pain when motor responses are not suppressed. If the qNOX index demonstrates adequate performance, it could provide clinicians with a tool for optimizing analgesic administration while minimizing opioid consumption.

STUDY DESIGN

This is a prospective, observational, single-arm cohort study evaluating CONOX monitor performance during procedural sedation without neuromuscular blockade at Ankara University Faculty of Medicine. The study involves no interventions beyond standard clinical care.

The study will enroll 120 adult patients (≥18 years) undergoing elective urological procedures (cystoscopy, ureteroscopy, transurethral resection) under MAC. These procedures involve intermittent painful stimulation and typically do not require neuromuscular blockade. Patient recruitment and data collection will occur over 4 months, followed by 2 months for analysis.

Processed EEG monitoring is part of standard practice in our department. The CONOX monitor will be used for all enrolled patients. The only study-specific procedure is video recording of monitoring displays (not patients) for subsequent analysis.

METHODS

Anesthesia Protocol:

Patients receive standard ASA monitoring. Anesthesia consists of intravenous fentanyl (1 mcg/kg) followed by propofol target-controlled infusion (TCI) using the Eleveld model. Initial target effect-site concentration is 1.5 mcg/mL, titrated to achieve adequate sedation depth (MOAAS ≤1). Patients maintain spontaneous ventilation with airway support as needed. No neuromuscular blockade is used.

Monitoring and Data Collection:

The CONOX monitor continuously records qCON (hypnotic depth), qNOX (nociception), EMG (electromyographic activity), and burst suppression ratio. Standard monitors record ECG, blood pressure, heart rate, SpO₂, and capnography. The TCI pump displays real-time propofol effect-site concentration.

All monitoring displays are video-recorded throughout procedures to capture synchronized data for post-hoc analysis. Researchers provide verbal timestamps to mark clinical events (drug administration, procedure start, motor responses). Videos capture only monitor screens, not patient images.

Primary Endpoint:

The primary endpoint is change in qNOX index from baseline to peak during spontaneous motor responses triggered by surgical stimulation. Motor responses include extremity/trunk movements, facial grimacing, or vocalization, identified by real-time clinical observation.

Data Analysis:

Video recordings are systematically reviewed to extract monitoring values at baseline and during clinical events. For motor response events, peak values and time-to-peak are recorded for each parameter.

STATISTICAL ANALYSIS

Power analysis determined 30 motor response events are required for paired t-test comparing baseline versus peak qNOX (alpha=0.05, power=0.95). Based on estimated 25% incidence and accounting for potential data loss, 120 patients will be enrolled.

Primary analysis uses paired t-test (or Wilcoxon test if non-normal) to compare qNOX at baseline versus during motor responses. ROC curve analysis evaluates discriminative ability of qNOX, heart rate, and blood pressure for predicting motor responses. Secondary analyses include correlation analyses and repeated measures analysis for induction/emergence dynamics. Statistical significance: p<0.05 (two-tailed).

ETHICS AND SAFETY

This observational study involves no interventions beyond standard care. All management decisions follow routine clinical practice. The study has ethics approval from Ankara University Faculty of Medicine Clinical Research Ethics Committee. Written informed consent is obtained from all participants. The study follows Declaration of Helsinki and Good Clinical Practice guidelines.

• Study Type: Observational
• Enrollment (Estimated): 120

Contacts and Locations

• Study Contact: Name: Cahit Sefer Uçar, MD; Phone Number: +905532774107; Email: cs.ucar@hotmail.com

Study Locations

• Turkey (Türkiye)
  • Altındağ
    • Ankara, Altındağ, Turkey (Türkiye), 06230
      • Recruiting
      • Ankara University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult patients (≥18 years) scheduled for elective urological procedures under monitored anesthesia care at Ankara University Faculty of Medicine. Patients will undergo standard procedural sedation with propofol target-controlled infusion and fentanyl, maintaining spontaneous ventilation without neuromuscular blockade.

Description

Inclusion Criteria:

• Age 18 years or older
• Scheduled for elective diagnostic or therapeutic urological procedures (cystoscopy, ureteroscopy, prostate biopsy, intradetrusor botulinum toxin injection) under monitored anesthesia care
• Able to provide written informed consent

Exclusion Criteria:

• Known central neurological disease (epilepsy, Alzheimer's disease, Parkinson's disease, stroke) or history of brain surgery
• Body Mass Index (BMI) ≥35 kg/m²
• Known allergy to anesthetic agents used in the study (propofol, fentanyl, lidocaine)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Procedural Sedation with CONOX Monitoring; Adult patients undergoing elective urological procedures under monitored anesthesia care with continuous CONOX monitoring. All patients receive standard procedural sedation with propofol target-controlled infusion (Eleveld model) and fentanyl (1 mcg/kg), maintaining spontaneous ventilation without neuromuscular blockade. The CONOX monitor continuously records qCON, qNOX, and EMG indices throughout the procedure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Quantium Nociception Index (qNOX) During Motor Responses to Noxious Stimulation	The Quantium Nociception Index (qNOX) is an electroencephalography-derived dimensionless index ranging from 0 to 99. The magnitude of change from baseline to peak qNOX value during spontaneous motor response episodes will be measured. Greater absolute change indicates better discriminative performance of the qNOX index in detecting nociception-evoked motor responses.	During the procedure (approximately 15-60 minutes per patient)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of qNOX Responsiveness Versus Hemodynamic Parameters During Motor Responses	Magnitude of change in qNOX index compared to changes in heart rate, mean arterial pressure and SPI during motor responses to noxious stimulation. Assessed by comparing percentage change from baseline for each parameter.	During motor response events (if occurred) throughout the surgical procedure
Correlation Between EMG Activity and qCON/qNOX Indices	Relationship between electromyographic (EMG) activity levels and qCON/qNOX index values throughout the procedure. Assessed using correlation analysis between EMG and each index.	Throughout the surgical procedure (approximately 15-60 minutes)
Incidence of Pain-Related Motor Responses During Procedural Sedation	Proportion of patients experiencing spontaneous motor responses triggered by noxious stimulation during urological procedures under standardized anesthetic protocol. Motor responses include extremity/trunk movement, facial grimacing, or vocalization.	During the surgical procedure (approximately 15-60 minutes)
Index Dynamics During Induction and Emergence from Sedation	Rate of change (slope) in qCON (Quantium Consciousness Index, 0-99 scale), qNOX (Quantium Nociception Index, 0-99 scale), and EMG (electromyographic activity, 0-100 scale) indices during sedation induction and emergence. Induction phase: from baseline to achievement of target sedation (MOAAS ≤1) Emergence phase: from TCI cessation to return of consciousness (response to verbal commands) Slopes will be calculated as the rate of index change per unit time (index units per minute) using linear regression for each phase. This standardized measure allows comparison of dynamics across different indices despite their different physiological meanings.	Induction: 0-10 minutes; Emergence: from TCI stop until recovery of consciousness

Collaborators and Investigators

• Sponsor: Ankara University
• Investigators: Principal Investigator: Çiğdem YILDIRIM GÜÇLÜ, MD, Ankara University

Publications and helpful links

General Publications

• Jensen EW, Valencia JF, Lopez A, Anglada T, Agusti M, Ramos Y, Serra R, Jospin M, Pineda P, Gambus P. Monitoring hypnotic effect and nociception with two EEG-derived indices, qCON and qNOX, during general anaesthesia. Acta Anaesthesiol Scand. 2014 Sep;58(8):933-41. doi: 10.1111/aas.12359. Epub 2014 Jul 4.
• Schuller PJ, Pretorius JPG, Newbery KB. Response of the Conox quantitative electroencephalographic monitor to neuromuscular block in awake volunteers. Br J Anaesth. 2025 Sep;135(3):660-667. doi: 10.1016/j.bja.2025.05.023. Epub 2025 Jul 18.
• Linassi F, Vide S, Ferreira A, Schneider G, Gambus P, Kreuzer M. Relationships between the qNOX, qCON, burst suppression ratio, and muscle activity index of the CONOX monitor during total intravenous anesthesia: a pilot study. J Clin Monit Comput. 2024 Dec;38(6):1281-1290. doi: 10.1007/s10877-024-01214-6. Epub 2024 Sep 12.

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2026
• Primary Completion (Estimated): April 30, 2026
• Study Completion (Estimated): May 30, 2026

Study Registration Dates

• First Submitted: February 10, 2026
• First Submitted That Met QC Criteria: February 10, 2026
• First Posted (Actual): February 17, 2026

Study Record Updates

• Last Update Posted (Actual): February 18, 2026
• Last Update Submitted That Met QC Criteria: February 15, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Propofol; Target Controlled Infusion; Procedural Sedation; EEG Monitoring; CONOX Monitor; qNOX Index; qCON Index
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Neurobehavioral Manifestations; Perceptual Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Agnosia
• Other Study ID Numbers: 2025/433

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: De-identified individual participant data are available from the corresponding author upon reasonable request.

Drug and device information, study documents

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