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.