Interventional sedation analysis (ISA) is a medical procedure that facilitates the execution of potentially painful or anxiety-inducing diagnostic and therapeutic interventions in specific patient populations. The effectiveness of ISA is assessed by monitoring the depth of sedation achieved in patients ^1,2. Numerous scales have been developed to monitor sedation depth, with the most commonly used being the Ramsay Sedation Scale (RSS), Michigan University Sedation Scale (MUSS), and Brussels Sedation Scale (BSS). Among these, the RSS remains the most widely utilized in clinical practice today ³. However, the application of these scales in clinical settings poses challenges, as their reliability depends heavily on the subjective interpretation of the evaluator. Additionally, these scales require the administration of painful or verbal stimuli at specific moments, which limits their ability to provide continuous and objective measurements ⁴.

The Ramsay Sedation Scale (RSS) was first introduced by Ramsay and colleagues in 1974 as a straightforward scoring system, which continues to be a predominant tool in intensive care units ⁵.The RSS is applicable not only in intensive care settings but also across various clinical scenarios where sedative and analgesic medications are administered ⁶. The scale consists of six levels: Level 1-patient is awake but anxious, agitated, or restless; Level 2-patient is awake, cooperative, oriented, and calm; Level 3-patient is asleep but responds to commands; Level 4-patient exhibits a brisk response to glabellar tap or loud auditory stimulus; Level 5-patient shows a sluggish response to such stimuli; and Level 6-patient exhibits no response to glabellar tap or loud auditory stimulus ⁷. The target sedation level for most clinical scenarios is typically Level 2. It remains one of the most widely utilized clinical evaluation methods to this day ⁸.

The University of Michigan Sedation Scale (MUSS) was developed to provide a simple and rapid method for assessing and documenting the depth of sedation in patients receiving sedative agents for diagnostic or therapeutic procedures. The scale ranges from 0 to 4: Level 0-patient is awake and alert; Level 1-patient responds to minimal verbal stimuli; Level 2-patient responds to moderate tactile stimuli; Level 3-patient requires deeper physical stimuli for arousal; and Level 4-patient does not respond to any stimuli. The MUSS was designed to be easy to use, reproducible, and objective ⁹.

The Brussels Sedation Scale (BSS) was primarily developed for use in intensive care settings, aiming to provide a simple, repeatable, and objective method for assessing sedation depth. The scale includes five levels, but unlike the RSS, it inverts the order: higher numerical values correspond to lighter levels of sedation. This approach is believed to be easier to apply and is conceptually similar to the Glasgow Coma Scale (GCS), where lower scores indicate deeper levels of unconsciousness. On the BSS, Level 1 corresponds to a patient who cannot be awakened and only responds to painful stimuli, such as trapezius muscle compression; Level 2 indicates a patient who does not respond to verbal stimuli but reacts to pain; Level 3 is for patients who respond to verbal commands; Level 4 indicates the patient is awake and alert; and Level 5 corresponds to a state of agitation ¹⁰.

The Bispectral Index (BIS) ranges from 0, which represents isoelectric EEG, to 100, indicating an awake brain. Following the administration of sedative and analgesic agents, a patient’s level of consciousness transitions through various stages, which are reflected in the BIS score. The BIS value decreases from 100, with a BIS of 60 indicating a reduced likelihood of consciousness, while values below 40 are indicative of deep hypnosis approaching an isoelectric EEG. The BIS value, which starts at 100 indicating an awake state of consciousness, gradually decreases as sedation deepens. A BIS value of 60 is associated with a significantly reduced likelihood of consciousness, while values below 40 are indicative of deep hypnosis, nearing an isoelectric EEG. BIS values within the range of 40 to 60 are considered to provide an effective hypnotic state suitable for general anesthesia, ensuring a rapid recovery. The Bispectral Index (BIS), derived from electroencephalography (EEG) signals, is widely regarded as a quantitative measure of anesthetic depth. This index is generated by advanced computational algorithms that analyze cerebral electrical activity, allowing for continuous and objective monitoring of sedation depth. The BIS technique facilitates the precise assessment of sedative and hypnotic effects of anesthetic agents, making it a valuable tool in clinical settings. Numerous studies have demonstrated the utility of EEG monitoring, particularly in intensive care units and operating rooms, for assessing sedation depth. Furthermore, in cases where general anesthesia is not administered but sedation is required, BIS monitoring has been reported as an effective alternative for determining anesthetic depth during procedures such as endoscopy, bronchoscopy, central catheter insertion, and dental interventions. It also serves as an alternative to traditional sleep staging systems in sleep studies ^11-14. This study aims to evaluate the correlation between the clinically subjective scales RSS, MUSS, and BSS and BIS monitoring in patients undergoing Interventional Sedation and Analgesia (ISA).

This study aims to evaluate the correlation between the clinically subjective scales RSS, MUSS, and BSS and BIS monitoring in patients undergoing Interventional Sedation and Analgesia (ISA).

Exclusion Criteria
Patients with a known diagnosis of epilepsy, those with pre-ISA impaired consciousness (e.g., mental metardation, Glasgow Coma Scale (GCS) ≤14, sequelae of cerebrovascular disease, dementia, intracranial mass, history of severe head trauma, and psychotic disorders), patients with significant airway obstruction (e.g., tumor, psychotic disorders, sleep apnea syndrome), patients on invasive or non-invasive ventilation, and those with skin lesions on the forehead were excluded from the study.

Sedation Protocol
Pediatric doses of midazolam (0.05-0.1 mg/kg/IV, with a maximum total dose of 10 mg) and meperidine (1 mg/kg) were administered. Medications were administered in accordance with established guidelines, avoiding high doses. The duration of the interventional procedures did not exceed 20 minutes, thus eliminating the need for premedication or additional doses of sedation.

Data Collection
Vital signs, including blood pressure, pulse, respiratory rate, and oxygen saturation (SatO₂), were measured and recorded at baseline (pre-ISA), at the start of the procedure, and at 5, 10, 15, and 20-minute intervals. GCS was also measured and documented at these same intervals. Sedation depth was assessed using the Ramsay Sedation Scale (RSS), Michigan University Sedation Scale (MUSS), and Brussels Sedation Scale (BSS), with values recorded by one of the research team members. BIS values were continuously monitored and recorded via a timed computer program connected to the BIS module using disposable electrodes affixed to the forehead.

Sedation Assessment
The sedative effects were anticipated to provide short-term anxiolytic and amnestic effects with minimal cardiovascular side effects, using a combination of midazolam and meperidine. The severity of pain was not assessed in this study. No complications were observed related to the sedation during the interventional procedures.

Considerations in Intensive Care Unit
In the intensive care setting, the quality of BIS signals may be affected by factors such as sweating, edema, and patient movement, as well as electrical interference from devices like electric beds, infusion pumps, ventilators, and heaters ¹⁵. Patients with metal stabilizers that could create artifacts in BIS monitoring were excluded. In certain cases, multiple EEG electrodes were used, particularly due to issues with sweating.

Statistical Analysis
The statistical analysis of the data was performed using the IBM SPSS Statistics Version 22.0 software package. Categorical variables were summarized as frequencies and percentages, while continuous variables were reported as means and standard deviations, or as medians and ranges where appropriate. The normality of continuous variables was assessed using the Kolmogorov-Smirnov test. For variables that did not meet the assumption of normal distribution, the relationships between these continuous variables were evaluated using the Spearman correlation coefficient. A p-value of less than 0.05 was considered statistically significant for all analyses.

Among of the 33 patients, who underwent interventional sedation analgesia, twenty (60.6%) patient were female and13 (33.3%) were male, with a female/male ratio of 1.53 (Table 1).

Table 1: Socio-Demographic characteristics of cases.

The patients had a mean age of 8 years and 6 months (ranging from 2 to 17 years). Midazolam was administered to 22 patients (66.7%), meperidine was given to 1 patient (3%), and a combination of midazolam and meperidine was administered to 10 patients (30.3%) for sedation and analgesia (Table 2).

Table 2: Medications used for interventional sedation and analgesic.

The lowest BIS value (77) among the patients, evaluated at the 0th, 5th, 10th, 15th, and 20th minutes of the procedure, was observed at the 15th minute. The mean vital signs of the patients are presented in Table 3.

Table 3: Averages of vital findings.

Then there was an increase in BIS values with an increasing slope. No significant correlation was detected between BIS and RSS, MUSS and BSS (p= 0,446) (p= 0,219) (p= 0,938) (Table 4).

Table 4: RSS, MUSS AND BSS mean walues with BIS.

Spearman Correlation Analysis revealed that, while no significant correlations were found with other measures, a significant correlation was observed between RSS and MUSS when compared to each other (p < 0.001) (Table 5). When considering RSS and MUSS values, a moderate correlation was observed between them (p = 0.007).

Table 5: RSS and MUSS mean values of the facts.

Currently, there is no universally accepted scale for monitoring sedation depth in pediatric patients. In this study, we evaluated the concordance between the widely utilized RSS, MUSS, and BSS scales, as well as BIS-a novel method of measurement used in the ICU for assessing sedation depth in patients under ISA. The RSS was developed to provide an objective assessment of drug-induced sedation and is based on a six-point scale, encompassing three awake states and three asleep states. However, despite its relative ease of use, distinguishing between levels 4 (patient is asleep but awakens to a glabellar tap or auditory stimulus) and 5 (patient is asleep but responds slowly to a glabellar tap or auditory stimulus) can be challenging ^16,17. Consequently, the BSS and MUSS scales were developed as alternatives. BIS, on the other hand, offers an objective method for evaluating sedation depth. In our study, no significant correlation was found between RSS, MUSS, BSS, and BIS. However, a no-table correlation was observed between RSS and MUSS. To our knowledge, no previous studies in the literature have compared these two scales in the manner we have. We believe that further research in this area is warranted. Berkenbosch et al. investigated the correlation between BIS and clinical sedation scales in pediatric patients aged 5-6 years who were sedated and mechanically ventilated in the intensive care unit. Their study assessed three sedation scales: the modified RSS, the Richmond Agitation-Sedation Scale (RASS), and the Pediatric Intensive Care Unit Sedation Scale (PICU scale). Despite the comprehensive analysis, no significant correlation was identified between these scales and BIS. However, the authors suggested that BIS might be more beneficial for monitoring deeper levels of sedation ¹⁸. In contrast, a study by Agrawal et al. ¹⁹ involving 20 pediatric patients found a strong correlation between BIS and the modified RSS. Similarly, Aneja et al. ²⁰ conducted a study on patients aged 1-16 years who were not under neuromuscular blockade and observed a significant concordance between BIS and RSS. Specifically, they determined that a BIS value of 42 marked the threshold between oversedation (RSS ≥ 5) and adequate sedation (RSS 2-5), while a BIS value of 76 corresponded to low sedation (RSS = 1). One potential explanation for the discrepancies observed between BIS and subjective sedation scores could be the timing of BIS measurements. During clinical assessments, patients are often stimulated with verbal or painful stimuli, which can lead to substantial increases in BIS values, rising from 50 to 80 or even 90. The timing of BIS measurement, whether taken before or after such stimulation, can significantly influence its correlation with clinical scoring ²¹. In our study, we also noted an increase in BIS values following stimulation. To ensure the accuracy of our assessments, we recorded basal BIS values in the absence of any prior stimulation before proceeding with the evaluation of clinical sedation scores.

Limitations of this study
In conclusion, no significant correlation was found between BIS monitoring and the compliance of RSS, BSS, and MUSS in patients who underwent ISA. However, a significant correlation was observed between RSS and MUSS. Our literature review revealed that no previous studies have compared four sedation scales-one of which is objective and the others subjective-in the manner conducted in our study. The-refore, it is recommended that future research focus on clinically prevalent sedation scales, with comparative analyses of study data conducted separately.

Acknowledgement
The authors express their sincere gratitude to Dr. Mehmet Yusuf Sarı for his invaluable assistance in securing ethics committee approval.