An Observational Prospective Study of Anesthetic Sensitivity Assessed by Alpha Band Power and Its Association With Emergence Time From Sevoflurane General Anesthesia in Young Adults.

General anesthesia (GA) is an essential technique in modern medicine, used to induce unconsciousness, analgesia, and immobility in patients during surgical procedures. Since no single drug can achieve all these conditions, a combination of agents acting on the central nervous system (CNS) is employed. These include GABAergic hypnotics, such as propofol and halogenated gases; opioids, such as remifentanil and fentanyl; and neuromuscular blocking agents, such as rocuronium. The co-administration of these drugs generates multiple interactions that allow anesthesia to be induced and maintained under predictable conditions, solidifying the concept of "balanced anesthesia." However, one of the major challenges in its management is the adequate titration of drugs according to the individual needs of each patient, in order to avoid both overdosing and underdosing, both of which pose potential risks to patient safety.

In this context, electroencephalography (EEG) has emerged as a key tool for monitoring anesthetic depth, providing real-time information on cerebral activity. The analysis of electroencephalographic patterns and spectrograms, particularly alpha wave power, has proven to be a useful indicator of the degree of decreased cerebral activity during general anesthesia. Furthermore, previous studies suggest that alpha wave power may correlate with anesthesia recovery time (Gutierrez et al., Anesthesia & Analgesia, 2021) and possibly with individual sensitivity to general anesthetics. However, this relationship has not yet been fully elucidated, as a systematic study confirming this correlation has not been conducted. Establishing a correlation between emergence time and alpha band power would allow us to determine individual sensitivity to the effects of general anesthetics.

General Objective:

To determine whether patients who are more sensitive to the effects of general anesthetics have a lower relative power in the alpha band and a longer emergence time from general anesthesia.

Specific Objectives:

• - To quantify the relative alpha power in the electroencephalogram (EEG) spectrogram using an anesthetic depth monitor during the maintenance phase of general anesthesia in the study cohort.
• - To precisely record the anesthetic emergence time, defined as the interval from the cessation of volatile anesthetic administration to the patient's recovery of consciousness (e.g., eye opening or response to verbal command).
• - To statistically determine the correlation and magnitude of association between the quantified relative alpha power and the measured anesthetic emergence time.

Working Hypothesis Patients exhibiting greater cerebral sensitivity to general anesthetics, as indicated by a lower magnitude of relative alpha power during the maintenance phase, will experience a statistically significant prolongation of the anesthetic emergence time.

Methodology Materials and Methods: Subjects Following approval by the Ethics Committee of the Hospital Clínico Universidad de Chile, we will conduct an observational study on a cohort of patients undergoing general anesthesia. Given that only parameters obtained from a monitor and the time it takes for a patient to recover consciousness will be observed, an exemption from obtaining informed consent was approved by the ethics committee.

Study Protocol Patients will undergo conventional general anesthesia without major interventions. A BIS™ anesthetic depth monitor, which is routinely used in clinical practice, will be utilized to record anesthetic depth. The anesthesiologist will be requested to document the drugs used and to maintain general anesthesia, as is normally performed at our hospital, with sevoflurane at a standard dose of 0.8 to 0.9 MAC. Once the surgery is finished and anesthetic emergence begins, the minute the sevoflurane supply is stopped will be recorded. The moment consciousness is recovered, determined by eye opening and response to verbal or tactile stimuli (as is typically done in all general anesthetics), will be recorded.

In detail, a traditional general anesthetic at the Hospital Clínico de la Universidad de Chile consists of:

• Intravenous bolus administration of fentanyl at a dose of 3 mcg/kg.
• Subsequently, intravenous lidocaine administration at a bolus dose of 1 mg/kg, followed by the administration of an intravenous bolus of propofol at a dose of 2 mg/kg.
• Once the patient loses consciousness, the NMBA IV is administered at a dose of 0.6 mg/kg of rocuronium.
• The patient is then orotracheally intubated and connected to a mechanical ventilator.
• Anesthetic maintenance is achieved with sevoflurane and repeated doses of fentanyl and/or rocuronium as needed.
• Basic and necessary monitoring at all times consists of an electrocardiogram, pulse oximetry, capnography, intermittent non-invasive blood pressure, and anesthetic depth monitoring.
• For anesthetic emergence, the effect of neuromuscular blockers must be reversed, and sevoflurane is eliminated until the patient recovers consciousness.

As this is an observational study, the clinician responsible for the patient will administer the drugs they deem necessary and perform the relevant clinical measures; we will only record these actions.

Statistics A descriptive statistical analysis will be performed for each type of variable, expressing the results as percentages, medians, or means as appropriate. The records from the anesthetic depth monitor will be analyzed using MATLAB to determine the magnitude of the power in the alpha band. The sample size was calculated assuming that the alternative hypothesis (H1) for the linear correlation between alpha power and emergence time is r² = 0.4 ± 0.3, while the null hypothesis (H0) is r² = 0. Considering a statistical power of 90%, an alpha error of 0.05, a two-tailed analysis, and a possible loss of 20% of the data, it was determined that 70 patients are required (calculation performed with G*Power 3.1.9.4). Statistical analyses will be conducted using GraphPad Prism and R.

Inclusion criteria

• Elective surgery under general anesthesia
• Age 35-50 years
• ASA physical status I-II

Exclusion criteria

• Neurological or psychiatric disorders
• Use of psychotropic drugs or opioids
• Altered consciousness
• BMI > 35 kg/m²
• Renal, cardiac, or hepatic dysfunction
• Emergency surgery
• Pregnancy
• Regional anesthesia