The present prospective within-subject observational study will evaluate whether unilateral brachial plexus block (BPB) induces measurable lateralized autonomic modulation, assesses using bilateral Nociception Level (NoL) monitoring during standardized intraoperative stimuli under general anesthesia. Regional anesthesia efficacy is traditionally assessed through sensory and motor examination. However, objective physiologic markers reflecting sympathetic modulation remain limited. Forty five adults undergoing upper extremity surgery with BPB and general anesthesia, bilateral NoL monitoring will be performed during local anesthetic injection, endotracheal intubation, and nasogastric tube placement. The primary aim to investigate whether the brachial plexus block induces unilateral modulation of post-operative nervous system activity, assessed by inter-limb differences in NoL values during predefined nociceptive stimuli under general anesthesia. The secondary aim to evaluate the correlation between postoperative metrics, postoperative pain intensity, and analgesic consumption. From a clinical perspective, bilateral autonomic monitoring may offer a novel adjunctive method for intraoperative confirmation of block activity, particularly in sedated or anesthetized patients where traditional sensory testing is not feasible. Furthermore, inter-limb autonomic gradients could represent a future research pathway for objective assessment of regional anesthesia effectiveness beyond subjective pain scores.

The hypotheses is that brachial plexus block (BPB) would induce an ipsilateral reduction in SANS activity compared to the contralateral side. The study intervention involved the standard administration of the BPB, a low-risk perineural injection of local anesthetics, conducted under real-time ultrasound guidance and monitored using NoL score measurements on both hands concurrently during endotracheal intubation. An ultrasound-guided single-shot BPB will be performed using 10 mL of 0.5% bupivacaine (50 mg) in all patients. The study duration for each participant approximately 5 hours. All participants undergo induction of general anesthesia using a standardized regimen: midazolam 0.025 mg/kg and fentanyl 0.25 mcg/kg prior to BPB, followed by propofol 2.5 mg/kg, fentanyl 0.75-1 mcg/kg, and rocuronium 0.7 mg/kg. Subsequently, participants will be intubated (including nasogastric tube placement) and ventilated with maintenance inhalational anesthetics, supplemented by continuous intravenous administration of the short-acting opioid remifentanil at doses of 30-70 ng/kg/min, adjusted according to hemodynamic parameters. Block efficacy will be assessed using postoperative pain (visual analog scale (VAS)), analgesic consumption, intraoperative analgesic consumption, and NoL measurements in the non-operated hand. In instances of suboptimal or failed block, all patients in this study will be provided with a backup perioperative analgesic regimen involving continuous intravenous administration of short-acting opioids and remifentanil at doses of 30-70 ng/kg/min .Safety assessments• Pre-anesthetic evaluation and eligibility for general and regional anesthesia• Standard monitoring will be performed according to the American Society of Anesthesiologists (ASA) o Pulse oximetry o Non-invasive blood pressure repeated measurement so 5-lead ECGo End tidal CO2• The principal investigator will assess adverse and serious adverse events, including identification, follow-up, documentation, and reporting to the IRB. Statistical analysis Primary Endpoint: The statistical null hypothesis posited that there would be no spatial differences in the NoL score measurements following BPB. Conversely, hypothesized that patients undergoing upper extremity surgery would exhibit lower ipsilateral hand NoL scores than the contralateral hand during noxious stimulation after BBP. Secondary Endpoints: The null hypothesis proposed that there would be no correlation between the NoL score measurements post-BPB and postoperative pain levels. Alternative hypothesis that a correlation exists between the contralateral hand NoL scores and postoperative pain levels in patients undergoing upper extremity surgery after BPB. Sample Size Determination Sample size calculation based on the primary endpoint, defined as the paired difference in NoL values between the blocked (ipsilateral) and contralateral limbs during endotracheal intubation. Based on preliminary observations and previously reported NoL variability, it is assumed that an expected mean paired difference of approximately 7 units, with a standard deviation of paired differences of 8 units. Using a two-sided paired t-test with a significance level (alpha) of 0.05 and a statistical power of 80%, a minimum of 34 evaluable subjects will be required. To account for potential exclusions and incomplete data, 45 participants are planned for enrollment. Statistical analysis This study will employ a prospective within-subject comparison design. Continuous variables will be presented as mean ± standard deviation, and categorical variables presented as counts and percentages. A pragmatic sample size was chosen based on the feasibility of previous NoL studies using within-subject designs. The study aims to enroll 45 patients to allow paired comparisons between the blocked and contralateral limbs during predefined nociceptive stimuli. The primary analysis based on paired comparisons of within-subject differences in NoL values between the blocked (ipsilateral) and non-blocked (contralateral) hands for each predefined stimulus (brachial plexus block injection, endotracheal intubation, and nasogastric tube placement). NoL index measured by a non-invasive probe attached to the index finger (in both arms, the operated hand and the contralateral unoperated arm as control) using an adhesive patch. The device manufactured by Medasense (Ramat Gan, Israel). The monitoring module model PMD-200. The device is indicated for assessing pain levels in unconscious patients. Paired t-tests were used for the comparisons. Secondary exploratory analyses will evaluate the correlations between aggregated intraoperative NoL exposure, expressed as the percentage of total monitoring time spent within predefined NoL ranges (lower than 10, 10-25, and higher than 25), and postoperative pain outcomes, including VAS scores and analgesic consumption. Pearson's correlation coefficients will be calculated for these analyses. All statistical tests two-sided, and a P value <0.05 will be considered statistically significant. Variables Independent variables: discrete variable• gender (male/female)• operated hand (left/right)continuous variables:• age (years)• weight (kg)• height (cm)• ASA score Dependent variables: discrete variables• VAS (1-10) continuous variables Anesthesia induction times (HH:MM)• Patient entering the room • Performing BPB • Performing intubation post operative• Nasogastric tube• Induction completed• Surgery and recovery times (HH:MM)• Surgery start• Surgery end• Transfer to Post Anesthetic Care Unit (PACU)• Discharge from PACU• NoL levels difference between right- and left-hands during anesthesia induction• Peak levels differences (NoL index values)• After BPB• After intubation• After nasogastric tube placement• Time of peak levels differences (seconds)• After BPB• After intubation• After nasogastric tube placement• Left-right difference between duration of NoL index higher than 25 (seconds)• NoL levels in non-operated hand from patient entering the operating room to discharge from the PACU (NoL index values temporal variations)• Total time of NoL index higher than 25 (min)• Total time of NoL index between 10-25 (min)• Total time of NoL index lower than 10 (min)• Analgetic treatment • Perioperative total Remifentanil consumption (mg)• Post operative Morphine consumption (mg)• Peri and post operative Non-Steroidal-Anti-Inflammatory Drugs (NSAIDs) consumption• Paracetamol (g)• Ketorolac (mg)• Dipyrone (g)

Inclusion Criteria:

• Age >18
• Upper extremity surgery
• Provision of signed and dated informed consent forms

Exclusion Criteria:

• Pregnant women
• Known allergic reaction to bupivacaine or other anesthetic medicine: Midazolam, Fentanyl, Propofol, Rocuronium, Remifentanil, Sevoflurane)
• Known coagulopathy resulting in bleeding tendency
• Thrombocytopenia
• Abnormal laboratory coagulation tests in the previous week = Anticoagulation therapy Participation in other study

forty five patients over 18 years old meeting inclusion criteria

Afer completion of study and publication, data may be concidered to be shared