The primary objective of this study is to investigate the effects of ESPB on NLR and PONV. The secondary objectives are to explore whether preoperative NLR can serve as a biomarker for PONV and to examine the analgesic effects of ESPB in spinal surgery and its influence on opioid medication dosage.

This prospective, single-center, double-blind, randomized controlled study was conducted at the First Affiliated Hospital of Shandong First Medical University, a tertiary university hospital in China. The study is registered with ClinicalTrials.gov (NCT06127966) and is scheduled to commence on November 1, 2023, with an expected completion time of 2 years. The study protocol adhered to the Intervention Trial Recommendation Statement and Uniform Standard Statement for Reporting Trials to ensure accurate reporting of trial results. We used the SPIRIT reporting guidelines (14).

This study was performed at The First Affiliated Hospital of Shandong First Medical University in Jinan City, Shandong Province.

The study will include 220 patients aged 18–80 years, classified as American Society of Anesthesiologists (ASA) grade I to III planning to undergo elective prone lumbar spine surgery under general anesthesia from August 1, 2025, to September 1, 2026. Each patient will provide written informed consent and be assigned randomly to a different group based on the inclusion and exclusion criteria. All patients participating in the trial were given 3 to 5 days to learn about the study before signing the informed consent form. Preoperatively, the NLR was calculated by dividing the neutrophil count by the lymphocyte count in the complete blood count. A preoperative NLR threshold value of 2 (23–29) was accepted; the patients were divided into two groups based on values above and below 2; each group comprised 110 patients. Patients with a preoperative NLR < 2 are included in Group A (n = 110); those with a preoperative NLR > 2 are included in Group B (n = 110). Using a random number table, Group A is divided into an ESPB (EA group, n = 55) and a control group (CA group, n = 55); Group B is divided into an ESPB (EB group, n = 55) and a control group (CB group, n = 55). Randomization is achieved using a computer-generated table of random numbers (Figure 1).

The inclusion criteria are patients aged 18–80 years scheduled for elective prone lumbar spine surgery under general anesthesia, specifically including one- or two-level posterior lumbar decompression, discectomy, or posterior lumbar interbody fusion (PLIF) for degenerative conditions. These patients must have an ASA classification of grade I to III and sign informed consent forms to participate in this clinical study.

The exclusion criteria include preoperative blood transfusion, uncontrolled systemic diseases, patients with known uncontrolled systemic inflammatory diseases (e.g., rheumatoid arthritis, lupus, or active infections), gastrointestinal system disorders, history of antiemetic (15) and anticholinergic drug use, history of adverse reactions related to surgery, deformity correction surgeries, defined as procedures involving instrumentation across three or more levels or aimed at correcting scoliosis or kyphosis, infection at the puncture site, coagulation disorders, long-term use of sedatives and analgesics before surgery, psychiatric disorders, language communication barriers, allergy to ropivacaine, involvement in other clinical studies in the last 3 months, history of previous lumbar surgery, and unwillingness to participate in this study.

For patients undergoing posterior lumbar spine surgery under general anesthesia, a researcher will assess whether the patient meets this study’s inclusion and exclusion criteria 1 day before the surgery. The participants who meet the inclusion criteria must sign an informed consent form after being fully informed of the study procedures, potential benefits, and risks. Preoperatively, the NLR will be calculated by dividing the neutrophil count by the lymphocyte count. The pre-calculated NLR threshold of 2 will be accepted. Patients with a preoperative NLR < 2 will be included in Group A (n = 110); those with a preoperative NLR > 2 will be included in Group B (n = 110). Using a random number table, Group A will be divided into ESPB (EA group, n = 55) and control groups (CA group, n = 55); Group B will be divided into ESPB (EB group, n = 55) and control groups (CB group, n = 55). The researcher will allocate the drugs using an envelope method to conceal the randomization sequence; a specially trained anesthesia nurse will deliver the implementation plan to the corresponding operating room before surgery.

Upon entering the operating room, standard intravenous access will be established; noninvasive blood pressure, electrocardiogram, and oxygen saturation (SpO₂) will be monitored. Considering that most patients undergoing this surgery are older and positioned prone, radial artery catheterization will be performed using the FloTrac sensor to enable invasive blood pressure monitoring and ensure patient safety. All patients will receive total intravenous anesthesia.

With the patient in the supine position, a face mask will be used for oxygenation and denitrogenation for 3 min before anesthesia induction. Anesthesia induction will include midazolam (0.02 mg/kg), sufentanil (0.2–0.3 μg/kg), propofol (1.5–2 mg/kg), and atracurium (0.6 mg/kg). After the disappearance of the eyelash reflex and jaw relaxation, tracheal intubation will be performed using a visual laryngoscope, and the endotracheal tube will be secured. Mechanical ventilation will be initiated by adjusting respiratory parameters.

After positioning the patient in the prone position, the appropriate lumbar vertebral level will be identified based on preoperative surgical markings using either surface landmarks or ultrasound. The ESPB will be performed bilaterally under ultrasound guidance based on the planned surgical levels. For single-level lumbar surgery (e.g., L3–L4), the block is administered at the transverse process of the upper vertebra (e.g., L3). For two-level surgery (e.g., L3–L5), the block is performed at the middle level (e.g., L4) to ensure optimal spread of local anesthetic. The skin at the puncture site will be disinfected with iodine. An ultrasound low-frequency convex array probe with a sterile sheath will be placed in the parasagittal direction, 3 cm lateral to the midline. The lumbar transverse process, overlying erector spinae, and latissimus dorsi muscles will also be identified. The needle will be advanced in-plane; upon contact with the bony transverse process, confirmation of the correct needle position will be obtained by aspirating 2–3 mL of isotonic saline for hydrodissection. In both EA and EB groups, 20 mL of 0.5% ropivacaine will be administered on each side for the lumbar transverse process surface, providing bilateral ESPB. In the CA and CB groups, 20 mL of 0.9% saline will be administered on each side under ultrasound guidance to the lumbar transverse process surface, serving as a control.

Anesthesia maintenance will utilize propofol (4–6 mg/kg/h) and remifentanil (12–20 μg/kg/h), targeting a BIS range of 40–60. Blood pressure and heart rate will be maintained within 20% of the preoperative baseline values, with adjustments made according to surgical needs. Atracurium will be added intermittently to maintain muscle relaxation. Ten minutes before the end of the surgery, the infusion of anesthetic drugs will be stopped; nonsteroidal anti-inflammatory drugs will not be administered to any patient before the incision or at the end of the surgery. If blood pressure and heart rate variations exceed 20% of the preoperative values, the corresponding medications (5 mg ephedrine, 0.2 mg atropine, 20 mg esmolol, or 0.5 mg nitroglycerin) will be administered promptly. Considering that glucocorticosteroids, such as dexamethasone, may affect the NLR values, they were not considered preoperatively or postoperatively (16).

All patients will receive a standardized 48-h postoperative patient-controlled intravenous analgesia (PCIA) regimen to ensure consistency in analgesic management and allow for objective assessment of analgesic efficacy and opioid consumption. The PCIA formulation will consist of 2 μg/kg sufentanil, 16 mg ondansetron, and 0.9% saline to a total volume of 100 mL. The PCIA device will have a background infusion rate of 2 mL/h, a bolus dose of 2 mL, and a lockout interval of 15 min with no background dose. The patients will be transferred to the PACU for postoperative recovery. If the Visual Analogue Scale (VAS) score at rest is ≥4, the patient or nurse anesthetist will press the PCIA button to administer the drug until the VAS score is <4. If the VAS score remains >4 after three consecutive presses (15 min between presses), the PCIA pump may be gradually adjusted upward in a single dose on demand until the patient’s VAS score is <4. After the pain episodes finish, the PCIA settings will be readjusted to the original parameters. Pain assessments will be conducted every 6 h. Postoperative follow-up data will be collected by designated personnel.

Demographic and clinical data will be collected from all patients, including age, sex, height, weight, body mass index, ASA classification, surgery duration, the intraoperative consumption of drugs, such as propofol and remifentanil, and total analgesic consumption in the first and second 24-h periods postoperatively. Nausea, vomiting, and antiemetic requirements will be recorded in the PACU for the first and second 24-h periods postoperatively. The VAS scores will be recorded at rest and during movement at 2, 4, 6, 8, 12, 24, and 48 h postoperatively. The time of the first pressing of the analgesic pump will be documented. The rescue analgesia rate and analgesic satisfaction scores will be assessed at 24 and 48 h postoperatively. Postoperative satisfaction will be evaluated (0 = dissatisfied, 1 = average, 2 = satisfied, and 3 = very satisfied). Postoperative awakening and extubation time will be recorded. The extubation criteria are that the patient resumes spontaneous breathing with a tidal volume ≥7 mL/kg, demonstrates swallowing reflex, and can follow instructions, maintaining SpO₂ above 90%. The duration of the postoperative PACU stay and discharge time will be recorded. The occurrence rates of opioid-related side effects will be recorded, including dizziness and urinary retention. The serum NET levels will be measured. In this study, we will assess NETs levels indirectly by quantifying cell-free double-stranded DNA (cf-dsDNA) in serum using the PicoGreen dsDNA quantitation method. Serum samples (5 mL) are collected, centrifuged, and stored at −20 °C. The working dye solution is prepared by diluting PicoGreen reagent 1:200 in TE buffer. A standard curve is constructed using serial dilutions of calf thymus DNA. Equal volumes of diluted sample and dye are mixed and incubated in the dark at room temperature for 5 min. Fluorescence intensity is measured using a fluorescence microplate reader, and the cf-dsDNA concentration (ng/mL) is calculated using the standard curve. This measurement serves as an indirect indicator of NET formation in the postoperative period.

Throughout the study, data will be gathered and managed securely and privately. Data will be collected automatically via the anesthetic information system and vital sign monitoring system. A nursing anesthetist will also collect some data manually. Participants will be identified throughout the study using code numbers rather than names unless otherwise specified. All relevant records and files will be archived for 5 years. During the study, the data will be accessible only to researchers who have signed confidential disclosure agreements and institutional or government auditors. Data without patient identification will be accessible to the general public after the study concludes.

There will be no patient or public involvement in the conduct, reporting, or dissemination of this research.

The post-enrollment timeline starts when the patient enters the operating room and ends when the patient leaves the PACU. All relevant variables will be recorded by individuals who are unaware of the grouping. The follow-up staff will evaluate the patient’s postoperative nausea and vomiting 48 h after the surgery to assess the relevant situation (Table 1).

To calculate the sample size for the primary research objective, use the “Tests for Two Ordered Categorical Variables” module in PASS software. Set the test power to 1 − β = 0.8 and significance level α = 0.05; use a 1:1 ratio between the NLR < 2 and NLR ≥ 2 groups. For the NLR < 2 group, the composition ratios of the PONV states considered as no, nausea, retching, and vomiting are 0.575, 0.050, 0.001, and 0.375, respectively. For the NLR ≥ 2 group, the composition ratios for PONV no, nausea, retching, and vomiting are 0.250, 0.100, 0.050, and 0.600, respectively. The calculated sample size is 94 cases, considering a 10% dropout rate. The final sample size is 106, with 53 patients in each group.

Use the “Tests for Two Proportions” module in PASS software to calculate the sample size for one of the secondary objectives: determining whether preoperative NLR can serve as a biomarker for PONV. Set the test power to 1 − β = 0.8 and significance level to α = 0.05; use a 1:1 ratio between the control and thoracic paravertebral nerve block groups. Nausea and vomiting rates are 8.3 and 33.3%, respectively. The calculated sample size is 82, considering a 10% dropout rate. The final sample size is 92, with 46 patients in each group.

The baseline NLR levels are first divided into two strata, and randomization is performed within each stratum. The sample size of each group in this study is 55.

Patients are grouped using block randomization; drug blinding is conducted by specialized personnel who are not directly involved in the clinical trial. Block randomization will be performed using random number tables generated by the SAS statistical software.

This trial is designed to be double-blinded; both the participants and follow-up personnel will be unaware of the group assignments. The overall randomization table is maintained by the personnel responsible for the statistics. The researchers prepare the drugs using an overall randomization table. Postoperative follow-up is conducted by anesthesia nurses who have received specialized training. Unblinding is conducted according to the normal procedures if no emergencies occur during the study. After the trial concludes, the Clinical Report Form (CRF) will be checked. Following signatures, unblinding will be performed to determine the group assignments of the study participants for statistical analysis and evaluation of efficacy differences between the experimental and control groups. Emergency unblinding is allowed only when the study drug affects the treatment or safety of the study participants. The principal investigator will be notified, and emergency unblinding will be performed based on the drug information provided in the emergency letter. This information will be noted in the CRF.

All data will be statistically analyzed using SPSS software (version 25.0). Continuous variables such as VAS scores will be represented by the mean ± standard deviation if they follow a normal distribution. An independent sample t-test will be employed to compare intergroup differences. If the data do not conform to a normal distribution, the Wilcoxon rank-sum test will be used to compare groups.

For categorical variables, such as sex, the chi-squared or Fisher’s exact test will be used to assess intergroup differences. For ordinal data, such as the degree of vomiting, the Wilcoxon rank-sum test will be used for between-group comparisons.