Comparing Two Nerve Block Methods for Pain Relief in Laparoscopic Hernia Surgery

The lifetime incidence of inguinal hernia is 27% in men and 3% in women. The primary treatment is surgical intervention. Postoperative pain is defined as acute pain that begins with surgical trauma and gradually decreases with tissue healing. As with all surgical procedures, the treatment and control of pain following inguinal hernia repair are of great importance. Adequate pain control enables faster recovery, reduces thromboembolic complications through early mobilization, decreases pulmonary complications by preventing restrictions in respiratory movements, sputum expectoration, and cough reflex, minimizes metabolic and endocrine stress responses, preserves cognitive functions, reduces the risk of chronic pain development, and shortens the duration of hospital stay. Preventing acute postoperative pain will also reduce the probability of chronic pain development.

In anesthetized patients, accurate pain assessment is crucial for the anesthesiologist to adjust analgesic drug levels. While adequate analgesic levels are critical to prevent unexpected movements, cardiovascular complications resulting from sympathetic reactions, and the development of pain memory, limiting dosage to the minimum effective level is desirable to avoid opioid-induced hyperalgesia, drug side effects, and to achieve shorter perioperative durations.

It is suggested that intraoperative hemodynamic and stress responses, as well as postoperative chronic pain syndromes, are primarily caused by the poor control of nociceptive conditions. Techniques have been developed for more effective monitoring of the analgesia component of anesthesia to guide the administration of analgesics in order to provide an appropriate balance of nociception and antinociception. Nociception monitoring can be achieved through "central nervous system-based," "autonomic nervous system-based," and "spinal reflex-based" monitors. Autonomic nervous system-based monitors include pupillometry, the Analgesia Nociception Index (ANI), the Surgical Pleth Index, the Nociception Level Index, and skin conductance monitors.

The Analgesia Nociception Index (ANI) monitor is derived from heart rate variability, ranging from 0 (maximal nociception) to 100 (maximal analgesia) to reflect the analgesia/nociception balance during general anesthesia, and it detects changes in sympathovagal balance caused by surgical stimuli in the heart rhythm. Higher ANI values represent higher parasympathetic activity and likely less pain. Pain monitors not only help us avoid unnecessary opioid consumption but also assist in reducing opioid-related side effects such as nausea-vomiting, urinary retention, opioid-induced hyperalgesia, and physical dependence.

The incidence of chronic postoperative pain in patients undergoing inguinal hernia repair has been observed to be approximately 22.3% at the 3rd month. Chronic pain development affects the patients' mood and daily living activities. Although there are many mechanisms in the pathology of chronic pain formation after inguinal hernia surgery, research has shown that the preemptive blockade of the iliohypogastric-ilioinguinal nerves is effective in reducing the incidence of postoperative acute and chronic pain.

While there are studies in the literature concerning acute pain development in patients undergoing open inguinal hernia repair who received either quadratus lumborum (QL) block or iliohypogastric-ilioinguinal nerve block, there is no study comparing the efficacy of preemptive applications of both blocks on intraoperative opioid consumption, acute pain, and chronic pain in laparoscopic inguinal hernia repair.

Quadratus lumborum block (QLB) application is one of the truncal blocks preferred in recent years in abdominal surgeries, providing effective analgesia. There are four different types: anterior, posterior, lateral, and intramuscular QLB. In a cadaver study conducted with methylene blue for anterior QLB application, it was observed that the ilioinguinal and iliohypogastric nerves were generally stained with methylene blue, and the genitofemoral nerve was stained at a low rate. Therefore, in patients undergoing inguinal hernia repair, the anterior quadratus lumborum block may be more effective than the ilioinguinal-iliohypogastric block in the treatment and prevention of acute pain.

In the literature, no study has been found that investigates the intraoperative follow-up guided by ANI monitoring and the effects on acute and chronic pain development of preemptive QLB and iliohypogastric-ilioinguinal nerve block applications in patients undergoing laparoscopic inguinal hernia repair. In this study, the remifentanil infusion will be titrated based on the nociception measured in the patient against painful stimuli caused by surgery via the Analgesia Nociception Index (ANI) monitor. It is expected that the amount of intraoperative opioid consumption will be lower due to the effect of the preemptive block applied to the patient. It is also expected that the incidence of acute and chronic pain will be lower in the group that requires less opioid during the intraoperative period. In the postoperative period, the amount of fentanyl (opioid) consumed and demanded via PCA (patient-controlled analgesia) is also expected to be lower in direct proportion to the group requiring less opioid during the intraoperative period. If these hypotheses are realized, we aim to ensure less postoperative opioid consumption, prevent the side effects of opioids, and reduce the incidence of acute and chronic pain.

Study Design:

The study is designed as a prospective, randomized, double-blind, two-parallel-group clinical trial. Following preoperative evaluation and randomization, patients will be monitored intraoperatively and throughout the first 24 hours postoperatively, with a follow-up assessment for the incidence of chronic pain at the fourth postoperative month. Randomization will be managed by the principal investigator. Patients will be enrolled in the study based on their order of participation using the specified web-based randomization tool. The investigator responsible for randomization will inform the practitioner administering the preemptive block regarding the assigned study arm. The anesthesiologist providing intraoperative and postoperative care will be blinded to the type of block performed. At the fourth postoperative month, patients will be assessed for chronic pain development by an anesthesiologist other than the principal investigators; the randomization code will be unblinded only at the data analysis stage.

Inclusion Criteria:

Patients who have not undergone previous inguinal hernia surgery Age 18 and over ASA physical status I-III BMI: 18-30 kg/m² Literate No known cognitive impairment Patients who are willing to participate in the study and provide informed consent No history of chronic pain and no chronic analgesic or opioid use

Exclusion Criteria:

Age under 18 ASA physical status IV or higher BMI > 30 kg/m² Presence of any chronic pain Chronic opioid consumption Known cognitive impairment Illiterate Visual or hearing impairment Infection at the injection site Coagulopathy Chronic hepatic or renal failure Peripheral neuropathy Allergy to local anesthetics Cardiac rhythm disorders, central/autonomic nervous system diseases, or presence of a pacemaker Use of medications that affect cardiac autonomic regulation

Randomization:

To minimize bias, 66 patients who meet the inclusion criteria and consent to participate will be randomized into two groups using the "Study Randomizer" (https://www.studyrandomizer.com) software, with volunteer codes assigned from G1 to G66. Stratification will not be performed during randomization. Once patients consent to participate, the investigator responsible for randomization will inform the practitioner who will perform the preemptive block regarding the assigned study arm. The anesthesiologist providing intraoperative and postoperative care will be blinded to the type of block performed. At the fourth month postoperatively, patients will be assessed for chronic pain development by an anesthesiologist other than the principal investigators; the randomization code will be unblinded only at the data analysis stage.

Study Arms and Investigational Products:

Group Quadratus Lumborum Block (Group QLB): Three trocars are placed for laparoscopic inguinal hernia repair. Two are positioned suprapubically and between the pubis and umbilicus, while the third trocar is placed in the contralateral periumbilical area. The procedures to be performed on patients in the "Group Quadratus Lumborum Block" are as follows:

Anterior Quadratus Lumborum Block on the side of the inguinal hernia repair (20 ml, 0.25% bupivacaine).

Rectus sheath block on the side of the third trocar entry (10 ml, 0.25% bupivacaine).

The total dose of local anesthetic was calculated to remain below the toxic dose.

Following the induction of general anesthesia:

1. For Anterior Quadratus Lumborum Block: Skin disinfection will be performed under aseptic-antisepsis standards. A convex ultrasound probe will be placed in the transverse plane at the posterior axillary line, cranial to the iliac crest. The "Shamrock sign," formed by the transverse process of the L4 vertebra, the psoas major muscle, the quadratus lumborum muscle, and the erector spinae muscle, will be visualized. The target zone for injection is the fascial plane between the quadratus lumborum and psoas major muscles. Using an in-plane approach, the block needle will be advanced from the posterior plane of the probe towards the thoracolumbar fascia anteriorly, targeting the plane between the quadratus lumborum and psoas major muscles. After a negative aspiration test with a 100 mm block needle, 2-3 ml of saline will be injected to verify needle tip placement via hydrodissection, followed by the administration of 20 ml of 0.25% bupivacaine.
2. For Rectus Sheath Block:

Skin disinfection will be performed under aseptic-antisepsis standards. A linear transducer will be placed transversely above the umbilicus, 1 cm lateral to the midline, to visualize the rectus abdominis muscle and the posterior rectus sheath.

A 100 mm block needle will be advanced in-plane through the rectus abdominis muscle until the tip reaches the space between the muscle and the posterior rectus sheath. After a negative aspiration test, 2-3 ml of saline will be injected to confirm position via hydrodissection, followed by the administration of 10 ml of 0.25% bupivacaine.

In the absence of contraindications, dexketoprofen 50 mg will be administered as an infusion at the start of surgery, and paracetamol 1 g IV will be administered 30 minutes before the end of surgery. Ondansetron 8 mg will be administered before extubation as an antiemetic. Dexamethasone 8 mg and pantoprazole 40 mg will be administered IV at the start of surgery.

Postoperative Analgesia Management:

A patient-controlled analgesia (PCA) device with fentanyl will be prepared, set to a 25 mcg bolus with a 15-minute lockout interval.

Patients will be instructed in the postoperative recovery unit to use the PCA device when their NRS-11 (Numeric Rating Scale) score is 4 or higher. If the patient's pain remains at an NRS score of 4 or higher despite using the device as instructed, 1 g of paracetamol will be administered IV as a rescue analgesic. If the pain score remains at 4 or higher 30 minutes after the completion of the paracetamol infusion, 50 mg of dexketoprofen will be administered as an infusion.

The total amounts of paracetamol, dexketoprofen, and fentanyl consumed by the patient will be monitored for 24 hours postoperatively.

Group Iliohypogastric-Ilioinguinal Nerve Block (Group ISB): Three trocars are placed for laparoscopic inguinal hernia repair. Two are positioned suprapubically and between the pubis and umbilicus, and the third is placed in the contralateral periumbilical area. Local anesthetic infiltration (a total of 5 ml of 0.25% bupivacaine) for the two trocars located suprapubically and between the umbilicus and pubis will be performed by the surgeon. A rectus sheath block will be performed on the side of the third trocar. The procedures to be performed on patients in the "Group Iliohypogastric-Ilioinguinal Nerve Block" are as follows:

Iliohypogastric-ilioinguinal nerve block on the side of the inguinal hernia repair (15 ml, 0.25% bupivacaine).

Rectus sheath block on the side of the third trocar entry (10 ml, 0.25% bupivacaine).

Local anesthetic infiltration at the first two trocar sites (5 ml, 0.25% bupivacaine).

Following the induction of general anesthesia:

1. For Iliohypogastric-Ilioinguinal Nerve Block: Skin disinfection will be performed under aseptic-antisepsis standards. A high-frequency linear ultrasound probe will be placed on an imaginary line between the anterior superior iliac spine (ASIS) and the umbilicus, moving medially and cephalad. The external oblique, internal oblique, and transversus abdominis muscles will be visualized. The ilioinguinal and iliohypogastric nerves will be visualized as hypoechoic structures within the fascia between the internal oblique and transversus abdominis muscles. The deep circumflex iliac artery may also be observed alongside the nerves; color Doppler should be used to differentiate the artery and avoid intravascular injection. After a negative aspiration test with a 50-100 mm block needle, 2-3 ml of saline will be injected to confirm position via hydrodissection, followed by the administration of 15 ml of 0.25% bupivacaine.
2. Subsequent Rectus Sheath Block:

Following the same procedures as in the QLB group, a rectus sheath block will be performed (10 ml, 0.25% bupivacaine).

Local anesthetic infiltration (total of 5 ml, 0.25% bupivacaine) at the two trocar sites will be performed by the surgeon.

(The postoperative analgesia management and adjuvant drug protocols are identical to the Group QLB protocol.)

Anesthesia Procedures:

Patients will be evaluated by an anesthesiologist for routine preoperative assessment, informed consent, and patient education. Patients who consent to participate will be provided with detailed information, and all their queries will be addressed. The study is planned as a prospective, randomized, double-blind clinical trial. It will be conducted on a total of 66 patients aged 18 and older, scheduled for inguinal hernia repair, with an American Society of Anesthesiologists (ASA) physical status of I-III. Following the recording of demographic data, standard ASA monitoring (non-invasive blood pressure, ECG, SpO2, EtCO2) will be supplemented by BIS and ANI monitoring, and general anesthesia will be induced. (The BIS device monitors depth of anesthesia via brain waves, while the ANI monitor is used in our operating theater to assess nociception and intraoperative pain status). General anesthesia will be induced with 1 mcg/kg fentanyl, 1 mg/kg lidocaine 2%, 1-3 mg/kg propofol (titrated under BIS guidance), and 1 mg/kg rocuronium. Airway security will be maintained via an endotracheal tube. Anesthesia will be maintained with propofol and remifentanil infusion. The starting infusion dose for remifentanil will be 0.04 mcg/kg/min.

Immediately following induction, patients will be randomized into the "Group Quadratus Lumborum Block (Group QLB)" and "Group Iliohypogastric-Ilioinguinal Nerve Block (Group ISB)" based on the randomization result obtained via the designated web-based tool (https://www.studyrandomizer.com).

Group QLB: 15 minutes prior to the start of surgery, patients will receive a unilateral anterior Quadratus Lumborum Block under general anesthesia on the side of the hernia repair. Additionally, a rectus sheath block will be performed for analgesia at the third trocar entry site. In the absence of contraindications, 50 mg IV dexketoprofen, 8 mg IV dexamethasone, and 40 mg IV pantoprazole will be administered at the start of surgery. Paracetamol 1 g IV will be administered 30 minutes before the end of surgery, and 8 mg ondansetron will be administered before extubation as an antiemetic.

Group ISB: Patients will receive an iliohypogastric-ilioinguinal nerve block under general anesthesia before the start of surgery. Additionally, a rectus sheath block will be performed for analgesia at the third trocar entry site. Local anesthetic infiltration will be performed by the surgical team at the first two trocar sites for preemptive analgesia. In the absence of contraindications, 50 mg IV dexketoprofen, 8 mg IV dexamethasone, and 40 mg IV pantoprazole will be administered at the start of surgery. Paracetamol 1 g IV will be administered 30 minutes before the end of surgery, and 8 mg ondansetron will be administered before extubation as an antiemetic.

In both groups, propofol infusion will be titrated to maintain a BIS value between 40 and 60.

Remifentanil Infusion Protocol: The starting infusion dose of remifentanil will be 0.04 mcg/kg/min. Mean ANI (ANIm) values typically fluctuate between 50 and 70 when adequate analgesia is achieved. An ANIm <50 indicates insufficient analgesia, while an ANIm >70 indicates excessive analgesic dosage. Therefore, if ANIm <50, the remifentanil infusion rate will be increased by 0.04 mcg/kg/min; if ANIm >70, the rate will be decreased by 0.04 mcg/kg/min. No changes will be made if the ANIm remains between 50 and 70.

Vital signs (blood pressure, heart rate, SpO2), BIS, ANIi, and ANIm values will be recorded at specified intervals (as outlined in the Intraoperative Routine Follow-up Form-1 and Form-2). The remifentanil infusion rate will be adjusted based on the ANIm value obtained every 4 minutes. Considering the onset of action of remifentanil, the ANIm will be re-evaluated after 4 minutes. If the ANIm remains outside the 50-70 range, the infusion rate will be adjusted again, and the response will be re-assessed after another 4 minutes. This process will continue until the ANIm is stabilized within the 50-70 range.

At the end of surgery, the total amount of propofol and remifentanil infused, as well as the minimum ANI mean value and its time of occurrence, will be recorded.

Perioperative Data Collection:

Intraoperative Data: For all patients, the following parameters will be recorded: blood pressure, heart rate, SpO2, BIS, ANIi, ANIm, the infusion rates of administered drugs, and any medication administration affecting the heart rate. Measurements will be taken at the following time points: before and after anesthesia induction; every 4 minutes after block administration; 15 minutes after block completion (before the first trocar insertion); 2 and 4 minutes after the insertion of all trocars and initiation of insufflation; before the dissection of the hernia sac; 2 and 4 minutes after the dissection of the hernia sac; 2 and 4 minutes after the completion of mesh placement; at the end of surgery; before extubation; 4 minutes after extubation; and at 4-minute intervals following the completion of the block. The total infused doses of propofol and remifentanil will be recorded at the end of surgery. Patients who require intraoperative medications that affect the heart rate, such as esmolol (Brevibloc), atropine, nitroglycerin, or ephedrine, will be excluded from the study.

Postoperative Data: All patients will be monitored using a data tracking form, starting from the recovery unit, with patient-controlled analgesia (PCA) using fentanyl. The PCA device will be set to a 25 mcg bolus dose with a 15-minute lockout interval.

Postoperative Follow-up: Data will be collected at the following time points: admission to and discharge from the Post-Anesthesia Care Unit (PACU), and at 2, 4, 6, 12, and 24 hours postoperatively (or at the time of hospital discharge). The parameters to be assessed include blood pressure, heart rate, SpO2, NRS scores at rest and during movement, nausea and vomiting, urinary retention, total fentanyl consumption, requirement for rescue analgesics, time to first mobilization, and patient/surgeon satisfaction (using a Likert scale).

Patients will be evaluated for chronic pain in the fourth postoperative month. NRS scores at rest and during movement will be assessed, and the S-LANSS (Self-Report Leeds Assessment of Neuropathic Symptoms and Signs) questionnaire will be administered to all patients.