The aim of this clinical randomized trial is to compare local infiltration analgesia (LIA) alone versus the combination of LIA with saphenous nerve (SN) block, block of the nerve to vastus medialis (NVM), and anterior femoral cutaneous nerve (AFCN) block in participants undergoing total knee arthroplasty (TKA). The primary outcome is pain intensity, measured using the Numerical Rating Scale (NRS) at multiple time points after surgery. Secondary outcomes include opioid consumption, time to mobilization, postoperative nausea and vomiting, length of hospital stay, neurological complications and differences in opioid consumption and NRS pain scores between general and spinal anesthesia.

Scientific Rationale and Background Total Knee Arthroplasty (TKA) requires effective perioperative pain management. Traditionally, Local Infiltration Analgesia (LIA)has been the standard method, sometimes combined with femoral nerve block. However, femoral nerve block impairs quadriceps motor function, making early mobilization-critical for postoperative rehabilitation-difficult for participants.

Recent advances have introduced purely sensory nerve block techniques that preserve motor function. The knee joint innervation is complex and involves multiple neural pathways. The Saphenous Nerve (SN), Nervus Vastus Medialis (NVM), and the Anterior Femoral Cutaneous Nerve (AFCN) are all branches of the femoral nerve that provide sensory innervation to the knee without contributing to motor control of the quadriceps. The adductor canal contains the SN and NVM, which are primarily sensory nerves. The AFCN travels superficially in the femoral triangle and innervates the skin of the anterior and medial thigh.

Studies have shown that adductor canal block (targeting SN and NVM) combined with LIA provides comparable pain relief to femoral nerve block without motor impairment. Additionally, the AFCN contributes to sensory innervation of the anterolateral and anteromedial aspects of the knee joint. Our hypothesis is that combining these three sensory blocks (SN, NVM, and AFCN) with LIA may provide superior pain control and reduced opioid consumption compared to LIA alone, while preserving motor function necessary for early mobilization.

Primary Research Questions

1. Does the combination of the SN block, the NVM block of and the AFCN block togheter with LIA provide better postoperative pain control compared to LIA alone?
2. Does the above combination reduce total postoperative opioid consumption? Secondary Research Questions

1. Does the nerve block combination facilitate earlier postoperative mobilization?
2. Does it reduce the incidence of postoperative nausea and vomiting?
3. What is the incidence of neurological complications (sensory deficits and motor impairment)?
4. Does the intervention affect length of hospital stay?

Randomization and Allocation Procedure Randomization is conducted the day before surgery by the responsible anesthesiologist using a computer-generated randomization sequence. The anesthesiologist draws a sealed randomization envelope containing the group allocation. The envelope accompanies the patient's medical record and case report forms (CRFs ) throughout the hospital stay and is verified in the operating room by the anesthesiologist.

Anesthesia type (general anesthesia with propofol and remifentanil using TCI (Target Controlled Infusion) with Eleveld pharmacokinetic model, or spinal anesthesia with 0.5% bupivacaine) is determined by clinical indication and is independent of randomization.

Arms and Interventions All patients receive standardized multimodal analgesia preoperatively: etoricoxib, paracetamol, oxycodone, and betamethasone.

Intervention Arm: Nervus Vastus Medialis (NVM) block + Saphenous Nerve (SN) block + Anterior Femoral Cutaneous Nerve (AFCN) block + Local Infilration Analgesia (LIA) All nerve blocks are performed under ultrasound guidance with strict sterile precautions.

1. NVM block:

   • In-plane ultrasound approach using a linear high-frequency transducer
   • Needle inserted from the lateral thigh, placed between vastus medialis and sartorius, lateral to the adductor membrane
   • Injection: 5 ml ropivacaine 5% with clonidine 1.875 micrograms per ml
   • NVM is visualized and surrounded by local anesthetic

2. SN block:

   - Same needle entry point as NVM block

   • Needle retracted and advanced toward the lateral border of the femoral artery
   • Sartorius posterior fascia is perforated; needle tip placed beside the SN
   • Injection: 10 ml ropivacaine 0.5% with clonidine 1.875 micrograms per ml
   • Hydrodissection of the adductor canal is observed; SN is completely surrounded by local anesthetic

3. AFCN block:

   - AFCN divides into multiple branches at the level of the femoral triangle

   - Nerves are located superficially above the superior sartorius fascia in loose subcutaneous fascia

   • Typically, 3-4 individual nerve branches are visualized
   • Needle retracted in-plane from the adductor canal approach
   • Individual branches blocked superficially above sartorius
   • Injection: 1 ml ropivacaine 5% with clonidine 1.875 micrograms per ml per branch

4. LIA:

   - LIA is administered by the surgeon before wound closure

   - 150 ml ropivacaine 2 mg/ml with 0.5 mg adrenaline is infiltrated periarticular around the knee capsule, collateral ligaments, under the patella, and subcutaneously

   Control Arm: LIA Only

   - LIA is administered by the surgeon before wound closure

   - 150 ml ropivacaine 2 mg/ml with 0.5 mg adrenaline is infiltrated periarticular around the knee capsule, collateral ligaments, under the patella, and subcutaneously

   Enrollment Planned Total Enrollment: 200 patients

   Principal Investigators:

   • Fredrik Fellert, MD, DESA, EDIC, EDEC, PhD student, Senior Consultant, VO Planned Operations, Trelleborg Hospital, Lund University, Sweden

   • Andreas Ekman, MD, PhD, DEAA, Senior Consultant, VO Planned Operations, Trelleborg Hospital, Lund University, Sweden
   • Fredrik Sjövall, MD, Associate Professor, Senior Consultant, Department of Perioperative and Intensive Care, Malmö University Hospital, Lund University, Sweden
   • Gunnar Flivik, MD, Associate Professor, Senior Consultant, Department of Orthopedics, Lund university Hospital, Lund University, Sweden

   Ethical Approval Ethics Committee: Swedish Ethical Review Authority (Etikprövningsmyndigheten) Approval Reference: 2025-06626-01 Approval Date: 2025-10-30 This study is conducted in accordance with the Declaration of Helsinki and applicable Swedish regulations for clinical research, including the Act on Ethical Review of Research Involving Humans (2003:460).

   Statistical Considerations:

   A priori sample size calculation was performed using a two-sample t test with a significance level (alpha) of 0.05 and statistical power of 0.80, assuming a between-group difference of 2 points on the NRS pain scale. This yielded an estimated requirement of 90 participants per group to achieve adequate power. Data will be analyzed using SPSS. Descriptive statistics will be presented as appropriate for the distribution of each variable. Group comparisons will be performed using chi-square test or Fisher's exact test for categorical variables, and independent-samples t test or Mann-Whitney U test for continuous variables, depending on assessment of normality.

Inclusion Criteria:

-Undergoing primary unilateral total knee arthroplasty

Exclusion Criteria:

• Pregnancy
• Coagulopathy or other bleeding disorder that precludes regional anesthesia
• Allergy to local anesthetics
• Inability to understand spoken and written Swedish
• Unwillingness to participate in the study

Individual participant data will be de-identified; each patient receives a unique enrollment number. De-identified study data will be stored in an Excel spreadsheet secured behind Lund University's institutional firewall. Data will not be shared publicly. Access to anonymized datasets may be considered upon reasonable request to the principal investigators, subject to GDPR compliance and institutional review approval.

Data Availability: Results and findings will be published in peer-reviewed journals and may be presented at scientific conferences. Individual patient data will remain confidential and protected in accordance with applicable data protection regulations.

Outcome assessor blinded; staff registering NRS pain scores and opioid consumption are blinded to group allocation. No sham block is used in the control group