2.1

Study design

Before the enrolment process, our local research ethics committee approved this prospective, randomized, and double-blind clinical trial (Approval number: 17,101,419 on May 6, 2021), and it was registered with the ClinicalTrials.gov.

The study began on May 20, 2021, and finished on July 31, 2023. It followed the Consolidated Standards of Reporting Trials (CONSORT) statement and was done in compliance with the Declaration of Helsinki-2013, with each patient providing written valid consent prior to participation.

Ninety-seven adult patients, aged from 18 to 65 yrs, with American Society of Anesthesiologists (ASA) physical status I – II, and scheduled for elective ACLR under spinal anesthesia were assessed for eligibility ( Fig. 1 ).

CONSORT flow diagram of participants. ACB group, adductor canal block group; IA group, intra-articular group.

Exclusion criteria were patient refusal, pregnancy, chronic opioid use or chronic pain syndrome, prior neuropathies, contraindications to peripheral nerve block (infection at the site of injection, coagulopathy, or allergy to local anesthetics), presence of cardiorespiratory or cerebrovascular illnesses, sever hypertension, diabetes mellitus, kidney or liver impairment.

2.2

Randomization and blinding

Patients were randomly allocated into two equal groups ( n = 36) based on a computer-generated randomization program in a double-blinded manner using opaque envelopes. Patients in the ACB group received an ACB with bupivacaine and dexamethasone 30 min before spinal anesthesia and sham intra-articular (IA) normal saline at the end of the operation. In IA group, patients received sham ACB with normal saline 30 min before spinal anesthesia and IA bupivacaine and dexamethasone at the end of the operation.

On the day of surgery, an anesthetist not involved in the study opened the envelopes and prepared the study solutions by the enrollment sequence.

The enrolled subjects, surgery nurse, surgeon, supervising anesthesiologist, and postoperative follow-up investigator were all blind to the group assignments.

2.3

Interventions and anesthesia

Standard monitoring, which includes non-invasive blood pressure, pulse oximetry, and electrocardiography (ECG), was initiated as soon as the patient entered the block procedure room. Patients were then premedicated with intravenous (IV) fentanyl 25 μg and IV midazolam 0.02 mg/kg for pain relief and anxiety reduction after a 22 G peripheral IV cannula insertion. Following this, patients were positioned supine with the surgical limb externally rotated at the hip and the knee flexed in preparation for the block procedure. The block site for each patient was sterilized using isopropyl alcohol swabs and chlorhexidine gluconate.

In the ACB group, an experienced anesthesiologist performed the ACB under ultrasound (US) guidance. To visualize the superficial femoral nerve in a short axis, a sterile high-frequency linear array transducer (13–6 MHz, SonoSite S-Nerve; SonoSite Inc., Bothell, WA, USA) was placed on the medial aspect of the mid-thigh. 1–2 ml of 1 % lidocaine was used to anesthetize the skin. Then, a 19-gauge, 100-mm insulated facet tip needle (SonoLong NanoLine cannula; Pajunk® GmbH, Geisingen, Germany) was inserted using an in-plane approach from the lateral to medial direction. The target of the needle tip was the superolateral corner of the femoral artery, located directly below the sartorius muscle, as the saphenous nerve can be difficult to identify. The needle was advanced to the hyperechoic zone lateral to the artery, which is bordered laterally by the vastus medialis and superiorly by the sartorius muscle. ^,

1–2 ml of normal saline was used for needle tip hydrolocation. After positioning the needle tip appropriately, 18 ml of bupivacaine 0.25 % combined with 2 ml of dexamethasone (8 mg) was injected. The injection was done slowly in 5 ml increments, with occasional aspiration to prevent intravascular injection. The drug solutions were evenly distributed around the saphenous nerve in a caudo-cephalad direction. A sham injection of 20 ml of sterile normal saline was then performed at the ACB site under ultrasound guidance in an attempt to simulate an actual block procedure in the IA group.

Sensory blocking was assessed on a dichotomous scale both before and after the ACB to determine if pinprick sensation was present along the distribution of the saphenous nerve, specifically at the medial malleolus and the medial infrapatellar area. Similarly, the sensation in the lateral malleolus and lateral infrapatellar area was tested to minimize the chance of patient bias or unblinding. If the medial malleolus or the medial infrapatellar area did not respond to pinpricks, the block was deemed successful.

In the IA group, at the end of surgery prior to skin closure, the surgeon injected 18 ml of bupivacaine 0.25 % combined with 2 ml of dexamethasone (8 mg) through the port site into the intra-articular space. The tourniquet remained inflated for an additional ten minutes. Before injecting the study solutions, the surgeon clamped the drain that had been inserted, and it remained clamped for an additional thirty minutes. Patients in the ACB group received a sham intra-articular injection of 20 ml of sterile normal saline.

All patients administered spinal anesthesia in the lateral position. A 27-gauge Quincke spinal needle was used in all patients with a paramedian approach. 3 ml of hyperbaric bupivacaine 0.5 % was injected into either the L3-L4 or L4-L5 intervertebral spaces. Every patient received IV paracetamol 1 g and every 6 h thereafter for analgesia and IV ondansetron 4 mg for prophylaxis against postoperative nausea and vomiting. Postoperative antiemetic treatment included ondansetron 4 mg IV, followed by metoclopramide 10 mg IV, as required.

2.4

Outcome assessment

The primary outcome was the time to the first analgesic request (h).

The secondary outcomes measured in the study were as follows: the intensity of postoperative pain, both at rest and during knee movement; the total analgesic doses used; as well as the patient’s quadriceps muscles strength.

The patients were taught to use the visual analogue scale (VAS) to rate their pain, with 0 indicating no pain and 10 indicating the highest level of pain. VAS scores were recorded at rest and during knee movement (at an active flexion of knee) at 6, 12, 18, and 24 h after surgery. If a patient’s VAS pain score was 3 or higher at any time during the entire study period (0–24 h after surgery), they were given IV ketorolac (30 mg) as a supplemental analgesic. This treatment was repeated every 8 h if needed. If a patient’s pain persisted for 30 min after receiving ketorolac, they were given an IV bolus of morphine at 0.05 mg/kg as a rescue analgesic. The total doses of ketorolac (mg) and morphine (mg) were reported.

The patients were examined in the supine position by a single observer who was blinded to group assignment to evaluate the strength of their quadriceps muscles. The assessment relies on a 6-point Medical Research Council (MRC) scale, ranging from 0 to 5. (0 = no contraction, 1 = flicker or minimal contraction, 2 = active motion in absence of gravity, 3 = active motion against gravity, 4 = active motion is present when moving against gravity and resistance, and 5 = normal muscle strength).

Every patient was asked to extend their legs three times, pausing for thirty seconds between each attempt, and the average of the three reading was recorded. The patient’s quadriceps muscle strength was tested at 6 h and 24 h after surgery.

Age, sex, weight, height, ASA class, side and duration of operation, were all recorded.

Patient satisfaction with analgesia measured on the following 3 point scale: 1= Satisfied, 2= Fair, 3= Unsatisfied was collected at 24 h postoperatively.

Side effects such as hypotension (defines as a decrease of mean arterial pressure >20 % of the baseline), bradycardia (defined as heart rate <60 beats per minute), nausea, vomiting, sedation, and manifestations of drug toxicity were treated and reported within the first 24 h after surgery.

2.5

Sample size calculation

The primary outcome variable in our study was the pain free time in minutes after surgery. According to a pilot study involving ten patients undergoing ACL at our institution, the mean time to the first ketorolac dose for patients who received ACB was 999 min, with a standard deviation (SD) of 408.91 min. We calculated that 30 subjects would be required for each group to detect a difference, assuming a 30 % increase in the IA group was considered clinically significant, an alpha error of 0.05, and a power of 80 %. To account for the potential dropout rate, 36 patients were recruited per group.

Statistical analysis:

Data entry and analysis were conducted using SPSS version 22 (Statistical Package for Social Science). The Kolmogorov-Smirnov test was used to verify if the data distribution was normal. Data were presented as mean and standard deviation (SD), mean and 95 % Confidence Interval (95 % CI), mean and standard error (SE), and numbers (percentages) as appropriate. The Fisher’s exact test or the Chi-squared test was employed to analyze categorical variables as appropriate. An independent samples t -test was utilized to compare quantitative variables between groups for parametric data, while the Mann-Whitney U test was used for non-parametric data. Changes in variables at different time points were compared using a 2-way repeated measures analysis of variance, followed by the Bonferroni test. Kaplan-Meier survival analysis was used to examine the time to the first ketorolac and morphine request (min). The significance level was kept at a P-value of less than 0.05.