Study Design and Patients
Following institutional review board approval, the trial was registered at www.clinicaltrials.gov and was assigned the registration number NCT02908711. The CONSORT (Consolidated Standards of Reporting Trials) statement guidelines were followed to perform this, randomized controlled trial and to present the results. Patients undergoing primary TKA by three of the authors (**, **, **) were screened for eligibility by the senior author (**) preoperatively. In order to eliminate the preemptive analgesic effect of neuraxial anesthesia, only patients that were planned to have the surgery under general anesthesia were included. Other inclusion criteria were patients older than 18 undergoing unilateral, primary TKA, ability to complete study procedures, and American Anaesthesiologists classification 1,2 and 3 .Exclusion criteria included: patient refusal to give written consent, patients with history of opioid dependence, abuse, or tolerance (defined as daily use more than 20-mg oxycodone equivalents at time of surgery), contraindication to peripheral nerve block (significant coagulopathy or active infection at the site of block), and pre-existing significant neuropathy in the operative extremity. Informed written consent was obtained from all patients.
Study subjects were randomized to receive either preemptive anesthesiologist-delivered, ultrasound-guided ABC (PreACB) or postoperative anesthesiologist-delivered, ultrasound-guided ABC (PostACB). Randomization was performed by an independent research statistician. Study allocation was put in opaque, sequentially numbered envelopes, which were opened by key personnel upon signing the consent. The patient remained blinded to the allocation.
Both the PreACB and PostACB were performed by experienced anesthesiologists that had performed more than 50 cases prior to the study. PreACBs were placed either in the regional anesthesia bay or the OR prior to anesthesia induction and surgery, or in the OR or Post anesthesia care unit immediately upon completion of surgery. Blocks were performed using a sterile technique while the patient is positioned supine. The needle insertion site, approximately 10cm proximal to the operated knee, is exposed. The skin is disinfected with 2% Chlorhexidine and the ultrasound probe placed in a sterile sleeve. The femoral artery is identified with a high frequency linear transducer (Philips 4-12L linear transducer with a frequency of 6-12 MHz, Milwaukee, WI or) proximal to the operative knee. The appropriate location for injection is determined by following the femoral artery cephalad until the artery is directly posterior to the Sartorius muscle. At this level, the saphenous nerve is located lateral to the femoral artery. An 18g insulated sonographic Tuohy needle (Pajunk GmbH, Geisingen, Germany) is inserted in an in-plane approach, under constant ultrasound visualization, through the Sartorius muscle to a final location in close proximity to the saphenous nerve. Once satisfied with needle placement and following negative aspiration, 20 cc of 0.5% ropivacaine is injected gradually through the needle under visualization, with recurrent aspirations to verify absence of intra-vascular injection signs. The subsequent TKA and anesthetic regimen were conducted per the standard of care at our institution. All patients underwent a cemented total knee utilizing a medial parapatellar approach, including patellar resurfacing. A tourniquet was used in all cases. Posterior capsule infiltration was administered with 20cc of 0.25% bupivacaine, as the preferred method of providing sciatic nerve analgesia (17, 18) ,per current institutional protocol.
Intraoperative analgesia was administered per anesthesiologists' discretion.
Postoperatively, all patients were given a standard regimen of IV acetaminophen 1000mg q8hr, and IV Tramadone 100 mg q8hr, both started intraoperatively prior to conclusion of surgery, and continuing for 48 hours. While in PACU, all patients will be administered a morphine patient controlled analgesia (PCA) infusion pump (Graesby 3300®, Smith Medical International Ltd. Watford, UK; IVAC® PCAM®, Cardinal Health Inc., Rolle, Switzerland), for at least 48 hours. Per institutional protocol, PCA will be connected after bolus loading of IV 0.1 mg/kg morphine in the PACU.
Bleeding and thrombo-embolism prophylaxis
All patients received Enoxaparin 40mg once daily for thrombophylaxis. All patients received a standard postoperative mobilization protocol, starting on POD1. A continuous passive motion machine (CPM) was not utilized. Per institutional protocol, all patients undergoing TKA received 1 gr of IV tranexamic acid intraoperatively, after induction of anesthesia, in order to reduce intra-operative bleeding(19).
Patients were enrolled for the study during the orthopedic surgical appointment upon the scheduling of the surgery. Upon enrollment, patients completed a baseline Knee Society score (KSS) questionnaire, had a VAS pain score recorded, and had their pre-operative analgesic medication documented. To assess the effect of pain with motion and overall strength, on post-operative day (POD) 1, the patients indicated their level of pain using VAS numeric scale (1-10). The Quality of recovery (QoR) score (20) was collected at two time points: 24 hours from the placement of the ACB and at 24 hours postoperatively.
In addition, at their 4-6 week orthopedic follow-up appointment, the enrolled patients completed a KSS and a QoR questionnaires, VAS scores were obtained and the consumption of analgesic medications was documented.
Sample Size and Statistical Analysis
We conducted an a priori sample size analysis aimed to determine how many patients would be required to detect a clinically important difference in pain with a power of 80% and alpha= 0.05. We considered a 2 points difference in reported pain to be a clinically relevant one, with a standard deviation within groups of 2. We then used an analysis of variance power analysis, based on these values, and it was determined that 20 patients per group was adequate. We therefore selected a final number of 25 patients per for the study. For the data analysis, continuous variables were tested for normality of distribution via the Shapiro-Wilk test. As none of the variables were normally distributed for both groups (p<0.05), it was decided to compare the groups using the Mann-Whitney U test. Categorical variables were examined using Pearson's chi-square test. Statistical significance was set as P < .05. All analyses were performed using SPSS (SPSS 24.0, IBM Inc., Somers, NY).