Enrollment
This study was approved by the Institutional Review Board of Peking Union Medical College Hospital in Beijing, China (#ZS-1030) and was registered at ClinicalTrials.gov (NCT03942133; date of registration: May 06, 2019; date of patient enrollment: May 11, 2019). Written informed consent was obtained from all participants before taking part. This manuscript adheres to the applicable Consolidated Standards of Reporting Trials guidelines and was conducted in accordance with the Declaration of Helsinki. Adult (≥18 years of age) patients with an American Society of Anesthesiologists (ASA) physical status classification of I to III who were scheduled for unilateral, primary TKA were approached for inclusion. Exclusion criteria were a body mass index (BMI) > 40, contraindications to peripheral nerve blocks, known daily intake of opioids (morphine, oxycodone, methadone, ketobemidone, fentanyl), alcohol or drug abuse, intolerance of nonsteroidal anti-inflammatory drugs, diabetes, lower limb neuropathy, and the inability to accurately describe postoperative pain to the investigators (e.g., a language barrier or a neuropsychiatric disorder).
Randomization and Blinding
Participants were randomized to either the proximal end or middle group with a ratio of 1:1 using a computer-generated sequence given by a professional statistician who was not otherwise involved in the study. Allocation concealment was ensured by the use of sealed, opaque, sequentially numbered envelopes which remained concealed until the block was performed.
All the ultrasound-guided continuous ACBs were conducted by a single senior experienced staff anesthesiologist (C.X.) in a dedicated procedure room, where all other surgeons, nurses (except the assistant research nurse in the procedure room), and study participants were not presented at the time of performing the block. Surgeries were conducted by the same surgical team blinded to subject allocation using a standardized approach.
Perioperative Management
All recruited subjects were interviewed on the day before surgery. Baseline pain severity and quadriceps strength of the operative leg were recorded. Subjects were informed of the postoperative continuous ACB and patient-controlled intravenous analgesia (PCIA) schedule, with a goal of maintaining pain scores <4 on an 11-point numerical rating scale (NRS, 0: no pain; 10: maximum pain imaginable). No preoperative medications were administered.
Catheter Insertion Procedure
All perineural catheter insertions were performed 40 min before surgery in a dedicated procedure room. Standard monitoring and peripheral venous access were established. Patients were placed in a supine position with the operative knee slightly flexed and externally rotated. With the ultrasound screen facing away from the patient, an ultrasound scan was carried out with a 13-6 MHz linear probe (Sonosite X-port, SonoSite Inc, Bothell, WA) which was positioned perpendicular to the skin in the medial upper-thigh region. The entire procedure was performed after strict aseptic precautions were taken and skin infiltration (2~3 mL of 1% lidocaine) was performed with a 100 mm, 17 gauge, insulated nerve block needle and a 19 gauge perineural catheter (SonoPlex Stim cannula; Pajunk, Geisingen, Germany).
For subjects randomized to the proximal end group, a short-axis dynamic scan was performed (Figure 1 A). The insertion site was defined by the ultrasound image as the location where the medial margins of the SM and ALM intersected13 (Figure 1 a). Then, the needle was inserted in-plane in a short-axis lateral-to-medial orientation, through the SM with the final needle tip positioned between the FA and SN (Figure 1 A, a). If the SN could not be well visualized, the needle tip was placed at a 5 o’clock position relative to the FA within the AC.21 For subjects randomized to the middle group, we used a slightly modified method described by Koscielniak-Nielsen.22 After identifying the proximal end of the AC in the short-axis view, the ultrasound transducer was rotated 90° to image the SN in the long-axis with the cranial end of the transducer aligned with the proximal end of the AC (Figure 1 B, b). To ensure adequate blinding of the block type to all research personnel performing follow-up evaluations, we choose a needle puncture site at a similar level as in the proximal end group (Figure 1 B). The needle was inserted in-plane in a long-axis with cranial-to-caudal orientation toward the location, 3~5 cm caudal to the proximal end of the canal, and with the needle tip placed deep into the SM and just superficial to the SN (Figure 1 B, b). If the SN could not be well visualized, the needle tip was placed lateral to the FA within the AC.21
In both groups, after hydro-dissection with 0.9% saline to confirm proper needle-tip placement within the AC, the perineural catheter was advanced 1~1.5 cm into the AC under direct ultrasound visualization. After withdrawing the needle, the perineural catheter was tunneled subcutaneously and secured to the upper part of the thigh with surgical glue and an occlusive dressing with an anchoring device. The time between needle skin entry to needle removal was recorded as the block performance time. Ten milliliters of 0.2% ropivacaine was injected as the loading dose via the catheter after negative aspiration. Catheter insertion success was defined as a decrease in the cutaneous sensation to pinprick in the SN distribution area over the ipsilateral medial calf within 30 min after injection. Subjects with a failed catheter insertion or misplaced catheter indicated by a lack of sensory change had their catheter replaced or were withdrawn from the study.
Intraoperative Management
A bispectral index (BIS) monitor was connected for all patients. General anesthesia was induced with intravenous midazolam (1 mg), fentanyl (2 μg/kg), propofol (1.5~2.0 mg/kg), and rocuronium (0.6 mg/kg). All patients received laryngeal mask airway intubation. Anesthesia was maintained with a sevoflurane and O2-N2O mixture to keep the BIS within 40~60. Intravenous fentanyl (1 μg /kg) and rocuronium bromide (0.6-0.9 mg/kg) were administered intraoperatively as needed. On completion of surgery, sevoflurane and N2O were discontinued and the neuromuscular blockade was reversed using neostigmine (50 μg/kg) and atropine (20 μg/kg). Extubation was carried out when patients were fully awake.
Postoperative Analgesia
Continuous ACB was initiated immediately after surgery in both groups using an electronic pump (Gemstar, Hospiria Inc., USA) to administer 0.2% ropivacaine at a rate of 6 ml/h through the catheter. PCIA was commenced using a pump set (Gemstar, Hospiria Inc., USA) to deliver boluses of 1.5~2 µg sufentanil with a 5-min lockout interval and no background infusion. The maximum permitted dosage of sufentanil was set at 8 µg/h. Continuous ACB and PCIA were continued until 48 h after the surgery in both groups. Intravenous parecoxib sodium (40 mg), Q12 h, was administered for 3 days postoperatively.
Outcomes and Data Collection
Patients were evaluated postoperatively at 0, 2, 4, 8, 12, 24, and 48 h. The primary outcome measure was the 24 h sufentanil consumption after surgery. The secondary outcome measures included sufentanil consumption at other postoperative time points; pain intensity both at rest and upon passive knee extension to 60° assessed with the NRS score; quadriceps motor strength assessed by a physiotherapist using Lovett’s 6-point scale (0 = no voluntary contraction possible, 1 = muscle flicker, but no movement of limb, 2 = active movement only with gravity eliminated, 3 = movement against gravity but without resistance, 4 = movement possible against some resistance and 5 = normal motor strength against resistance) preoperatively and postoperatively;23 time to ambulation after surgery defined as the time from the end of surgery until ambulation assisted by a walker or ward nurse; episodes of PONV within 48 h after surgery; patient’s satisfaction with anesthesia and analgesia, which were separately assessed at 48 h using a 5-point scale (5, very satisfied; 4, satisfied; 3, neither satisfied nor dissatisfied; 2, dissatisfied; 1, very dissatisfied); and block-related complications including puncture point infection, leakage, catheter dislodgment, and falling down. The durations of postoperative length of stay were also retrieved from electronic medical records.
Sample Size
The sample size requirement was calculated based on a pilot study (n=10) performed at our institution between January 2019 and February 2019 in which the mean (standard deviation, SD) cumulative 24 h sufentanil consumption after TKA was 0.235 (0.172) µg/kg in the proximal end group and 0.376 (0.188) µg/kg in the middle group. A sample size of 28 patients would be needed for a power (1-beta) of 0.80 and a significance level (alpha) of 0.05. Since it is presumed that 24 h sufentanil consumption may not follow a normal distribution, and since a calculation which assumes a normal distribution might underestimate the sample size, we planned to enroll 31 patients per group.
Statistical Analysis
The statistical analyses were performed using SPSS version 15.0 (SPSS Inc., Chicago, IL, USA). Variables and demographics that followed a normal distribution are expressed as the mean (standard deviation) and were analyzed using a Student’s t-test. Variables that did not follow a normal distribution are presented as the median (interquartile range, IQR) and were analyzed using the Mann-Whitney U test. Categorical data are reported as the proportion or percentage and were analyzed using the Chi-squared test. P-values <0.05 (two-sided) were considered statistically significant.