This study was conducted to see if dexamethasone administered with local anesthetic for the subgluteal sciatic nerve block could prolong the analgesic duration and improve postoperative analgesia in patients undergoing ACL reconstruction using a hamstring tendon autograft. This randomized controlled double-blind study was approved by the Shimane University Hospital ethical committee on 28th August, 2017 (study number 2821) and registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN000028930) on 4th September, 2017. The study was conducted between September 2017 and March 2018. Patients (American Society of Anesthesiologists physical status 1–2) undergoing unilateral arthroscopic ACL reconstruction using an ipsilateral hamstring tendon autograft under quadruple peripheral nerve blocks without spinal anesthesia or general anesthesia were included. Patients who had contraindications to peripheral nerve blocks, a history of diabetes mellitus, or any neurologic disease were excluded. Written informed consent was obtained from 22 patients (and/or a guardian of patients under 20 years old). The patients were randomly divided into two groups to receive 20 ml of 0.5% ropivacaine with dexamethasone sodium phosphate 4 mg (4 mg per 1 ml, Fuji Pharma Co., Ltd., Tokyo, Japan) (group P) or 1 ml of normal saline (group C) for single subgluteal sciatic nerve block in a 1:1 ratio. Our institutional clinical trial center conducted randomization using computer-generated sequence of random numbers and informed an investigator which group the patient would be assigned to on the day before surgery. An anesthesiologist who was not involved in the block procedure, anesthesia or postoperative measurements prepared the local anesthetic solution used for sciatic nerve block without labeling for group allocation. Patients were blinded to their group assignment.
In the operation room, a standard noninvasive monitor was applied and an intravenous line was secured for all patients. Midazolam 1–2 mg and fentanyl 50 μg was intravenously given for sedation before block performance, while the patients remained responsive to verbal cues. All patients received single-injection subgluteal sciatic and obturator nerve blocks, and continuous femoral nerve block under ultrasound guidance. Single-injection lateral cutaneous femoral nerve block was added in patients who did not develop anesthesia on the lateral aspect of the thigh approximately five minutes after the femoral nerve block. The blocks were performed under aseptic technique and the supervision of an experienced regional anesthesiologist (S.S.).
First, subgluteal sciatic nerve block was conducted with a patient in the lateral position with the side to be blocked uppermost. An 1–5 MHz convex transducer (LOGIQ e Premium; GE Healthcare, Tokyo, Japan) was positioned to visualize the short axis view of the sciatic nerve at the subgluteal level, and a 100-mm, 21-gauge block needle (SonoPlex STIM; PAJUNK, Geisingen, Germany) was inserted in-plane under ultrasound image . A nerve stimulator (RasinPlex HRP-10; Hakko, Chikuma, Japan) with a pulse duration of 0.1 ms and a stimulating frequency of 2 Hz was used to confirm the sciatic nerve . The local anesthetic solution according to the study protocol was injected around the target nerve. Then a patient was turned to the supine position to receive femoral, obturator, and lateral cutaneous femoral nerve blocks using a 4–12 MHz linear transducer (LOGIQ e Premium; GE Healthcare, Tokyo, Japan). Femoral nerve block was conducted using a 25-gauge catheter over the needle (Contiplex C; B. Braun, Meisungen, Germany) with short axis view, in-plain approach. The needle was inserted from the lateral to medial direction and 15 ml of 0.5% ropivacaine was injected incrementally around the femoral nerve. The catheter was next placed and fixed with sterile tape. Obturator nerve block was conducted using a 21-gauge block needle (SonoPlex STIM; PAJUNK, Geisingen, Germany), and 10 ml of ropivacaine was injected (5 ml each for two fascial planes; between adductor longus and adductor brevis muscles and between adductor brevis and adductor magnus muscles) . Lateral cutaneous femoral nerve block was added, if necessary, by using 1–3 ml of 1% mepivacaine using a 22-gauge needle under ultrasound guidance .
After confirming loss of cold sensation on the knee and lower leg, surgery was started. Patients were sedated as requested with a bolus intravenous injection of midazolam or a continuous infusion of propofol. Fentanyl 50 μg was intravenously injected by the attending anesthesiologist when the surgical anesthesia was deemed inadequate. No additional local anesthetics were administered during surgery. The same orthopedic team conducted each surgery. Continuous infusion of 0.17% levobupivacaine at 4 ml/h and patient control analgesia (PCA) with a bolus of 3 ml (30 min lock out time) using an elastomeric infusion pump (COOPDECH Ballonjector 300 PCA set; Daiken Medical, Izumi, Japan) via the femoral nerve catheter was started immediately after surgery and continued for 48 h. The routine postoperative analgesic regimen consisted of loxoprofen sodium 180 mg/day administered orally. Oral or intravenous acetaminophen and a diclofenac suppository were used for rescue analgesia.
Analgesic duration was assessed by measuring the time from the completion of block procedure to first pain on the knee. Duration of motor block was assessed by measuring the time from block to the first ankle movement. Patients were preoperatively asked to record the times when they first felt noticeable pain on the knee and when they noticed the return of both dorsal flexion and planter flexion of the ankle. Other measurements were conducted by anesthesiologists who were blinded to the group allocation and not involved in the block procedure. Visual analogue pain scores (VAS: 0, no pain; 100, worst pain imaginable) at rest and on movement were assessed at 18, 24 and 48 h after blocks. During that same 48 h period, worst VAS, the number of patient-controlled analgesia (PCA) via the femoral nerve catheter, any additional analgesic required and all complications were also assessed.
Perineural dexamethasone was abandoned in our hospital a few months after the completion of study 1, due to a concern regarding its off-label use in Japan as well as in many other countries and possible mix-up among local anesthetic solutions used for different peripheral nerve blocks. Alternately, dexamethasone 4 mg has been administered intravenously at the discretion of an anesthesiologist since then. Study 2 was conducted retrospectively to evaluate the effects of intravenous dexamethasone 4 mg as compared with those of perineural dexamethasone to the sciatic nerve block and effects with no dexamethasone in patients undergoing ACL reconstruction using a hamstring tendon autograft. The Shimane University Hospital ethical committee gave approval to this study on 15th October, 2018 (study number 3390). We then collected intraoperative and postoperative data of patients who received peripheral nerve blocks as a care standard and were registered in the regional anesthesia database in our department. Written informed consent was waived because the study was limited to pre-existing data. Registry data includes detailed information on block performance, sensory and motor blockade, postoperative pain levels and complications in the early postoperative period (for 48 h). All patients enrolled in study 1 were also included in study 2. Data of patients (ages 14–59 years) undergoing unilateral ACL reconstruction using a hamstring tendon autograft under quadruple nerve blocks as described above without general anesthesia or spinal anesthesia between September 2017 and September 2018 were retrieved. Patients (including those who were enrolled in study 1) were divided into three groups: patients who did not receive dexamethasone (either perineurally or intravenously) (group 1), patients who received dexamethasone 4 mg intravenously (group 2), and patients who received dexamethasone 4 mg along with local anesthetic for subgluteal sciatic nerve block (group 3). Sciatic, femoral and obturator nerve blocks were conducted using 0.5% ropivacaine as described above. The intraoperative anesthesia, postoperative pain management and postoperative assessments were similarly conducted to those in study 1.
The primary outcome of both studies was the duration of analgesia, defined as time after the block procedure until the first pain was felt. The secondary outcomes of the studies included duration of motor block, pain scores and the number of PCA required. In study 1, we hypothesized that perineural dexamethasone 4 mg co-administrated with 0.5% ropivacaine would extend the duration of analgesia compared with 0.5% ropivacaine alone. Sample size calculation for study 1 was conducted based on our preliminary data to detect the 7 h difference with SD of 4.6 h. The results showed that 14 patients (7 in each group) were required (α set at 0.05 and β set at 0.2) and the number was increased to 22 patients (11 in each group) to compensate for potential dropouts. Sample size calculation for study 2 was not conducted because the study was conducted retrospectively.
Statistical analysis was performed using SPSS 23.0 software for Windows (SPSS Inc., Chicago, IL). The two-tailed Student’s t-test was used for parametric statistics and the values were expressed as mean ± SD. The Mann–Whitney U-test and Kruskal–Wallis test were applied for non-parametric statistics and the results were expressed as median (interquartile range). The chi-square test or Fisher’s exact test were used for categorical data. The Bonferroni correction was applied when appropriate and a p-value < 0.05 was considered statistically significant.