Effect of two concentrations of ropivacaine on rebound pain after retreat of iliac fascia block in patients undergoing total knee arthroplasty：a prospective, double-blind randomized controlled trial

Effect of two concentrations of ropivacaine on rebound pain after retreat of iliac fascia block in patients undergoing total knee arthroplasty：a prospective, double-blind randomized controlled trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Effect of two concentrations of ropivacaine on rebound pain after retreat of iliac fascia block in patients undergoing total knee arthroplasty：a prospective, double-blind randomized controlled trial Qin Qin, Zong-rui Huang, Xin-yi Wang, Jing-xuan Wang, Bing-rong Jin, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5377904/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective: The aim of this research was to evaluate the effect of two different local anesthetic concentrations on rebound pain following Fascial Iliac Compartment Block (FICB) retreat in patients undergoing total knee arthroplasty (TKA). Method: 48 patients undergoing unilateral TKA under elective general anesthesia were randomly divided into two groups (n=24): the 0.1% ropivacaine group (Group A) and the 0.3% ropivacaine group (Group B). Before anesthesia, two groups of patients underwent a single ultrasound guided- FICB above the inguinal ligament, with 40 mL of 0.1% or 0.3% ropivacaine; all patients underwent perioperative multimodal analgesia. The first outcomes are incidence and degree of postoperative rebound pain; secondary outcomes are remedial analgesia rate within 48h postoperatively, opioid consumption from 0-24 h and 24-48 h postoperatively, NRS scores and muscle strength scores at rest and exercise at 24h and 48h postoperatively, and intravenous serum concentrations of interleukin-6 (IL-6) and tumor necrosis factor α(TNF-α) before surgery and at 24 and 48 h after surgery. Results: In group A , the incidence of postoperative rebound pain was lower ( P <0.01), and the degree of rebound pain was milder ( P <0.01). The remedial analgesia rate was lower within 48 h after surgery ( P <0.05); opioid consumption was lower at 0-24 h after surgery ( P <0.01); the postoperative NRS score at 24 h was lower ( P <0.01), while the muscle strength score was higher ( P <0.01); There was no statistically significant difference in intravenous serum concentrations of IL-6 and TNF-α before surgery, and at 24 and 48 h after surgery. Conclusion: The incidence of rebound pain after the resolution of FICB with low-concentration ropivacaine was lower, and low-concentration ropivacaine FICB was more suitable for multimodal analgesia in TKA patients. Total Knee Arthroplasty Ropivacaine Postoperative Analgesia Nerve Block Rebound Pain Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Total Knee Arthroplasty (TKA) often leads to severe postoperative pain for patients both physiologically and psychologically. Peripheral nerve block is an important component of analgesic treatment after TKA. A single preoperative peripheral nerve block reduces the intraoperative anesthesia dose and provides relatively perfect analgesia for 24-48 h postoperatively [1] . Fascial Iliac Compartment Block (FICB) is widely used to control acute pain after TKA [2,3] . A single FICB has been reported to be effective in reducing patients' pain within 12 to 24 h after TKA. However, the use of remedial analgesic medication is increased in patients who receive a single nerve block between 24 and 48 h postoperatively compared to those who do not receive this treatment, and these patients experience more intense pain after the effects of the nerve block have worn off [5,6] . This sharp increase in pain after the disappearance of the peripheral nerve block has been described as “Rebound Pain”. Rehabilitation exercises usually initiate 48-72 h postoperatively after TKA, but rebound pain may delay the onset of rehabilitation exercises in patients, reducing the effectiveness of rehabilitation exercises and prolonging the length of hospitalization [5] . Therefore, the study about the pathogenesis of rebound pain and the reduction and prevention of rebound pain can promote the postoperative recovery of TKA patients, which is conducive to the more rational use of regional blockade for perioperative analgesia in TKA [7,8] . Rebound pain was first reported in some outpatient surgery patients, occurring after the regression of nerve blockade, with characteristics such as rapid onset, rapid progression to peak pain intensity, and unpredictability. Young patients, females, orthopedic surgeries, and non-use of intraoperative dexamethasone are high-risk factors for the development of rebound pain [9,10,11] . The rebound pain following nerve block analgesia is multifactorial, and there are currently few studies reporting whether the concentration of local anesthetics affects the occurrence of rebound pain. Some clinical studies have reported that 0.1% ropivacaine for an epidural block can achieve good labor analgesia [12] and does not affect maternal motor function. Whether a low concentration of 0.1% ropivacaine reduces the incidence of rebound pain after FICB in TKA patients is unclear. Materials and Methods General Information The study was a single-center, double-blind, prospective, randomized controlled study, which was approved by the Ethics Committee of Suzhou Xiangcheng People's Hospital (2022-KY-05; October 14, 2022) and funded by The Second Affiliated Hospital of Soochow University Discipline Construction Torrent Project (XKTJ-TD202008) and Suzhou Applied Basic Research on Livelihood Science and Technology for Healthcare (SYS2019074). All patients signed an informed consent form. We selected 48 patients who underwent TKA from December 2022 to December 2023 in this hospital. Age 55-75 years, BMI 18 kg/m 2 -30 kg/m 2 , ASA class II-III. Exclusion criteria: coagulation disorders, peripheral neuropathy, allergy to local anesthetics, severe cardiopulmonary disease, history of chronic pain, long-term use of opioids, psychiatric disorders, history of cerebrovascular disease, history of knee surgery, and inability to comprehend pain scores and intravenous self-controlled analgesia. Elimination criteria: temporary preoperative change of anesthesia; unanticipated difficulties or tourniquet time exceeding 90 min during surgery; intraoperative complications requiring transfer to the ICU for further treatment; postoperative adverse events requiring a second surgery; and postoperative patients with severe pain (NRS ≥ 7 points) in whom the nerve block had not yet subsided. Randomization and Intervention Patients were divided into 2 groups using the SPSS random number method (n=24): 0.1% ropivacaine group (Group A) and 0.3% ropivacaine group (Group B). Group A and Group B: In the preoperative preparation room, peripheral venous access was established, and electrocardiogram, non-invasive blood pressure, and pulse oximetry were monitored. Based on multimodal analgesia, a single ultrasound-guided FICB with 40 mL of 0.1% and 0.3% ropivacaine was performed above the inguinal ligament in the preoperative preparation room. All patients had FICB performed by the same senior anesthesiologist, who was unaware of the grouping. The patients were placed in the flat position, the skin was disinfected and taped, and a Sonosite SII ultrasound (Sonosite Corporation, USA) was used for localization and in-plane guidance of the puncture. FICB: A high-frequency wire-array probe (6-14 Hz) was selected and placed vertically in the middle and outer third of the inguinal ligament on the operative side, and the ultrasound image identified the external abdominal oblique, internal abdominal obliques, transversus abdominis, iliac muscle, deep spinous iliac artery, and iliac fascia. The needle was inserted from the caudal to the cephalic side. Under ultrasound guidance, after the tip of the needle reached the deep surface of the iliac fascia and no blood was withdrawn, the iliac fascia and iliopsoas muscle fascia were separated with the application of the water separation technique, and the deep surface of the iliac fascia was injected with 40 mL of two different concentrations of ropivacaine. 30 minutes after the block is completed, if there is a decrease in pinprick sensation on the anterior thigh skin, the block is defined as successful. Multimodal Analgesia Program In the preoperative preparation room, peripheral venous access was established and different concentrations of ropivacaine FICB were performed; intraoperatively, the surgeon injected a "Cocktail" (ropivacaine 100mg, morphine 10mg, epinephrine 1 mg, and saline diluted to 100 mL) into the posterior capsule of the knee cavity, the medial collateral ligament, the patellar ligament, and subcutaneously in the incision. Postoperatively, patients were given Patient-Controlled Intravenous Analgesia (PCIA, sufentanil 1 μg/mL, PCA dose 3 mL, 30-min lockout) to maintain an NRS score of <4; if the NRS score was ≥4, remedial analgesic morphine 5-10 mg intramuscularly was given. Celecoxib sodium 0.2 g orally 3 times daily was given 2 d postoperatively. Anesthesia Methods The patients' NRS scores at rest and during exercise were measured before and 30 min after FICB, and skin sensory loss and quadriceps muscle strength in the anterior thigh were assessed. The surgery was completed under general anesthesia. General anesthesia induction: dexamethasone 0.1 mg·kg -1 , propofol 2.0 mg·kg -1 , sufentanil 0.5 μg·kg -1 , and rocuronium bromide 0.6 mg·kg -1 visual laryngoscopic endotracheal intubation followed by connection to a ventilator for mechanical ventilation. Pressure-controlled volume-assured mode ventilation with a tidal volume of 8-10 mg·kg -1 , an inspiratory to expiratory ratio of 1:2, a ventilation rate of 12-16 breaths/min, and a maintenance PETCO 2 of 35-45 mmHg. Anesthesia Maintenance: Hydrostatic-inspiratory anesthesia, sevoflurane maintained at 0.6 MAC, propofol 2-4 mg·kg -1 ·h -1 , remifentanil 0.25-2.00 μg·kg -1 ·min -1 , intraoperative maintenance of BIS 40-60, systolic blood pressure fluctuations of not more than 20%. After induction of general anesthesia, ephedrine 6 mg IV was given prophylactically to prevent hypotension before loosening the tourniquet, and ephedrine 6 mg IV was given if the systolic blood pressure was less than 90 mmHg or 30% of the basal value occurred during the operation. If the systolic blood pressure exceeds 160 mmHg or 30% of the basal value, give uradil 12.5-25 mg IV. Stop the drug at the end of the operation, remove the tracheal tube, and send it to the Postoperative Anesthesia Care Unit (PACU) for observation. Observation Outcomes The primary outcomes were the incidence of rebound pain at the surgical site after FICB subsided and the degree of pain after the block subsided. Definition of rebound pain: rebound pain was defined as the occurrence of the highest NRS score greater than or equal to 7 within 12 h after nerve block regression. The specific time of regression of the nerve block cannot be precisely defined at present, and in this study, the time of the first compression of the analgesic pump was used as the time of regression of FICB. Secondary outcomes: time to first postoperative analgesic pump press, effective number of presses for self-controlled analgesia, postoperative remedial analgesia rate, postoperative 0-24 h/24-48 h opioid consumption, postoperative NRS scores and muscle strength scores at rest and in activity at 24 h/48 h postoperatively, preoperative/postoperative 24 h/postoperative 48 h ELISA assay (Mutisciences, Inc.Guangzhou, China) interleukin-6 (IL-6, Human IL-6 ELISA Kit EK106/2-96) and tumor necrosis factor-α (TNF-α, Human TNF-a ELISA Kit EK182-96); and the incidence of postoperative nausea and vomiting (PONV) within 48 h postoperatively. The muscle power score refers to the modified Bromage score: the patient is in a supine position, and a 10-15 cm cushion is placed under the knee of the operated side. The patient is instructed to lift the lower leg with force; 0 points: the lower leg cannot move at all; 1 point: muscle contraction is observed, and the lower leg moves slightly but cannot lift off the bed surface; 2 points: the lower leg can be lifted off the bed surface, but cannot resist external force; 3 points: the lower leg can be lifted off the bed surface and can resist a certain amount of external force. The postoperative opioid dosage is standardized and converted to the dosage of sufentanil. The conversion of the dosage between morphine and sufentanil is completed online at https://clincalc.com/opioids. Statistical Analysis Based on the preliminary trial results (n=10), the incidence of rebound pain in the high-concentration and low-concentration groups is 20% and 50%, respectively. Assuming a test power of 0.8 and a significance level of 0.05, a sample size of 20 is required. Considering a 20% dropout rate, at least 24 patients should be included in each group. Statistical analysis was performed using the SPSS 20.0 software. Normally distributed continuous data were expressed as mean ± standard deviation (±s), and inter-group comparisons were conducted using t-tests or one-way ANOVA. Non-normally distributed continuous data were expressed as median (M) and interquartile range (IQR), with inter-group comparisons performed using the Mann-Whitney U test. Categorical data comparisons were conducted using the χ² test or Fisher's exact probability test. A P value of <0.05 was considered statistically significant. Results General Information A total of 55 patients were included in this study; 3 were excluded due to postoperative bleeding and 4 were excluded due to delayed removal of drains because of bleeding risk. There was no statistically significant difference in age, BMI, gender, ASA classification, and length of hospitalization between the two groups; intraoperative remifentanil consumption was increased in Group A patients compared with Group B (Table 1). Table 1 Baseline Characteristics and Intraoperative Medication in Two Groups Group Examples (n) Age (y) BMI (kg/m 2 ) Sex (Male/Female) ASA (Ⅱ/Ⅲ) （ n ） Intraoperative remifentanil consumption (μg ) Length of hospitalization (d) Group A 24 68.8±4.6 25.2±1.6 10/14 11/13 540.0（460.0~930.0） 7.0（5.0~8.5） Group B 24 67.4±4.8 25.4±1.2 13/11 14/10 500.0（390.0~600.0） 7.0（7.0~10.0） t/χ 2 /Z 1.084 -0.653 0.725 -1.995 -0.427 P >0.05 >0.05 >0.05 >0.05 0.05 Compared with group B, group A had a lower incidence of rebound pain ( P <0.01) and milder postoperative rebound pain ( P <0.01) (Figure 1). The time of FICB regression could not be precisely measured in the clinical setting, and the time of the first analgesic pump compression was taken as the time of FICB regression in this study. Compared with Group B, Group A requested the first postoperative analgesia earlier ( P <0.01), indicating that patients in the low-concentration group experienced earlier regression of FICB. The number of effective presses on the analgesic pump within 48 h postoperatively was lower ( P <0.01), and the rate of remedial analgesia was also lower ( P <0.05). Additionally, the consumption of opioid medications within 48 h postoperatively was reduced ( P <0.01), while there was no statistically significant difference in opioid consumption between the two groups during the 24-48 h postoperative period. This indicates that the difference in sufentanil consumption primarily occurred within the first 24 h postoperatively (Figure 2). Compared with group B, patients in group A had lower exercise NRS scores at 24 h postoperatively ( P <0.01), and there was no statistically significant difference in resting NRS scores; there was no statistically significant difference in both resting and exercise NRS scores at 48 h postoperatively (Figure 3). Blood inflammation-related factor IL-6 and TNF-α concentrations were not statistically different between the two groups at preoperative, 24 h, and 48 h postoperatively (Figure 4). Compared with group B, patients in Group A had higher muscle strength scores at 24 h postoperatively ( P <0.01); there was no statistical difference in muscle strength scores and PONV incidence at 48 h postoperatively (Table 2). No adverse events such as local anesthetic poisoning, puncture site infection, hematoma, or delayed block recovery occurred in either group. Table 2 Comparison of the incidence of PONV and muscle strength within the 48 h postoperatively between the two groups Group Examples (n) Number of cases of PONV（%） Postoperative muscle strength 24 h 48 h Group A 24 13（55） 1.0（1.0-2.0） 2.0（1.0~2.0） Group B 24 9（40） 0（0-1.0） 1.0（1.0~2.0） χ 2 /Z 0.104 -3.528 -1.731 P >0.05 0.05 Discussion In this study, patients undergoing TKA in the high-concentration group (0.3% ropivacaine) exhibited a higher incidence of rebound pain following FICB, and the severity of rebound pain was more pronounced. After the occurrence of rebound pain, opioid consumption in the 0-24 h period was higher, which is similar to the findings of Dada et al. [13] ; the remedial analgesia rate in the high-concentration group was higher than that in the low-concentration group. Although patients of the low-concentration group pressed the analgesic pump earlier, the effective press counts within 48 h postoperatively were fewer; moreover, the total opioid consumption within 48 h postoperatively did not increase, the remedial analgesia rate was lower, the 24 h movement NRS score was lower, and muscle strength recovery was better. Additionally, patients in the low-concentration group did not exhibit significant increases in serum interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) concentrations at preoperative, 24 h, and 48 h postoperative time points (Figure 4). TKA is associated with significant trauma and requires early postoperative rehabilitation training; therefore, patients often experience severe pain for 48 h or longer postoperatively. In this study, under the same volume, the high-concentration group received a higher concentration and larger dose of ropivacaine, resulting in a longer duration of nerve block. The duration of blockade from a single high-concentration injection rarely exceeded 48 h. While the nerve block remained effective, patients in the high-concentration group typically didn’t use the analgesic pump for additional analgesia. However, since the resolution of the nerve block often occurred within a few minutes to tens of minutes, exhibiting a rapid "on-off" transition [7] , and by that time, plasma opioids may have already been fully metabolized. Therefore, when the nerve block suddenly wore off, the sufentanil administered via the analgesic pump may not have provided timely and adequate coverage for the pain signals that emerged after block resolution, leading to the so-called "rebound pain." This study suggests that patients in the high-concentration group exhibited the aforementioned disadvantages during the transition from neuraxial analgesia to intravenous analgesia, which was one of the main reasons for the occurrence of rebound pain. In the low-concentration group, the nerve block duration was shorter and the intensity was lower, prompting patients to initiate analgesic pump use earlier, thereby maintaining a certain plasma concentration of sufentanil intraoperatively and postoperatively. Analgesia in the low-concentration group could smoothly translate from nerve-block-dominated analgesia to intravenous drug analgesia. Continuous adductor canal block may have been one of the ideal options to simultaneously address the issues of insufficient analgesia duration and quadriceps femoris muscle strength decline after blockade [14,15] ; however, it also involved catheter-related technical demands and risks of complications. It is reported that methods to reduce postoperative rebound pain include intravenous administration of ketamine and the addition of adjuvants to nerve-blocking medications [16,17] . Although adding adjuvants could extend the analgesic duration of nerve block agents, ensuring that block resolution occurred after the period of severe postoperative pain, for TKA patients, simply prolonging block duration by increasing local anesthetic concentration or adding adjuvants had limited effectiveness and was difficult to comprehensively cover the entire postoperative pain cycle [18] . Recent studies indicated that a novel ultra-long-acting local anesthetic, liposomal bupivacaine, could last up to 72 h; liposomal bupivacaine adductor canal block could effectively reduce opioid consumption and improve postoperative analgesia after TKA, but its efficacy and optimal concentration in FICB required further investigation [19] . Developing a more reasonable multimodal analgesia management plan [20] to transition patients from nerve block analgesia to pharmacological analgesia may have been an effective strategy to alleviate rebound pain; furthermore, multimodal analgesia could also alleviate postoperative anxiety and depression among patients undergoing TKA, improved postoperative recovery, shortened hospital stays, and offered other benefits [21] . Through animal experiments, it has been found that high-concentration local anesthetics affect the physiological electrical activity of nerve fibers, leading to aseptic inflammation around the nerves. [22] ; Clinically, the hyperalgesia caused by perineural inflammation after the resolution of neural blockade may contribute to the occurrence of postoperative rebound pain. [13,23] . IL-6 and TNF-α were pro-inflammatory factors produced by inflammatory cells in periarticular tissues and synovium after TKA, and previous studies showed that IL-6 and TNF-α peaked on the first postoperative day [24,25,26] . In this study, cytokine levels on postoperative day 1 were similar between the low-concentration and high-concentration groups, indicating that low-concentration local anesthetics used in FICB did not increase intraoperative stress-related inflammatory cytokines in patients. This suggested that 0.1% ropivacaine and 0.3% ropivacaine had similar effects in reducing postoperative stress levels. Notably, 0.1% ropivacaine exhibited significant sensory-motor block dissociation characteristics, did not affect quadriceps femoris muscle strength (Table 2), and reduced systemic discomfort caused by prolonged forced positioning, which may have been one of the reasons for the lower 24 h movement NRS scores in the low-concentration group patients. Many postoperative pains were predictable and acceptable, but limb numbness, movement limitations, and rebound pain caused by high-concentration local anesthetic regional nerve blocks could reduce patients' overall satisfaction with postoperative analgesia from regional nerve blocks [6] . Reducing the occurrence of rebound pain after a nerve block could enhance the utility of nerve blocks for perioperative analgesia. There were some limitations in this study. To more comprehensively block the sensory nerve branches around the knee joint, in addition to fascia iliaca block, the surgeon performed periarticular capsule block intraoperatively. To minimize the impact of periarticular capsule block, the same surgeon was selected to perform the procedures in this study; however, this study only compared the high-concentration group and the low-concentration group, and it was necessary to expand the sample size to further systematically explore the effects of different concentration gradients of local anesthetics on rebound pain. The results of this study indicated that, in multimodal analgesia for patients after TKA, the incidence of rebound pain after the resolution of FICB with low-concentration ropivacaine was lower and the muscle strength score at 24 h postoperatively was higher, which facilitated early postoperative rehabilitation training and improved patient satisfaction with analgesia. Low-concentration ropivacaine FICB was more suitable for multimodal analgesia in TKA patients. Declarations Acknowledgements We would like to acknowledge the hard and dedicated work of all the staff that implemented the intervention and evaluation components of the study. Funding This study was funded by The Second Affiliated Hospital of Soochow University Discipline Construction Torrent Project (XKTJ-TD202008) and Suzhou Applied Basic Research on Livelihood Science and Technology for Healthcare (SYS2019074). Ethics approval and consent to participate This study was conducted with approval fromtheEthics Committee of Suzhou Xiangcheng People's Hospital (2022-KY-05; October 14, 2022). This study was conducted in accordance with the declaration of Helsinki. Written informed consent was acquired from all participating patients or their legal representatives. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. Patient consent for publication Obtained. References Marty P, Chassery C, Rontes O, et al. 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Int J Mol Sci. 2016;17(3):339. 10.3390/ijms17030339 . Published 2016 Mar 4. Bagry H, de la Cuadra Fontaine JC, Asenjo JF, et al. Effect of a continuous peripheral nerve block on the inflammatory response in knee arthroplasty. Reg Anesth Pain Med. 2008;33(1):17–23. 10.1016/j.rapm.2007.06.398 . Langkilde A, Jakobsen TL, Bandholm TQ, et al. Inflammation and post-operative recovery in patients undergoing total knee arthroplasty-secondary analysis of a randomized controlled trial. Osteoarthritis Cartilage. 2017;25(8):1265–73. 10.1016/j.joca.2017.03.008 . Martin F, Martinez V, Mazoit JX, et al. Antiinflammatory effect of peripheral nerve blocks after knee surgery: clinical and biologic evaluation. Anesthesiology. 2008;109(3):484–90. 10.1097/ALN.0b013e318182c2a1 . Additional Declarations No competing interests reported. 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b Comparison of rebound pain levels between the two groups. ** \u003cem\u003eP\u003c/em\u003e\u0026lt;0.01\u003c/p\u003e","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-5377904/v1/6544b837295fb77f028158b1.png"},{"id":71139125,"identity":"6618f743-967a-4512-b803-57a1dfea8207","added_by":"auto","created_at":"2024-12-11 13:38:15","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":137249,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAnalgesic pump use and remedial analgesia in two groups of patients\u003c/strong\u003e（n=24）a Comparison of the time to the first press for analgesia between the two groups; b Comparison of the number of effective compressions within 48 h after surgery between the two groups; c Comparison of the rate of remedial analgesia within 48 h postoperatively between the two groups; d Comparison of opioid consumption (morphine-equivalent conversion to sufentanil) between the two groups at 0-24 h, 24-48 h and 0-48 h postoperatively. ns \u003cem\u003eP\u003c/em\u003e \u0026gt;0.05, *\u003cem\u003eP\u003c/em\u003e\u0026lt;0.05, **\u003cem\u003eP\u003c/em\u003e\u0026lt;0.01.\u003c/p\u003e","description":"","filename":"Fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-5377904/v1/de2c8542824ab56fe710c734.png"},{"id":71138376,"identity":"1837b14a-2503-4415-8800-20881c83b05c","added_by":"auto","created_at":"2024-12-11 13:30:15","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":96141,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eNRS scores at rest and during exercise between the two groups at 24 and 48 h postoperatively. \u003c/strong\u003e(n=24). ns \u003cem\u003eP\u003c/em\u003e \u0026gt;0.05 **\u003cem\u003eP\u003c/em\u003e\u0026lt;0.01.\u003c/p\u003e","description":"","filename":"Fig3.png","url":"https://assets-eu.researchsquare.com/files/rs-5377904/v1/75d9e6d7f49f82dc77359154.png"},{"id":71140428,"identity":"6c08aa08-d924-4cc2-9b35-ac2e77755ce5","added_by":"auto","created_at":"2024-12-11 13:46:15","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":105704,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparison of blood inflammatory factors between the two groups preoperatively, and at 24 and 48 h postoperatively. \u003c/strong\u003e(n=24）a Comparison of IL-6 concentrations preoperatively, and at 24 and 48 h postoperatively; b Comparison of TNF-α concentrations preoperatively, and at 24 and 48 h postoperatively. ns \u003cem\u003eP\u003c/em\u003e \u0026gt;0.05.\u003c/p\u003e","description":"","filename":"Fig4.png","url":"https://assets-eu.researchsquare.com/files/rs-5377904/v1/53310312f5091c9001098124.png"},{"id":87984776,"identity":"470c0f23-eef5-40a0-b54d-1aa17b051015","added_by":"auto","created_at":"2025-07-31 07:02:20","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1238632,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5377904/v1/0845c06e-ee46-4767-b21a-ca2a2fa43b73.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Effect of two concentrations of ropivacaine on rebound pain after retreat of iliac fascia block in patients undergoing total knee arthroplasty：a prospective, double-blind randomized controlled trial","fulltext":[{"header":"Introduction","content":"\u003cp\u003eTotal Knee Arthroplasty (TKA) often leads to severe postoperative pain for patients both physiologically and psychologically. Peripheral nerve block is an important component of analgesic treatment after TKA. A single preoperative peripheral nerve block reduces the intraoperative anesthesia dose and provides relatively perfect analgesia for 24-48 h postoperatively \u003csup\u003e[1]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eFascial Iliac Compartment Block (FICB) is widely used to control acute pain after TKA \u003csup\u003e[2,3]\u003c/sup\u003e. A single FICB has been reported to be effective in reducing patients\u0026apos; pain within 12 to 24 h after TKA. However, the use of remedial analgesic medication is increased in patients who receive a single nerve block between 24 and 48 h postoperatively compared to those who do not receive this treatment, and these patients experience more intense pain after the effects of the nerve block have worn off \u003csup\u003e[5,6]\u003c/sup\u003e. This sharp increase in pain after the disappearance of the peripheral nerve block has been described as \u0026ldquo;Rebound Pain\u0026rdquo;. Rehabilitation exercises usually initiate 48-72 h postoperatively after TKA, but rebound pain may delay the onset of rehabilitation exercises in patients, reducing the effectiveness of rehabilitation exercises and prolonging the length of hospitalization\u003csup\u003e\u0026nbsp;[5]\u003c/sup\u003e. Therefore, the study about the pathogenesis of rebound pain and the reduction and prevention of rebound pain can promote the postoperative recovery of TKA patients, which is conducive to the more rational use of regional blockade for perioperative analgesia in TKA \u003csup\u003e[7,8]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eRebound pain was first reported in some outpatient surgery patients, occurring after the regression of nerve blockade, with characteristics such as rapid onset, rapid progression to peak pain intensity, and unpredictability. Young patients, females, orthopedic surgeries, and non-use of intraoperative dexamethasone are high-risk factors for the development of rebound pain \u003csup\u003e[9,10,11]\u003c/sup\u003e. The rebound pain following nerve block analgesia is multifactorial, and there are currently few studies reporting whether the concentration of local anesthetics affects the occurrence of rebound pain. Some clinical studies have reported that 0.1% ropivacaine for an epidural block can achieve good labor analgesia \u003csup\u003e[12]\u003c/sup\u003e and does not affect maternal motor function. Whether a low concentration of 0.1% ropivacaine reduces the incidence of rebound pain after FICB in TKA patients is unclear.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e\u003cstrong\u003eGeneral Information\u0026nbsp;\u003c/strong\u003eThe study was a single-center, double-blind, prospective, randomized controlled study, which was approved by the Ethics Committee of \u0026nbsp;Suzhou Xiangcheng People\u0026apos;s Hospital (2022-KY-05; October 14, 2022)\u0026nbsp;and funded by The Second Affiliated Hospital of Soochow University Discipline Construction Torrent Project (XKTJ-TD202008) and Suzhou Applied Basic Research on Livelihood Science and Technology for Healthcare (SYS2019074). All patients signed an informed consent form. We selected 48 patients who underwent TKA from December 2022 to December 2023 in this hospital. Age 55-75 years, BMI 18 kg/m\u003csup\u003e2\u003c/sup\u003e-30 kg/m\u003csup\u003e2\u003c/sup\u003e, ASA class II-III. Exclusion criteria: coagulation disorders, peripheral neuropathy, allergy to local anesthetics, severe cardiopulmonary disease, history of chronic pain, long-term use of opioids, psychiatric disorders, history of cerebrovascular disease, history of knee surgery, and inability to comprehend pain scores and intravenous self-controlled analgesia.\u0026nbsp;Elimination criteria: temporary preoperative change of anesthesia; unanticipated difficulties or tourniquet time exceeding 90 min during surgery; intraoperative complications requiring transfer to the ICU for further treatment; postoperative adverse events requiring a second surgery; and postoperative patients with severe pain (NRS\u0026nbsp;\u0026ge;\u0026nbsp;7 points) in whom the nerve block had not yet subsided.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRandomization and Intervention\u0026nbsp;\u003c/strong\u003ePatients were divided into 2 groups using the SPSS random number method (n=24): 0.1% ropivacaine group (Group A) and 0.3% ropivacaine group (Group B). Group A and Group B: In the preoperative preparation room, peripheral venous access was established, and electrocardiogram, non-invasive blood pressure, and pulse oximetry were monitored. Based on multimodal analgesia, a single ultrasound-guided FICB with 40 mL of 0.1% and 0.3% ropivacaine was performed above the inguinal ligament in the preoperative preparation room. All patients had FICB performed by the same senior anesthesiologist, who was unaware of the grouping. The patients were placed in the flat position, the skin was disinfected and taped, and a Sonosite SII ultrasound (Sonosite Corporation, USA) was used for localization and in-plane guidance of the puncture. FICB: A high-frequency wire-array probe (6-14 Hz) was selected and placed vertically in the middle and outer third of the inguinal ligament on the operative side, and the ultrasound image identified the external abdominal oblique, internal abdominal obliques, transversus abdominis, iliac muscle, deep spinous iliac artery, and iliac fascia. The needle was inserted from the caudal to the cephalic side. Under ultrasound guidance, after the tip of the needle reached the deep surface of the iliac fascia\u0026nbsp;and no blood was withdrawn, the iliac fascia and iliopsoas muscle fascia were separated with the application of the water separation technique, and the deep surface of the iliac fascia was injected with 40 mL of two different concentrations of ropivacaine. 30 minutes after the block is completed, if there is a decrease in pinprick sensation on the anterior thigh skin, the block is defined as successful.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMultimodal Analgesia Program\u003c/strong\u003e In the preoperative preparation room, peripheral venous access was established and different concentrations of ropivacaine FICB were performed; intraoperatively, the surgeon injected a \u0026quot;Cocktail\u0026quot; (ropivacaine 100mg, morphine 10mg, epinephrine 1 mg, and saline diluted to 100 mL) into the posterior capsule of the knee cavity, the medial collateral ligament, the patellar ligament, and subcutaneously in the incision. Postoperatively, patients were given Patient-Controlled Intravenous Analgesia (PCIA, sufentanil 1 \u0026mu;g/mL, PCA dose 3 mL, 30-min lockout) to maintain an NRS score of \u0026lt;4; if the NRS score was \u0026ge;4, remedial analgesic morphine 5-10 mg intramuscularly was given. Celecoxib sodium 0.2 g orally 3 times daily was given 2 d postoperatively.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAnesthesia Methods\u003c/strong\u003e The patients\u0026apos; NRS scores at rest and during exercise were measured before and 30 min after FICB, and skin sensory loss and quadriceps muscle strength in the anterior thigh were assessed. The surgery was completed under general anesthesia. General anesthesia induction: dexamethasone 0.1 mg\u0026middot;kg\u003csup\u003e-1\u003c/sup\u003e, propofol 2.0 mg\u0026middot;kg\u003csup\u003e-1\u003c/sup\u003e, sufentanil 0.5 \u0026mu;g\u0026middot;kg\u003csup\u003e-1\u003c/sup\u003e, and rocuronium bromide 0.6 mg\u0026middot;kg\u003csup\u003e-1\u003c/sup\u003e visual laryngoscopic endotracheal intubation followed by connection to a ventilator for mechanical ventilation. Pressure-controlled volume-assured mode ventilation with a tidal volume of 8-10 mg\u0026middot;kg\u003csup\u003e-1\u003c/sup\u003e, an inspiratory to expiratory ratio of 1:2, a ventilation rate of 12-16 breaths/min, and a maintenance PETCO\u003csub\u003e2\u003c/sub\u003e of 35-45 mmHg. Anesthesia Maintenance: Hydrostatic-inspiratory anesthesia, sevoflurane maintained at 0.6 MAC, propofol 2-4 mg\u0026middot;kg\u003csup\u003e-1\u003c/sup\u003e\u0026middot;h\u003csup\u003e-1\u003c/sup\u003e, remifentanil 0.25-2.00 \u0026mu;g\u0026middot;kg\u003csup\u003e-1\u003c/sup\u003e\u0026middot;min\u003csup\u003e-1\u003c/sup\u003e, intraoperative maintenance of BIS 40-60, systolic blood pressure fluctuations of not more than 20%. After induction of general anesthesia, ephedrine 6 mg IV was given prophylactically to prevent hypotension before loosening the tourniquet, and ephedrine 6 mg IV was given if the systolic blood pressure was less than 90 mmHg or 30% of the basal value occurred during the operation. If the systolic blood pressure exceeds 160 mmHg or 30% of the basal value, give uradil 12.5-25 mg IV. Stop the drug at the end of the operation, remove the tracheal tube, and send it to the Postoperative Anesthesia Care Unit (PACU) for observation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObservation Outcomes\u003c/strong\u003e The primary outcomes were the incidence of rebound pain at the surgical site after FICB subsided and the degree of pain after the block subsided. Definition of rebound pain: rebound pain was defined as the occurrence of the highest NRS score greater than or equal to 7 within 12 h after nerve block regression. The specific time of regression of the nerve block cannot be precisely defined at present, and in this study, the time of the first compression of the analgesic pump was used as the time of regression of FICB. Secondary outcomes: time to first postoperative analgesic pump press, effective number of presses for self-controlled analgesia, postoperative remedial analgesia rate, postoperative 0-24 h/24-48 h opioid consumption, postoperative NRS scores and muscle strength scores at rest and in activity at 24 h/48 h postoperatively, preoperative/postoperative 24 h/postoperative 48 h ELISA assay (Mutisciences, Inc.Guangzhou, China) interleukin-6 (IL-6, Human IL-6 ELISA Kit EK106/2-96) and tumor necrosis factor-\u0026alpha; (TNF-\u0026alpha;, Human TNF-a ELISA Kit EK182-96); and the incidence of postoperative nausea and vomiting (PONV) within 48 h postoperatively. The muscle power score refers to the modified Bromage score: the patient is in a supine position, and a 10-15 cm cushion is placed under the knee of the operated side. The patient is instructed to lift the lower leg with force; 0 points: the lower leg cannot move at all; 1 point: muscle contraction is observed, and the lower leg moves slightly but cannot lift off the bed surface; 2 points: the lower leg can be lifted off the bed surface, but cannot resist external force; 3 points: the lower leg can be lifted off the bed surface and can resist a certain amount of external force. The postoperative opioid dosage is standardized and converted to the dosage of sufentanil. The conversion of the dosage between morphine and sufentanil is completed online at https://clincalc.com/opioids.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u0026nbsp;\u003c/strong\u003eBased on the preliminary trial results (n=10), the incidence of rebound pain in the high-concentration and low-concentration groups is 20% and 50%, respectively. Assuming a test power of 0.8 and a significance level of 0.05, a sample size of 20 is required. Considering a 20% dropout rate, at least 24 patients should be included in each group. Statistical analysis was performed using the SPSS 20.0 software. Normally distributed continuous data were expressed as mean \u0026plusmn; standard deviation (\u0026plusmn;s), and inter-group comparisons were conducted using t-tests or one-way ANOVA. Non-normally distributed continuous data were expressed as median (M) and interquartile range (IQR), with inter-group comparisons performed using the Mann-Whitney U test. Categorical data comparisons were conducted using the \u0026chi;\u0026sup2; test or Fisher\u0026apos;s exact probability test. A \u003cem\u003eP\u003c/em\u003e value of \u0026lt;0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eGeneral Information\u003c/strong\u003e A total of 55 patients were included in this study; 3 were excluded due to postoperative bleeding and 4 were excluded due to delayed removal of drains because of bleeding risk. There was no statistically significant difference in age, BMI, gender, ASA classification, and length of hospitalization between the two groups; intraoperative remifentanil consumption was increased in Group A patients compared with Group B (Table 1).\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1 Baseline Characteristics and Intraoperative Medication in Two Groups\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 10.0694%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6319%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eExamples\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4167%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(y)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4167%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBMI\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.625%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(Male/Female)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.02778%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eASA\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(Ⅱ/Ⅲ)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e（\u003c/strong\u003e\u003cstrong\u003en\u003c/strong\u003e\u003cstrong\u003e）\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.1875%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIntraoperative remifentanil consumption\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(\u0026mu;g )\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.625%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLength of hospitalization\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(d)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 10.0694%;\"\u003e\n \u003cp\u003eGroup A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.6319%;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.4167%;\"\u003e\n \u003cp\u003e68.8\u0026plusmn;4.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.4167%;\"\u003e\n \u003cp\u003e25.2\u0026plusmn;1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e10/14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.02778%;\"\u003e\n \u003cp\u003e11/13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.1875%;\"\u003e\n \u003cp\u003e540.0（460.0~930.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.625%;\"\u003e\n \u003cp\u003e7.0（5.0~8.5）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 10.0694%;\"\u003e\n \u003cp\u003eGroup B\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6319%;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4167%;\"\u003e\n \u003cp\u003e67.4\u0026plusmn;4.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4167%;\"\u003e\n \u003cp\u003e25.4\u0026plusmn;1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.625%;\"\u003e\n \u003cp\u003e13/11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.02778%;\"\u003e\n \u003cp\u003e14/10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.1875%;\"\u003e\n \u003cp\u003e500.0（390.0~600.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.625%;\"\u003e\n \u003cp\u003e7.0（7.0~10.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 10.0694%;\"\u003e\n \u003cp\u003et/\u0026chi;\u003csup\u003e2\u003c/sup\u003e/Z\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6319%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4167%;\"\u003e\n \u003cp\u003e1.084\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4167%;\"\u003e\n \u003cp\u003e-0.653\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.625%;\"\u003e\n \u003cp\u003e0.725\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.02778%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.1875%;\"\u003e\n \u003cp\u003e-1.995\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.625%;\"\u003e\n \u003cp\u003e-0.427\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 10.0694%;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11.6319%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4167%;\"\u003e\n \u003cp\u003e\u0026gt;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.4167%;\"\u003e\n \u003cp\u003e\u0026gt;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.625%;\"\u003e\n \u003cp\u003e\u0026gt;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 9.02778%;\"\u003e\n \u003cp\u003e\u0026gt;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 17.1875%;\"\u003e\n \u003cp\u003e\u0026lt;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15.625%;\"\u003e\n \u003cp\u003e\u0026gt;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCompared with group B, group A had a lower incidence of rebound pain (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.01) and milder postoperative rebound pain (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.01) (Figure 1). The time of FICB regression could not be precisely measured in the clinical setting, and the time of the first analgesic pump compression was taken as the time of FICB regression in this study. Compared with Group B, Group A requested the first postoperative analgesia earlier (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.01), indicating that patients in the low-concentration group experienced earlier regression of FICB. The number of effective presses on the analgesic pump within 48 h postoperatively was lower (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.01), and the rate of remedial analgesia was also lower (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.05). Additionally, the consumption of opioid medications within 48 h postoperatively was reduced (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.01), while there was no statistically significant difference in opioid consumption between the two groups during the 24-48 h postoperative period. This indicates that the difference in sufentanil consumption primarily occurred within the first 24 h postoperatively (Figure 2).\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCompared with group B, patients in group A had lower exercise NRS scores at 24 h postoperatively (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.01), and there was no statistically significant difference in resting NRS scores; there was no statistically significant difference in both resting and exercise NRS scores at 48 h postoperatively (Figure 3). Blood inflammation-related factor IL-6 and TNF-\u0026alpha; concentrations were not statistically different between the two groups at preoperative, 24 h, and 48 h postoperatively (Figure 4).\u003c/p\u003e\n\u003cp\u003eCompared with group B, patients in Group A had higher muscle strength scores at 24 h postoperatively (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.01); there was no statistical difference in muscle strength scores and PONV incidence at 48 h postoperatively (Table 2). No adverse events such as local anesthetic poisoning, puncture site infection, hematoma, or delayed block recovery occurred in either group.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2 Comparison of the incidence of PONV and muscle strength\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ewithin the 48 h postoperatively between the two groups\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003eGroup\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003eExamples\u003c/p\u003e\n \u003cp\u003e(n)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003eNumber of cases of PONV（%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003ePostoperative muscle strength\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e24 h\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e48 h\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eGroup A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e13（55）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.0（1.0-2.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.0（1.0~2.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eGroup B\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e9（40）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0（0-1.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.0（1.0~2.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026chi;\u003csup\u003e2\u003c/sup\u003e/Z\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.104\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-3.528\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-1.731\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026gt;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026lt;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026gt;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, patients undergoing TKA in the high-concentration group (0.3% ropivacaine) exhibited a higher incidence of rebound pain following FICB, and the severity of rebound pain was more pronounced. After the occurrence of rebound pain, opioid consumption in the 0-24 h period was higher, which is similar to the findings of Dada et al. \u003csup\u003e[13]\u003c/sup\u003e; the remedial analgesia rate in the high-concentration group was higher than that in the low-concentration group. Although patients of the low-concentration group pressed the analgesic pump earlier, the effective press counts within 48 h postoperatively were fewer; moreover, the total opioid consumption within 48 h postoperatively did not increase,\u0026nbsp;the remedial analgesia rate was lower, the 24 h movement NRS score was lower, and muscle strength recovery was better. Additionally, patients in the low-concentration group did not exhibit significant increases in serum interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-\u0026alpha;) concentrations at preoperative, 24 h, and 48 h postoperative time points (Figure 4).\u003c/p\u003e\n\u003cp\u003eTKA is associated with significant trauma and requires early postoperative rehabilitation training; therefore, patients often experience severe pain for 48 h or longer postoperatively. In this study, under the same volume, the high-concentration group received a higher concentration and larger dose of ropivacaine, resulting in a longer duration of nerve block. The duration of blockade from a single high-concentration injection rarely exceeded 48 h. While the nerve block remained effective, patients in the high-concentration group typically\u0026nbsp;didn\u0026rsquo;t\u0026nbsp;use the analgesic pump for additional analgesia.\u0026nbsp;However, since the resolution of the nerve block often occurred within a few minutes to tens of minutes, exhibiting a rapid \u0026quot;on-off\u0026quot; transition \u003csup\u003e[7]\u003c/sup\u003e, and by that time, plasma opioids may have already been fully metabolized. Therefore, when the nerve block suddenly wore off, the sufentanil administered via the analgesic pump may not have provided timely and adequate coverage for the pain signals that emerged after block resolution, leading to the so-called \u0026quot;rebound pain.\u0026quot;\u003c/p\u003e\n\u003cp\u003eThis study suggests that patients in the high-concentration group exhibited the aforementioned disadvantages during the transition from neuraxial analgesia to intravenous analgesia, which was one of the main reasons for the occurrence of rebound pain. In the low-concentration group, the nerve block duration was shorter and the intensity was lower, prompting patients to initiate analgesic pump use earlier, thereby maintaining a certain plasma concentration of sufentanil intraoperatively and postoperatively. Analgesia in the low-concentration group could smoothly translate from nerve-block-dominated analgesia to intravenous drug analgesia. Continuous adductor canal block may have been one of the ideal options to simultaneously address the issues of insufficient analgesia duration and quadriceps femoris muscle strength decline after blockade \u003csup\u003e[14,15]\u003c/sup\u003e; however, it also involved catheter-related technical demands and risks of complications.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIt is reported that methods to reduce postoperative rebound pain include intravenous administration of ketamine and the addition of adjuvants to nerve-blocking medications \u003csup\u003e[16,17]\u003c/sup\u003e.\u0026nbsp;Although adding adjuvants could extend the analgesic duration of nerve block agents, ensuring that block resolution occurred after the period of severe postoperative pain, for TKA patients, simply prolonging block duration by increasing local anesthetic concentration or adding adjuvants had limited effectiveness and was difficult to comprehensively cover the entire postoperative pain cycle \u003csup\u003e[18]\u003c/sup\u003e. Recent studies indicated that a novel ultra-long-acting local anesthetic, liposomal bupivacaine, could last up to 72 h; liposomal bupivacaine adductor canal block could effectively reduce opioid consumption and improve postoperative analgesia after TKA, but its efficacy and optimal concentration in FICB required further investigation\u0026nbsp;\u003csup\u003e[19]\u003c/sup\u003e. Developing a more reasonable multimodal analgesia management plan\u0026nbsp;\u003csup\u003e[20]\u003c/sup\u003e to transition patients from nerve block analgesia to pharmacological analgesia may have been an effective strategy to alleviate rebound pain; furthermore, multimodal analgesia could also alleviate postoperative anxiety and depression among patients undergoing TKA, improved postoperative recovery, shortened hospital stays, and offered other benefits \u003csup\u003e[21]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eThrough animal experiments, it has been found that high-concentration local anesthetics affect the physiological electrical activity of nerve fibers, leading to aseptic inflammation around the nerves.\u003csup\u003e[22]\u003c/sup\u003e; Clinically, the hyperalgesia caused by perineural inflammation after the resolution of neural blockade may contribute to the occurrence of postoperative rebound pain.\u0026nbsp;\u003csup\u003e[13,23]\u003c/sup\u003e. IL-6 and TNF-\u0026alpha; were pro-inflammatory factors produced by inflammatory cells in periarticular tissues and synovium after TKA, and previous studies showed that IL-6 and TNF-\u0026alpha; peaked on the first postoperative day\u0026nbsp;\u003csup\u003e[24,25,26]\u003c/sup\u003e.\u0026nbsp;In this study, cytokine levels on postoperative day 1 were similar between the low-concentration and high-concentration groups, indicating that low-concentration local anesthetics used in FICB did not increase intraoperative stress-related inflammatory cytokines in patients.\u0026nbsp;This suggested that 0.1% ropivacaine and 0.3% ropivacaine had similar effects in reducing postoperative stress levels.\u003c/p\u003e\n\u003cp\u003eNotably, 0.1% ropivacaine exhibited significant sensory-motor block dissociation characteristics, did not affect quadriceps femoris muscle strength (Table 2), and reduced systemic discomfort caused by prolonged forced positioning, which may have been one of the reasons for the lower 24 h movement NRS scores in the low-concentration group patients. Many postoperative pains were predictable and acceptable, but limb numbness, movement limitations, and rebound pain caused by high-concentration local anesthetic regional nerve blocks could reduce patients\u0026apos; overall satisfaction with postoperative analgesia from regional nerve blocks\u0026nbsp;\u003csup\u003e[6]\u003c/sup\u003e. Reducing the occurrence of rebound pain after a nerve block could enhance the utility of nerve blocks for perioperative analgesia.\u003c/p\u003e\n\u003cp\u003eThere were some limitations in this study. To more comprehensively block the sensory nerve branches around the knee joint, in addition to fascia iliaca block, the surgeon performed periarticular capsule block intraoperatively. To minimize the impact of periarticular capsule block, the same surgeon was selected to perform the procedures in this study; however, this study only compared the high-concentration group and the low-concentration group, and it was necessary to expand the sample size to further systematically explore the effects of different concentration gradients of local anesthetics on rebound pain.\u003c/p\u003e\n\u003cp\u003eThe results of this study indicated that, in multimodal analgesia for patients after TKA, the incidence of rebound pain after the resolution of\u0026nbsp;FICB\u0026nbsp;with low-concentration ropivacaine was lower and the muscle strength score at 24 h postoperatively was higher, which facilitated early postoperative rehabilitation training and improved patient satisfaction with analgesia. Low-concentration ropivacaine FICB was more suitable for multimodal analgesia in TKA patients.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to acknowledge the hard and dedicated work of all the staff that implemented the intervention and evaluation components of the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was funded by The Second Affiliated Hospital of Soochow University Discipline Construction Torrent Project (XKTJ-TD202008) and Suzhou Applied Basic Research on Livelihood Science and Technology for Healthcare (SYS2019074).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted with approval fromtheEthics Committee of \u0026nbsp;Suzhou Xiangcheng People\u0026apos;s Hospital (2022-KY-05; October 14, 2022). This study was conducted in accordance with the declaration of Helsinki. Written informed consent was acquired from all participating patients or their legal representatives.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatient consent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eObtained.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMarty P, Chassery C, Rontes O, et al. Combined proximal or distal nerve blocks for postoperative analgesia after total knee arthroplasty: a randomised controlled trial. 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J Orthop Surg Res. 2023;18(1):712. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s13018-023-04192-8\u003c/span\u003e\u003cspan address=\"10.1186/s13018-023-04192-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWilliams BA, Hough KA, Tsui BY, et al. Neurotoxicity of adjuvants used in perineural anesthesia and analgesia in comparison with ropivacaine. Reg Anesth Pain Med. 2011;36(3):225\u0026ndash;30. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/AAP.0b013e3182176f70\u003c/span\u003e\u003cspan address=\"10.1097/AAP.0b013e3182176f70\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVerlinde M, Hollmann MW, Stevens MF, et al. Local Anesthetic-Induced Neurotoxicity. 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Anesthesiology. 2008;109(3):484\u0026ndash;90. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/ALN.0b013e318182c2a1\u003c/span\u003e\u003cspan address=\"10.1097/ALN.0b013e318182c2a1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Total Knee Arthroplasty, Ropivacaine, Postoperative Analgesia, Nerve Block, Rebound Pain,","lastPublishedDoi":"10.21203/rs.3.rs-5377904/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5377904/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective: \u003c/strong\u003eThe aim of this research was to evaluate the effect of two different local anesthetic concentrations on rebound pain following Fascial Iliac Compartment Block (FICB) retreat in patients undergoing total knee arthroplasty (TKA).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethod:\u003c/strong\u003e 48 patients undergoing unilateral TKA under elective general anesthesia were randomly divided into two groups (n=24): the 0.1% ropivacaine group (Group A) and the 0.3% ropivacaine group (Group B). Before anesthesia, two groups of patients underwent a single ultrasound guided- FICB above the inguinal ligament, with 40 mL of 0.1% or 0.3% ropivacaine; all patients underwent perioperative multimodal analgesia. The first outcomes are incidence and degree of postoperative rebound pain; secondary outcomes are remedial analgesia rate within 48h postoperatively, opioid consumption from 0-24 h and 24-48 h postoperatively, NRS scores and muscle strength scores at rest and exercise at 24h and 48h postoperatively, and intravenous serum concentrations of interleukin-6 (IL-6) and tumor necrosis factor α(TNF-α) before surgery and at 24 and 48 h after surgery.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eIn group A\u003cstrong\u003e, \u003c/strong\u003ethe incidence of postoperative rebound pain was lower (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.01), and the degree of rebound pain was milder (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.01). The remedial analgesia rate was lower within 48 h after surgery (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.05); opioid consumption was lower at 0-24 h after surgery (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.01); the postoperative NRS score at 24 h was lower (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.01), while the muscle strength score was higher (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.01); There was no statistically significant difference in intravenous serum concentrations of IL-6 and TNF-α before surgery, and at 24 and 48 h after surgery.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e The incidence of rebound pain after the resolution of FICB with low-concentration ropivacaine was lower, and low-concentration ropivacaine FICB was more suitable for multimodal analgesia in TKA patients.\u003c/p\u003e","manuscriptTitle":"Effect of two concentrations of ropivacaine on rebound pain after retreat of iliac fascia block in patients undergoing total knee arthroplasty：a prospective, double-blind randomized controlled trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-11 13:30:10","doi":"10.21203/rs.3.rs-5377904/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"96cb4611-583b-47d7-b15b-05e2e017af6a","owner":[],"postedDate":"December 11th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-07-31T06:54:11+00:00","versionOfRecord":[],"versionCreatedAt":"2024-12-11 13:30:10","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5377904","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5377904","identity":"rs-5377904","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}