Efficacy of compound betamethasone combined with ropivacaine in iliac fascial space nerve block analgesia
Artificial femoral head replacement (AFHR) is primarily indicated for the treatment of femoral head fractures, necrosis, and femoral neck fractures , . The majority of patients undergoing AFHR are elderly and often present with multiple comorbidities, which renders them less tolerant to the risks associated with surgery and analgesia. Moreover, the pain resulting from surgical trauma can trigger a cascade of stress responses in the body, significantly heightening the risk of perioperative complications and delaying recovery , . Iliac fascial space nerve block analgesia (IFNBA) is frequently utilized during AFHR, often in conjunction with subarachnoid analgesia. Ropivacaine, a long-acting amide local anesthetic, is the most commonly used agent in IFNBA due to its superior ability to selectively block sensory nerve fibers over motor fibers. It achieves anesthetic effects by inhibiting sodium ion channels in nerve cells, leading to effective nerve conduction blockade, while presenting lower toxicity to the central nervous system and myocardium, thus ensuring greater safety and controllability – . The use of adjunctive medications has been shown to enhance the efficacy of local anesthetics, accelerate the onset of sensory and motor blocks, and improve analgesic outcomes without significant adverse reactions. Currently, the selection of adjuvant agents for local anesthetics remains a prominent area of research, with dexamethasone being the most commonly employed corticosteroid adjunct in IFNBA – . Compound betamethasone represents a promising alternative as a local anesthetic adjuvant, characterized by its prolonged duration of action, extending beyond four weeks. Its local application effectively reduces inflammatory exudation and enhances local blood circulation, thereby alleviating acute postoperative pain when combined with local anesthetics , . While compound betamethasone has been primarily studied in brachial plexus blocks, paravertebral nerve blocks, and transverse abdominal plane blocks – , its application in lower limb nerve blocks remains underexplored. This study aims to evaluate the anesthetic efficacy of ropivacaine combined with compound betamethasone in IFNBA for patients undergoing AFHR, providing a theoretical foundation for the selection of clinical anesthetic agents.   Subjects From January 2022 to June 2022, 70 patients requiring IFNBA analgesia undergoing AFHR surgery at our hospital were included in this prospective study. Using Excel randomization, 70 patients were divided into study group ( n = 35) and control group ( n = 35). The study group received ropivacaine combined with compound betamethasone analgesia regimen, while the control group only received ropivacaine analgesia regimen (Fig. ). This study protocol was formulated in accordance with the requirements of the Declaration of Helsinki of the World Medical Association. It was approved by the Ethics Committee of Chengde Central Hospital (NO. CDCHLL2022-401), and the informed consent forms were obtained from all patients. This study was previously registered at Chinese Clinical Trial Registry (No. ChiCTR2100052214, Date: 22/10/2021). Inclusion and exclusion criteria Inclusion criteria Patients undergoing artificial femoral head replacement (AFHR) surgery. Patients aged over 65 years. Patients classified as American Society of Anesthesiologists (ASA) grades I to III. Patients with a body mass index (BMI) ranging from 19.1 to 28 kg/m². Exclusion criteria Patients with a known allergy to ropivacaine or compound betamethasone. Patients diagnosed with peripheral neuropathy. Patients exhibiting severe dysfunction of the heart, lungs, liver, or kidneys. Patients with inflammation or infection at the injection site. Patients who have previously received opioid analgesics. Patients with a history of mental illness. Patients with malignant tumors. Patients sustaining multiple traumatic injuries. Patients with an inguinal hernia. Patients requesting a postoperative analgesia pump. Patients with diabetes. Treatment protocol All patients received subarachnoid anesthesia combined with ultrasound-guided IFNBA. Upon admission to the operating room, venous access was routinely established, baseline indicators including heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), oxygen saturation (SpO 2 ), and electrocardiogram were monitored, and oxygen was administered with a mask. The iliofascial nerve block was carried out using the P300 model produced by Siemens. The ultrasonic probe was placed in the inguinal ligament, and the femoral artery of the tested patient was scanned by ultrasound to carefully identify the iliofascial fascia, deep circumflex iliac artery, iliopsoas muscle, femoral nerve and other tissue structures (Fig. ). The nerve puncture needle was inserted into the skin at an Angle of 30°, and drugs were injected after the puncture needle reached the iliofascial space through ultrasound observation. The study group received 30 ml of mixed anesthetic (including 7 mg betamethasone and the rest 0.4% ropivacaine), while the control group received only 0.4% ropivacaine 30 ml. For ilioinguinal nerve block, the two groups were injected with corresponding local anesthetics respectively, followed by subarachnoid analgesia. Both groups received 2 ml of 0.375% bupivacaine with a low density, and the analgesia level was controlled at T10. The duration of postoperative analgesia and the dosage of analgesic drugs were recorded (Oxycodone and flurbiprofen ester were used as analgesic drugs in both groups, including 1 mg/kg of oxycodone during operation, 1 mg/kg of oxycodone after operation, 200 mg of flurbiprofen ester diluted into normal saline to 100 ml, and the infusion rate was 2 ml/h). Outcome indicators Blind method: The randomization in this study was based on random numbers generated by the randomization sequence in SPSS 22.0 software. Personnel involved in this randomization process did not participate in patient recruitment or drug administration. An anesthesiologist who was not involved in the study was selected from the department to prepare the study drugs in syringes of the same specification according to the randomization groups. Blinding was implemented for patients, surgeons, anesthesiologists participating in the study, follow-up personnel, and data analysts. Primary outcome measures: The VAS pain scores (Fig. ) at rest and during movement were observed and recorded at 6 h, 12 h, 24 h, and 48 h postoperatively. The Ramsay sedation scores (Table ) were recorded before the block and at 6 h, 12 h, 24 h, and 48 h postoperatively in both groups. Secondary outcome measures: The duration of analgesia, patient satisfaction, and changes in inflammatory factor levels before and after surgery in both groups were recorded and compared. Indicators of inflammatory factor levels, including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), were measured and collected before, at the completion of surgery, 24 h and 72 h after surgery. Blood was drawn via the cubital vein. 5 ml of venous blood was placed in a sterile non-anticoagulant tube, and then centrifuged at 3000 rpm for 10 min to collect the supernatant. The levels of TNF-α and IL-6 were determined by enzyme-linked immunoassay kit. The duration of analgesia refers to the time between the end of anesthetic drug injection and the time when the patient feels significant pain in the surgical incision after surgery. Evaluation of postoperative analgesia satisfaction: Patient satisfaction was assessed by the study team according to the Houston Pain Status Questionnaire (HPOI). HPOI mainly includes eight dimensions: pain expectation, pain experience, pain’s impact on emotions, pain’s impact on the body or daily life, satisfaction with pain control or relief methods, satisfaction with pain control education, satisfaction with pain care, and overall satisfaction with pain control. The score for each dimension is 1–10, with a total score of 80. The lower the score, the worse the patient satisfaction. The total score of ≥ 72 is satisfactory, 48–72 is generally satisfactory, and < 48 is unsatisfactory. Satisfaction = (total number of cases - dissatisfied cases)/Total number of cases ×100% . Long-term follow-up index: Patients in both groups were followed up for 3 months after surgery, and adverse reactions such as puncture site infection, superficial surgical site infection, deep surgical site infection, lower extremity venous embolism, pulmonary embolism, nausea and vomiting, and delayed wound healing were recorded in both groups. Sample size calculation Sample size determination was conducted prior to the study using G*Power software (version 3.1.9.4). We aimed to achieve a significance level (α) of 0.05 (two-tailed) and a power (1-β) of 0.90 to detect a clinically significant difference in the visual analogue scale (VAS) pain scores between the two groups. Based on previous studies and pilot data, we estimated an effect size of 0.8 for the difference in VAS scores. Utilizing these parameters, the calculation indicated that a total of 70 patients, with 35 patients in each group, would provide adequate power to detect the anticipated difference. This sample size was deemed sufficient to ensure the robustness of our statistical analyses. Statistical analysis Data collected in this study were analyzed using SPSS version 22.0 software. The normality of continuous variables was assessed using the Shapiro-Wilk test, in conjunction with graphical representations such as histograms and Q-Q plots. Normally distributed measurement data are presented as mean ± standard deviation (SD), while non-normally distributed data are expressed as median (interquartile range). Comparisons between groups were conducted using the Student’s t-test for normally distributed data and the Mann-Whitney U test for non-parametric distributions. Categorical data are reported as n , with differences between the two groups analyzed using chi-square tests or Fisher’s Exact Test, as appropriate. A two-sided significance level of 0.05 was established for all statistical tests.   From January 2022 to June 2022, 70 patients requiring IFNBA analgesia undergoing AFHR surgery at our hospital were included in this prospective study. Using Excel randomization, 70 patients were divided into study group ( n = 35) and control group ( n = 35). The study group received ropivacaine combined with compound betamethasone analgesia regimen, while the control group only received ropivacaine analgesia regimen (Fig. ). This study protocol was formulated in accordance with the requirements of the Declaration of Helsinki of the World Medical Association. It was approved by the Ethics Committee of Chengde Central Hospital (NO. CDCHLL2022-401), and the informed consent forms were obtained from all patients. This study was previously registered at Chinese Clinical Trial Registry (No. ChiCTR2100052214, Date: 22/10/2021).   Inclusion criteria Patients undergoing artificial femoral head replacement (AFHR) surgery. Patients aged over 65 years. Patients classified as American Society of Anesthesiologists (ASA) grades I to III. Patients with a body mass index (BMI) ranging from 19.1 to 28 kg/m². Exclusion criteria Patients with a known allergy to ropivacaine or compound betamethasone. Patients diagnosed with peripheral neuropathy. Patients exhibiting severe dysfunction of the heart, lungs, liver, or kidneys. Patients with inflammation or infection at the injection site. Patients who have previously received opioid analgesics. Patients with a history of mental illness. Patients with malignant tumors. Patients sustaining multiple traumatic injuries. Patients with an inguinal hernia. Patients requesting a postoperative analgesia pump. Patients with diabetes.   Patients undergoing artificial femoral head replacement (AFHR) surgery. Patients aged over 65 years. Patients classified as American Society of Anesthesiologists (ASA) grades I to III. Patients with a body mass index (BMI) ranging from 19.1 to 28 kg/m².   Patients with a known allergy to ropivacaine or compound betamethasone. Patients diagnosed with peripheral neuropathy. Patients exhibiting severe dysfunction of the heart, lungs, liver, or kidneys. Patients with inflammation or infection at the injection site. Patients who have previously received opioid analgesics. Patients with a history of mental illness. Patients with malignant tumors. Patients sustaining multiple traumatic injuries. Patients with an inguinal hernia. Patients requesting a postoperative analgesia pump. Patients with diabetes.   All patients received subarachnoid anesthesia combined with ultrasound-guided IFNBA. Upon admission to the operating room, venous access was routinely established, baseline indicators including heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), oxygen saturation (SpO 2 ), and electrocardiogram were monitored, and oxygen was administered with a mask. The iliofascial nerve block was carried out using the P300 model produced by Siemens. The ultrasonic probe was placed in the inguinal ligament, and the femoral artery of the tested patient was scanned by ultrasound to carefully identify the iliofascial fascia, deep circumflex iliac artery, iliopsoas muscle, femoral nerve and other tissue structures (Fig. ). The nerve puncture needle was inserted into the skin at an Angle of 30°, and drugs were injected after the puncture needle reached the iliofascial space through ultrasound observation. The study group received 30 ml of mixed anesthetic (including 7 mg betamethasone and the rest 0.4% ropivacaine), while the control group received only 0.4% ropivacaine 30 ml. For ilioinguinal nerve block, the two groups were injected with corresponding local anesthetics respectively, followed by subarachnoid analgesia. Both groups received 2 ml of 0.375% bupivacaine with a low density, and the analgesia level was controlled at T10. The duration of postoperative analgesia and the dosage of analgesic drugs were recorded (Oxycodone and flurbiprofen ester were used as analgesic drugs in both groups, including 1 mg/kg of oxycodone during operation, 1 mg/kg of oxycodone after operation, 200 mg of flurbiprofen ester diluted into normal saline to 100 ml, and the infusion rate was 2 ml/h).   Blind method: The randomization in this study was based on random numbers generated by the randomization sequence in SPSS 22.0 software. Personnel involved in this randomization process did not participate in patient recruitment or drug administration. An anesthesiologist who was not involved in the study was selected from the department to prepare the study drugs in syringes of the same specification according to the randomization groups. Blinding was implemented for patients, surgeons, anesthesiologists participating in the study, follow-up personnel, and data analysts. Primary outcome measures: The VAS pain scores (Fig. ) at rest and during movement were observed and recorded at 6 h, 12 h, 24 h, and 48 h postoperatively. The Ramsay sedation scores (Table ) were recorded before the block and at 6 h, 12 h, 24 h, and 48 h postoperatively in both groups. Secondary outcome measures: The duration of analgesia, patient satisfaction, and changes in inflammatory factor levels before and after surgery in both groups were recorded and compared. Indicators of inflammatory factor levels, including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), were measured and collected before, at the completion of surgery, 24 h and 72 h after surgery. Blood was drawn via the cubital vein. 5 ml of venous blood was placed in a sterile non-anticoagulant tube, and then centrifuged at 3000 rpm for 10 min to collect the supernatant. The levels of TNF-α and IL-6 were determined by enzyme-linked immunoassay kit. The duration of analgesia refers to the time between the end of anesthetic drug injection and the time when the patient feels significant pain in the surgical incision after surgery. Evaluation of postoperative analgesia satisfaction: Patient satisfaction was assessed by the study team according to the Houston Pain Status Questionnaire (HPOI). HPOI mainly includes eight dimensions: pain expectation, pain experience, pain’s impact on emotions, pain’s impact on the body or daily life, satisfaction with pain control or relief methods, satisfaction with pain control education, satisfaction with pain care, and overall satisfaction with pain control. The score for each dimension is 1–10, with a total score of 80. The lower the score, the worse the patient satisfaction. The total score of ≥ 72 is satisfactory, 48–72 is generally satisfactory, and < 48 is unsatisfactory. Satisfaction = (total number of cases - dissatisfied cases)/Total number of cases ×100% . Long-term follow-up index: Patients in both groups were followed up for 3 months after surgery, and adverse reactions such as puncture site infection, superficial surgical site infection, deep surgical site infection, lower extremity venous embolism, pulmonary embolism, nausea and vomiting, and delayed wound healing were recorded in both groups.   Sample size determination was conducted prior to the study using G*Power software (version 3.1.9.4). We aimed to achieve a significance level (α) of 0.05 (two-tailed) and a power (1-β) of 0.90 to detect a clinically significant difference in the visual analogue scale (VAS) pain scores between the two groups. Based on previous studies and pilot data, we estimated an effect size of 0.8 for the difference in VAS scores. Utilizing these parameters, the calculation indicated that a total of 70 patients, with 35 patients in each group, would provide adequate power to detect the anticipated difference. This sample size was deemed sufficient to ensure the robustness of our statistical analyses.   Data collected in this study were analyzed using SPSS version 22.0 software. The normality of continuous variables was assessed using the Shapiro-Wilk test, in conjunction with graphical representations such as histograms and Q-Q plots. Normally distributed measurement data are presented as mean ± standard deviation (SD), while non-normally distributed data are expressed as median (interquartile range). Comparisons between groups were conducted using the Student’s t-test for normally distributed data and the Mann-Whitney U test for non-parametric distributions. Categorical data are reported as n , with differences between the two groups analyzed using chi-square tests or Fisher’s Exact Test, as appropriate. A two-sided significance level of 0.05 was established for all statistical tests.   Baseline clinical characteristics A total of 70 patients underwent AFHR surgery, with the study group comprising 35 patients (mean age: 64.36 ± 9.08 years; 21 males and 14 females) and the control group comprising 35 patients (mean age: 64.13 ± 9.21 years; 20 males and 15 females). There were no statistically significant differences between the two groups of patients in terms of gender, age, BMI, ASA grades, preoperative static VAS score, preoperative dynamic VAS score, preoperative Ramsay sedation score, preoperative TNF-α levels, and preoperative IL-6 levels. ( P > 0.05) (Table ). Comparison of postoperative VAS Pain scores At 12 and 24 h postoperatively, the static and dynamic VAS pain scores in the study group were significantly lower than those in the control group ( P < 0.001). However, there were no significant differences in static and dynamic VAS pain scores between the two groups at 6 and 48 h postoperatively ( P > 0.05).(Table ). Comparison of Postoperative Ramsay Sedation scores At 6 and 12 h after surgery, the Ramsay sedation scores in the study group were significantly higher than those in the control group ( P < 0.001). No significant differences in Ramsay sedation scores were found between the two groups at 24 and 48 h postoperative ( P > 0.05) (Table ). Comparison of postoperative inflammatory factor levels The levels of TNF-α and IL-6 in the study group were significantly lower than those in the control group at the completion of surgery, as well as at 24 and 72 h after surgery ( P < 0.001) (Table ). Comparison of duration of postoperative analgesia and patient satisfaction The duration of postoperative analgesia and patient satisfaction in the study group were all significantly greater than those in the control group ( P < 0.05) (Table ). Comparison of postoperative adverse reactions Patients in both groups were followed up for 3 months after surgery, and no puncture site infection, lower extremity artery embolism, pulmonary embolism or deep infection occurred. In the study group, superficial surgical site infection occurred in 1 case (2.86%), delayed wound healing in 3 cases (8.57%), nausea and vomiting in 2 cases (5.71%). In the control group, there were 2 cases of superficial infection (5.71%), 2 cases of delayed wound healing (5.71%), and 3 cases of nausea and vomiting (8.57%). There was no statistical significance in the incidence of the above adverse reactions between groups ( P > 0.05) (Table ).   A total of 70 patients underwent AFHR surgery, with the study group comprising 35 patients (mean age: 64.36 ± 9.08 years; 21 males and 14 females) and the control group comprising 35 patients (mean age: 64.13 ± 9.21 years; 20 males and 15 females). There were no statistically significant differences between the two groups of patients in terms of gender, age, BMI, ASA grades, preoperative static VAS score, preoperative dynamic VAS score, preoperative Ramsay sedation score, preoperative TNF-α levels, and preoperative IL-6 levels. ( P > 0.05) (Table ).   At 12 and 24 h postoperatively, the static and dynamic VAS pain scores in the study group were significantly lower than those in the control group ( P < 0.001). However, there were no significant differences in static and dynamic VAS pain scores between the two groups at 6 and 48 h postoperatively ( P > 0.05).(Table ).   At 6 and 12 h after surgery, the Ramsay sedation scores in the study group were significantly higher than those in the control group ( P < 0.001). No significant differences in Ramsay sedation scores were found between the two groups at 24 and 48 h postoperative ( P > 0.05) (Table ).   The levels of TNF-α and IL-6 in the study group were significantly lower than those in the control group at the completion of surgery, as well as at 24 and 72 h after surgery ( P < 0.001) (Table ).   The duration of postoperative analgesia and patient satisfaction in the study group were all significantly greater than those in the control group ( P < 0.05) (Table ).   Patients in both groups were followed up for 3 months after surgery, and no puncture site infection, lower extremity artery embolism, pulmonary embolism or deep infection occurred. In the study group, superficial surgical site infection occurred in 1 case (2.86%), delayed wound healing in 3 cases (8.57%), nausea and vomiting in 2 cases (5.71%). In the control group, there were 2 cases of superficial infection (5.71%), 2 cases of delayed wound healing (5.71%), and 3 cases of nausea and vomiting (8.57%). There was no statistical significance in the incidence of the above adverse reactions between groups ( P > 0.05) (Table ).   For elderly patients with femoral head fractures, healing can be challenging, and functional loss is common. Anterior femoral head replacement (AFHR) is an effective surgical treatment for such fractures. However, postoperative pain can be severe, and the short duration of single-injection subarachnoid analgesia and peripheral nerve block analgesia impedes timely early functional exercise, thereby delaying recovery. To address this, we investigated the analgesic efficacy of combining subarachnoid analgesia with ultrasound-guided iliac fascia nerve block (IFNBA) for AFHR surgery – . Our findings demonstrate that IFNBA is not only straightforward to administer but also offers a high success rate in pain relief, significantly improving both acute and chronic postoperative pain while minimizing adverse effects. Previous studies have reported positive outcomes with IFNBA in other types of surgery. For instance, Wang utilized ultrasound-guided IFNBA in patients with intertrochanteric femur fractures, showing more accurate anesthetic effects and improved hemodynamic stability compared to traditional methods . Another study found that combining ultrasound-guided high IFNBA with sacral plexus block in elderly patients with hip fractures led to better analgesia and reduced narcotic use, with minimal cognitive impact . Despite its benefits, local anesthesia can have adverse reactions, such as respiratory depression, nausea, vomiting, and urinary retention. Therefore, extending the analgesic effects of local anesthetics is a growing concern. Ropivacaine is preferred for peripheral nerve blocks due to its high safety profile and effectiveness , . Betamethasone, identified as a promising adjuvant through literature review, has been primarily studied in brachial plexus, paravertebral, and transverse abdominal muscle plane blocks , – . The study results showed that the anesthetic effect of IFNBA combined in iliac fascia block was more lasting, and the analgesic effect was good, and the inflammatory response of patients was also improved to a certain extent. The main components of compound betamethasone are betamethasone sodium phosphate and betamethasone dipropionate. After betamethasone enters the ropivacaine solution, part of it is present in pellet form, and pellet steroids are thought to be a local reserve that gradually decays and releases steroids, leading to a more lasting effect . Other studies have shown that the combination of compound betamethasone and local anesthetics increases the duration of analgesic action by prolonging the half-life of ropivacaine. Betamethasone is easy to bind to extracellular receptors, thus changing the molecular arrangement on the surface of the cell membrane, resulting in membrane obstruction and blocking the entry and exit of certain substrates, metabolites and water, which extends the half-life of ropivacaine in human body to a certain extent . The study results of Zhang et al. showed that when compound betamethasone was added to ropivacaine for analgesia after knee joint replacement, the VAS scores of patients with static and dynamic pain at 12 h and 24 h after surgery were significantly lower than those in the control group, and the number of patients in the study group using flurbiprofen axidate for analgesia was significantly lower than that in the control group, and the satisfaction with analgesia in study group was higher . The results of this study were basically consistent with the above results. Compound betamethasone plus ropivacaine applied to IFNBA resulted in significantly lower static and dynamic VAS pain scores at 12 and 24 h after surgery than that of the control group, and the duration of postoperative analgesia was significantly longer than that in the control group. It can be seen that the compound betamethasone combined with ropivacaine in peripheral nerve block can indeed prolong the time of labor pain and improve the analgesic effect. In addition, the study group had a higher satisfaction rate of analgesia, which was 80%, indicating that the addition of compound betamethasone could effectively improve the postoperative quality of life of patients. Cytokines such as IL-6 and TNF are linked to immune responses, acute inflammation, and chronic inflammation. Compound betamethasone, a long-acting corticosteroid with potent glucocorticoid and mild salocorticoid activities, has substantial anti-inflammatory effects , , . Our study showed significantly lower levels of TNF-α and IL-6 in the study group compared to the control group at surgery completion, and 24 and 72 h after surgery. This reduction may result from compound betamethasone’s ability to decrease capillary permeability and inhibit IL and TNF secretion, thus mitigating inflammation and tissue damage. Additionally, Ramsay sedation scores at 6 and 12 h after surgery were significantly higher in the study group, likely due to the extended anesthetic effects from the combined drug regimen. This study has limitations, including a small sample size that affects result generalizability and the absence of dexamethasone combined with ropivacaine as a control, preventing direct comparison of betamethasone’s superiority. Future research with larger sample sizes is needed to further explore and confirm the clinical advantages of combining ropivacaine with compound betamethasone in IFNBA.   For patients undergoing AFHR, the combination of ropivacaine and compound betamethasone in IFNBA offers superior analgesia, higher patient satisfaction, and effective reduction of inflammatory status, warranting its clinical promotion and application.   