Continuous Intra-Incisional Bupivacaine for Postoperative Analgesia after Hip Nailing Surgery: A Randomized Clinical Trial

Background The effectiveness of continuous wound infiltration (CWI) as a postoperative pain-control technique has been shown in many surgical procedures. This study investigates the effect of CWI of local anesthetic on postoperative pain control in intertrochanteric fracture patients undergoing hip nailing surgery. Methods In this randomized clinical trial, 48 patients who were scheduled for hip nailing surgery were randomly assigned to receive (n = 24) or not receive (n = 24) bupivacaine infusion through a catheter inside the surgical wound, postoperatively. Pain intensity (NRS), required dose of morphine, and drug-related complications within 24 hours of the intervention were assessed and compared. Results Pain intensity was significantly lower in the bupivacaine group both during the recovery room stay and in the ward in the first 24 hours after the procedure (P < 0.001). In the recovery room, the control group patients had a higher morphine consumption compared to the bupivacaine group (P < 0.001) and requested it earlier than the bupivacaine group (60 (45–60) vs. 360 (195–480) minutes) (P < 0.001). In the ward, all control group patients used the PCA morphine pump, while only 54% of the bupivacaine group self-administered morphine through the pump, with a significantly lower total morphine consumption (1 (0–2) vs. 10 (5–14) mg, P < 0.001). None of the patients in the bupivacaine group required additional morphine, while 37.5% of the control requested additional morphine (P=0.002). Altogether, the control group had a higher total morphine consumption compared to the bupivacaine group in the first 24 hours (10.5 (6–15.5) vs. 1 (0–2) mg, P < 0.001). Conclusion CWI of bupivacaine helps better pain reduction during the early postoperative hours while it reduces opioid consumption, minimizes nausea and vomiting, and improves patient satisfaction.


Introduction
Orthopedic patients undergoing surgery often experience the highest incidence of pain compared to other types of operations [1,2].Deep incision with considerable tissue dissection and muscle, bone, and vascular exposure following major orthopedic surgeries causes intense nociceptive stimulations of the musculoskeletal tissue and signifcant postoperative pain [3].Inadequate management of postoperative pain in orthopedic patients results in delayed recovery time and mobilization and leads to prolonged hospitalization.Additionally, it contributes to increased healthcare costs and reduces patient satisfaction, ultimately impairing their quality of life [4].To manage this postoperative pain in orthopedic surgeries, various techniques such as intravenous analgesia, epidural analgesia, and peripheral nerve block techniques have been employed.
Systemic analgesic agents like narcotics and nonsteroidal anti-infammatory drugs are commonly used for pain relief in orthopedic surgeries.However, they are sometimes moderately efective in major orthopedic surgeries and also come with well-documented side efects such as nausea, vomiting, and respiratory depression [5,6].Although local anesthetic drugs provide adequate analgesia and reduce the need for systemic medication, frequent painful injections would be harmful since they increase the risk of surgical wound infection and hematoma [7].
Continuous wound infltration (CWI) using especially designed catheters is a safe and efective alternative to other regional anesthetic techniques like nerve blocks and spinalepidural anesthesia.Te efectiveness of CWI as a postoperative pain-control technique has been revealed in cardiac, thoracic, extensive gynecologic [8], and orthopedic procedures like arthroscopic ACL surgery [9], bone graft extraction [10], spine surgeries [11], and hip arthroplasty [12].Considering the high incidence of intertrochanteric fracture in the elderly population and the risks associated with using common analgesics (e.g., nonsteroidal anti-infammatory drugs and narcotics) and because of some age-related comorbidities, more efective postoperative pain-control techniques with fewer adverse efects should be sought.
Tis study investigates the efect of continuous wound infusion of bupivacaine on postoperative pain control in intertrochanteric fracture patients undergoing hip nailing surgery.

Methods
Tis randomized clinical trial was conducted in a tertiary hospital for orthopedic surgery afliated with Shiraz University of Medical Sciences.It involved intertrochanteric fracture patients scheduled for hip nailing surgery.Te study obtained approval from the university Research Ethics Committee (IR.SUMS.MED.REC.1398.99)and was registered in IRCT (IRCT2018092204108N1).

Study Population.
Patients aged 50 to 80 years with ASA physical status I and II and intertrochanteric fracture were enrolled, excluding those with a history of uncontrolled seizures, infection at the spinal injection site, coagulation disorders, renal and liver failure, allergic reaction to the study agents, drug dependency, and those unable or unwilling to participate.Eligible patients provided written informed consent and were randomly assigned to either the control (control) or intervention (bupivacaine) groups.

Study Design.
Participants underwent preoperative pain score assessments and were instructed on using a PCA pump and a pain assessment tool (numerical rating scale (NRS)).Spinal anesthesia was administered, utilizing hyperbaric bupivacaine 0.5% (12.5 mg) and fentanyl (10 µg) below the L3 intervertebral space with aseptic precautions.At the end of the procedure, in the intervention group, a 15 cm multiorifce tip catheter (InflteraLong 600, PAJUNK, Geisingen, Germany) [13] was placed subfascially (below the fascia iliaca) by the surgeon, and a 30 mL bolus dose of 0.25% bupivacaine (bupivacaine, Mylan, 100 mg/20 mL vial, Delpharm, France) was injected through the catheter immediately after implantation.Te catheter was connected to an elastomeric pump containing 100 mL of 0.25% bupivacaine, providing a constant anesthetic infusion at a rate of 6 mL/hr.No catheter was inserted in the control group.Both groups received intravenous morphine via PCA pumps in the ward, with a 1 mg bolus dose and a 7-minute lockout interval, without a baseline infusion.

Study Assessment.
In the recovery room, the time from the end of the operation to the frst request for analgesia was recorded.Pain intensity was assessed using the NRS every 15 minutes (at 15, 30, 45, and 60 minutes) while the patient was in a static state.Intravenous morphine was administered as the sole analgesic.For NRS <4, no intervention was given.For NRS between 4 and 7, 1 mg IV morphine was given every 5 minutes until the pain intensity dropped below 4. For NRS >7, 2 mg IV morphine was administered until the pain score dropped below 7, and then managed according to the protocol for NRS between 4 and 7. Te total morphine consumption in the recovery room was recorded.
In the ward, pain was managed using a PCA pump loaded with a 1 mg/ml morphine sulfate solution syringe.Additional morphine was given as needed according to the abovementioned protocol.Pain intensity was assessed every 15 minutes in the recovery and every 2 hours within the next 24 hours in the ward.Morphine side efects (respiratory depression, pruritus, urinary retention, nausea, and vomiting) were evaluated every 4 hours.Te complications would be managed according to the hospital local protocols.Te patient's ability to perform activities such as getting in and out of bed, standing from a chair, and walking was assessed using the Cumulated Ambulation Score.

Statistical Analysis.
Data were analyzed using SPSS 21 (IBM, USA) and GraphPad Prism 9 software.Continuous variables were reported as mean ± SD or median (IQR).Independent sample t-test and Mann-Whitney U test were used for continuous variables.Categorical variables were reported as numbers and percentages, and the chi-square test and Fisher exact test were used for categorical outcome variables.Repeated-measures ANOVA test was utilized for analyzing data over time, with Bonferroni correction applied for pairwise comparisons.Statistical signifcance was defned as P < 0.05.

Sample Size and Randomization.
Te research involved 24 participants in each group (control � 24 and bupivacaine � 24).It was determined to ensure an 80% power and a type I error of 0.05 in detecting a 20 mm diference in mean NRS scores.It was assumed that the mean NRS score for the bupivacaine group was 30 mm and that for the control group was 10 mm, with a standard deviation of 24 mm.Tus, a minimum of 24 patients per treatment group was required.Participants were assigned to groups using block randomization with 6 blocks of sizes 6 and 8 (block list extract from https://www.sealedenvelope.com)(Figure 1).

Results
No signifcant diferences were observed between the bupivacaine and control groups with regard to age, sex, weight, BMI, and preoperative pain score (P > 0.05), as shown in Table 1.
Table 2 demonstrates the data regarding morphine administration in the bupivacaine and control groups.

Pain Score in Recovery
Room and Ward.In the recovery room (Figure 2(a)), the repeated-measures analysis showed that neither the time efect nor the interaction between time and groups was statistically signifcant (P � 0.77, P � 0.59).However, the group efect was signifcant (P < 0.001).It means that throughout the recovery room period, the control group consistently had signifcantly higher pain levels (NRS) compared to the bupivacaine group.
In the ward (Figure 2(b)), the repeated-measures analysis revealed signifcant efects for time, the interaction between time and groups, and the group efect (P < 0.001).After applying the Bonferroni correction (P � 0.004) for the 12-time points, it was revealed that at 1, 3, 5, 7, and 10 hours, the pain intensity in the control group was signifcantly higher than that of the bupivacaine group (P < 0.001).Beyond the 10-hour time point, the pain intensity in the control group decreased sharply and although the pain intensity in the control group remained higher than that of the bupivacaine group, this diference was not statistically signifcant (P > 0.004).

Drug-Related
Complications.Te control group had signifcantly higher incidence of nausea and vomiting compared to the bupivacaine group (25% vs. 0%, P � 0.02).However, there were no signifcant diferences between the groups in terms of itching, decreased blood pressure, and urinary retention (P > 0.05).

Patient Satisfaction and Movement Ability.
Te level of patient global satisfaction in the bupivacaine group was signifcantly higher than that of the control group (87.5% vs. 33.3%,P < 0.001).As shown in Table 3, no signifcant differences were observed between the study groups regarding the patient's independence in three activities assessed using the Cumulated Ambulation Score (P > 0.05).

Discussion
Postoperative pain is a major concern after orthopedic surgeries, impacting patients' physical function and quality of life.In this randomized clinical trial, while the demographic data and preoperative pain scores were matched between the groups, we investigated the efect of continuous wound infusion of 0.25% bupivacaine on reducing postoperative pain in patients undergoing hip nailing surgery for intertrochanteric fractures.

Key Findings
(1) Te bupivacaine group had a longer time to the frst request for analgesia and lower morphine consumption both in the recovery room and in the ward compared to the control group.(2) Troughout the frst postoperative 24 hours, patients with continuous bupivacaine infusion had lower mean pain intensity, especially during the recovery room stay and the initial hours in the ward.(3) Bupivacaine infusion increased patients' satisfaction, but there were no signifcant diferences in performing the assessed activities independently between the two groups of the study.(4) Nausea and vomiting were reduced in the bupivacaine group, while itching, hypotension, and urinary retention were similar between groups.

Pain Research and Management
Previous studies have examined the efcacy of continuous local anesthetic infusion in diferent surgical procedures.In a study of patients undergoing total knee arthroplasty (TKA), Karen Toftdahl et al. detected that intraarticular application of analgesics (ropivacaine (2 mg/ mL), 1 mL ketorolac (30 mg/mL), and 1 mL epinephrine (0.5 mg/mL)) signifcantly decreased pain scores during activity and consumption of opioids on the frst postoperative day [14].Ropivacaine continuous wound injection could efciently alleviate postoperative pain and decrease blood loss and the length of hospital stay after spine fusion surgery and laparoscopic cholecystectomy [15,16].
However, our fndings contradict previous studies [17,18] where continuous intra-articular infusion of bupivacaine (0.25%, 4 mL/h) did not provide pain relief or reduce medication use after anterior cruciate ligament reconstruction.Tis lack of efectiveness may be due to the choice and dosage of the local anesthetic.Te fow rate of 4 mL/h may have been insufcient for efective pain relief in a major orthopedic procedure.Improper catheter placement is another possible reason, as it could have prevented bupivacaine from reaching the nociceptors.
In accordance with others [11], except for the incidence of postoperative nausea and vomiting, we observed similar rates of hypotension, itching, and urinary retention in both groups.Furthermore, no cases of respiratory depression occurred.Te lower incidence of nausea and vomiting in our study's intervention group might be due to less morphine consumption compared to the control group.It is worth noting that patients with cardiac and respiratory disease are at increased risk for opioid-induced respiratory dysfunction (OIRD) [19], so the likelihood of respiratory complications is lower in patients with ASA I and II, which were the inclusion criteria for our study.

Conclusion
In conclusion, the efcacy of continuous wound infusion of bupivacaine on postoperative pain control in intertrochanteric fracture patients undergoing hip nailing surgery was tested.Our study showed that continuous wound analgesia injection provides superior pain control, reduces opioid consumption, minimizes nausea and vomiting, and improves patient satisfaction.Tis therapy could be considered as a part of a multimodal analgesia regimen to alleviate postoperative pain of hip nailing surgery.

Table 1 :
Comparison of demographic and baseline data between the study groups.
Te values are represented as mean ± SD or numbers (percentages).

Table 2 :
Information about morphine uses of the studied groups in the recovery room and ward.
* Signifcant P value.Pain Research and Management none of the bupivacaine group patients required additional morphine, while 37.5% of the control group requested extra morphine in addition to what they received from the PCA pump (P � 0.002).