Reduced Opioid Consumption with Pericapsular Nerve Group Block for Hip Surgery: A Randomized, Double-Blind, Placebo-Controlled Trial

The pericapsular nerve group (PENG) block targets the nerves innervating the anterior hip surface; however, few studies on this technique are currently available. We investigated the effects of the PENG block on postoperative opioid consumption after a hip surgery. This was a randomized, double-blind, placebo-controlled study conducted at a single institution. Fifty patients undergoing hip surgery were randomly allocated, 25 in each group, to receive a PENG block either using 25 mL of 0.5% ropivacaine (PENG group) or 25 mL of saline (control group). The primary outcome was the total opioid consumption 24 h postoperatively. The secondary outcomes were postoperative pain scores, time to first opioid demand, sensory block efficiency, quadriceps muscle strength, complications, and patient satisfaction. Compared with those in the control group, patients in the PENG group had a significantly lower total opioid consumption 24 h postoperatively (440.72 ± 242.20 μg vs. 611.07 ± 313.89 μg, P = 0.037) and significantly lower pain scores at 30 min postblock and 6 postoperatively (P < 0.001 and P < 0.001, respectively). The time to first opioid demand was significantly shorter in the control group than in the PENG group (P < 0.001). Sensory block effectiveness was better in the PENG group 30 min postblock and 6 and 12 h postoperatively than in the control group. Patient satisfaction was also better in the PENG group than in the control group. There were no differences in the other outcomes. The PENG block reduced the total opioid consumption in the first 24 h after hip surgery with no significant effects on quadriceps muscle strength and complication rate. This study was registered at the Korea Clinical Research Information Service (cris.nih.go.kr; Reg. No. KCT0006348) on July 16, 2021.


Introduction
A hip fracture is an orthopedic emergency with a high mortality rate [1]. In patients with hip fractures, perioperative pain control is signifcantly important as inadequately controlled pain can impair early rehabilitation and functional recovery and reduce patient satisfaction after surgery [2,3]. In addition, efective perioperative analgesia minimizes the need for intravenous opioid use and thereby reduces the incidence of opioid-related adverse efects [4,5]. Ultrasound-guided peripheral nerve blocks for hip surgery, such as the femoral nerve block (FNB), fascia iliaca compartment block (FICB), and lumbar plexus block (LPB), have been widely used as they provide pain relief and reduce the use of opioid and nonopioid analgesics, thus decreasing the rate of analgesia-related side efects [6,7]. However, these peripheral nerve blocks have disadvantages in terms of motor weakness of the quadriceps, which may result in a prolonged hospital stay and the length of rehabilitation.
Te pericapsular nerve group (PENG) block is a relatively recently described nerve block technique targeting the nerves innervating the anterior surface of the hip joint that has excellent analgesic efects and no quadriceps weakness [1]. Te anterior hip joint capsule is innervated by the obturator, accessory obturator, and femoral nerves [1,8,9]. Terefore, Girón-Arango et al. [1] suggested that these nerves should be the main targets for hip analgesia that can be expected to reduce pain and subsequent side efects after a hip surgery.
Tere are currently several case reports and randomized controlled clinical trials of PENG [1,[10][11][12][13][14]. Aliste et al. [10] say that the PENG block results in better preservation of motor function than FICB. Lin et al. [11] report that quadriceps strength was better preserved with the PENG block. In addition, there is clinical research the PENG block is suited for more complete hip analgesia compared with FICB [12]. However, although each of these studies showed the efect of PENG block, they say that further randomized controlled trials using a larger sample size are needed to prove its clinical signifcance. Tis study aimed to investigate the efects of the PENG block for hip surgery on postoperative opioid consumption and related side efects, as well as on quadriceps muscle strength. We hypothesized that total opioid consumption would be lower in the group receiving PENG block up to 24 hours postoperatively, and quadriceps weakness would not be diferent compared to the placebo group. Tus, we determined the efectiveness of the PENG block for hip surgery.

Materials and Methods
Tis was a randomized, double-blind, placebo-controlled study conducted at a single institution. Tis study was approved by the Institutional Review Board (IRB No. DAU-HIRB-21-129, approved on June 23, 2021) and registered at the Korea Clinical Research Information Service in cris.nih.go.kr (KCT0006348) on July 16, 2021, prior to patient recruitment. All patients were informed about the anesthesia and surgery procedures and provided written informed consent before enrollment. Tis study was conducted in accordance with the tenets of the Helsinki Declaration and is reported following the Consolidated Standards for Reporting Trials guidelines. In reporting this study, we adhered to the CONSORT 2010 checklist recommendations.
Te study population included patients aged 30-90 years who were scheduled to undergo hip surgery under general anesthesia at our hospital from July 2021 to January 2022, who had an American Society of Anesthesiologists physical status class I, II, or III, and who had agreed to receive a PENG block. All patients did not receive any other rescue blocks while waiting for surgery. Te exclusion criteria were as follows: an infection in the area where the block is performed, chronic opioid dependence, morbid obesity (body mass index > 35 kg/m 2 ), neurological defcits, bleeding tendency, allergy to ropivacaine (HANLIM Pharmaceutical, Seoul, Korea), poorly controlled diabetes, pregnancy, psychosis, and a lack of consent.
Patients were randomly allocated to receive a PENG block with either 25 mL of 0.5% ropivacaine (PENG group) or 25 mL of isotonic saline solution (control group) before surgery. We used computer-generated randomization with 1 : 1 intergroup ratio. Te random assignment table was prepared using the nQuery Advisor ® version 7.0 (Statsols, BMDP Statistical Software Inc., Cork, Ireland), and the size of the block was randomly selected. Sequentially numbered, sealed envelopes were prepared. A study assistant, not involved in the anesthesia of study participants, would open the sealed envelope containing group allocation and prepare 25 mL of 0.5% ropivacaine or 25 mL of isotonic saline solution. Another assistant would double-check the procedure. To ensure blinding, one anesthesiologist who was masked for group allocation performed the block, and another anesthesiologist who did not perform the block assessed the intraoperative and postoperative efects of the block. Intraoperative block efect refers to measuring the efect 30 minutes after the block procedure. During this time, preparations for surgery were made, so it was described as intraoperative. Other investigators who were not involved in the data collection evaluated the block result. Block result means measuring the success and failure of a block based on the efects of the block collected by the investigator after the block was implemented. Tis fnal investigator, who was aware of the group allocation but did not participate in the actual block procedure, excluded data that met the PENG block failure criteria and then forwarded the fnal data to the statistician. Terefore, the only person who was aware of a block failure was the fnal investigator, who was not involved in the actual block procedure. Investigators, except for the fnal investigator, patients, care providers, outcome assessors, and the statistician were all blinded to the group allocation. Hip surgery was performed by the same surgical team on all patients. In both groups, patients received light sedation with intravenous midazolam 0.03 mg/kg. Acetaminophen 1 g, ketorolac 30 mg, and dexamethasone 0.1 mg/ kg were administered intravenously before surgery as multimodal preemptive analgesia.
Te PENG block was performed with the patients placed in the supine position. A high-frequency linear ultrasound transducer (12-3 MHz; HS40 device; Samsung Medison Ultrasound, Seoul, Republic of Korea) was placed in a transverse plane on the anterior superior iliac spine to identify the anterior inferior iliac spine, iliopubic eminence, and psoas tendon. Using the in-plane technique, the block needle (a 22-gauge Echoplex Plus needle; Vygon Vet. Ltd., UK) was advanced in a lateral-to-medial direction until the needle tip was placed between the iliopubic eminence and psoas tendon. After negative aspiration, 25 mL of 0.5% ropivacaine or saline solution was injected ( Figure 1).
Te block was always performed by the same anesthesiologists who had performed almost 50 PENG blocks before patient enrollment started. Te sensory block was initially assessed 30 min after block administration by pinprick testing using the jagged edges of a broken tongue depressor applied to the skin over the anterior and medial thigh, within the sensory distribution area of the femoral and obturator nerves [13,15]. Block failure was defned as a case in which there was no decrease in the numerical rating scale (NRS) score by 1 point 30 min postblock and there was no sensory decrease in either the anterior or medial region of the thigh. Repeated block assessment was performed 6, 12, and 24 h postoperatively to determine whether the block was continuous. For each innervation territory, the block was evaluated using a 3-point scale: 0 � no block, 1 � analgesia (the patient can feel touch but not cold), and 2 � anesthesia (the patient cannot feel touch) [16].
All patients were induced by standardized endotracheal general anesthesia with propofol (2-2.5 mg/kg), rocuronium 2 Pain Research and Management (0.6-2 mg/kg), and fentanyl (0.9 μg/kg) and were maintained with propofol and sevofurane. Because the PENG block targets peripheral articular branches, surgical wound infltration with local anesthetic was necessary. All patients received a wound infltration of 20 mL ropivacaine 0.375% from the surgeon at the end of the surgical procedure to eliminate any confounding factor linked to the patients' perception of superfcial pain.
For postoperative pain management, all patients received the same multimodal analgesia, which included oral acetaminophen 325 mg and tramadol 37.5 mg at 12 h intervals. In addition, intravenous patient-controlled analgesia (IV-PCA) was prepared at a total volume of 100 mL by mixing 20 μg/kg of fentanyl and 0.6 mg of Ramosetron in a saline solution. Te baseline infusion rate, bolus demand dose, and lock-out time were 1 mL/h, 1 mL, and 10 min, respectively. All patients were trained on the use of the IV-PCA pump (Accufuser Plus M1015M; Woo Young Medical, Seoul, Republic of Korea) before surgery. Te pump was connected at the end of the surgery, and the initial time of IV-PCA was recorded. Opioid consumption was evaluated 24 h after surgery. Patients were instructed to use the pump only if the NRS pain score was greater than 4 points. An additional opioid was administered when the NRS pain score was equal to or greater than 4 points, despite the use of the IV-PCA pump.
Te primary outcome was the cumulative IV fentanyl equivalent (IFE) consumption (μg) during the frst postoperative 24 h. Te remnant volume of the IV-PCA cocktail was measured 24 h after surgery, and the fentanyl dosage used up to that time point was calculated. Te IV morphine was converted to IFE.
Te secondary outcomes included the following: pain score, time to frst opioid demand, sensory block efectiveness 30 min postblock and at 6, 12, and 24 h postoperatively, quadriceps muscle strength at 6, 12, and 24 h postoperatively, postoperative complications, and patient satisfaction. Pain intensity was evaluated using an NRS, with scores ranging from 0 to 10, with 0 indicating the absence of pain and 10 indicating the worst possible pain. Pain scores were recorded before PENG block administration, 30 min postblock, and 6, 12, 18, and 24 h postoperatively. At the time of pain score recording, patients were instructed to perform a straight leg raise of the afected limb to 15°. Te time to frst opioid demand was defned as the time from arrival at the postanesthesia care unit to the frst PCA bolus or other additional opioids, whichever was frst, and was categorized every 3 h until postoperative 24 h. Quadriceps muscle strength on the operated side was evaluated before PENG block administration and at 6, 12, and 24 h postoperatively by knee extension testing in the supine position with the patients' hips fexed at 45°and knees fexed at 90°. Patients were instructed to extend the knee frst against gravity and then against resistance. Knee extension was graded according to a 3-point scale: 0 � normal strength (extension against gravity and resistance), 1 � paresis (extension against gravity but not against resistance), and 2 � paralysis (no extension possible) [10,17]. Any complications occurring within 24 h after surgery were recorded. Patients' general satisfaction was classifed as satisfed or unsatisfed.
Sample size calculation was performed using the nQuery Advisor ® version 7.0 (Statsols, BMDP Statistical Software Inc., Cork, Ireland). Te calculation was based on the average total IV fentanyl consumption with mean ± standard deviation (SD) values for hip surgery in the frst postoperative 24 h at our hospital over the past year. Te retrospective survey of 100 patients after hip surgery revealed a mean ± SD of 630 ± 370 μg during the frst 24 hours after surgery. We decided that the minimum relevant reduction of IV fentanyl consumption was 50% (efect size: 0.851) with a level of signifcance (α) � 0.05 (two-sided) and power 80% (1 − β) for active versus placebo block. Allowing a 20% dropout rate, the required sample size was 58 patients in total [18,19].
All statistical analyses were performed using IBM ® SPSS ® Statistics software version 26.0 (IBM Corp., Armonk, NY, USA). P values less than 0.05 were considered statistically signifcant. Te data are presented frequently with percentages for categorical variables and mean ± SD for continuous variables. Diferences in study participants' characteristics were compared across subgroups with the chi-square test or Fisher's exact test for categorical variables and the independent t-test or Mann-Whitney's U test as appropriate. To check if its distribution is normal, we used Shapiro-Wilk's test. Two-way repeated measures analysis of variance (two-way RM ANOVA) was used to compare repeated measured numeric variables in groups and within each group, and the Bonferroni procedure was applied in post hoc analyses.

Results
During the study period, 58 patients were assessed for eligibility. One patient did not provide informed consent, and one did not meet the inclusion criteria due to previously diagnosed neurological defcits. Te remaining 56 patients were randomly and equally allocated between the two groups. Tree patients in the control group were lost to follow-up. One of them was required to undergo again the surgery within 24 h postoperatively because of bleeding in the surgical site. Te other two patients suddenly wanted to be excluded from this study. Tree patients in the PENG group showed no NRS reduction or sensory decrease; thus, PENG block failed. In total, 50 patients completed this study and could be included in the fnal analysis ( Figure 2). Tere were no clinically relevant diferences between the groups in terms of patient's characteristics (Table 1). Te IFE consumption in the frst postoperative 24 h was signifcantly lower in the PENG group than in the control group (440.72 ± 242.20 μg vs. 611.07 ± 313.89 μg, P � 0.037) (Figure 3 and Table 2).
In a two-way repeated measures ANOVA analysis, NRS signifcantly decreased during the six assessment periods (P < 0.001), and post hoc analyses revealed that this signifcant change in NRS stemmed from a signifcant improvement in both groups. Tis change was diferent between groups (P < 0.001) and the interaction between group and time was also signifcant (P < 0.001), and NRS signifcantly decreased rapidly from postblock 30 min in the PENG group compared to the control group.
Additionally, we performed Mann-Whitney test at each assessment timepoint for exploratory analysis, and Bonferroni-adjusted P values were presented ( Figure 4 and Table 3).
Te time to frst opioid demand was signifcantly different between the two groups, with most patients of the PENG group requiring analgesia after more than 12 h after surgery (Table 4). Statistically signifcant diferences between the groups were also observed in the sensory block efectiveness 30 min postblock and 6 and 12 h postoperatively (P < 0.001); however, there was no signifcant diference at 24 h postoperatively (P � 0.490) ( Figure 5).
Tere were no signifcant intergroup diferences in quadriceps muscle strength at any of the assessment time points (Table 4). Patient's satisfaction was signifcantly greater in the PENG group than in the control group (22 vs. 13, P � 0.005).
Regarding postoperative complications, the incidence of hypotension, nausea, vomiting, dizziness, headache, delirium, respiratory depression, and vascular puncture was similar in the two groups. No local anesthetic toxicity or neurological complications were recorded in either group.

Discussion
In this study, the opioid-sparing efect of the PENG block was less than what we hypothesized. Based on our prior retrospective study, we expected a 50% reduction in IFE consumption in the frst 24 h following surgery; however, the observed reduction was lower. Tis diference remained statistically signifcant, but not clinically. Tis is consistent with international eforts to achieve opioid-free or opioidminimized anesthesia to reduce the risk of addiction and opioid-related side efects due to the long-term use of opioids [17]. Te patients in our control group exhibited higher IFE consumption during the 24 h postoperative period, although a multimodal analgesic regimen was applied.
Although we observed a signifcant decrease in IFE consumption and the NRS pain scores, the majority of patients still required rescue analgesics within 24 h after surgery. Notably, no patients in the PENG group required rescue analgesics during the frst postoperative 6 h, compared with 14 patients in the control group. Although this fnding is diferent from that of Del Buono et al. [14], that the PENG block has the best clinical efcacy during the frst postoperative 24 h with respect to the duration of the block, we could expect the reduction of total opioid consumption and postoperative complications related to opioid consumption until hospital discharge.
Te major targets of the PENG block are the peripheral articular branches of the femoral, obturator, and accessory obturator nerves [1], which dominate the sensory innervation of the medial and anterior aspects of the thigh [13,15]. Terefore, we divided the thigh into two categories (medial and anterior) and investigated the sensory block's efectiveness at several time points. We found signifcantly better block efectiveness in the PENG group 30 min postblock and 6 h postoperatively, but not at 24 h postoperatively. Furthermore, statistically, we observed a signifcant diference in pain score reduction between the groups up to 6 h postoperatively, with a greater pain score reduction in the PENG group than in the control group, although all patients used the IV-PCA pump. Te lesser diference in pain score reduction after 6 h postoperatively is due to the fact that bolus usage and total opioid consumption in the control group were greater than those in the PENG group. Tese may indicate that the duration of the PENG block efect ranges from 6 to 12 h.
Te PENG block had no signifcant efects on the quadriceps muscle strength or incidence of postoperative complications. Tese fndings are consistent with previously reported fndings on the PENG block [11,13]. Anatomical studies have shown that the high branches of the femoral nerve and obturator nerve are distributed in the anterior hip capsule, while the accessory obturator nerve is distributed in the medial hip capsule [9,10,20]. Moreover, the highest concentration of nociceptive fbers was located in the anterior and superolateral hip capsules [20]. As the PENG block can most efectively target the nociceptive fbers, it may be an alternative regional analgesia technique to other peripheral blocks, such as the FNB, FICB, and LPB. It also has a potential motor-sparing efect compared to FICB and FNB. Tis is because it mainly targets the peripheral articular branches [1,20].
In this study, quadriceps muscle strength in the frst 24 h after surgery was intact in the majority of patients in both groups. Preserved quadriceps muscle strength is important because it enables patients to ambulate earlier after hip joint surgery, resulting in reduced pain, fewer complications, and a shorter hospital stay [21][22][23]. However, we observed a decrease in muscle strength in some patients in the PENG group. Yu et al. [24] reported that superfcial local anesthetic injection and needle positioning medial to the psoas tendon may be contributing factors for quadriceps weakness. Some authors have reported a possible obturator motor blockade in the setting of a PENG block if a large anesthetic amount is injected [25]. In fact, we used a larger volume of local anesthetic (25 mL vs. 20 mL) compared with that used by Girón-Arango et al. [1]. As the PENG block is a feld block, volume is essential for its success. Yu et al. [24] reported that some of the large local anesthetics may spread superfcially and result in an inadvertent FNB or FICB, considering the location of the femoral nerve relative to the psoas tendon. Because we used a larger volume for the PENG block in our study, some patients might have quadriceps weakness. In addition, referring to Figure 5, 92% of the patients in the PENG group experienced a sensory decrease and only 4 percent of the patients experienced a complete sensory block. Tese 4% of patients may have been caused by FNB. However, there is a limit to prove this in our study. When we evaluated the sensory block, we relied on the subjective feeling that the patient described. In the case of the patients themselves, they didn't know whether or not they were receiving the placebo injection, so in a small percentage of patients, it was thought that the sensory block may have occurred due to the placebo efect.
Furthermore, the PENG block is often a deeper block, which is why visualizing the needle tip during the procedure can be difcult. Terefore, if the needle tip is positioned medially along the iliopubic eminence, an obturator motor blockade may occur [24,26]. In addition, Acharya and Lamsal [13] reported a technical difculty with the in-plane approach. Tat is, when the needle is introduced laterally, the anterior inferior iliac spine comes in the needle path. Tus, the needle needs to be adjusted, which may lead to missed targets [13]. FICB and FNB are superfcial blocks performed near the target structure of the PENG block. Terefore, superfcial injection of local anesthetics while performing a PENG block may result in inadvertent FICB or FNB, which may explain the presence of quadriceps weakness after surgery [24]. Future studies are required to further investigate this aspect.
In this study, the incidence of postoperative complications, including delirium, respiratory depression, hypotension, nausea, vomiting, headache, dizziness, vascular puncture, and local anesthetic toxicity, was not signifcantly diferent between the two groups. Tis fnding corresponds to the results of previous studies [11,13]. Notably, patients' satisfaction was higher in the PENG group than in the control group.
Tis study has some limitations. First, we administered a single-shot PENG block for postoperative pain relief. Several trials using catheters to prolong the duration of the  Figure 3: Comparison in intravenous fentanyl equivalent consumption (μg) during the frst postoperative 24 hrs, presented as mean ± standard deviation (SD). IV, intravenous; PENG, pericapsular nerve group; control, control group. * A statistically signifcant diference. P values were derived by the independent t-test. Te Shapiro-Wilk test was employed to test the normality assumption.     [27]. Del Buono et al. [14] used catheters to extend the PENG block. Tey left a catheter in the space between the psoas muscle and the iliopubic eminence for postoperative analgesia. No patient required an additional opioid, and no complications were observed during or after catheter removal. Prado-Kittel et al. [15] also performed a continuous PENG block by placing the catheter between the pubic branch and the tendon of the psoas muscle. Tey   found that the continuous PENG block provided excellent pain relief and extended analgesia to include the distal femoral region. However, both of these publications are case series. Tus, it is necessary to establish the safety and efcacy of the single-shot PENG block and to conduct subsequent studies to clarify its clinical signifcance. Moreover, Lee et al. [28] reported that the addition of a low dose of naloxone to 0.375% ropivacaine for FNB prolonged the duration of the time to the frst request for rescue analgesia and reduced the amount of supplementary opioids consumed without any signifcant adverse efects. Terefore, we need to study how to prolong the duration of a single block using ropivacaine with added adjuvants and what adjuvants can be added to ropivacaine to extend the duration of the block. Second, we only investigated patients during the frst postoperative 24 h. Wylde et al. [29] reported that major hip procedures were accompanied by severe pain, particularly within the frst 48 h. Further studies with long-term patient follow-up are required to investigate the efects of the PENG block in relation to chronic pain development. Tird, because IV-PCA has a lock-out time, it was not possible to press whenever the patients wanted, and through preinstructing, patients were instructed to press only when the NRS score was 4 or higher. If it was possible to press at the patients' demand without such instruction or lock-out time, there may have been diferences in total consumption. However, the side efects of opioid overuse should be considered, and both groups had to be assessed at the same time interval because they could not be assessed at every moment, 24 h a day. Moreover, if the pain was not controlled with PCA alone, additional analgesics were administered as necessary and calculated as IFE.

Conclusions
In conclusion, the PENG block with 25 mL of 0.5% ropivacaine signifcantly decreases opioid consumption during the frst postoperative 24 h and reduces pain scores during the frst postoperative 6 h while having no signifcant efects on the quadriceps muscle motor strength. For these reasons, it can be considered for pain management in hip surgery.

Data Availability
It is being stored on the hospital's data server. Due to personal information issues, it cannot be provided collectively. Te authors will provide it separately if there is a later request.

Ethical Approval
Tis study was approved by the Institutional Review Board of the Dong-A University Hospital (IRB No. DAUHIRB-21-129) on June 23, 2021.